Persistence, diagnostic specificity and genetic liability for context-processing deficits in schizophrenia

Abstract

Context-processing deficits have been shown in schizophrenia during first-episode, medication-naïve status, that persist after short-term antipsychotic treatment and also in first-degree relatives of individuals with schizophrenia. To confirm longer term persistence of deficits, we examined schizophrenia patients (n=63) during first-episode, medication-naïve status through to one-year follow-up, compared to healthy control (n=83) and non-schizophrenia psychosis comparison (n=47) groups, as well as unaffected first-degree relatives of individuals with schizophrenia (n=31). Context-processing ability assessed by performance on the AX-CPT (Continuous Performance Test) at baseline, 8 weeks, 6 months, and 1 year (relatives only at baseline). Reaction time, error rates and signal detection indices (d′-context) of context processing were analyzed. Linear discriminant analyses (LDA) on early timepoints (baseline, 8 weeks) were conducted to predict confirmatory diagnosis (schizophrenia vs. psychosis control) at 6 months. Schizophrenia patients showed evidence of impaired context-processing relative to both the healthy and psychosis comparator groups at baseline and continued through to 1 year. While context-processing impairments persisted in schizophrenia patients through one year, the impairments in psychosis controls, which were more modest at baseline, remitted at follow-up. First-degree relatives showed deficits that were intermediate between the schizophrenia and healthy control groups. LDA showed 67% classification rates for distinguishing schizophrenia from non-schizophrenia psychosis. The persistence, diagnostic specificity and association with genetic liability give support for context processing impairments serving as a cognitive endophenotype for schizophrenia and that evaluation of context processing could contribute to diagnostic assessments.

Impaired Context Processing is Attributable to Global Neuropsychological Impairment in Schizophrenia and Psychotic Bipolar Disorder

“…2,5,[7][8][9]11,13,22 Rather, we observed that the schizophrenia and schizoaffective disorder groups had comparable false alarm rates on BX and AY trials, while bipolar proband and control groups demonstrated higher false alarm rate on AY trials. These findings suggest that impaired performance on expectancy tasks in schizophrenia and schizoaffective disorder are not attributable to impaired context processing per se, and that patients with bipolar disorder have greater difficulty on expectancy tasks due to deficits in response inhibition, consistent with findings of inhibitory deficits among this group.…”

“…2,[7][8][9][10][11] Findings of impaired context processing among unaffected relatives 9,12,13 and among those with schizoptypal personality disorder have also been reported, 14 suggesting that impairment in this ability may represent an endophenotype for schizophrenia.…”

Establishing a novel cognitive task in rats of relevance to schizophrenia

“…The robust changes that have been detected using CPTs have lead to the suggestion that CPT deficits could be considered an endophenotype of schizophrenia, fitting the Gottesman and Gould (2003) criteria (Gottesman and Gould, 2003;Gur et al, 2007). The CPT protocol has been widely used with results robustly demonstrating deficits in people with schizophrenia and first-degree relatives (Snitz et al, 2006;Delawalla et al, 2008;MacDonald, 2008;Richard et al, 2013). Deficits have been shown to be stable from before first-episode of psychosis, during medication and remission, and performance errors do not correlate with psychotic symptoms in non-schizophrenia patients experiencing psychosis (Snitz et al, 2006;Richard et al, 2013).…”

“…The CPT protocol has been widely used with results robustly demonstrating deficits in people with schizophrenia and first-degree relatives (Snitz et al, 2006;Delawalla et al, 2008;MacDonald, 2008;Richard et al, 2013). Deficits have been shown to be stable from before first-episode of psychosis, during medication and remission, and performance errors do not correlate with psychotic symptoms in non-schizophrenia patients experiencing psychosis (Snitz et al, 2006;Richard et al, 2013). Together these findings suggest that deficits on CPT are at the foundations of this disorder.…”

“…The human CPT exists in many versions with deficits in schizophrenia patients widely reported (Earle-Boyer et al, 1991;Cornblatt and Keilp, 1994). These deficits have even been suggested to represent an endophenotype of schizophrenia as there is evidence of mild deficits in first-degree relatives, stability in patients from first-episode through to remission, and a lack of correlation between severity of psychotic symptoms and CPT deficits (Chen and Faraone, 2000;Snitz et al, 2006;Gur et al, 2007;Delawalla et al, 2008;Richard et al, 2013). A common feature of continuous performance tasks is the rapid presentation of stimuli where the subject is required to monitor, identify and respond to target stimuli.…”