Dynamic and Static Cognitive Deficits in Schizophrenia and Bipolar Disorder After the First Episode.

Few studies have comprehensively examined the profile of cognitive functioning in first episode psychosis patients throughout the lifespan, and from first episode to chronic stage. We assessed functioning in general and specific cognitive functions, comparing both schizophrenia (N = 64) and bipolar I (N = 19) patients to controls (N = 103). Participants were from a population-based, case-control study of first episode psychosis patients, who were followed prospectively up to 10 years post first admission. A cognitive battery was administered at baseline and follow-up. By combining longitudinal and cross-sectional data, we were able to examine the cognitive profile of patients and controls throughout the entire age range of our sample (16-65). Schizophrenia patients exhibited widespread declines in IQ, executive function, visual memory, language ability, and verbal knowledge. However, the ages at which these declines occurred differed between functions. Deficits in verbal memory, working memory, processing speed, and visuospatial ability, on the other hand, were present at the first episode, and remained relatively static thereafter. Bipolar I patients also showed declines in IQ, verbal knowledge, and language ability, albeit at different ages to schizophrenia patients and only in verbal functions. Deficits on measures of verbal memory, processing speed, and executive function remained relatively static. Thus, both schizophrenia and bipolar I patients experienced cognitive decline in general and specific functions after the first episode, but the age at which these declines occurred differed between disorder and function. Cognitive remediation efforts may be most fruitful when targeting individual functions during specific time periods throughout adulthood.

Cognitive Change in Schizophrenia and Other Psychoses in the Decade Following the First Episode.

OBJECTIVE: Schizophrenia is associated with a marked cognitive impairment that is widely believed to remain stable after illness onset. Yet, to date, 10-year prospective studies of cognitive functioning following the first episode with good methodology are rare. The authors examined whether schizophrenia patients experience cognitive decline after the first episode, whether this decline is generalized or confined to individual neuropsychological functions, and whether decline is specific to schizophrenia. METHODS: Participants were from a population-based case-control study of patients with first-episode psychosis who were followed prospectively up to 10 years after first admission. A neuropsychological battery was administered at index presentation and at follow-up to patients with a diagnosis of schizophrenia (N=65) or other psychoses (N=41) as well as to healthy comparison subjects (N=103). RESULTS: The schizophrenia group exhibited declines in IQ and in measures of verbal knowledge and of memory, but not processing speed or executive functions. Processing speed and executive function impairments were already present at the first episode and remained stable thereafter. The magnitude of declines ranged between 0.28 and 0.66 standard deviations. Decline in measures of memory was not specific to schizophrenia and was also apparent in the group of patients with other psychoses. Healthy individuals with low IQ showed no evidence of decline, suggesting that a decline is specific to psychosis. CONCLUSIONS: Patients with schizophrenia and other psychoses experience cognitive decline after illness onset, but the magnitude of decline varies across cognitive functions. Distinct mechanisms consequent to the illness and/or psychosocial factors may underlie impairments across different cognitive functions.

Neuropsychological function at first episode in treatment-resistant psychosis: findings from the ÆSOP-10 study.

BACKGROUND: Neuropsychological investigations can help untangle the aetiological and phenomenological heterogeneity of schizophrenia but have scarcely been employed in the context of treatment-resistant (TR) schizophrenia. No population-based study has examined neuropsychological function in the first-episode of TR psychosis. METHODS: We report baseline neuropsychological findings from a longitudinal, population-based study of first-episode psychosis, which followed up cases from index admission to 10 years. At the 10-year follow up patients were classified as treatment responsive or TR after reconstructing their entire case histories. Of 145 cases with neuropsychological data at baseline, 113 were classified as treatment responsive, and 32 as TR at the 10-year follow-up. RESULTS: Compared with 257 community controls, both case groups showed baseline deficits in three composite neuropsychological scores, derived from principal component analysis: verbal intelligence and fluency, visuospatial ability and executive function, and verbal memory and learning (p values⩽0.001). Compared with treatment responders, TR cases showed deficits in verbal intelligence and fluency, both in the extended psychosis sample (t = -2.32; p = 0.022) and in the schizophrenia diagnostic subgroup (t = -2.49; p = 0.017). Similar relative deficits in the TR cases emerged in sub-/sensitivity analyses excluding patients with delayed-onset treatment resistance (p values<0.01-0.001) and those born outside the UK (p values<0.05). CONCLUSIONS: Verbal intelligence and fluency are impaired in patients with TR psychosis compared with those who respond to treatment. This differential is already detectable - at a group level - at the first illness episode, supporting the conceptualisation of TR psychosis as a severe, pathogenically distinct variant, embedded in aberrant neurodevelopmental processes.

Gender differences in neuropsychological performance across psychotic disorders--a multi-centre population based case-control study.

BACKGROUND: Patients with schizophrenia and other psychoses exhibit a wide range of neuropsychological deficits. An unresolved question concerns whether there are gender differences in cognitive performance. METHODS: Data were derived from a multi-centre population based case-control study of patients with first-episode psychosis. A neuropsychological test battery was administered to patients with a diagnosis of schizophrenia or schizoaffective disorder (N=70, 36% females), bipolar/mania (N=34, 60% females), depressive psychosis (N=36, 58% females) and healthy controls (N=148, 55% females). Generalized and specific cognitive deficits were compared. RESULTS: There was strong evidence for disorder-specific gender differences in neuropsychological performance. Males and females with schizophrenia showed similar pervasive neuropsychological impairments. In psychotic depressive disorder females performed worse than males across neuropsychological measures. Differences in neuropsychological performance between males and females with bipolar/manic disorder were restricted to language functions. Symptom severity did not contribute to the observed gender differences. CONCLUSIONS: Early in the course of psychotic illness, gender related factors appear to moderate the severity of cognitive deficits in depressive psychosis and bipolar/mania patients.

Differential relationship between neurological and cognitive dysfunction in first episode psychosis patients and in healthy individuals.

The minor neurological and cognitive deficits consistently reported in psychoses may reflect the same underlying brain dysfunction. Still, even in healthy individuals minor neurological abnormalities are associated with worse cognitive function. Therefore, establishing which neurological and cognitive deficits are specific to psychosis is essential to inform the pathophysiology of this disorder. We evaluated a large epidemiological sample of patients with first episode psychosis (n=242) and a population-based sample of healthy individuals (n=155), as part of the AESOP study. We examined neurological soft signs using the Neurological Evaluation Scale (Buchanan and Heinrichs, 1989), and generalized and specific cognitive deficits (memory; verbal abilities; attention, concentration and mental speed; executive functions and working memory; language; visual constructual/perceptual abilities). In patients, more neurological signs across all subscales were associated with worse general cognitive function, while in controls this was only present for sensory integration and sequencing signs. Furthermore, in patients, but not in healthy individuals, more sensory integrative signs were associated with deficits in specific cognitive domains, such as memory, verbal abilities, language, visual/perceptual, executive function (p ranging <0.001-0.002); sequencing signs with language, executive function, and attention (p<0.001-0.004); and motor signs with poorer verbal abilities (p=0.001). These findings indicate the presence of specific associations between neurological and cognitive deficits in psychosis that are distinct from those of healthy individuals.

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.

Is there a link between childhood trauma, cognition, and amygdala and hippocampus volume in first-episode psychosis?

Patients with psychosis have higher rates of childhood trauma, which is also associated with adverse effects on cognitive functions such as attention, concentration and mental speed, language, and verbal intelligence. Although the pathophysiological substrate for this association remains unclear, these cognitive deficits may represent the functional correlate of changes observed in relation to trauma exposure in structures such as the amygdala and the hippocampus. Interestingly, these structures are often reported as altered in psychosis. This study investigated the association between childhood trauma, cognitive function and amygdala and hippocampus volume, in first-episode psychosis. We investigated 83 patients with first-episode psychosis and 63 healthy controls. All participants underwent an MRI scan acquired with a GE Sigma 1.5-T system, and a standardized neuropsychological assessment of general cognition, memory, processing speed, executive function, visuo-spatial abilities, verbal intelligence, and language. In a subsample of the patients (N=45) information on childhood trauma was collected with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q). We found that amygdala, but not hippocampus, volume was significantly smaller (p=0.001) in patients compared to healthy controls. There was a trend level interaction for hippocampus volume between group and sex (p=0.056). A history of childhood trauma was associated with both worse cognitive performance and smaller amygdala volume. This smaller amygdala appeared to mediate the relationship between childhood trauma and performance on executive function, language and verbal intelligence in patients with psychosis. This points to a complex relationship between childhood trauma exposure, cognitive function and amygdala volume in first-episode psychosis.

Childhood trauma and cognitive function in first-episode affective and non-affective psychosis.

BACKGROUND: A history of childhood trauma is reportedly more prevalent in people suffering from psychosis than in the general population. Childhood trauma has also been linked to cognitive abnormalities in adulthood, and cognitive abnormalities, in turn, are one of the key clinical features of psychosis. Therefore, this study investigated whether there was a relationship between childhood trauma and cognitive function in patients with first-episode psychosis. The potential impact of diagnosis (schizophrenia or affective psychosis) and gender on this association was also examined. METHODS: Data were available for 138 first-episode psychosis patients and 138 geographically-matched controls recruited from a catchment area based organisation. History of childhood trauma was obtained using the Childhood Experience of Care and Abuse Questionnaire. Cognitive function was assessed through a comprehensive and standardised neuropsychological test battery. RESULTS: A history of childhood trauma was associated with worse cognitive performances, predominantly in affective psychoses, and in male patients. No association between a history of childhood trauma and cognition was found amongst female patients, or female controls. CONCLUSIONS: The results need replication, but underline the necessity of investigating biological and psychosocial mechanisms underlying these subjects' sensitivity to the negative effect of childhood stress.

Criminal offending and distinguishing features of offenders among persons experiencing a first episode of psychosis.

AIMS: Persons with severe mental illness (SMI) are at increased risk of criminal offending, particularly violent offending, as compared with the general population. Most offenders with SMI acquire convictions prior to contact with mental health services. This study examined offending among 301 individuals experiencing their first episode of psychosis. METHODS: Patients provided information on sociodemographic and clinical variables and completed a neurological soft sign examination and neuropsychological tests. Additional information was extracted from clinical files and official criminal records. RESULTS: The results show that 33.9% of the men and 10.0% of the women had a record of criminal convictions, and 19.9% of the men and 4.6% of the women had been convicted of at least one violent crime. Proportionately more male and female patients than men and women in the general UK population had prior convictions for violent crimes. In a multivariate model including background and clinical variables, only one variable distinguished the male offenders. African-Caribbean ethnicity was associated with a threefold increase in the odds of offending (odds ratio=3.84, 95% confidence interval 1.03-14.37). Offenders, as compared with non-offenders, obtained significantly lower premorbid and current intelligence quotient scores and similar scores on tests of neurological soft signs, working memory and executive functions. CONCLUSIONS: At contact with mental health services for a first episode of psychosis, significant numbers of patients have records of criminal convictions and thereby a high risk for future violent behaviour. These patients require specific interventions, in addition to medication, to reduce offending and aggressive behaviour.

Specific and generalized neuropsychological deficits: a comparison of patients with various first-episode psychosis presentations.

OBJECTIVE: Overwhelming evidence suggests that compromised neuropsychological function is frequently observed in schizophrenia. Neurocognitive dysfunction has often been reported in other psychotic disorders, although there are inconsistencies in the literature. In the context of four distinct diagnostic groups, the authors compared neuropsychological performance among patients experiencing their first psychotic episode. METHOD: Data were derived from a population-based, case-control study of patients with first-episode psychosis. A neuropsychological test battery was administered to patients with a diagnosis of schizophrenia (N=65), bipolar disorder or mania (N=37), depressive psychosis (N=39), or other psychotic disorders (N=46) following index presentation, as well as to healthy comparison subjects (N=177). The presence of specific and generalized cognitive deficits was examined. RESULTS: The schizophrenia group presented widespread neuropsychological impairments and performed significantly worse than healthy comparison subjects on most neuropsychological measures. Patients with other psychotic disorders and depressive psychosis also demonstrated widespread impairments. Deficits in patients with bipolar disorder or mania were less pervasive but evident in performance scores on verbal memory and fluency tests. Differences between the four patient groups and healthy comparison subjects and among the patient groups were attenuated after controlling for differences in general cognitive ability (IQ). CONCLUSIONS: Early in their course, cognitive deficits are present in all psychotic disorders but are most severe and pervasive in schizophrenia and least pervasive in bipolar disorder and mania.

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.

Neuropsychological correlates of eye movement abnormalities in schizophrenic patients and their unaffected relatives.

Impairments on neuropsychological and eye movement tasks have been demonstrated in schizophrenic patients and also reported in their unaffected relatives. However, it is not clear to what extent these phenotypes overlap. This study examined the relationship between specific eye movement and neuropsychological measures. The relationship between performance on eye movement and neuropsychological tasks was measured in 79 schizophrenic patients (63% from multiply affected families), 129 of their healthy first-degree relatives, and 72 normal controls. Antisaccade scores were correlated with most measures of neurocognitive functioning, and this correlation was strongest in schizophrenic patients in all cases. In the schizophrenic patients, but not their relatives or controls, the antisaccade distractibility error (ADE) score correlated significantly with current intelligence, verbal memory (immediate and delayed recall), and associative learning. In the case of crystallised IQ and delayed verbal memory, smaller correlations were present in unaffected relatives, although neither survived Bonferroni correction. Smooth pursuit performance was unrelated to any neuropsychological measure. Our study suggests that antisaccade errors are likely to represent part of a generalized neuropsychological deficit in schizophrenia.

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.

Neurological abnormalities and cognitive ability in first-episode psychosis.

BACKGROUND: It remains unclear if the excess of neurological soft signs, or of certain types of neurological soft signs, is common to all psychoses, and whether this excess is simply an epiphenomenon of the lower general cognitive ability present in psychosis. AIMS: To investigate whether an excess of neurological soft signs is independent of diagnosis (schizophrenia v. affective psychosis) and cognitive ability (IQ). METHOD: Evaluation of types of neurological soft signs in a prospective cohort of all individuals presenting with psychoses over 2 years (n=310), and in a control group from the general population (n=239). RESULTS: Primary (P<0.001), motor coordination (P<0.001), and motor sequencing (P<0.001) sign scores were significantly higher in people with any psychosis than in the control group. However, only primary and motor coordination scores remained higher when individuals with psychosis and controls were matched for premorbid and current IQ. CONCLUSIONS: Higher rates of primary and motor coordination signs are not associated with lower cognitive ability, and are specific to the presence of psychosis.

Neurological abnormalities and cognitive ability in first-episode psychosis.

BACKGROUND: It remains unclear if the excess of neurological soft signs, or of certain types of neurological soft signs, is common to all psychoses, and whether this excess is simply an epiphenomenon of the lower general cognitive ability present in psychosis. AIMS: To investigate whether an excess of neurological soft signs is independent of diagnosis (schizophrenia v. affective psychosis) and cognitive ability (IQ). METHOD: Evaluation of types of neurological soft signs in a prospective cohort of all individuals presenting with psychoses over 2 years (n=310), and in a control group from the general population (n=239). RESULTS: Primary (P<0.001), motor coordination (P<0.001), and motor sequencing (P<0.001) sign scores were significantly higher in people with any psychosis than in the control group. However, only primary and motor coordination scores remained higher when individuals with psychosis and controls were matched for premorbid and current IQ. CONCLUSIONS: Higher rates of primary and motor coordination signs are not associated with lower cognitive ability, and are specific to the presence of psychosis.

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.

The relationship between eye movement and brain structural abnormalities in patients with schizophrenia and their unaffected relatives.

Schizophrenia is associated with subtle eye movement and brain structural abnormalities, but the extent to which these abnormalities occur in the same individuals is unclear. The relationship between quantitative measures of eye movement task performance (smooth pursuit and antisaccade) and MRI volumetric measurements (whole brain volume, prefrontal region, lateral ventricles, third ventricle, hippocampus, and cerebellum) was assessed in 70 patients with schizophrenia or schizoaffective disorder, 105 of their unaffected first-degree relatives and 68 controls. There was a lack of correlation between eye movement and morphometric abnormalities suggesting largely separable neurobiological pathways underlying the morphological and the eye movement deviations that have previously been identified in these patients. However, in the total sample, smaller prefrontal lobe volume was significantly associated with longer latency of correct antisaccades (partial correlation r=-0.22, p=0.01) in line with previous studies demonstrating the importance of frontal lobe structures in performance of the antisaccade task. Also larger third ventricular volume was associated with larger mean amplitude of intrusive saccades during smooth pursuit (r=0.28, p=0.01). There were no significant between-group differences in the relationship between measures of eye movement and morphometry.

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.