HYPOTHESIS ANDTHEORY ARTICLE published: 21 January 2013 doi: 10.3389/fpsyg.2012.00624 Cognitive and neuroplasticity mechanisms by which congenital or early blindness may confer a protective effect against schizophrenia Steven M. Silverstein 1,2 *,Yushi Wang 1 and Brian P. Keane 1,2,3 1 University Behavioral HealthCare, University of Medicine and Dentistry of New Jersey, Piscataway, NJ, USA 2 Department of Psychiatry, University of Medicine and Dentistry of New Jersey, RobertWood Johnson Medical School, Piscataway, NJ, USA 3 Rutgers University Center for Cognitive Science, Piscataway, NJ, USA Edited by: Michael Green, University of California Los Angeles, USA Reviewed by: Yue Chen, McLean Hospital, USA Jonathan K. Wynn, University of California Los Angeles, USA *Correspondence: Steven M. Silverstein, University Behavioral HealthCare, University of Medicine and Dentistry of New Jersey, 151 Centennial Avenue, Piscataway, NJ 08854, USA. e-mail: silvers1@umdnj.edu Several authors have noted that there are no reported cases of people with schizophre- nia who were born blind or who developed blindness shortly after birth, suggesting that congenital or early (C/E) blindness may serve as a protective factor against schizophrenia. By what mechanisms might this effect operate? Here, we hypothesize that C/E blindness offers protection by strengthening cognitive functions whose impairment characterizes schizophrenia, and by constraining cognitive processes that exhibit excessive flexibility in schizophrenia. After briefly summarizing evidence that schizophrenia is fundamentally a cognitive disorder, we review areas of perceptual and cognitive function that are both impaired in the illness and augmented in C/E blindness, as compared to healthy sighted indi- viduals. We next discuss: (1) the role of neuroplasticity in driving these cognitive changes in C/E blindness; (2) evidence that C/E blindness does not confer protective effects against other mental disorders; and (3) evidence that other forms of C/E sensory loss (e.g., deaf- ness) do not reduce the risk of schizophrenia. We conclude by discussing implications of these data for designing cognitive training interventions to reduce schizophrenia-related cognitive impairment, and perhaps to reduce the likelihood of the development of the disorder itself. Keywords: schizophrenia, blindness, perception, cognition, vision, vision disorders, plasticity INTRODUCTION Over the past 60 years, several authors (Chevigny and Braverman, 1950; Abely and Carton, 1967; Horrobin, 1979; Riscalla, 1980; Feierman, 1982; Sanders et al., 2003) have postulated that con- genital or early (C/E) blindness may serve as a protective factor against the development of schizophrenia. Supporting data derive from several sources, including literature reviews, examination of cohorts of blind patients in psychiatric hospitals, and surveys of agencies that treat large numbers of blind people. The most recent of these Sanders et al. (2003) noted that across all past papers, there has not been even one reported case of a congenitally blind person who developed schizophrenia. While we identified one reported case of a blind “schizophrenic” child (Stewart and Sardo, 1965), the 6-year-old described in that paper had many symp- toms of autism and no symptoms of psychosis, and would almost certainly be diagnosed with an autism-spectrum disorder using DSM-III (American Psychiatric Association, 1980) or later crite- ria. In contrast to the lack of cases of people with C/E blindness who meet modern criteria for schizophrenia, reports do exist of people who develop both blindness and schizophrenia later in life (Checkley and Slade, 1979). We therefore hypothesize that it is the brain changes that occur secondary to C/E blindness – rather than blindness per se – that protect against schizophrenia. How- ever, the mechanisms that confer this apparent protection have not yet been identified. In this paper, we advance the hypothesis that protection occurs by (1) strengthening the perceptual and cognitive functions whose impairment forms the essential nature of schizophrenia; and (2) constraining cognitive processes that are excessively neuroplastic in the illness. In the discussion below, after briefly summarizing the position that schizophrenia is fundamentally a cognitive (i.e., information- processing) disorder, we review evidence that a cluster of per- ceptual and cognitive functions is at once markedly impaired in schizophrenia and significantly augmented in C/E blindness, com- pared to healthy sighted individuals (see Table 1). In subsequent sections, we explicate the role of neuroplasticity in driving these perceptual and cognitive differences, we provide evidence that C/E blindness does not confer protection against other mental disor- ders (e.g., depression, anorexia nervosa) and finally we argue that other forms of C/E sensory loss (e.g., deafness) do not reduce the risk of schizophrenia. We conclude by noting the implications of these data for designing cognitive training interventions for patients and people at high risk for the disorder, and for developing interventions to prevent schizophrenia. SCHIZOPHRENIA AS A COGNITIVE DISORDER: KRAEPELIN AND DEMENTIA PRAECOX REVISITED Although the most obvious clinical features of schizophrenia include psychotic symptoms such as hallucinations, delusions, and bizarre behavior, it has long been thought that such symptoms www.frontiersin.org January 2013 |Volume 3 | Article 624 | 1