Cognitive Trouble a ‘Robust’ Predictor of Psychosis (Source: Medscape, 11.11.2016)
Neurocognitive impairment, particularly involving attention and memory, is a “robust” characteristic of individuals at clinical high risk (CHR) for psychosis.
Clinical high risk individuals were significantly impaired compared with control persons with respect to attention and working memory (P < .001) and declarative memory (P < .001) and performed significantly worse on 14 of 19 neuropsychological tests. But the mean effect size (ES) across the 19 neuropsychological tests was small (Cohen d = 0.30).
However, the 89 CHR individuals who experienced conversion to psychosis had large deficits in attention and working memory and declarative memory (Cohen d, approximately 0.80) compared with control persons and performed significantly worse on these measures than CHR individuals who did not experience conversion to psychosis (Cohen d, 0.28 and 0.48, respectively).
These results were not accounted for by general cognitive ability, current depression, or use of medication, alcohol, or cannabis, the researchers say.
“To our knowledge, this is the largest and most definitive study of cognition in the high-risk period before onset of psychosis/schizophrenia,” Dr Seidman said in a statement. “This is part of a paradigm shift in the way we are focusing on the earlier, prodromal phase of the disorder in an effort to identify those most likely to develop psychosis.”
The distinct profile of performance across domains, especially in those at CHR who subsequently experienced conversion, suggests that “at the incipient psychotic phase, specific forms of neurocognition are affected and are predictive of later psychosis,” they add.
“Neurocognitive tests used in concert with other clinical and psychobiological measures may enhance prediction of psychosis or functional outcome,” the researchers conclude.
New Reference Point
The results provide a new reference point for clinicians and researchers by elucidating the profile of neurocognitive deficits associated with the prodrome as well as their potential as risk markers for conversion to clinical psychosis.
Schizophrenia or Schizophrenias? The Challenge of Genetic Parsing of a Complex Disorder (Centre for Clinical Research in Neuropsychiatry and the School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth. 2015, February )
Schizophrenia is a broad clinical entity defined by arrays of subjective symptoms, behavioral signs, and variable patterns of course.
As early as 1911, Bleuler coined the term schizophrenia due to the non- uniformity of its clinical presentation. He stated that, “it is not a disease in the strict sense, but appears to be a group of diseases”. During subsequent decades of research into its etiology and neurobiology, researchers have explored numerous biological indicators tentatively associated with the disorder, including neurocognitive dysfunction, brain dysmorphology, and neurochemical abnormalities.
In the recent past, genetic linkage and association studies have targeted multiple candidate loci and genes, but failed to demonstrate that any specific gene variant or a combination of genes is either necessary or sufficient to cause schizophrenia. A likely conceptual impediment is that we still do not know whether schizophrenia is a single disease process with pleiotropic manifestations at the level of cerebral organization and symptoms, or a collection of etiologically divergent, only marginally overlapping, disorders.
The symptoms of schizophrenia span a wide range of psychopathology and display an extraordinary amount of inter-individual variability and temporal inconstancy. Diagnosis is based primarily on the interpretation of subjective experiences as reported by the patient. Schizophrenia geneticists are facing a particularly difficult task, seeking to discover specific variants and genes contributing to an over inclusive diagnostic category for which no specific biological substrate has yet been identified. As a consequence, the phenomenological similarity of patients, selected for genetic and other biological research by the current diagnostic criteria, is modest at best, and may be disconcertingly low at worst.
Arnedo et al. proposes a purely data-driven approach to the exploration of the genotype phenotype relationships in schizophrenia and to the resolution of the “missing heritability” problem. The authors re-analyzed the Molecular Genetics of Schizophrenia which employed a structured diagnostic interview (the Diagnostic Interview for Genetic Studies) to characterize the symptom profiles. One of the sets had a risk of 100%, indicating that all members were schizophrenia cases. Different SNP sets were associated with particular symptom patterns, which aggregated into eight tentative clinical syndromes, differing from one another by severity and the ratio of positive to negative symptoms. The authors proposed that the heritability of schizophrenia is not “missing” but is in fact distributed over a large number of genotypic-phenotypic subsets. This supports the hypothesis that schizophrenia is a composite collection of partially overlapping but distinct disorders underpinned by separate genotypic networks.
The study finds tentative support for the proposition that schizophrenia is not a nosological monolith but a collection of partially overlapping clinical syndromes, each of them associated with a relatively discrete set of genetic polymorphisms.