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“To see or not to see: that is the question.” The “Protection-Against-Schizophrenia” (PaSZ) model: evidence from congenital blindness and visuo-cognitive aberrations

Identifieur interne : 002800 ( Ncbi/Merge ); précédent : 002799; suivant : 002801

“To see or not to see: that is the question.” The “Protection-Against-Schizophrenia” (PaSZ) model: evidence from congenital blindness and visuo-cognitive aberrations

Auteurs : Steffen Landgraf [Allemagne] ; Michael Osterheider [Allemagne]

Source :

RBID : PMC:3696841

Abstract

The causes of schizophrenia are still unknown. For the last 100 years, though, both “absent” and “perfect” vision have been associated with a lower risk for schizophrenia. Hence, vision itself and aberrations in visual functioning may be fundamental to the development and etiological explanations of the disorder. In this paper, we present the “Protection-Against-Schizophrenia” (PaSZ) model, which grades the risk for developing schizophrenia as a function of an individual's visual capacity. We review two vision perspectives: (1) “Absent” vision or how congenital blindness contributes to PaSZ and (2) “perfect” vision or how aberrations in visual functioning are associated with psychosis. First, we illustrate that, although congenitally blind and sighted individuals acquire similar world representations, blind individuals compensate for behavioral shortcomings through neurofunctional and multisensory reorganization. These reorganizations may indicate etiological explanations for their PaSZ. Second, we demonstrate that visuo-cognitive impairments are fundamental for the development of schizophrenia. Deteriorated visual information acquisition and processing contribute to higher-order cognitive dysfunctions and subsequently to schizophrenic symptoms. Finally, we provide different specific therapeutic recommendations for individuals who suffer from visual impairments (who never developed “normal” vision) and individuals who suffer from visual deterioration (who previously had “normal” visual skills). Rather than categorizing individuals as “normal” and “mentally disordered,” the PaSZ model uses a continuous scale to represent psychiatrically relevant human behavior. This not only provides a scientific basis for more fine-grained diagnostic assessments, earlier detection, and more appropriate therapeutic assignments, but it also outlines a trajectory for unraveling the causes of abnormal psychotic human self- and world-perception.


Url:
DOI: 10.3389/fpsyg.2013.00352
PubMed: 23847557
PubMed Central: 3696841

Links toward previous steps (curation, corpus...)


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PMC:3696841

Le document en format XML

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</TEI>
<pmc article-type="review-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Front Psychol</journal-id>
<journal-id journal-id-type="iso-abbrev">Front Psychol</journal-id>
<journal-id journal-id-type="publisher-id">Front. Psychol.</journal-id>
<journal-title-group>
<journal-title>Frontiers in Psychology</journal-title>
</journal-title-group>
<issn pub-type="epub">1664-1078</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">23847557</article-id>
<article-id pub-id-type="pmc">3696841</article-id>
<article-id pub-id-type="doi">10.3389/fpsyg.2013.00352</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Psychology</subject>
<subj-group>
<subject>Review Article</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>“To see or not to see: that is the question.” The “Protection-Against-Schizophrenia” (PaSZ) model: evidence from congenital blindness and visuo-cognitive aberrations</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Landgraf</surname>
<given-names>Steffen</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Osterheider</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Department for Forensic Psychiatry and Psychotherapy, District Hospital, University Regensburg</institution>
<country>Regensburg, Germany</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Berlin School of Mind and Brain, Humboldt Universität zu Berlin</institution>
<country>Berlin, Germany</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: Steven Silverstein, University of Medicine and Dentistry of New Jersey, USA</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: Mahesh Menon, University of Toronto, Canada; José Alberto González-Hernández, Hermanos Ameijeiras Hospital, Cuba</p>
</fn>
<corresp id="fn001">*Correspondence: Steffen Landgraf, Department of Forensic Psychiatry and Psychotherapy, District Hospital, University Regensburg, Haus 45, Raum 001, Universitätsstraße 84, 93053 Regensburg, Germany e-mail:
<email xlink:type="simple">steffen.landgraf@ukr.de</email>
</corresp>
<fn fn-type="other" id="fn002">
<p>This article was submitted to Frontiers in Psychopathology, a specialty of Frontiers in Psychology.</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>01</day>
<month>7</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="collection">
<year>2013</year>
</pub-date>
<volume>4</volume>
<elocation-id>352</elocation-id>
<history>
<date date-type="received">
<day>31</day>
<month>1</month>
<year>2013</year>
</date>
<date date-type="accepted">
<day>30</day>
<month>5</month>
<year>2013</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2013 Landgraf and Osterheider.</copyright-statement>
<copyright-year>2013</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0/">
<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.</license-p>
</license>
</permissions>
<abstract>
<p>The causes of schizophrenia are still unknown. For the last 100 years, though, both “absent” and “perfect” vision have been associated with a lower risk for schizophrenia. Hence, vision itself and aberrations in visual functioning may be fundamental to the development and etiological explanations of the disorder. In this paper, we present the “
<bold>P</bold>
rotection-
<bold>A</bold>
gainst-
<bold>S</bold>
chi
<bold>z</bold>
ophrenia” (PaSZ) model, which grades the risk for developing schizophrenia as a function of an individual's visual capacity. We review two vision perspectives: (1) “Absent” vision or how congenital blindness contributes to PaSZ and (2) “perfect” vision or how aberrations in visual functioning are associated with psychosis. First, we illustrate that, although congenitally blind and sighted individuals acquire similar world representations, blind individuals compensate for behavioral shortcomings through neurofunctional and multisensory reorganization. These reorganizations may indicate etiological explanations for their PaSZ. Second, we demonstrate that visuo-cognitive impairments are fundamental for the development of schizophrenia. Deteriorated visual information acquisition and processing contribute to higher-order cognitive dysfunctions and subsequently to schizophrenic symptoms. Finally, we provide different specific therapeutic recommendations for individuals who suffer from visual impairments (who never developed “normal” vision) and individuals who suffer from visual deterioration (who previously had “normal” visual skills). Rather than categorizing individuals as “normal” and “mentally disordered,” the PaSZ model uses a continuous scale to represent psychiatrically relevant human behavior. This not only provides a scientific basis for more fine-grained diagnostic assessments, earlier detection, and more appropriate therapeutic assignments, but it also outlines a trajectory for unraveling the causes of abnormal psychotic human self- and world-perception.</p>
</abstract>
<kwd-group>
<kwd>schizophrenia</kwd>
<kwd>blindness</kwd>
<kwd>visual aberrations</kwd>
<kwd>Protection-Against-Schizophrenia (PaSZ)</kwd>
<kwd>vision therapy</kwd>
<kwd>continuous diagnostic criteria</kwd>
<kwd>early detection</kwd>
<kwd>cognition</kwd>
</kwd-group>
<counts>
<fig-count count="2"></fig-count>
<table-count count="2"></table-count>
<equation-count count="0"></equation-count>
<ref-count count="350"></ref-count>
<page-count count="23"></page-count>
<word-count count="21073"></word-count>
</counts>
</article-meta>
</front>
<body>
<sec id="s1">
<title>Introduction</title>
<sec>
<title>The protection-against-schizophrenia model</title>
<p>“To see or not to see” may be the fundamental question by which we can elucidate the still unknown causes (Insel,
<xref ref-type="bibr" rid="B135">2010</xref>
) of one of the most devastating human experiences – schizophrenia. For the last 100 years, both “absent” and “perfect” vision have been associated with a lower risk for the disorder (Landgraf et al.,
<xref ref-type="bibr" rid="B168">2012</xref>
; Silverstein et al.,
<xref ref-type="bibr" rid="B285">2013</xref>
). Therefore, we argue that vision itself and aberrations in visual functioning may be fundamental to the development of the disorder and, thus, may provide important information about its causes. In this article, we present the “
<bold>P</bold>
rotection-
<bold>A</bold>
gainst-
<bold>S</bold>
chi
<bold>z</bold>
ophrenia” (PaSZ) model by reviewing human visual functioning from two perspectives: (1) “Absent” vision or how congenital blindness contributes to PaSZ and (2) “perfect” vision or how aberrations in visual functioning are associated with an increased risk for psychotic symptomatology. Grading the risk for developing schizophrenia as a function of an individual's visual capacity, we argue that (early) diagnostic and interventional approaches need to be specific to the patient's visual capacity. On the one hand, individuals who suffer from visual deterioration (who previously had “normal” visual skills) may reduce their risk for developing schizophrenia through an
<italic>improvement</italic>
in visual capacity. On the other hand, individuals who suffer from visual impairment (who have never developed “normal” vision) may, in fact, reduce their risk for schizophrenia through a
<italic>decline</italic>
in visual capacity (Figure
<xref ref-type="fig" rid="F1">1</xref>
). Hence, rather than categorizing human behavior into, e.g., “normal” and “mentally disordered,” as has traditionally been the practice of diagnostic manuals (APA,
<xref ref-type="bibr" rid="B12a">2000</xref>
; WHO,
<xref ref-type="bibr" rid="B326">2007</xref>
), our approach may be the first to use a continuous scale to represent psychiatrically relevant human behavior. This not only provides a scientific basis for more fine-grained diagnostic assessments, earlier detection, and more appropriate therapeutic assignments, but this model also outlines a trajectory for unraveling the causes of the schizophrenia disorder.</p>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption>
<p>
<bold>The “
<underline>P</underline>
rotection-
<underline>A</underline>
gainst-
<underline>S</underline>
chi
<underline>z</underline>
ophrenia” (PaSZ) Model.</bold>
The continuous PaSZ model depicts the relative risk for schizophrenia as a function of the continuous variable visual capacity. Whereas both “absent” vision (congenital blindness) and “perfect” vision (“supernormal” vision) may be associated with a decreased risk for schizophrenia, the model suggests that the risk for developing schizophrenia increases from both ends of the visual capacity continuum toward a “peak risk” (Landgraf et al.,
<xref ref-type="bibr" rid="B168">2012</xref>
; Silverstein et al.,
<xref ref-type="bibr" rid="B285">2013</xref>
). The location of this peak risk has yet to be determined experimentally. However, the peak has important implications for the understanding of the etiology, development, and therapy of the disorder: individuals suffering from visual impairment (located to the left of the peak), who never developed “normal” vision, may reduce their risk for developing schizophrenia through a
<italic>decline</italic>
in visual capacity. Individuals suffering from visual deterioration (located to the right of the peak), who previously had “normal” visual skills, may reduce their risk for developing schizophrenia through an
<italic>improvement</italic>
in visual capacity. Note that the model does not make a concrete assumption on the association between vision capacity and risk for schizophrenia (linear, exponential, etc.). Instead, we suggest that extensive longitudinal and epidemiological investigations, also controlling for age-related visual capacity decline (Ofan and Zohary,
<xref ref-type="bibr" rid="B222">2007</xref>
; Cattaneo et al.,
<xref ref-type="bibr" rid="B51a">2008</xref>
), are necessary to elaborate this issue. In this context, visual capacity may comprise but is not limited to measures of visual acuity (near/far), sensitivity to light, motion, and color, visual field size, and stereoscopic vision. To the best of our knowledge, this is the first model that uses a continuous (more vs. less psychotic) rather than a categorical (“normal” vs. “mentally disordered”) approach to represent psychiatrically relevant human behavior. Abbreviations: PaSZ = Protection-Against-Schizophrenia; SZ = schizophrenia; Prodromals = individuals identified at ultra-high risk for developing schizophrenia; 1st episode patients = patients with schizophrenia that have had one (identified) psychotic episode; Chronic patients = patients with schizophrenia that have had at least three (identified) psychotic episodes.</p>
</caption>
<graphic xlink:href="fpsyg-04-00352-g0001"></graphic>
</fig>
<p>Current models of developmental trajectories of schizophrenia emphasize the prognostic value of subclinical disease expressions. In his inspirational
<italic>Nature</italic>
article, National Institute of Mental Health Director Insel (
<xref ref-type="bibr" rid="B135">2010</xref>
) describes
<disp-quote>
<p>“psychosis as a late, potentially preventable stage of the illness” (p. 187).</p>
</disp-quote>
</p>
<p>Thus, current diagnostic criteria and etiological models of the disease may be indicative of only ultimate disease stages. Even more problematic, the
<italic>prognostic</italic>
or prodromal]
<xref ref-type="fn" rid="fn0001">
<sup>1</sup>
</xref>
criteria of schizophrenia are still being defined in terms of diagnostic symptomatology, i.e., sub-threshold phenotypic expressions of actual full-blown psychotic episodes (Klosterkotter et al.,
<xref ref-type="bibr" rid="B154">2001</xref>
; McGorry et al.,
<xref ref-type="bibr" rid="B203">2003</xref>
; Yung et al.,
<xref ref-type="bibr" rid="B335">2005</xref>
). Currently, to be identified as prodromal for an impending psychosis, individuals need to present one of the following three criteria: (1) attenuated (sub-threshold) psychotic symptoms, (2) BLIPS or brief limited intermittent psychotic symptoms (lasting less than 1 week and disappearing spontaneously), and (3) functional deterioration in the presence of vulnerability (they must suffer from schizotypal personality disorder or have a first-degree relative who has psychosis) (McGorry et al.,
<xref ref-type="bibr" rid="B203">2003</xref>
; Miller et al.,
<xref ref-type="bibr" rid="B208">2003</xref>
; Yung et al.,
<xref ref-type="bibr" rid="B335">2005</xref>
). Other descriptions of prodromal individuals, such as basic symptoms (Moyer and Landauer,
<xref ref-type="bibr" rid="B112a">1967</xref>
; Gross,
<xref ref-type="bibr" rid="B112b">1969</xref>
,
<xref ref-type="bibr" rid="B113">1989</xref>
; Klosterkotter et al.,
<xref ref-type="bibr" rid="B153">1997</xref>
,
<xref ref-type="bibr" rid="B154">2001</xref>
) by which early and late prodromal phases are distinguished (Niendam et al.,
<xref ref-type="bibr" rid="B219">2007</xref>
; Schultze-Lutter et al.,
<xref ref-type="bibr" rid="B280">2007</xref>
; Simon et al.,
<xref ref-type="bibr" rid="B286">2007</xref>
),
<xref ref-type="fn" rid="fn0002">
<sup>2</sup>
</xref>
also presume symptom continuity along with the progression of the disease. The (scientifically) recognized stages of schizophrenia include, in fact, the prodrome, the first-episode, and the stabilized chronic syndrome. Problematically, current early detection and intervention are based on the theoretical yet unproven assumption that symptoms of schizophrenia extend continuously from the prodrome to the stabilized syndrome (Gross,
<xref ref-type="bibr" rid="B112b">1969</xref>
,
<xref ref-type="bibr" rid="B113">1989</xref>
; Klosterkotter et al.,
<xref ref-type="bibr" rid="B153">1997</xref>
,
<xref ref-type="bibr" rid="B154">2001</xref>
; Simon et al.,
<xref ref-type="bibr" rid="B287">2006</xref>
; Niendam et al.,
<xref ref-type="bibr" rid="B219">2007</xref>
; Schultze-Lutter et al.,
<xref ref-type="bibr" rid="B280">2007</xref>
; McGorry,
<xref ref-type="bibr" rid="B202">2010</xref>
). Consequently, prodromal approaches have not yielded high predictive power in their ability to identify transitions to full-blown psychosis (Gottesman and Erlenmeyer-Kimling,
<xref ref-type="bibr" rid="B105">2001</xref>
; Miller et al.,
<xref ref-type="bibr" rid="B209">2002</xref>
; McGorry et al.,
<xref ref-type="bibr" rid="B203">2003</xref>
; Yung et al.,
<xref ref-type="bibr" rid="B333">2003</xref>
,
<xref ref-type="bibr" rid="B334">2004</xref>
,
<xref ref-type="bibr" rid="B335">2005</xref>
; Haroun et al.,
<xref ref-type="bibr" rid="B119">2006</xref>
; Olsen and Rosenbaum,
<xref ref-type="bibr" rid="B223">2006a</xref>
,
<xref ref-type="bibr" rid="B224">b</xref>
). In their recent review, Gee and Cannon (
<xref ref-type="bibr" rid="B99">2011</xref>
) found that only about one third of prodromal individuals eventually convert to psychosis. Two thirds remain symptomatic at a sub-threshold level or recover completely. Hence, we and other researchers argue that current diagnostic criteria (APA,
<xref ref-type="bibr" rid="B12a">2000</xref>
) systematically underestimate the individuality of symptoms (Andreasen,
<xref ref-type="bibr" rid="B11">2007</xref>
; Nelson et al.,
<xref ref-type="bibr" rid="B216">2008</xref>
), neglecting, for example, the fact that psychoses are often experienced in phases that include self-disturbances (Parnas et al.,
<xref ref-type="bibr" rid="B230">1998</xref>
; Sass and Parnas,
<xref ref-type="bibr" rid="B276">2001</xref>
,
<xref ref-type="bibr" rid="B277">2003</xref>
) and visuo-cognitive impairments (Elvevag and Goldberg,
<xref ref-type="bibr" rid="B82">2000</xref>
; Andreasen and Black,
<xref ref-type="bibr" rid="B12">2006</xref>
; Keefe and Harvey,
<xref ref-type="bibr" rid="B149">2012</xref>
; Landgraf et al.,
<xref ref-type="bibr" rid="B168">2012</xref>
). This means, first, that prodromal extrapolations of current diagnostic criteria become less valid or less useful the earlier the prognostic verdict is acquired. Second, there may be underlying factors that are not included in the diagnostic criteria of schizophrenia and treatment options; nevertheless, these factors may be crucial for understanding the ontogenetic development and etiology of the disorder. Thus, there is still an imperative need for stage-specific disease progression markers to precisely predict deterioration and the functional outcome. One promising factor for this kind of progression marker is visually mediated cognition.</p>
</sec>
<sec>
<title>Goals of the review</title>
<p>Since the introduction of the term
<italic>“Schizophrenia”</italic>
by Bleuler (
<xref ref-type="bibr" rid="B26">1908</xref>
), a plethora of scientific articles have stressed the importance of vision aberrations in schizophrenia. By contrast, “absent” and “perfect” vision have, to the best of our knowledge, been associated with a lower risk for developing schizophrenia. Hence, visual information acquisition and/or processing at some point in life appears to be necessary but not sufficient for the human brain to develop psychosis. Only disturbed visual processing may be sufficient. We therefore present the idea of the continuous PaSZ model, for which we review two vision-related indicators of the etiology and development of the disease.</p>
<p>In the first part of this paper – the blindness perspective – we review cognitive alterations with regard to real-world mental representations, neurofunctional reorganization, and multisensory integration in congenitally blind individuals. We assess how these altered functions provide insight into the developmental causes of schizophrenia and the protection against it.</p>
<p>In the second part – the vision perspective – we provide evidence for how abnormalities in the visual system can lead to schizophrenia. Specifically, we show that visual information acquisition and processing deficits progress along with the progression of the disease. We describe how perceptual abnormalities contribute to higher-order cognitive dysfunctions and subsequently lead to diagnostic phenotypic expressions (symptoms).</p>
<p>Finally, in the third part – the therapeutic perspective – we review interventional implications of the PaSZ model. Specifically, we show how both an
<italic>increase in visual impairment</italic>
and a
<italic>decrease in visual deterioration</italic>
may contribute to lowering a person's risk for schizophrenia.</p>
</sec>
</sec>
<sec>
<title>The blindness perspective on schizophrenia</title>
<sec>
<title>A whole world without vision</title>
<p>Understanding blindness may shed light on the nature and etiological causes of schizophrenia. Specifically, the ways in which blind individuals perceive and mentally represent the world may hold the key to identifying vision-specific mediations of schizophrenia. Some information can be perceived by only one modality; for example, vision is needed to perceive stars in the sky or hue, and audition is needed to perceive pitch. More importantly, amodal world representations have been proposed to have fundamental importance for the development and expression of schizophrenia (Andreasen,
<xref ref-type="bibr" rid="B11">2007</xref>
; Fletcher and Frith,
<xref ref-type="bibr" rid="B89">2009</xref>
; Insel,
<xref ref-type="bibr" rid="B135">2010</xref>
). Interestingly, since the famous example of William Molyneux's letter to John Locke in 1688, some people have questioned whether or not blindness affects amodal world representations:
<disp-quote>
<p>
<italic>“Suppose a man born blind, and now adult, and then taught by his touch to distinguish between a cube and a sphere of the same metal, and the same bigness, so as to tell, when he felt one and the other, which is the cube, which is the sphere. Suppose then, the cube and the sphere placed on a table, and the blind man to be made to see. Query, whether by sight, before he touched them, he could distinguish, and tell, which is the globe, which is the cube?”</italic>
(Degenaar,
<xref ref-type="bibr" rid="B74">1996</xref>
)</p>
</disp-quote>
</p>
<p>Almost two and a half centuries later, Von Senden (
<xref ref-type="bibr" rid="B318">1932</xref>
) studied patients in whom blindness was surgically cured. These patients could localize but not discriminate between a cube and a sphere immediately after the operation. However, because other researchers have refuted Von Senden's results (Gregory and Wallace,
<xref ref-type="bibr" rid="B112">1963</xref>
; Morgan,
<xref ref-type="bibr" rid="B212">1977</xref>
; Hollins,
<xref ref-type="bibr" rid="B126">1989</xref>
; Cattaneo and Vecchi,
<xref ref-type="bibr" rid="B51">2011</xref>
) and rapid cross-modal transfer indicates that the underlying mental representations may be rather similar in nature (Held et al.,
<xref ref-type="bibr" rid="B123">2011</xref>
), an ultimate conclusion to the question is still missing.</p>
<p>According to the International Classification of Diseases (ICD-10) (WHO,
<xref ref-type="bibr" rid="B326">2007</xref>
), visual impairment is defined as 6/18–3/60 of the visual acuity of an unimpaired sighted individual. Being blind entails less than 3/60 of a sighted person's visual acuity or a central visual field of less than 10°. Whereas 161–259 million individuals suffer from visual impairment worldwide, 37–42 million individuals of the world's population fulfill ICD-10's criteria for blindness (Resnikoff et al.,
<xref ref-type="bibr" rid="B258">2004</xref>
; Dandona and Dandona,
<xref ref-type="bibr" rid="B69">2006</xref>
). About 1.4 million of them are younger than 15 years; 30 million are older than 50. In contrast to individuals with schizophrenia, only 12% of all blind individuals live in developed countries. The most common causes of blindness are cataracts, glaucoma, and age-related macular degeneration (Resnikoff et al.,
<xref ref-type="bibr" rid="B258">2004</xref>
).</p>
<p>Schizophrenia affects approximately 70–80 million individuals worldwide, independent of cultural background, ethnicity, or social status (Andreasen and Black,
<xref ref-type="bibr" rid="B12">2006</xref>
). Men and women are similarly affected (Markowitch,
<xref ref-type="bibr" rid="B195">1997</xref>
). Given the prevalence estimates of both diseases, at least 0.00605% of the world's population, or approximately 450,000 individuals should suffer from both blindness
<italic>and</italic>
schizophrenia. Whereas it is important to keep in mind that the absence of proof (of individuals suffering from both conditions simultaneously) is not proof of absence, the protection mechanism appears specific to blindness (e.g., there are congenitally deaf individuals who become psychotic) and to schizophrenia (e.g., individuals are not protected against other psychiatric diseases) (Silverstein et al.,
<xref ref-type="bibr" rid="B285">2013</xref>
). To account for the lack of individuals who meet the diagnostic criteria for both congenital blindness and schizophrenia, Sanders et al. (
<xref ref-type="bibr" rid="B273">2002</xref>
,
<xref ref-type="bibr" rid="B274">2003</xref>
) have suggested that dynamic adaptations of NMDA (N-Methyl-
<sc>d</sc>
-Aspartic) receptor channels in the visual cortex may account for cognitive functioning that is insusceptible to psychosis in the blind. However, this point of view may be incomplete because functional reorganization in visually deprived individuals also occurs in brain areas other than the visual information processing sites of sighted individuals (Weeks et al.,
<xref ref-type="bibr" rid="B325">2000</xref>
; Burton et al.,
<xref ref-type="bibr" rid="B35">2006</xref>
; Silverstein and Keane,
<xref ref-type="bibr" rid="B284">2011b</xref>
). Reorganization, thus, depends on brain maturation (Kujala et al.,
<xref ref-type="bibr" rid="B164">2000</xref>
) and the functional interaction of subsystems in the
<italic>developing</italic>
brain (Striem-Amit et al.,
<xref ref-type="bibr" rid="B298">2012a</xref>
).</p>
<p>Silverstein and colleagues have a different point of view. According to these authors, cognitive coordination is impaired in patients with schizophrenia due to impaired NMDA ion receptor flow (Phillips and Silverstein,
<xref ref-type="bibr" rid="B236">2003</xref>
; Silverstein and Keane,
<xref ref-type="bibr" rid="B283">2011a</xref>
). Because occipital (perceptual) and non-occipital (cognitive) activity is required for cognitive organization to occur, early AND late visual processing deficits are associated with the progression of the disease and altered cognitive performance. Psychotic symptoms are, therefore, closely related to disturbed visual information acquisition and processing, which may, in turn, result in brain networks and functionality that are susceptible to psychosis. Stated differently, experiencing the world without vision may be qualitatively similar to but functionally different from experiencing the world as a sighted individual. We consequently consider the following questions in this first part of the review: (i) What evidence is there that blind individuals cognitively represent and experience the world similarly to sighted individuals? (ii) What changes in neurofunctional organization and multisensory integration are necessary for blind individuals to experience the world similarly to sighted individuals? (iii) And most decisively for the present review, how do these changes contribute to PaSZ?</p>
</sec>
<sec>
<title>“Blind” perception and cognition</title>
<p>On the one hand, there is no doubt that non-visual perceptual advantages are present in blind individuals (Cattaneo and Vecchi,
<xref ref-type="bibr" rid="B51">2011</xref>
). Congenitally blind individuals have shown superior performance compared to sighted controls, for example, in auditory sound localization and speech discrimination tasks (Muchnik et al.,
<xref ref-type="bibr" rid="B213">1991</xref>
; Lessard et al.,
<xref ref-type="bibr" rid="B183">1998</xref>
; Roder et al.,
<xref ref-type="bibr" rid="B266">1999</xref>
; Kujala et al.,
<xref ref-type="bibr" rid="B164">2000</xref>
) as well as in haptic two-point discrimination tasks (Roder and Neville,
<xref ref-type="bibr" rid="B261">2003</xref>
). Interestingly, cognitive and behavioral development can be delayed to up to 2 years in congenitally blind children compared to sighted ones (Warren,
<xref ref-type="bibr" rid="B323">1994</xref>
). This may be due to the fact that visual information is memorized, discriminated, and explored more quickly than auditory or haptic information. In fact, auditory and haptic
<italic>memory</italic>
is limited due to
<italic>serial</italic>
information channeling; auditory
<italic>discrimination</italic>
and tactile
<italic>exploration</italic>
is limited due to
<italic>simultaneous</italic>
information channeling. This means that specific attention-orienting and stimulus-awareness mechanisms are necessary for visual but not other perceptual domains (Posner et al.,
<xref ref-type="bibr" rid="B245">1976</xref>
; Phillips and Silverstein,
<xref ref-type="bibr" rid="B236">2003</xref>
). These mechanisms, in turn, have been described as relevant for the development of schizophrenia (Butler et al.,
<xref ref-type="bibr" rid="B41">2005</xref>
,
<xref ref-type="bibr" rid="B38">2007</xref>
; Johnson et al.,
<xref ref-type="bibr" rid="B138">2005</xref>
; Kim et al.,
<xref ref-type="bibr" rid="B151">2005</xref>
; Haenschel et al.,
<xref ref-type="bibr" rid="B114">2007</xref>
).</p>
<p>On the other hand, amodal mental representations, e.g., how the idea of a “tree” is represented in the brain, are independent of their perceptual source (Avraamides et al.,
<xref ref-type="bibr" rid="B15">2004</xref>
; Barsalou,
<xref ref-type="bibr" rid="B18">2008</xref>
). In other words, no matter which modality this information is perceived through (e.g., audition, touch, vision), the ultimate mental representations are similar. And this is true for real-world mental representations of blind and sighted individuals as Cattaneo and Vecchi (
<xref ref-type="bibr" rid="B51">2011</xref>
) put it so eloquently:
<disp-quote>
<p>
<italic>“Our brain, indeed, doesn't need our eyes to ‘see’…”</italic>
(p. 3).</p>
</disp-quote>
</p>
<p>In line with this argument, Pascual-Leone and Hamilton (
<xref ref-type="bibr" rid="B232">2001</xref>
) proposed that specialized neural functionality is formed as a consequence of receptive field input to brain structures. Hence, there may be no
<italic>a priori</italic>
functional segregation of the human brain. Instead, the existence of small receptive perceptual fields, which are required for quick categorization, and large receptive fields, which are necessary to coordinate thought processes, result in the specialization of cortical regions for processing “visual” or “auditory” information. The authors refer to the
<italic>metamodal</italic>
brain as a “mixture of expert architecture” (p. 15) (Pascual-Leone and Hamilton,
<xref ref-type="bibr" rid="B232">2001</xref>
) and argue that sighted and congenitally blind individuals have an equivalence of amodal representations.</p>
<p>A plethora of investigations have, in fact, provided evidence of this equivalence. First, higher-order cognitive abilities, and spatial abilities in particular, have shown no differences between congenitally blind and sighted individuals, for example, in mental scanning and rotation (Craig,
<xref ref-type="bibr" rid="B63">1973</xref>
; Marmor and Zaback,
<xref ref-type="bibr" rid="B196">1976</xref>
; Carpenter and Eisenberg,
<xref ref-type="bibr" rid="B48">1978</xref>
; Kerr,
<xref ref-type="bibr" rid="B150">1983</xref>
; Zimler and Keenan,
<xref ref-type="bibr" rid="B337">1983</xref>
; Vecchi et al.,
<xref ref-type="bibr" rid="B314">2004</xref>
) or allocentric referencing tasks (Tinti et al.,
<xref ref-type="bibr" rid="B309">2006</xref>
). Investigations of the mental number line (Moyer and Landauer,
<xref ref-type="bibr" rid="B112a">1967</xref>
; Dehaene et al.,
<xref ref-type="bibr" rid="B75">1999</xref>
; Krueger et al.,
<xref ref-type="bibr" rid="B163">2008</xref>
,
<xref ref-type="bibr" rid="B162">2011</xref>
; Landgraf et al.,
<xref ref-type="bibr" rid="B174">2010b</xref>
) have shown similar spatial representations in congenitally blind and healthy sighted individuals (Castronovo and Seron,
<xref ref-type="bibr" rid="B50">2007</xref>
). Hence, in congenitally blind individuals, equivalent amodal (spatial) representations can apparently be formed from perceptual cues other than vision. Interestingly, in this same experiment, congenitally blind individuals were able to classify the numbers one and two more quickly than sighted individuals. The authors attributed this effect to the serial processing of tactile and auditory information. Blind individuals may be more accustomed to the idea of distinguishing perceptual phenomena with regard to number counting, especially one and two (e.g., counting steps).</p>
<p>Second, whereas a lack of visual input is detrimental to some tasks, the superior performance of sighted individuals has been shown to disappear when visual task demands are increased. For example, in a 3-D working memory task, congenitally blind individuals performed as well as sighted individuals when information input exceeded visual information processing capacities (Cornoldi et al.,
<xref ref-type="bibr" rid="B61">1991</xref>
). Furthermore, in matching standard figures and line drawings, congenitally blind and late blind individuals did not differ in their reaction times and error rates (Heller and Kennedy,
<xref ref-type="bibr" rid="B124">1990</xref>
). The authors interpreted their results as indicating that visual imagery and visual experience appear unnecessary for tactile perspective taking. Interestingly, Vecchi et al. (
<xref ref-type="bibr" rid="B314">2004</xref>
) reported that the memory of locations decreased with an increasing number of visuo-spatial (VS) representations that had to be held in working memory. This shows that higher task demands, such as speed, interactive images, and movement, may account for performance decreases in blind individuals. Remarkably, the performance of schizophrenia patients also declines when task demands are increased, indicating a coping mechanism for imprecise visual information acquisition (Landgraf et al.,
<xref ref-type="bibr" rid="B170">2011a</xref>
,
<xref ref-type="bibr" rid="B171">b</xref>
).</p>
<p>Third, it has been proposed that visual input deprivation may lead not only to perceptual enhancement in congenitally blind individuals (Rauschecker,
<xref ref-type="bibr" rid="B253">1995</xref>
; Lessard et al.,
<xref ref-type="bibr" rid="B183">1998</xref>
; Roder et al.,
<xref ref-type="bibr" rid="B266">1999</xref>
) but also to improved attentional capacities (Cattaneo et al.,
<xref ref-type="bibr" rid="B51a">2008</xref>
). Better performance in higher-order cognitive abilities has, in fact, been observed in various memory span (Tillman and Bashaw,
<xref ref-type="bibr" rid="B308">1968</xref>
; Smits and Mommers,
<xref ref-type="bibr" rid="B292">1976</xref>
; Pozar,
<xref ref-type="bibr" rid="B247">1982</xref>
; Hull and Mason,
<xref ref-type="bibr" rid="B131">1995</xref>
; Roder et al.,
<xref ref-type="bibr" rid="B264">2001</xref>
; Amedi et al.,
<xref ref-type="bibr" rid="B8">2003</xref>
; Roder and Rosler,
<xref ref-type="bibr" rid="B262">2003</xref>
; Raz et al.,
<xref ref-type="bibr" rid="B255">2007</xref>
) and auditory attention tasks (Roder et al.,
<xref ref-type="bibr" rid="B263">1996</xref>
,
<xref ref-type="bibr" rid="B266">1999</xref>
,
<xref ref-type="bibr" rid="B264">2001</xref>
; Roder and Rosler,
<xref ref-type="bibr" rid="B262">2003</xref>
). Van Velzen et al. (
<xref ref-type="bibr" rid="B312">2006</xref>
) investigated early and late attention indicators in congenitally blind and sighted individuals with electroencephalographic (EEG) recordings. The authors found that early but not late attention modulation could be elicited in blind individuals, indicating that late cognitive coordination mechanisms may be important for the development of psychosis. Late attention indicators also depended heavily on having the individual focus on task-relevant external spatial reference frames, an ability that has been compromised in patients with schizophrenia (Dreben et al.,
<xref ref-type="bibr" rid="B77">1995</xref>
; Parnas et al.,
<xref ref-type="bibr" rid="B231">2001</xref>
; Johnson et al.,
<xref ref-type="bibr" rid="B138">2005</xref>
; Cavezian et al.,
<xref ref-type="bibr" rid="B53">2007</xref>
; Coleman et al.,
<xref ref-type="bibr" rid="B58">2009</xref>
; Landgraf et al.,
<xref ref-type="bibr" rid="B171">2011b</xref>
). In fact, patients with chronic schizophrenia have been found to display a deficit in the disengagement and reorientation of attention (Posner et al.,
<xref ref-type="bibr" rid="B244">1988</xref>
; Daban et al.,
<xref ref-type="bibr" rid="B66">2004</xref>
; Gouzoulis-Mayfrank et al.,
<xref ref-type="bibr" rid="B108">2007</xref>
; Kebir et al.,
<xref ref-type="bibr" rid="B146">2008</xref>
,
<xref ref-type="bibr" rid="B147">2010</xref>
) even without medication (Amado et al.,
<xref ref-type="bibr" rid="B5">2009</xref>
). Hence, the interaction between bottom-up and top-down processes may provide insight into the immunity against psychosis that blind individuals appear to have (see the Protective Mechanism “Cognition” in Table
<xref ref-type="table" rid="T1">1</xref>
).</p>
<table-wrap id="T1" position="float">
<label>Table 1</label>
<caption>
<p>
<bold>Protection-against-schizophrenia (PaSZ) – contributions from congenital blindness</bold>
.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" rowspan="1" colspan="1">
<bold>Protective mechanism</bold>
</th>
<th align="left" rowspan="1" colspan="1">
<bold>Functional aspects</bold>
</th>
<th align="left" rowspan="1" colspan="1">
<bold>Affected in blindness</bold>
</th>
<th align="left" rowspan="1" colspan="1">
<bold>Training options for schizophrenia patients</bold>
</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1">Cognition</td>
<td align="left" rowspan="1" colspan="1">Attentional capacities</td>
<td align="left" rowspan="1" colspan="1">Selectively higher capacities</td>
<td align="left" rowspan="1" colspan="1">Attentional training, cognitive remediation (attentiveness, re-orienting, alertness, memory span, stimuli disengagement)</td>
</tr>
<tr>
<td rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">Inhibition of task-irrelevant stimuli</td>
<td align="left" rowspan="1" colspan="1">Higher sophistication</td>
<td align="left" rowspan="1" colspan="1">Strategy flexibility (top-down eye-movement control, verbal vs. spatial strategy use)</td>
</tr>
<tr>
<td rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">Serial processing</td>
<td align="left" rowspan="1" colspan="1">Higher sophistication</td>
<td align="left" rowspan="1" colspan="1">Training of serial information processing (serial memory, counting, inhibition)</td>
</tr>
<tr>
<td rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">Strategic cognitive adaptation</td>
<td align="left" rowspan="1" colspan="1">Greater flexibility to adapt to task demands</td>
<td align="left" rowspan="1" colspan="1">Teaching strategies to circumvent limitations of high task demands (speed paradigms, interactive images, movement control, resource allocation)</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Neurofunctioning</td>
<td align="left" rowspan="1" colspan="1">Amodal representations</td>
<td align="left" rowspan="1" colspan="1">Similar to sighted</td>
<td align="left" rowspan="1" colspan="1">Sensory substitution</td>
</tr>
<tr>
<td rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">Information processing</td>
<td align="left" rowspan="1" colspan="1">Different neurofunctional specificity</td>
<td align="left" rowspan="1" colspan="1">Neurofunctional reorganization (neurofeedback) Compensational neurofunctioning</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Multisensory integration</td>
<td align="left" rowspan="1" colspan="1">Sequence integration</td>
<td align="left" rowspan="1" colspan="1">Haptic or acoustic, reference frames, navigation, self vs. others</td>
<td align="left" rowspan="1" colspan="1">Reliance change on visual information</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Multisensory Integration</td>
<td align="left" rowspan="1" colspan="1">Intermodal interference</td>
<td align="left" rowspan="1" colspan="1">Generally less pronounced</td>
<td align="left" rowspan="1" colspan="1">Recalibration of how information from different modalities is weighed (e.g., social aspects of non-visual stimuli, size estimations, local processing, memory)</td>
</tr>
<tr>
<td rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">Lateralization</td>
<td align="left" rowspan="1" colspan="1">Better interhemispheric information flow</td>
<td align="left" rowspan="1" colspan="1">Improvement of interhemispheric communication and processing (e.g., dichotic listening, Simon effect)</td>
</tr>
<tr>
<td rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">Temporal integration</td>
<td align="left" rowspan="1" colspan="1">Less affected by intermodal distracters</td>
<td align="left" rowspan="1" colspan="1">Less reliance on visual information (e.g., serial processing, time estimation, and perception training)</td>
</tr>
<tr>
<td rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">Imagery</td>
<td align="left" rowspan="1" colspan="1">Similar to sighted</td>
<td align="left" rowspan="1" colspan="1">Recalibration of multisensory specificity (imagery tasks, mental rotation, action monitoring)</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec>
<title>Neurofunctional reorganization and compensation</title>
<p>The ability to behaviorally compensate for visual deprivation is another indication that there are equivalent amodal representations in sighted and congenitally blind individuals (Pascual-Leone and Hamilton,
<xref ref-type="bibr" rid="B232">2001</xref>
; Knauff and May,
<xref ref-type="bibr" rid="B157">2006</xref>
; Cattaneo et al.,
<xref ref-type="bibr" rid="B51a">2008</xref>
). However, because up to 35% of neocortical functioning in sighted humans is devoted to visual information processing (Gilbert and Walsh,
<xref ref-type="bibr" rid="B101">2004</xref>
), blind and sighted individuals may differ considerably in their neurofunctional processing. In sighted individuals, cortical activity has traditionally been ascribed to region-specific functionality (Kanwisher,
<xref ref-type="bibr" rid="B140">2010</xref>
), such as visual information processing being ascribed to occipital activity. However, blindfolding sighted individuals for a 5-days period has been found to lead to behaviorally relevant neurofunctional changes (Kauffman et al.,
<xref ref-type="bibr" rid="B144">2002</xref>
) that mimick the supranormal auditory performance of blind individuals (Rauschecker,
<xref ref-type="bibr" rid="B253">1995</xref>
; Lessard et al.,
<xref ref-type="bibr" rid="B183">1998</xref>
; Roder et al.,
<xref ref-type="bibr" rid="B266">1999</xref>
). This not only implies that neurofunctional reorganization occurs in the adult human brain (Kujala et al.,
<xref ref-type="bibr" rid="B164">2000</xref>
), but also indicates that cortical functionality may be determined by information processing necessities (Cohen et al.,
<xref ref-type="bibr" rid="B56">1997</xref>
) and innate pathways (Striem-Amit et al.,
<xref ref-type="bibr" rid="B300">2012c</xref>
) rather than brain regions.</p>
<p>Blind individuals have been found to employ compensatory neurofunctional strategies to overcome visual information deprivation. Using positron emission tomography (PET), Sadato et al. (
<xref ref-type="bibr" rid="B272">1996</xref>
,
<xref ref-type="bibr" rid="B271">1998</xref>
) were the first to find a relation between activity in the occipital cortex and non-visual perception and cognition. Specifically, the authors found that during braille reading and non-braille haptic tasks, the primary, and medial occipital lobes were activated in individuals who became blind both early and late in life. In sighted individuals, on the other hand, these haptic tasks were associated with activity in non-occipital regions, such as the bilateral inferior parietal lobes, as well as the left primary sensorimotor area, insula, and prefrontal regions. In subsequent studies, congenitally blind individuals have shown recruitment of the occipital cortex during higher linguistic and (Cohen et al.,
<xref ref-type="bibr" rid="B56">1997</xref>
; Burton et al.,
<xref ref-type="bibr" rid="B34">2003</xref>
,
<xref ref-type="bibr" rid="B35">2006</xref>
; Gilbert and Walsh,
<xref ref-type="bibr" rid="B101">2004</xref>
; Raz et al.,
<xref ref-type="bibr" rid="B254">2005</xref>
; Amedi et al.,
<xref ref-type="bibr" rid="B9">2007</xref>
) auditory motion processing (Poirier et al.,
<xref ref-type="bibr" rid="B243">2006</xref>
), as well as during the localization of auditory signals (Weeks et al.,
<xref ref-type="bibr" rid="B325">2000</xref>
), tactile processing (Sadato et al.,
<xref ref-type="bibr" rid="B270">2002</xref>
), and tongue stimulation (Kupers et al.,
<xref ref-type="bibr" rid="B165">2006</xref>
). Finally, even sighted individuals have shown non-visual information processing in visual areas. In a sophisticated transcranial magnet stimulation (TMS) paradigm, Lewald et al. (
<xref ref-type="bibr" rid="B186">2004</xref>
) demonstrated that the temporary disruption of occipital activity can deteriorate auditory localization in sighted individuals.</p>
<p>These results led us to postulate the following two assumptions: first, neurofunctional plasticity in congenitally blind individuals includes reorganization in non-visual cortical areas, which has been confirmed, for example, in lingual and posterior fusiform gyri (Smith and Gasser,
<xref ref-type="bibr" rid="B290">2005</xref>
; Striem-Amit et al.,
<xref ref-type="bibr" rid="B298">2012a</xref>
). Therefore, the reorganization of non-visual cortical areas in patients with schizophrenia may be important for the development of the disorder. Second, non-visual information processing in the occipital lobe of blind individuals resembles visual information processing in the occipital lobes of sighted individuals (Burton et al.,
<xref ref-type="bibr" rid="B36">2010</xref>
). Thus, whereas functional and most likely also structural processing mechanisms are similar between blind and sighted individuals, the contents of the information (visual vs. non-visual) are different.</p>
<p>This has direct consequences for the development of schizophrenia (see also the Protective Mechanism “Neurofunctioning” in Table
<xref ref-type="table" rid="T1">1</xref>
). If brain structures are not utilized according to their functional and structural specificity, this could result in psychosis or at least in subclinical symptoms. For example, as mentioned above, depriving sighted individuals of their vision for 5 days can lead to neurofunctional and cognitive changes (Kauffman et al.,
<xref ref-type="bibr" rid="B144">2002</xref>
). This means that not only eye-related dysfunction but also functional changes in the primary and secondary occipital cortex can lead to hallucinations (Kazui et al.,
<xref ref-type="bibr" rid="B145">2009</xref>
; Schadlu et al.,
<xref ref-type="bibr" rid="B279">2009</xref>
). Further, individuals suffering from the so-called Charles Bonnet Syndrom (CBS) have reported visual hallucinations as a consequence of visual deterioration (ffytche and Howard,
<xref ref-type="bibr" rid="B88">1999</xref>
; ffytche,
<xref ref-type="bibr" rid="B87">2009</xref>
). Hallucinations due to the CBS can vary widely, comprising abstract geometric patterns, mosaic vision (tessellopsia), increased color vision (hyperchomatopsia), and miniturizations and magnifications of objects (micropsia and macropsia), and can occur for several minutes (70%), seconds (18%), or hours (12%) (Hughes,
<xref ref-type="bibr" rid="B130">2013</xref>
). There are two main theories about how CBS develops. The release theory claims that a mixture of impaired and unimpaired neuronal signals from the visual cortex lead to hallucinatory interpretations in the higher-order association cortices. This is similar to our argument that schizophrenia patients can profit from giving
<italic>more</italic>
weight to visual information in multisensory integration tasks. Hence vision training may be supplementarily useful to cognitive remediation programs. On the other hand, the deprivation theory of CBS argues that reduced sensory input may result in spontaneous image production in the visual association cortex, thus leading to visual hallucinations. This implies, as indicated by the PaSZ model, that perceptual deprivation
<italic>per se</italic>
is not sufficient for psychosis protection to occur. Instead, functional and possibly structural cortical reorganization need to be taken into consideration to avoid psychosis. In fact, there is strong evidence that brain regions are not adequately utilized in schizophrenia because patients use more sequential information processing strategies (Fatemi and Folsom,
<xref ref-type="bibr" rid="B85">2009</xref>
; Landgraf et al.,
<xref ref-type="bibr" rid="B170">2011a</xref>
,
<xref ref-type="bibr" rid="B172">c</xref>
) possibly due to impaired higher-order cognitive deficits, i.e., in single- or multisensory integration (Park and Holzman,
<xref ref-type="bibr" rid="B225">1992</xref>
; Park et al.,
<xref ref-type="bibr" rid="B228">2002</xref>
; Tek et al.,
<xref ref-type="bibr" rid="B306">2002</xref>
; Landgraf et al.,
<xref ref-type="bibr" rid="B169">2008</xref>
; Fuller et al.,
<xref ref-type="bibr" rid="B96">2009</xref>
).</p>
</sec>
<sec>
<title>Multisensory integration</title>
<p>The integration of information from multiple modalities has been found to improve performance compared to using one single perceptual channel alone (Calvert et al.,
<xref ref-type="bibr" rid="B46">2003</xref>
). In fact, multisensory integration allows the brain to generate a coherent amodal view of the self and the world (Smith and Gasser,
<xref ref-type="bibr" rid="B290">2005</xref>
). Supramodal information, such as spatial and temporal information, is coded by all human perceptual systems and allows the comparison of multisensory integration between, for example, blind and sighted individuals. For the scope of this review, we restrict our considerations of multisensory integration to temporal and spatial processes that involve haptic, auditory, and, for sighted individuals, visual capacities. For a review of olfactory and gustatory perception regarding visual and auditory multisensory integration, please refer to Walla (
<xref ref-type="bibr" rid="B321">2008</xref>
) or Zampini and Spence (
<xref ref-type="bibr" rid="B336">2012</xref>
).</p>
<p>Efficient multisensory integration remaps information into amodal representations. In the absence of visual input, this remapping may develop differently (see Protective Mechanism “Multisensory Integration” in Table
<xref ref-type="table" rid="T1">1</xref>
) (Hotting et al.,
<xref ref-type="bibr" rid="B127">2004</xref>
; Roder et al.,
<xref ref-type="bibr" rid="B265">2004</xref>
; Wallace et al.,
<xref ref-type="bibr" rid="B322">2004</xref>
). For example, in congenitally blind individuals, judging the temporal order of tactile stimuli with the right or left hand is not affected by whether the hands are in normal or crossed-over positions. By contrast, sighted individuals show longer reaction times when their hands are crossed, implying interference between visual and tactile external frames of reference (Roder et al.,
<xref ref-type="bibr" rid="B265">2004</xref>
,
<xref ref-type="bibr" rid="B260">2007</xref>
; Collignon et al.,
<xref ref-type="bibr" rid="B59">2007</xref>
). Hotting et al. (
<xref ref-type="bibr" rid="B127">2004</xref>
) reported that the influence of task-irrelevant auditory tones for tactile discrimination is stronger in sighted than in congenitally blind individuals. Interestingly, humans deprived of vision between 5 and 24 months after birth due to retinal cataracts showed less auditory-visual interference and integration later in life than normally developing sighted individuals (Putzar et al.,
<xref ref-type="bibr" rid="B250">2007</xref>
). In line with these observations, the brain regions responsible for visual imagery (e.g., the fusiform face area) may retain their functional specificity even decades after the onset of blindness in late blind individuals (Goyal et al.,
<xref ref-type="bibr" rid="B109">2006</xref>
). In fact, there may be a specific critical period during which neurofunctional plasticity to sensory loss is maximal (Sathian,
<xref ref-type="bibr" rid="B278">2005</xref>
). Until now, the duration of that time window has been unclear, but it has been proposed to be between 10 and 14 years for visual information processing (Cohen et al.,
<xref ref-type="bibr" rid="B57">1999</xref>
; Ofan and Zohary,
<xref ref-type="bibr" rid="B222">2007</xref>
), implying that this may be a critical period for cortical changes regarding the protection and development of schizophrenia as well. Although changes in cortical functioning might not occur until several years after sensory deprivation (Cattaneo et al.,
<xref ref-type="bibr" rid="B51a">2008</xref>
), the overall evidence implies that ontogenetic development must occur to establish the multi-sensory integration interferences observed in sighted individuals. Therefore, it can be hypothesized that this development may be impaired in patients with schizophrenia, thus leading to impaired or unusual performances in multisensory integration tasks.</p>
<p>In sighted individuals, auditory information processing is heavily influenced by other modalities and prior knowledge. Alain and Arnott (
<xref ref-type="bibr" rid="B3">2000</xref>
) distinguished between auditory attention (allocation of attentional resources to perceptual objects), auditory object discrimination (perception of sound attributes across a certain time period), and auditory event perception (perception of sound at a particular time, in a certain place, and having specific characteristics). The authors argue that auditory information quality impacts cognitive performance in all of these stages. For example, degradation of auditory information influences comprehension and memory differently in younger and older listeners (Pichora-Fuller and Singh,
<xref ref-type="bibr" rid="B239">2006</xref>
). Furthermore, the characteristics of speakers are processed in parallel with semantic information. Whereas female voices are associated with more extraversion and openness, male voices are associated with higher emotional stability and greater agreeableness (Imhof,
<xref ref-type="bibr" rid="B134">2010</xref>
). This is in line with other studies that have shown that identical semantic information is interpreted differently depending on whether the person is perceived as male or female (Addington,
<xref ref-type="bibr" rid="B1">1968</xref>
; Knapp and Hall,
<xref ref-type="bibr" rid="B156">2002</xref>
). Hence, auditory processing is inextricably linked to non-auditory information, thus implying that the working memory demands of listeners include the stream of the sound, semantic cues, and perceptual voice cues. Patients with schizophrenia have been shown to struggle when asked to integrate these perceptual cues with other cues (Hardoy et al.,
<xref ref-type="bibr" rid="B118">2004</xref>
; Leitman et al.,
<xref ref-type="bibr" rid="B180">2005</xref>
; Butler et al.,
<xref ref-type="bibr" rid="B39">2008a</xref>
,
<xref ref-type="bibr" rid="B37">2009</xref>
). Interestingly, integrating non-auditory and auditory information directly from perceptual cues can be tested in multi-sensory integration tasks. For example, clustering task-irrelevant stimuli should not affect the performance of blind individuals if multisensory integration occurs in a manner that is similar to what has been observed in healthy individuals (Alain and Arnott,
<xref ref-type="bibr" rid="B3">2000</xref>
).</p>
<p>Another auditory phenomenon is the so-called “right ear advantage,” which refers to the observation that auditory information is processed with greater ease (more quickly, less erroneously) by the right ear compared to the left. In fact, it has been observed that left frontal lobe lesions diminish the advantage of the right ear (Hugdahl et al.,
<xref ref-type="bibr" rid="B128">2003</xref>
), indicating a functional preference for auditory information processing in the left frontal lobe. Congenitally blind individuals have shown a less pronounced right ear advantage, thus outperforming sighted individuals in, for example, dichotic listening tasks (Hugdahl et al.,
<xref ref-type="bibr" rid="B129">2004</xref>
; Castronovo and Seron,
<xref ref-type="bibr" rid="B50">2007</xref>
). It may be interesting to investigate whether patients with schizophrenia would perform like sighted or blind individuals in this paradigm. If schizophrenia patients' performance more closely resembles the performance of sighted individuals, this would be an indication of their local processing preference. If, however, the patients' performance was more like that of blind individuals, this may be attributable to a lower reliance on multisensory integration.</p>
<p>Congenitally blind individuals have been found to rely less on multisensory integration, thus leading to strategic compensatory behavior. On the one hand, they recognize haptic stimuli more quickly than sighted individuals, due to, for example, more efficient sensory information processing during the first 100 ms after stimulus onset (Roder et al.,
<xref ref-type="bibr" rid="B263">1996</xref>
). On the other hand, however, if blind individuals were to employ an adequate multisensory integration strategy, they might perform equally as well as sighted individuals. In a haptic mental imagery memory task, Cornoldi et al. (
<xref ref-type="bibr" rid="B62">2009</xref>
) showed that congenitally blind individuals performed worse than healthy controls only when they adopted a spatial strategy but not when they adopted a verbal strategy. Mental representations of size are more erroneously influenced by multisensory information in sighted than in blind individuals (Bartley et al.,
<xref ref-type="bibr" rid="B19">1955</xref>
; Bolles and Bailey,
<xref ref-type="bibr" rid="B27">1956</xref>
). Smith et al. (
<xref ref-type="bibr" rid="B291">2005</xref>
) showed that size estimations of real objects are less error-prone in congenitally blind individuals compared to sighted controls. Instead, blind individuals rely more on a haptic memory strategy to perform these tasks. This implies that multisensory integration involving touch depends on task characteristics, and a lack of visual input can be compensated for by adequate strategies (Postma et al.,
<xref ref-type="bibr" rid="B246">2007</xref>
). In fact, perceptual and long-term memory may be used to encounter multisensory integration deficits in blind individuals. Possibly patients with schizophrenia may profit from this strategy as well.</p>
<p>It is noteworthy that multimodal integration has been found to change with age. Warren and Pick (
<xref ref-type="bibr" rid="B323a">1970</xref>
) found that auditory localization is strongly influenced by visual perceptual input in sighted adults but not in sighted children. Furthermore, auditory-proprioceptive integrations may be influenced by the increasing importance of vision with increasing age in sighted individuals. Pitch direction changes are better discriminated by blind individuals than by sighted controls even when the stimuli are presented 10 times more quickly but only when individuals became blind at an early age (Gougoux et al.,
<xref ref-type="bibr" rid="B107">2004</xref>
). Age at the onset of blindness has been shown to regulate the use of visual reference frames in haptic and auditory perception (Roder et al.,
<xref ref-type="bibr" rid="B265">2004</xref>
,
<xref ref-type="bibr" rid="B260">2007</xref>
). However, these effects may also be attributable to the fact that blind individuals show better skills in processing unimodal perceptual inputs (Hotting and Roder,
<xref ref-type="bibr" rid="B126a">2004</xref>
; Hotting et al.,
<xref ref-type="bibr" rid="B127">2004</xref>
). More importantly, for congenitally blind individuals, if no change was observed across time in these functions, the weighing of intermodal information could be assumed to follow different developmental trajectories in blind and sighted individuals. Regarding schizophrenia, patients may start out with already impaired preconditions in their multi-sensory integration abilities. Hence, visual information in patients with schizophrenia may not be given enough multisensory integration weight. Instead, in their attempt to compensate perceptually, schizophrenia patients would integrate more perceptual information from other modalities than sighted controls, possibly leading to their preference for local information processing (Landgraf et al.,
<xref ref-type="bibr" rid="B171">2011b</xref>
).</p>
</sec>
</sec>
<sec>
<title>The vision perspective on schizophrenia</title>
<sec>
<title>The vision-space-body-and-cognitive-identity model of schizophrenia</title>
<p>Thus far, we have argued that the inability to perceive and process visual information prevents congenitally blind individuals from becoming psychotic. Specifically, we have shown that PaSZ in congenitally blind individuals may be associated with the acquisition of information and reorganizations of processing at cognitive, neurofunctional, and multisensory levels of integration. It appears that more than “zero” vision AND impaired visual processing must occur simultaneously in order to render the human brain susceptible to psychosis. This determines the visual impairment part of the PaSZ model (left side of the curve in Figure
<xref ref-type="fig" rid="F1">1</xref>
).</p>
<p>In our laboratory, we have developed a model that shows the processing levels at which the deteriorations in visual capacity contribute to the development of psychosis. The ViSBI, short for
<bold>Vi</bold>
sion-
<bold>S</bold>
pace-
<bold>B</bold>
ody-and-cognitive-
<bold>I</bold>
dentity, model of schizophrenia (Landgraf et al.,
<xref ref-type="bibr" rid="B168">2012</xref>
) shows that deficits in the acquisition and processing of visuo-cognitive information increase along with the progression of the disorder and are, indeed, associated with higher-order cognitive dysfunctions and expression of symptoms. We now turn our attention to “Biomoehrchen schmecken gut” the corresponding visual deterioration part of the PaSZ model (right side of the curve in Figure
<xref ref-type="fig" rid="F1">1</xref>
).</p>
</sec>
<sec>
<title>Visual information acquisition</title>
<p>Visual information acquisition accounts for more than 80% of the perceptual input in humans and is therefore considered to provide the foundation for amodal world representations (Lüer et al.,
<xref ref-type="bibr" rid="B192">1988</xref>
; Becker,
<xref ref-type="bibr" rid="B21">1991</xref>
; Leigh and Zee,
<xref ref-type="bibr" rid="B179">1999</xref>
). Deficits in visual information acquisition have been described extensively in patients with schizophrenia (see “Vision” complex in Figure
<xref ref-type="fig" rid="F2">2</xref>
). Deficits deteriorate along the continuum from the prodrome to the full-blown syndrome, i.e., with the progression of the disease. One of the longest and best-studied types of deteriorations is that of oculomotor deficits. They not only jeopardize the availability of visual information but also impair the spatial and temporal accuracy of individuals. Hence, they are crucial for the formation of concepts of the self and the surrounding world.</p>
<fig id="F2" position="float">
<label>Figure 2</label>
<caption>
<p>
<bold>The Progressive
<underline>Vi</underline>
sion-
<underline>S</underline>
pace-
<underline>B</underline>
ody-and-Cognitive-
<underline>I</underline>
dentity (ViSBI) model of schizophrenia.</bold>
Source: Reprinted with kind permission from Bentham Science Publishers. Note. The progressive ViSBI model stresses vision-related deteriorations from prodrome to chronic syndrome that may lead to schizophrenia. The model comprises four complexes: “Vision,” “Space,” “Body,” and “cognitive Identity. ”The “Vision,” “Space,” and “Body” complexes are reviewed in the sections on “The Vision Perspective on Schizophrenia“ in the current paper. The “Cognitive Identity” complex (shadowed in gray) is hypothesized as a part of the model (see Landgraf et al.,
<xref ref-type="bibr" rid="B168">2012</xref>
). Complexes are sub-divided into specific research areas (e.g., in the “Vision” complex: oculomotricity and scanning) and disease progression status (prodromal, first episode, and chronic schizophrenia patients). Tasks listed in each row indicate deficient performance of the corresponding patient group. Some areas have not been investigated in schizophrenia patients (“suggestions for further research”). The “Visual Input” triangle in the middle indicates that (congenital) blindness may prevent these mechanisms from taking place because visual perceptual input is required for this pattern of aberrations to occur. Abbreviations: prodromal = individuals identified at ultra-high risk for developing schizophrenia; first episode = patients with schizophrenia that have had one (identified) psychotic episode; chronic = patients with schizophrenia that have had at least three (identified) psychotic episodes; SPEM = smooth pursuit eye movements; n-back = spatial n-back task.</p>
</caption>
<graphic xlink:href="fpsyg-04-00352-g0002"></graphic>
</fig>
<p>Oculomotor deficits are least pronounced in prodromal individuals. Only a few studies have demonstrated that prodromal individuals show an increased rate of errors in the antisaccade paradigm (Nieman et al.,
<xref ref-type="bibr" rid="B217">2007</xref>
). In first-episode schizophrenia patients, deficits have been described with regard to antisaccade errors, reaction time, and accuracy (Broerse et al.,
<xref ref-type="bibr" rid="B32">2001</xref>
; Ettinger et al.,
<xref ref-type="bibr" rid="B83">2004</xref>
; Hutton et al.,
<xref ref-type="bibr" rid="B133">2004</xref>
). Furthermore, deficits such as a higher error rate in memory-guided saccades and lower acuity in predictive saccades have been reported (Krebs et al.,
<xref ref-type="bibr" rid="B161">2001</xref>
; Hutton et al.,
<xref ref-type="bibr" rid="B133">2004</xref>
; Keedy et al.,
<xref ref-type="bibr" rid="B148">2006</xref>
). In chronic patients, all these deficits have been observed (e.g., Karoumi et al.,
<xref ref-type="bibr" rid="B141">2001</xref>
; Brownstein et al.,
<xref ref-type="bibr" rid="B33">2003</xref>
; Reuter et al.,
<xref ref-type="bibr" rid="B259">2006</xref>
; Radant et al.,
<xref ref-type="bibr" rid="B252">2007</xref>
; Amado et al.,
<xref ref-type="bibr" rid="B6">2008</xref>
; Landgraf et al.,
<xref ref-type="bibr" rid="B169">2008</xref>
). In addition, chronic patients have shown lower acuity in memory-guided saccades (Crawford et al.,
<xref ref-type="bibr" rid="B64">1995a</xref>
; Park et al.,
<xref ref-type="bibr" rid="B227">1995</xref>
; McDowell and Clementz,
<xref ref-type="bibr" rid="B200">1996</xref>
; Radant et al.,
<xref ref-type="bibr" rid="B251">1997</xref>
; Karoumi et al.,
<xref ref-type="bibr" rid="B142">1998</xref>
; McDowell et al.,
<xref ref-type="bibr" rid="B199">2001</xref>
). Although there is some debate about the usefulness of oculomotor deficits in schizophrenia research (e.g., Calkins and Iacono,
<xref ref-type="bibr" rid="B43">2000</xref>
; Brownstein et al.,
<xref ref-type="bibr" rid="B33">2003</xref>
; Calkins et al.,
<xref ref-type="bibr" rid="B42">2004</xref>
,
<xref ref-type="bibr" rid="B45">2008</xref>
; Levy et al.,
<xref ref-type="bibr" rid="B185">2004</xref>
,
<xref ref-type="bibr" rid="B184">2008</xref>
; Boudet et al.,
<xref ref-type="bibr" rid="B28">2005</xref>
; Heydebrand,
<xref ref-type="bibr" rid="B125">2006</xref>
), deficits have been identified as schizophrenia spectrum markers (Amador et al.,
<xref ref-type="bibr" rid="B7">1991</xref>
; Sweeney et al.,
<xref ref-type="bibr" rid="B304">1994</xref>
; Faraone et al.,
<xref ref-type="bibr" rid="B84">1995</xref>
; McDowell and Clementz,
<xref ref-type="bibr" rid="B201">1997</xref>
; Rosenberg et al.,
<xref ref-type="bibr" rid="B267">1997</xref>
; Avila et al.,
<xref ref-type="bibr" rid="B14">2002</xref>
; Kathmann et al.,
<xref ref-type="bibr" rid="B143">2003</xref>
), independent of clinical state (Calkins et al.,
<xref ref-type="bibr" rid="B44">2003</xref>
; Kallimani et al.,
<xref ref-type="bibr" rid="B139">2009</xref>
), or medication (Crawford et al.,
<xref ref-type="bibr" rid="B65">1995b</xref>
; Muller et al.,
<xref ref-type="bibr" rid="B214">1999</xref>
). Furthermore, oculomotor aberrations have been found to fulfill some endophenotypic characteristics (Gottesman and Gould,
<xref ref-type="bibr" rid="B106">2003</xref>
; Calkins et al.,
<xref ref-type="bibr" rid="B45">2008</xref>
).</p>
<p>Another interesting phenomenon regarding the acquisition of visual information is eye-movement strategies. Eye-movement strategies allow for a meaningful and useful succession of visual information input with regard to, for example, goal attainment or planning behavior (Land and Furneaux,
<xref ref-type="bibr" rid="B167">1997</xref>
). Deficits in eye-movement strategies may lead to inefficient visual input and may thus alter an individual's perception of the world. As seen in oculomotor deficits, the severity of eye-movement-strategy deficits increases with the increasing progression and severity of schizophrenia. Prodromal individuals have rarely been studied in visual scanning paradigms. Koethe et al. (
<xref ref-type="bibr" rid="B158">2006</xref>
,
<xref ref-type="bibr" rid="B159">2009</xref>
) showed that abnormal binocular depth inversion was specific to prodromal individuals. Furthermore, first-episode schizophrenia patients have shown an abnormal clustering of fixations and shorter visual scanpaths when scanning faces, landscapes, and abstract patterns (Benson et al.,
<xref ref-type="bibr" rid="B22">2007</xref>
). The largest deteriorations have been reported for stabilized chronic patients with schizophrenia, with fewer fixations, shorter scanpaths, narrower clustering of fixations, and avoidance of predefined features in different visual scanning tasks (e.g., Gaebel et al.,
<xref ref-type="bibr" rid="B98">1987</xref>
; Gordon et al.,
<xref ref-type="bibr" rid="B104">1992</xref>
; Kurachi et al.,
<xref ref-type="bibr" rid="B166">1994</xref>
; Phillips and David,
<xref ref-type="bibr" rid="B235">1997</xref>
; Williams et al.,
<xref ref-type="bibr" rid="B328">1999</xref>
; Loughland et al.,
<xref ref-type="bibr" rid="B190">2002</xref>
,
<xref ref-type="bibr" rid="B191">2004</xref>
; Minassian et al.,
<xref ref-type="bibr" rid="B210a">2005</xref>
; Koethe et al.,
<xref ref-type="bibr" rid="B158">2006</xref>
).</p>
<p>In our own laboratory, we found that, in contrast to healthy controls, chronic schizophrenia patients do not adapt their eye-movement strategies to task demands but instead use similar strategies regardless of task difficulty (Landgraf et al.,
<xref ref-type="bibr" rid="B171">2011b</xref>
). In other words, patients employ the same visual scanning strategy no matter whether the task is easy or difficult. In another study, we even found that chronic schizophrenia patients use a less efficient information acquisition strategy more often than healthy controls (Landgraf et al.,
<xref ref-type="bibr" rid="B170">2011a</xref>
). This implies that inefficient visual information acquisition impedes patients from obtaining (task-) relevant information. Patients have probably noticed that inflexible visual scanning suits most of the demands they encounter in their daily lives. One intriguing question concerning the discussion of blindness and schizophrenia is whether patients are unable to develop other strategies from birth on or whether patients develop the use of only one strategy despite being able to develop others.</p>
<p>These findings imply the following. First, patients with schizophrenia attribute less weight to visual information and are not able to integrate visual information as well as healthy sighted individuals. This means that patients' deficient performances on higher-order cognitive tasks, therefore, can be accounted for by lower-level visual aberrations. Second, patients' visual channels are still “open.” Hence, they are unable to obtain cognitive and neurofunctional reorganization in the same way as blind individuals. This suggests that PaSZ may be available in two directions. On the one hand, if patients learn to put
<italic>more</italic>
weight on visual information in the same way that healthy sighted individuals do, they may lower their risk for a psychotic episode. On the other hand, if patients are taught to put
<italic>less</italic>
weight on visual information and reorganize their neurofunctional information processing, they might be able to stabilize their self and world perceptions in the same way that blind individuals do (See “Vision Training: Decline vs. Improvement” for further details on vision training).</p>
</sec>
<sec>
<title>Visual information processing</title>
<p>Aberrant visual information processing (see “Space” complex in Figure
<xref ref-type="fig" rid="F2">2</xref>
) deteriorates thought processes, contributing to cognitive dysfunctions. It has been acknowledged that cognitive deficits may be one of the best predictors of the development of psychosis (Elvevag and Goldberg,
<xref ref-type="bibr" rid="B82">2000</xref>
; Insel,
<xref ref-type="bibr" rid="B135">2010</xref>
; Keefe and Harvey,
<xref ref-type="bibr" rid="B149">2012</xref>
), and this link could provide the basis for quantitative stage markers of the disease. Most of the paradigms used in schizophrenia cognition research are visual tasks. Moreover, fundamental associations between visuo-spatial (VS) abilities and oculomotor capacities (Leigh and Zee,
<xref ref-type="bibr" rid="B179">1999</xref>
; Hutton et al.,
<xref ref-type="bibr" rid="B133">2004</xref>
; Lawrence et al.,
<xref ref-type="bibr" rid="B177">2004</xref>
; Pierrot-Deseilligny et al.,
<xref ref-type="bibr" rid="B240">2005</xref>
; Milea et al.,
<xref ref-type="bibr" rid="B207">2007</xref>
) indicate that disturbances in the VS domain may stem from oculomotor dysfunctions in patients with schizophrenia. Some of the cognitive domains deficient in patients with schizophrenia include but are not limited to VS memory (Goldman-Rakic,
<xref ref-type="bibr" rid="B103">1994</xref>
; Green et al.,
<xref ref-type="bibr" rid="B111">2000</xref>
; Piskulic et al.,
<xref ref-type="bibr" rid="B241">2007</xref>
; Landgraf et al.,
<xref ref-type="bibr" rid="B172">2011c</xref>
), VS attention (Posner et al.,
<xref ref-type="bibr" rid="B244">1988</xref>
; Danckert et al.,
<xref ref-type="bibr" rid="B68">2004</xref>
; Granholm and Verney,
<xref ref-type="bibr" rid="B110">2004</xref>
; Gouzoulis-Mayfrank et al.,
<xref ref-type="bibr" rid="B108">2007</xref>
), and VS executive functions (Laws,
<xref ref-type="bibr" rid="B178">1999</xref>
; Eisenberg and Berman,
<xref ref-type="bibr" rid="B81">2010</xref>
; Landgraf et al.,
<xref ref-type="bibr" rid="B170">2011a</xref>
,
<xref ref-type="bibr" rid="B171">b</xref>
,
<xref ref-type="bibr" rid="B172">c</xref>
). An impressive number of studies have actually shown that the development of schizophrenia may be associated with these cognitive deficits and that these cognitive deficits could be stage-specific (Heaton et al.,
<xref ref-type="bibr" rid="B121">1994</xref>
; Niendam et al.,
<xref ref-type="bibr" rid="B218">2006</xref>
; Fusar-Poli et al.,
<xref ref-type="bibr" rid="B97">2007</xref>
; Lysaker et al.,
<xref ref-type="bibr" rid="B193">2007</xref>
; Langdon and Ward,
<xref ref-type="bibr" rid="B176">2008</xref>
; Picard et al.,
<xref ref-type="bibr" rid="B237">2009</xref>
; Barlati et al.,
<xref ref-type="bibr" rid="B17">2012</xref>
).</p>
<p>Visuo-spatial cognitive deficits in prodromal individuals are controversial. Some studies have shown a greater number of errors and inferior performance in prodromal individuals compared to healthy controls on spatial delayed-response tasks (Wood et al.,
<xref ref-type="bibr" rid="B332">2003</xref>
; Bartok et al.,
<xref ref-type="bibr" rid="B20">2005</xref>
; Smith et al.,
<xref ref-type="bibr" rid="B289">2006</xref>
; Kimhy et al.,
<xref ref-type="bibr" rid="B152">2007</xref>
; Nieman et al.,
<xref ref-type="bibr" rid="B217">2007</xref>
). Other investigations have not confirmed this observation (Brewer et al.,
<xref ref-type="bibr" rid="B30">2005</xref>
; Lencz et al.,
<xref ref-type="bibr" rid="B182">2006</xref>
; Niendam et al.,
<xref ref-type="bibr" rid="B218">2006</xref>
; Pukrop et al.,
<xref ref-type="bibr" rid="B249">2007</xref>
). The reasons for this controversy have not yet been resolved. Possibly, heterogeneous results are due to imprecise diagnoses of the schizophrenia prodrome (high rate of false negatives), demographic differences between participating groups, or task simplicity (Wood et al.,
<xref ref-type="bibr" rid="B332">2003</xref>
; Conklin et al.,
<xref ref-type="bibr" rid="B60">2005</xref>
; Longevialle-Henin et al.,
<xref ref-type="bibr" rid="B189">2005</xref>
; Fusar-Poli et al.,
<xref ref-type="bibr" rid="B97">2007</xref>
; Pukrop and Klosterkotter,
<xref ref-type="bibr" rid="B248">2010</xref>
). Nevertheless, prodromal individuals have been consistently reported to display deficient performances on the Trail Making Tests (TMT) A and B and the Wechsler Memory Scale (WMS-R) visual reproduction task parts I and II (Hawkins et al.,
<xref ref-type="bibr" rid="B120">2004</xref>
; Brewer et al.,
<xref ref-type="bibr" rid="B30">2005</xref>
).</p>
<p>First-episode patients have shown deficient performances on a number of VS cognitive tasks. For example, they have shown aberrant memory on VS delayed-response tasks (Goldman-Rakic,
<xref ref-type="bibr" rid="B103">1994</xref>
; Park et al.,
<xref ref-type="bibr" rid="B227">1995</xref>
; Rybakowski and Borkowska,
<xref ref-type="bibr" rid="B269">2002</xref>
; Simon et al.,
<xref ref-type="bibr" rid="B286">2007</xref>
), Gestalt perception (Parnas et al.,
<xref ref-type="bibr" rid="B231">2001</xref>
), and the TMT (Rybakowski and Borkowska,
<xref ref-type="bibr" rid="B269">2002</xref>
; Simon et al.,
<xref ref-type="bibr" rid="B286">2007</xref>
). This implies moderate deficits in these patients.</p>
<p>Chronic patients have shown the strongest aberrations on VS tasks. Their deficits include abnormal performance on delayed-response tasks (Park and Holzman,
<xref ref-type="bibr" rid="B225">1992</xref>
; Goldman-Rakic,
<xref ref-type="bibr" rid="B103">1994</xref>
; Glahn et al.,
<xref ref-type="bibr" rid="B102">2003</xref>
; Park et al.,
<xref ref-type="bibr" rid="B229">2003</xref>
; Saperstein et al.,
<xref ref-type="bibr" rid="B275">2006</xref>
; Genderson et al.,
<xref ref-type="bibr" rid="B100">2007</xref>
), figure search (Longevialle-Henin et al.,
<xref ref-type="bibr" rid="B189">2005</xref>
), mental rotation (de Vignemont et al.,
<xref ref-type="bibr" rid="B73">2006</xref>
; Halari et al.,
<xref ref-type="bibr" rid="B115">2006</xref>
), Gestalt perception (O'Donnell et al.,
<xref ref-type="bibr" rid="B221">1996</xref>
; Parnas et al.,
<xref ref-type="bibr" rid="B231">2001</xref>
; Cavezian et al.,
<xref ref-type="bibr" rid="B53">2007</xref>
; Kimhy et al.,
<xref ref-type="bibr" rid="B152">2007</xref>
), spatial span (Cannon et al.,
<xref ref-type="bibr" rid="B47">2000</xref>
; Perry et al.,
<xref ref-type="bibr" rid="B234">2001</xref>
; Manoach et al.,
<xref ref-type="bibr" rid="B194">2005</xref>
; Genderson et al.,
<xref ref-type="bibr" rid="B100">2007</xref>
; Thoma et al.,
<xref ref-type="bibr" rid="B307">2007</xref>
), 3-D real-world navigation Daniel et al. (
<xref ref-type="bibr" rid="B70">2007</xref>
), and referencing (Landgraf et al.,
<xref ref-type="bibr" rid="B173">2010a</xref>
; Mazhari et al.,
<xref ref-type="bibr" rid="B198">2010</xref>
). According to a meta-analysis, there is an overall effect size of −1.00 regarding VS working memory deficits in chronic schizophrenia patients (Piskulic et al.,
<xref ref-type="bibr" rid="B241">2007</xref>
), and these deficits are independent of gender differences (Albus et al.,
<xref ref-type="bibr" rid="B4">1997</xref>
; Reichenberg et al.,
<xref ref-type="bibr" rid="B257">2002</xref>
; Voglmaier et al.,
<xref ref-type="bibr" rid="B317">2005</xref>
; Halari et al.,
<xref ref-type="bibr" rid="B115">2006</xref>
; Wolitzky et al.,
<xref ref-type="bibr" rid="B331">2006</xref>
). Hence, visual information processing appears to be deteriorated in schizophrenia, increases with the progression of the disease, and is related to basic visual acquisition. It may be interesting to compare patients' performance to the performance of the blind in non-visual versions of these paradigms. Even though they have never been able to integrate visual information, blind individuals should outperform patients with schizophrenia on spatial tasks. This would indicate that schizophrenia patients' severely altered visual information processing is strongly associated with their deficits in visual information acquisition. We hypothesize that patients with schizophrenia could especially profit from the neurofunctional and cognitive reorganization observed in blind individuals. The most important question, however, for the consideration of PaSZ is whether or not VS deficits are associated with higher-order cognitive dysfunctions and the symptoms of schizophrenia.</p>
</sec>
<sec>
<title>From visual deterioration to symptoms</title>
<p>Basic visual acquisition and processing dysfunctions in patients with schizophrenia suggest a relation to phenotypic symptomatology. In other words, someone who is not able to obtain accurate and precise (visual) information cannot process this information adequately and thus may suffer from deficient amodal representations of the world. Scientifically, visual scanning deficits and oculomotor deteriorations are related to higher-order cognitive dysfunctions (e.g., theory of mind, perspective taking) and social cognition (Adolphs,
<xref ref-type="bibr" rid="B2">2003</xref>
; Amodio and Frith,
<xref ref-type="bibr" rid="B10">2006</xref>
; Kluwe-Schiavon et al.,
<xref ref-type="bibr" rid="B155">2013</xref>
), as well as to functional outcomes in schizophrenia (Green et al.,
<xref ref-type="bibr" rid="B111">2000</xref>
; Benson et al.,
<xref ref-type="bibr" rid="B22">2007</xref>
). In fact, the temporo-parietal junction (TPJ), involved in perspective taking and theory of mind, and the insular cortex, involved in body-related multisensory integrations (Arzy et al.,
<xref ref-type="bibr" rid="B13">2006</xref>
; Cavanna and Trimble,
<xref ref-type="bibr" rid="B52">2006</xref>
; Danckert and Ferber,
<xref ref-type="bibr" rid="B67">2006</xref>
; Schwabe and Blanke,
<xref ref-type="bibr" rid="B281">2007</xref>
; Mitchell,
<xref ref-type="bibr" rid="B211">2008</xref>
), have been associated with psychotic states (Penfield,
<xref ref-type="bibr" rid="B233">1955</xref>
; Blanke et al.,
<xref ref-type="bibr" rid="B25">2005</xref>
; Vercammen et al.,
<xref ref-type="bibr" rid="B315">2010</xref>
), and impaired whole body and body-part processing in patients with schizophrenia (Tan et al.,
<xref ref-type="bibr" rid="B305">2006</xref>
; Butler et al.,
<xref ref-type="bibr" rid="B40">2008b</xref>
; Suchan,
<xref ref-type="bibr" rid="B302">2008</xref>
). It has been hypothesized that the failure to predict the sensory consequences of motor commands (Frith et al.,
<xref ref-type="bibr" rid="B95">1992</xref>
,
<xref ref-type="bibr" rid="B93">2000a</xref>
,
<xref ref-type="bibr" rid="B94">b</xref>
; Friston and Frith,
<xref ref-type="bibr" rid="B92">1995</xref>
; Blakemore et al.,
<xref ref-type="bibr" rid="B24">2002</xref>
; Frith,
<xref ref-type="bibr" rid="B92a">2005</xref>
) and the improper planning of motor sequences (Delevoye-Turrell et al.,
<xref ref-type="bibr" rid="B76">2003</xref>
; Coello and Delevoye-Turrell,
<xref ref-type="bibr" rid="B55">2007</xref>
; Voss et al.,
<xref ref-type="bibr" rid="B319">2010</xref>
; Waters and Badcock,
<xref ref-type="bibr" rid="B324">2010</xref>
) are both essential to schizophrenia symptoms. Furthermore, motor-related deficits in chronic and first-episode patients with schizophrenia include an altered pattern of self-recognition, for example, in the rubber hand illusion (Franck et al.,
<xref ref-type="bibr" rid="B91">2001</xref>
; Versmissen et al.,
<xref ref-type="bibr" rid="B316">2007</xref>
), the inability to distinguish between the self and others (Schwabe and Blanke,
<xref ref-type="bibr" rid="B281">2007</xref>
; Ebisch et al.,
<xref ref-type="bibr" rid="B80">2012</xref>
), and the identification of the source of self- or externally generated movements (de Vignemont et al.,
<xref ref-type="bibr" rid="B73">2006</xref>
). This implies, on the one hand, that symptom-related deficits in schizophrenia encompass a cognitive component (Bowins,
<xref ref-type="bibr" rid="B29">2011</xref>
). On the other hand, these results point toward the critical role of multisensory integration deficits in patients (Friston and Frith,
<xref ref-type="bibr" rid="B92">1995</xref>
; Fourneret et al.,
<xref ref-type="bibr" rid="B90">2002</xref>
) (see “Body” complex in Figure
<xref ref-type="fig" rid="F2">2</xref>
).</p>
<p>Because multisensoriality and amodality, as well as self and world representations have already been discussed for blind individuals, there are two things to note. First, the neural sites for multisensory integration may differ between patients with schizophrenia and blind individuals. This would mean that dissimilar neurofunctional processes are conducted. These processes and sites may represent good candidates for early detection markers and possible interventions for schizophrenia. Second, blind individuals and patients with schizophrenia have something in common regarding multisensory integration: they assign less weight to visual information. Blind individuals do so due to the absence of visual input; patients with schizophrenia may do so because they have deficits in visual information acquisition and processing. However, the underlying neurofunctional processes differ and may be an indication of the protective mechanisms of blindness. Interestingly, there is a strong association between oculomotor function and multisensory integration (for reviews, see, e.g., Previc,
<xref ref-type="bibr" rid="B247a">1998</xref>
; Milner and Goodale,
<xref ref-type="bibr" rid="B210">2006</xref>
). Dysfunctions of visual information acquisition and processing have actually been found to be correlated with multisensory integration deficits (Park and Holzman,
<xref ref-type="bibr" rid="B226">1993</xref>
; Ross et al.,
<xref ref-type="bibr" rid="B268">1998</xref>
; Jansen et al.,
<xref ref-type="bibr" rid="B136">2002</xref>
; Nieman et al.,
<xref ref-type="bibr" rid="B217">2007</xref>
; Picard et al.,
<xref ref-type="bibr" rid="B237">2009</xref>
) and symptomatology (Gaebel et al.,
<xref ref-type="bibr" rid="B98">1987</xref>
; Lencz et al.,
<xref ref-type="bibr" rid="B181">2003</xref>
; Semerari et al.,
<xref ref-type="bibr" rid="B282">2003</xref>
; Varga et al.,
<xref ref-type="bibr" rid="B313">2007</xref>
) in schizophrenia patients. Moreover, whereas cross-modal influences are dominated by visual information in patients (de Gelder et al.,
<xref ref-type="bibr" rid="B72">2005</xref>
), there is strong evidence that multisensory integration is compromised in chronic patients (Vrtunski et al.,
<xref ref-type="bibr" rid="B320">1993</xref>
; Marvel et al.,
<xref ref-type="bibr" rid="B197">2004</xref>
; Picard et al.,
<xref ref-type="bibr" rid="B238">2008</xref>
; Van den Stock et al.,
<xref ref-type="bibr" rid="B311">2011</xref>
; Castagna et al.,
<xref ref-type="bibr" rid="B49">2012</xref>
). Multisensory facilitation that is established potentially to compensate for deficient unisensory processing in patients with schizophrenia (Javitt,
<xref ref-type="bibr" rid="B137">2009</xref>
; Williams et al.,
<xref ref-type="bibr" rid="B327">2010</xref>
; Stone et al.,
<xref ref-type="bibr" rid="B297">2011</xref>
) may need to be altered with regard to its reliance on visual information processing (de Gelder et al.,
<xref ref-type="bibr" rid="B72">2005</xref>
). Subsequently, patients might benefit from similar cognitive and perceptual protection against the disease as observed in blind individuals. The degree to which the neglect of visual information integration overlaps between blind and schizophrenic patients in multisensory integration may be an indicator of the severity of schizophrenia. We hypothesize that a greater degree of overlap would indicate a less severe schizophrenia outcome.</p>
</sec>
</sec>
<sec>
<title>The therapeutic perspective on schizophrenia</title>
<sec>
<title>Continuous diagnostic criteria</title>
<p>In the previous section, we demonstrated that deteriorations in the acquisition and processing of visual information increase the risk for developing schizophrenia. We established a critical relation between lower- as well as higher-order visual deteriorations and symptom expression in schizophrenia. Whereas fundamental oculomotor and strategic eye-movement deficits may impact the
<italic>acquisition</italic>
of visual information, information
<italic>processing</italic>
deficits point toward VS cognitive aberrations. Both visual information acquisition and processing dysfunctions have been found to increase in severity with the progression of the disorder and are correlated with symptomatic expressions of the disease.</p>
<p>The PaSZ model postulates a continuous relation between visual capacity and the risk of developing schizophrenia. This means that looking at disturbances in vision from a disease progression perspective obviates the need for symptom-based prodromal criteria. Instead, because cognitive deficits can be depicted on much more fine-grained continua than psychotic symptoms (Saperstein et al.,
<xref ref-type="bibr" rid="B275">2006</xref>
; Uhlhaas and Mishara,
<xref ref-type="bibr" rid="B310">2007</xref>
), we argue that a graded stage model of schizophrenia based on visual functioning will contribute to more reliable diagnostic and especially prodromal criteria for schizophrenia. More importantly, however, are the therapeutic implications of the model, which we will discuss in this final section of the review.</p>
</sec>
<sec>
<title>Vision training: decline VS. improvement</title>
<p>So far, we have presented evidence for why the relative risk of developing schizophrenia is allegedly zero for congenitally blind individuals and for individuals with supernormal visual capacities. According to the PaSZ model, the risk of developing schizophrenia increases from both ends of the visual capacity continuum (congenital blindness and “supernormal” vision) toward a “peak risk” (Figure
<xref ref-type="fig" rid="F1">1</xref>
). Thus, depending on the person's initial visual capacity, a decrease in visual impairment or an increase in visual deterioration may similarly
<italic>elevate</italic>
the risk of developing schizophrenia. Consequently, therapeutic efforts may be differentially effective: a
<italic>decline</italic>
in a person's visual capacity (increase of visual impairment) may be more beneficial for an individual with visual impairment who never had “normal” visual skills in the first place. By contrast, an
<italic>improvement</italic>
in a person's visual capacity (decrease of visual deterioration) may be more beneficial for an individual with visual deterioration, that is, who had at some point developed “normal” vision. However, the difference between those two therapeutic approaches may not be clear cut as there is, until now, no clear agreement about (1) how much aberrations of visual functioning corresponds to the highest risk for schizophrenia and (2) whether or not an increase in visual impairment (e.g., via sensory substitution) actually corresponds to a decline in visual functioning.</p>
<p>Nevertheless, vision improvement training is indispensable for PaSZ when the affected individual suffers from visual deterioration. Regarding information
<italic>acquisition</italic>
(see “Acquisition of visual information” in Table
<xref ref-type="table" rid="T2">2</xref>
), patients should be visually trained to obtain the necessary task-relevant visual information and should be given the tools needed to interpret this information. This means that it may be beneficial to train individuals to utilize task-specific and successful eye-movement strategies. Patients should be taught to direct their attention (eye movements) and cognitive resources (pupil dilation, neurofunctionality) to task-relevant visual information: to look where the information is, to avoid information overload, and to access the “big picture” instead of focusing on attention-captivating details (Johnson et al.,
<xref ref-type="bibr" rid="B138">2005</xref>
; Longevialle-Henin et al.,
<xref ref-type="bibr" rid="B189">2005</xref>
; Cavezian et al.,
<xref ref-type="bibr" rid="B53">2007</xref>
; Coleman et al.,
<xref ref-type="bibr" rid="B58">2009</xref>
; Landgraf et al.,
<xref ref-type="bibr" rid="B171">2011b</xref>
). In addition, training should establish a link between how much weight is given to visual and non-visual information in multisensory integration tasks. Patients should learn when it is advantageous to rely on visual information (fast, parallel processing) and when it is advantageous to rely on non-visual information (slow, sequential processing). This may help them to build more reliable amodal representations of the world, to orient themselves better, and to avoid confusion.</p>
<table-wrap id="T2" position="float">
<label>Table 2</label>
<caption>
<p>
<bold>“Protection-against-schizophrenia” (PaSZ) – contributions from visual information acquisition and processing</bold>
.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" rowspan="1" colspan="1">
<bold>Protective mechanism</bold>
</th>
<th align="left" rowspan="1" colspan="1">
<bold>Functional aspects</bold>
</th>
<th align="left" rowspan="1" colspan="1">
<bold>Training options for schizophrenia patients</bold>
</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1">Acquisition of visual information</td>
<td align="left" rowspan="1" colspan="1">Scanning for task-relevant information</td>
<td align="left" rowspan="1" colspan="1">Directing cognitive resources to the target</td>
</tr>
<tr>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">Avoiding information overload</td>
</tr>
<tr>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">Global information processing</td>
</tr>
<tr>
<td rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">Weighing of information</td>
<td align="left" rowspan="1" colspan="1">Learning when to rely on which type of information:
<list list-type="simple">
<list-item>
<p>Visual information = fast, parallel</p>
</list-item>
<list-item>
<p>Non-visual information = slow, sequential</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Processing of visual information</td>
<td align="left" rowspan="1" colspan="1">Neurofunctional sites</td>
<td align="left" rowspan="1" colspan="1">Avoiding brain regions associated with symptoms</td>
</tr>
<tr>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">
<list list-type="simple">
<list-item>
<p>Hallucinations, delusions</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td rowspan="1" colspan="1"></td>
<td align="left" rowspan="1" colspan="1">Sensory substitution</td>
<td align="left" rowspan="1" colspan="1">Learning how to decode visual and spatial information about the environment from non-visual cues</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>Interestingly, visual deterioration has been associated with the risk for criminal behavior (Bachara and Zaba,
<xref ref-type="bibr" rid="B16">1978</xref>
; Zinkus and Gottlieb,
<xref ref-type="bibr" rid="B338">1978</xref>
; Lane,
<xref ref-type="bibr" rid="B175">1980</xref>
; McKay and Brumback,
<xref ref-type="bibr" rid="B204">1980</xref>
; Broder et al.,
<xref ref-type="bibr" rid="B31">1981</xref>
; Clack,
<xref ref-type="bibr" rid="B54">1990</xref>
), one of the strongest indicators of a severe course (Steinert,
<xref ref-type="bibr" rid="B296">1998</xref>
; Nedopil,
<xref ref-type="bibr" rid="B215">2007</xref>
; Hutton et al.,
<xref ref-type="bibr" rid="B132">2012</xref>
), outcome (Leygraf,
<xref ref-type="bibr" rid="B187">1988</xref>
; Haller et al.,
<xref ref-type="bibr" rid="B117">2001</xref>
; Soyka and Morhart-Klute,
<xref ref-type="bibr" rid="B294">2002</xref>
; Soyka et al.,
<xref ref-type="bibr" rid="B293">2002</xref>
; Fazel et al.,
<xref ref-type="bibr" rid="B86">2009</xref>
; Nitschke et al.,
<xref ref-type="bibr" rid="B220">2011</xref>
; Kooyman et al.,
<xref ref-type="bibr" rid="B160">2012</xref>
), and relapse (Soyka et al.,
<xref ref-type="bibr" rid="B295">2004</xref>
; Witt et al.,
<xref ref-type="bibr" rid="B329">2013</xref>
) in schizophrenia. Specifically, it was argued that in very young children and juveniles, perceptual deficits lead to a higher rate of learning disabilities, specifically reading problems. These problems, in turn, may exclude children from further participating in social interactions and, subsequently, could lead to frustration and feelings of exclusion. It was concluded that visual deterioration in children facilitates the development of delinquent and criminal behavior (Slaton and Jorgensen,
<xref ref-type="bibr" rid="B288">1958</xref>
; Dzik,
<xref ref-type="bibr" rid="B78">1966</xref>
,
<xref ref-type="bibr" rid="B79">1975</xref>
). Vision training was established to counteract this problem and, in fact, it has been found to be effective for reducing criminal behavior and recidivism (Berman,
<xref ref-type="bibr" rid="B23">1989</xref>
). Because (i) schizophrenia is strongly associated with criminal behavior AND with visual deterioration and (ii) vision training may reduce criminal behavior, the implementation of vision training may be effective for reducing outcome severity in schizophrenia.</p>
<p>Vision training regarding information processing (see “Processing of visual information” in Table
<xref ref-type="table" rid="T2">2</xref>
) may be achieved by functional reorganization. Patients can be taught to utilize different neurofunctional pathways via neurofeedback. Neurofeedback from functional real-time MRI can be used to regulate one's own brain activity, as has been shown predominantly for affective disorders (Linden et al.,
<xref ref-type="bibr" rid="B188">2012</xref>
; Micoulaud-Franchi et al.,
<xref ref-type="bibr" rid="B206">2012</xref>
) but also for the dopamine system (Sulzer et al.,
<xref ref-type="bibr" rid="B303">2013</xref>
) and in Tourette's syndrome (Messerotti Benvenuti et al.,
<xref ref-type="bibr" rid="B205">2011</xref>
). Patients with schizophrenia may learn to avoid certain brain structures associated with hallucinative experiences, such as the Insula and the TPJ. Instead, activation patterns from blind individuals could be mimicked, that is, patients could be taught to activate the occipital lobe for non-visual information processing. Moreover, lower-
<italic>and</italic>
also higher-order visual information processing may be a target for neurofeedback training in patients with schizophrenia.</p>
<p>Producing declines in a person's visual capacity may be a more radical but also a more effective intervention method especially when the affected individual is suffering from visual impairment. An interesting approach here entails sensory substitution devices for patients with schizophrenia. Intriguingly, vision-deprived individuals can learn to behave in a manner similar to sighted individuals, that is, they may perceive depth, localization, and distance information in real-time from non-visual cues. In a series of inspiring reports, Amedi and colleagues as well as other research groups have shown that visual information can be transmitted via non-visual cues, thus allowing blind individuals to perceive and construct a 3-D image of their environment. The vision-deprived individual obtains VS information auditorily, that is, s/he
<italic>hears</italic>
visual information. Studies have shown that this type of sensory substitution is easily learned by blindfolded and blind individuals (Amedi et al.,
<xref ref-type="bibr" rid="B9">2007</xref>
; Collignon et al.,
<xref ref-type="bibr" rid="B59">2007</xref>
; Reich et al.,
<xref ref-type="bibr" rid="B256">2012</xref>
). With regard to the etiological considerations of schizophrenia, one interesting research question would be whether or not teaching blind individuals “to see” with sensory substitution devices could circumvent the protective mechanisms of congenital blindness against schizophrenia. This means that if individuals who have acquired the ability to decode VS information from non-visual (e.g., auditory) cues did not develop schizophrenia, cortical reorganization would contribute significantly to blind individuals' immunity against psychosis. However, if this was not the case, modality-unspecific world representations would be more crucial. Sensory substitution devices could then be used for patients with schizophrenia to induce neurofunctional compensation and reorganization for impaired (and possibly deteriorated) visual capacities, accordingly.</p>
<p>The fact that functional reorganization due to sensory deprivation is age-specific is important for all vision trainings (Cohen et al.,
<xref ref-type="bibr" rid="B57">1999</xref>
; Sathian,
<xref ref-type="bibr" rid="B278">2005</xref>
; Ofan and Zohary,
<xref ref-type="bibr" rid="B222">2007</xref>
; Cattaneo et al.,
<xref ref-type="bibr" rid="B51a">2008</xref>
). For example, independent of sensory input or visual experience, certain brain areas maintain stimulus selectivity (Striem-Amit et al.,
<xref ref-type="bibr" rid="B299">2012b</xref>
), indicating that the human brain has intrinsic constraints with regard to functional plasticity (Striem-Amit et al.,
<xref ref-type="bibr" rid="B301">2012d</xref>
). These constraints must be taken into account when implementing vision training programs.</p>
<p>Finally, visual capacity and schizophrenia show gender effects. Interestingly, disease-related cognitive deficits are not different for men and women, implying that VS capacities do not affect patients' cognitive deficits (Albus et al.,
<xref ref-type="bibr" rid="B4">1997</xref>
; Halari et al.,
<xref ref-type="bibr" rid="B115">2006</xref>
; Wolitzky et al.,
<xref ref-type="bibr" rid="B331">2006</xref>
; Landgraf et al.,
<xref ref-type="bibr" rid="B173">2010a</xref>
). Nevertheless, there are some distinctions regarding the clinical trajectories of men and women who suffer from schizophrenia. Women are diagnosed at an average age of 26.5 years, whereas men are diagnosed earlier at around 21.4 years (Markowitch,
<xref ref-type="bibr" rid="B195">1997</xref>
). Furthermore, comorbid substance abuse is more frequent in men than in women (Ochoa et al.,
<xref ref-type="bibr" rid="B220a">2012</xref>
). Only 7% of female patients with schizophrenia compared to 22% of male patients are convicted of a crime after being discharged from the forensic facility (Soyka et al.,
<xref ref-type="bibr" rid="B295">2004</xref>
). Demo-graphically, 55% of all female forensic patients are single, 15% are married, and 25% are divorced (Melzer,
<xref ref-type="bibr" rid="B204a">2001</xref>
). By contrast, the vast majority of male forensic patients are single (85%), and only 15% are married or divorced (Leygraf,
<xref ref-type="bibr" rid="B187">1988</xref>
; Nowara,
<xref ref-type="bibr" rid="B220b">1993</xref>
). Suicide rates differ between male and female patients, and men more often successfully commit suicide than women (Markowitch,
<xref ref-type="bibr" rid="B195">1997</xref>
). When researchers have examined the continuity perspective of schizophrenia, they have rarely taken these gender differences into consideration.</p>
</sec>
</sec>
<sec sec-type="conclusion" id="s2">
<title>Conclusion</title>
<p>The ability to see appears necessary but not sufficient for schizophrenia symptoms to develop. The PaSZ model provides a
<italic>continuous</italic>
measure for assessing the risk of schizophrenia. It suggests that, first, “absent” and “perfect” vision are associated with a lower risk of developing the disorder. Second, there is a peak in schizophrenia risk where visual capacity disturbances are “ideal” for the development of psychosis. Third, both declines AND improvements in visual functioning may improve PaSZ depending on the visual capacities (impaired, deteriorated) of the affected individuals. We argue that the understanding of the causes of schizophrenia and its development can be derived from a continuous vision-based model. And in this review, we presented evidence for this point of view from the “blindness” and the “vision” perspective, ultimately deriving interventional recommendations.</p>
<p>In the “blindness” part, we provided clues about what protects visually impaired, that is, congenitally blind individuals from psychosis. While blind individuals have cognitive experiences that are similar to sighted individuals, they show alterations in cognition (attentional capacities, inhibition of task-irrelevant stimuli, serial processing, strategic adaptation), neurofunctioning (amodal representations, information processing reorganization), and multisensory integration (interference, lateralization, temporal integration, imagery). In fact, these considerations raise the question of how much visual information processing is actually necessary for a person to become vulnerable to psychosis. Or, in other words, how little visual impairment is still protective against manifesting psychotic episodes. Future studies should investigate this and other questions regarding candidates for schizophrenia-specific developmental trajectories. In line with these assumptions, we already hypothesized in a former work that tasks that tap into multisensory integration and full-body motor and navigational control may improve discrimination rates between different disease stages (Landgraf et al.,
<xref ref-type="bibr" rid="B168">2012</xref>
). Nevertheless, individual differences may also contribute to qualitative and quantitative alterations in cognitive functioning regarding blind, vision impaired, and sighted schizophrenic patients (Heller and Kennedy,
<xref ref-type="bibr" rid="B124">1990</xref>
; Cornoldi et al.,
<xref ref-type="bibr" rid="B61">1991</xref>
; Andreasen and Black,
<xref ref-type="bibr" rid="B12">2006</xref>
; Andreasen,
<xref ref-type="bibr" rid="B11">2007</xref>
; Cattaneo et al.,
<xref ref-type="bibr" rid="B51a">2008</xref>
).</p>
<p>In the “vision” part, we demonstrated that deteriorated vision, in the form of disturbed visual information acquisition and processing, can lead to the development of schizophrenia symptoms. Specifically, we showed that basic functions, such as oculomotor control and strategic eye movements, are disturbed. Moreover, visuo-cognitive aberrations appear to be based on these deficits, thus resulting in a pattern that leads to motor and self-perception disturbances. These considerations allowed us to pinpoint the etiological underpinnings of schizophrenia because they show that deteriorated visual information acquisition and processing may contribute to the establishment of higher-order cognitive dysfunctions and subsequent symptoms. From a developmental point of view it could be argued that visual capacities may never develop normally in individuals with schizophrenia. If this was the case, the PaSZ model predicts that the majority (if not all) of patients with schizophrenia would be found on the “visual impairment” rather than the “visual deterioration” side. In addition, future research should identify vision- and cognition-related disease stages and determine the time point at which (or the time period in which) interventions may be most important and most effective.</p>
<p>In the “therapeutic” part, we proposed interventional strategies that resulted from the “blindness” and the “vision” perspectives. Decisively, declines in visual capacity (impairment)
<italic>and</italic>
improvements in visual capacity (deterioration) may increase PaSZ. We formulated treatment options, including vision training, with regard to visual information acquisition (scanning for task-relevant information, weighing information) and processing (neurofunctional sites, sensory substitution). In fact, cortical functional reorganization appears to be most crucial for successful interventions and may be induced by neurofeedback or sensory substitution. Hence, whereas patients would undoubtedly profit from being trained to improve and put
<italic>more</italic>
weight on visual functioning, we argue that learning how to decline and put
<italic>less</italic>
weight on visual functioning – the way (congenitally) blind individuals do – may lead to an even stronger protection against psychosis.</p>
<p>In this context, it has to be kept in mind that not all patients suffering from schizophrenia show visual dysfunctions and not all individuals with visual dysfunctions develop schizophrenia. On the one hand, this could be due to the fact that the PaSZ model may only apply to a specific subgroup of patients/individuals. For example, the influence of monocular vision, neurofunctional compensatory mechanisms, and genetic effects need to be investigated in the future. Further, it would be interesting to characterize specific subgroups along etiological dimensions. On the other hand, however, this may also indicate that the current diagnostic (and prodromal) criteria for schizophrenia are too coarse in order to dissociate between different etiological factors. Hence the PaSZ model may provide a fine-grained tool that assesses psychotic symptomatology on the basis of developmental trajectories in much greater detail than current diagnostic procedures. This would result in greater diagnostic precision and, in turn, better therapeutic assignments for affected individuals.</p>
<p>Overall, this review stresses that although the ability to see makes us human (Hegel,
<xref ref-type="bibr" rid="B122">1807</xref>
; Darwin,
<xref ref-type="bibr" rid="B71">1859</xref>
; Plato,
<xref ref-type="bibr" rid="B242">380 BC</xref>
; Wittgenstein,
<xref ref-type="bibr" rid="B330">1921</xref>
), it also precludes our “PaSZ.” In his “Metaphor of the Sun,” the great Greek philosopher Plato lets his teacher, Socrates, argue that the most important of all senses,
<italic>vision</italic>
, determines our ways of thinking and how we experience the world (Halfwassen,
<xref ref-type="bibr" rid="B116">2006</xref>
). Hence, our task of understanding the contribution of the visual system to psychosis will not only eventually lead us to be better able to predict, diagnose, and heal one of the most devastating mental disorders. It will also increase our understanding of how visual functioning influences our ways of thinking and, therefore, our mere existence as human beings.</p>
<sec>
<title>Conflict of interest statement</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
</sec>
</body>
<back>
<ack>
<p>Christine M. Urbanski inspires this work. The paper profited from conversations with Elke van der Meer and the SCHAM group. The authors are deeply indebted to the members of the Department of Forensic Psychiatry and Psychotherapy in Regensburg, as well as to the three reviewers for their constructive comments on earlier drafts of this manuscript. Inka Bauer, Jonathan Moreno, and Jane Zagorski helped with language editing. Finally, the authors would like to openly thank the journal's guest editor, Steven Silverstein, for providing us with this fruitful opportunity of inviting and accepting our paper.</p>
</ack>
<fn-group>
<fn id="fn0001">
<p>
<sup>1</sup>
For intelligibility, we use the term “prodromal” to refer to prodromal, ultra-high risk (UHR), or other patients assumed to experience signs of an impending psychotic episode.</p>
</fn>
<fn id="fn0002">
<p>
<sup>2</sup>
Substantial overlap exists between the different approaches (Simon et al.,
<xref ref-type="bibr" rid="B287">2006</xref>
).</p>
</fn>
</fn-group>
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<affiliations>
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<tree>
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<name sortKey="Landgraf, Steffen" sort="Landgraf, Steffen" uniqKey="Landgraf S" first="Steffen" last="Landgraf">Steffen Landgraf</name>
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