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The last 30 years have been marked by the emergence of transformative technologies for the study of brain structure-function relations, and these have been deployed vigorously to help unravel the mysterious causes for, and treatments for the schizophrenia syndrome. Despite the progress, the ultimate goal—to identify a “smoking gun,” in the form of a cognitive, a functional anatomical or a genetic signature responsible for the brain pathology underlying schizophrenia—remains elusive. This collection of articles from global leaders in neuropsychological research on schizophrenia makes poignant how much our thinking has changed over the last three decades, but also that we still have more questions than answers about the fundamental neurobiological underpinnings of schizophrenia.
To put the progress in perspective, we may recall the conclusions of Heaton et al. (1978), following their incisive review of neuropsychological studies of psychiatric disorders:
“The finding that chronic or process schizophrenics look like organics on neuropsychological tests might be considered surprising … One fairly popular explanation … is that … motivational deficiencies and thought disorders are responsible … the implication is that these deficits are functional in nature. This explanation cannot be ruled out on the basis of currently available evidence, but it can be questioned” (page 156); and “[it is likely that] chronic schizophrenics will appear organic on neuropsychological testing because a significant proportion of them are organic” (page 157).
These prescient (and diplomatic) statements signal what was then a prevalent dualistic perspective, the echoes of which are now only faint. For example, one may note that the term “organic” was effectively scrubbed from the DSM-IV, contrasting to its conspicuous presence in the DSM-III. If the 21st century is one day seen as marking the death of dualism in psychiatric taxonomies, this may be considered a victory for neuropsychology, neuroimaging (which provided compelling evidence of structural brain anomalies (Johnstone et al. 1976)), and genetics (confirming heritability of ~80% for the schizophrenia syndrome). Whatever the driving forces, it is now commonplace to seek biological explanations for both the causes and treatments of schizophrenia, and this reflects a sea change in thinking for which neuropsychology can claim significant credit.
The reviews in this issue offer snapshots from multiple perspectives embraced in 21st century research on the neuropsychology of schizophrenia. These papers show that neuropsychology has become central to the study of both the causes and treatments of schizophrenia.
While these studies provide an enormous breadth and depth of coverage, no collection of papers can reflect the complete spectrum of current thinking about the neuropsychology of schizophrenia nor predict well what the “next big thing” may be. Recent genome-wide association studies have highlighted what is likely to be greater complexity of schizophrenia genetics than was previously anticipated, with thousands of common alleles each having small contributions to risk for both schizophrenia and bipolar disorder (The International Schizophrenia Consortium 2009). It is now also clearer that a broad collection of “generalist” genes likely explain the heritability of diverse cognitive traits (Butcher et al. 2006). These observations suggest that neuropsychology research is primed to move beyond the custom of studying cognitive domains that were originally validated with respect to discrete brain lesions, and begin to redefine neuropsychological constructs with respect to distributed neural systems functions, cellular systems and signaling pathways, and molecular variations (Bilder et al. 2009b, c; Sabb et al. 2009).
Neuropsychology research and practice are further poised to capitalize on the revolution in information technology. Not long ago it would be reasonable to believe that the “wisdom of crowds” was an obvious oxymoron. But the success of Wikipedia and other social collaborative networking applications have made it clear that large numbers of individuals can generate novel intellectual products with high utility. Some applications already enable collaborative knowledge-base development for cognitive phenotypes, linking hypotheses about cognitive concepts to the empirical data on which these hypotheses are based (Bilder et al. 2009a, b, c; Sabb et al. 2008), and a new Society for Neuroinformatics in Neuropsychology has just been established (see http://www.scnn.org/). There is further hope that similar efforts can bear fruit for clinical neuropsychology, by establishing collaborative databases and developing open-access assessment instruments. These strategies may one day overcome some of the limitations of laboratory- and clinic-based methods, and enable knowledge to be accumulated from much larger communities, substantially complementing and extending current methods. Working together with patient-oriented networks, there is hope that in another three decades, a special issue on the neuropsychology of schizophrenia will have answers to many of our current questions, and that previously unimaginable enigmata will have replaced those that we confront today.
Supported by the NIH Roadmap for Medical Research/Common Fund, including Consortium for Neuropsychiatric Phenomics grants UL1DE019580 and PL1MH083271.
Disclosures There are no conflicts of interest to report.
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