Linear and non-linear associations of symptom dimensions and cognitive function in first-onset psychosis.

BACKGROUND: Associations between symptom dimensions and cognition have been mainly studied in non-affective psychosis. The present study investigated whether previously reported associations between cognition and four symptom dimensions (reality distortion, negative symptoms, disorganisation and depression) in non-affective psychosis generalise to a wider spectrum of psychoses. It also extended the research focus to mania, a less studied symptom dimension. METHODS: Linear and non-linear (quadratic, curvilinear or inverted-U-shaped) associations between cognition and the above five symptom dimensions were examined in a population-based cohort of 166 patients with first-onset psychosis using regression analyses. RESULTS: Negative symptoms showed statistically significant linear associations with IQ and processing speed, and a significant curvilinear association with verbal memory/learning. Significant quadratic associations emerged between mania and processing speed and mania and executive function. The contributions of mania and negative symptoms to processing speed were independent of each other. The findings did not differ between affective and non-affective psychoses, and survived correction for multiple testing. CONCLUSIONS: Mania and negative symptoms are associated with distinct patterns of cerebral dysfunction in first-onset psychosis. A novel finding is that mania relates to cognitive performance by a complex response function (inverted-U-shaped relationship). The associations of negative symptoms with cognition include both linear and quadratic elements, suggesting that this dimension is not a unitary concept. These findings cut across affective and non-affective psychoses, suggesting that different diagnostic entities within the psychosis spectrum lie on a neurobiological continuum.

Neuropsychological functioning in first-episode schizophrenia.

BACKGROUND: Identifying neurocognitive subtypes in schizophrenia may help establish neurobiologically meaningful subtypes of the disorder, but is frequently confounded by differences in intellectual function between individuals with schizophrenia and controls. AIMS: To examine neuropsychological performance in individuals with epidemiologically based, first-onset schizophrenia and intellectually matched controls. METHOD: Using standard IQ and reading tests, we examined the proportions of 101 people with epidemiologically derived, first-onset schizophrenia/schizoaffective disorder and 317 community controls, falling into three a priori defined intellectual categories: 'stable good', 'deteriorated poor' and 'stable poor'. Neuropsychological function was compared between intellectually matched participants with schizophrenia and control subgroups. RESULTS: Multiple deficits in executive function, processing speed and verbal memory, but not visual/spatial perception/memory, were detected in all participant groups with schizophrenia compared with controls. The average effect size across the affected domains ranged from small to medium to large in the stable good, deteriorated poor and stable poor subgroups of participants with schizophrenia, respectively. CONCLUSIONS: Compared with intellectually matched controls, people with epidemiologically derived, first-onset schizophrenia/schizoaffective disorder show multiple deficits in executive function, processing speed and verbal memory.

Selective deficits in semantic verbal fluency in patients with a first affective episode with psychotic symptoms and a positive history of mania.

OBJECTIVES: Neurocognitive dysfunction is likely to represent a trait characteristic of bipolar disorder, but the extent to which it comprises 'core' deficits as opposed to those secondary to longstanding illness or intellectual decline is unclear. We investigated neuropsychological performance in an epidemiologically derived sample of patients with a first affective episode with psychotic symptoms and a positive history of mania, compared to community controls. METHODS: Using a nested case-control, population-based study, measures of episodic and working memory, executive function, processing speed, and visual-spatial perception were compared between 35 patients with a first affective episode with psychotic symptoms and a positive history of mania, and 274 community controls, as well as a subgroup of 105 controls matched on current IQ ('good' versus 'poor') and IQ trajectory ('stable', 'declined', or 'improved') with the patients (three controls per case). RESULTS: Compared to the extended control sample, probands showed a suggestive deficit in short-term verbal recall, and a significant deficit in semantic fluency. Only the latter was detectable in the comparison with the IQ-matched controls. All other neurocognitive domains showed intact performance or nonsignificant deficits of small effect sizes compared to both control groups. Semantic fluency showed no association with symptoms or duration of untreated illness. CONCLUSIONS: Patients with a first affective episode with psychotic symptoms and a positive history of mania show an isolated, selective deficit in semantic verbal fluency, against a background of generally preserved neurocognitive function. This pattern seems to contrast with the more widespread neuropsychological dysfunction seen in schizophrenia.

Duration of untreated psychosis and neuropsychological function in first episode psychosis.

PURPOSE: We investigated whether duration of untreated psychosis (DUP) prior to first presentation was associated with cognitive function in first episode psychosis (FEP) subjects. We predicted that longer DUP would be associated with greater neurocognitive impairment. METHOD: 180 subjects with schizophrenia (and 93 subjects with Other Psychoses) performed a neurocognitive battery assessing IQ, verbal learning, working memory, visual learning and speed of processing. DUP was defined as the number of days between first onset of psychotic symptoms and first contact with psychiatric services. RESULTS: Longer DUP was associated with impaired performance in verbal IQ (p=0.04), verbal learning (p=0.02), and verbal working memory (p=0.04) in FEP subjects with schizophrenia. These associations remained significant for verbal IQ when scores were corrected for age, gender, educational level and ethnicity. CONCLUSIONS: Longer DUP is associated with poorer neurocognitive ability in schizophrenia subjects at time of first presentation. Since this was a cross-sectional study we can not tell whether longer DUP was a cause or a consequence of the poorer performance.

Saccadic distractibility is elevated in schizophrenia patients, but not in their unaffected relatives.

BACKGROUND: Saccadic distractibility, as measured by the antisaccade task, has attracted attention as a putative endophenotypic marker for schizophrenia. Some studies have suggested that this measure is elevated in the unaffected relatives of schizophrenia patients. However, recent studies have called this into question and the topic remains controversial. METHOD: Saccadic distractibility was measured in 53 patients with DSM-IV schizophrenia, 80 unaffected first-degree relatives and 41 unaffected controls.Results. Schizophrenia patients performed worse than relatives and controls combined (p<0.00001), but relatives did not differ significantly from controls. Performance in multiply affected families was no worse than that in singly affected families. Relatives with a high presumed genetic risk for schizophrenia performed no worse than other relatives. The performance of the patients did not predict that of their relatives. CONCLUSIONS: These results demonstrate that saccadic distractibility is strongly associated with disease status but not with genetic loading for schizophrenia. We conclude that saccadic distractibility is unlikely to be useful as an endophenotypic marker in schizophrenia.