Early sustained recovery following first episode psychosis: Evidence from the AESOP10 follow-up study.

OBJECTIVE: To describe the characteristics of individuals with early sustained recovery following first episode psychosis. METHODS: Individuals with a first episode psychosis were followed-up for ten years. Comparisons were made between those with Early Sustained Recovery and those with Other Course types. RESULTS: Of 345 individuals, n=43 (12.5%) had Early Sustained Recovery. They were more likely than those with Other Course types to be female (OR=2.45; 95% CI: 1.25-4.81); employed (OR=2.39; 95% CI: 1.22-4.69); in a relationship (OR=2.68; 95% CI: 1.35-5.32); have a short DUP (OR=2.86; 95% CI: 1.37-5.88); and have a diagnosis other than schizophrenia, particularly mania (OR=6.39; 95% CI: 2.52-16.18) or brief psychosis (OR=3.64; 95% CI: 1.10-12.10). CONCLUSIONS: Sustained recovery from first episode psychosis occurs in a minority.

Ten-year outcomes in first episode psychotic major depression patients compared with schizophrenia and bipolar patients.

We aimed to investigate long-term outcomes in psychotic major depression patients compared to schizophrenia and bipolar/manic psychosis patients, in an incidence sample, while accounting for diagnostic change. Based on Aetiology and Ethnicity in Schizophrenia and Other Psychoses (ÆSOP and ÆSOP-10), a first episode psychosis cohort was followed-up 10years after first presentation. The Schedules for Clinical Assessment in Neuropsychiatry, WHO Life Chart and Global Assessment of Functioning were used to assess clinical, social and service use outcomes. Seventy-two PMD patients, 218 schizophrenia patients and 70 psychotic bipolar disorder/mania patients were identified at baseline. Differences in outcome between PMD and bipolar patients based on baseline and lifetime diagnosis were minimal. Differences in clinical, social and service use outcomes between PMD and schizophrenia were more substantial with PMD patients showing better outcomes on most variables. However, there was some weak evidence (albeit not quite statistically significant at p<0.05) based on lifetime diagnoses that PMD patients were more likely to attempt suicide (OR 2.31, CI 0.98-5.42, p0.055) and self-harm (OR 2.34, CI 0.97-5.68, p0.060). PMD patients have better social and service use outcomes compared to people with schizophrenia, but may be more likely to attempt suicide or self-harm. This unique profile is important for clinicians to consider in any risk assessment.

Biological and psychosocial risk factors for psychotic major depression.

AIMS: Few studies have investigated risk factors for psychotic major depression (PMD). We aimed to investigate the biological and psychosocial risk factors associated with PMD compared with other psychotic disorders. METHODS: Based on the aetiology and ethnicity in schizophrenia and other psychoses (ÆSOP) study, we used a case-control study to identify and recruit, at baseline and 10-year follow-up, all first episode cases of psychosis, presenting for the first time to specialist mental health services in defined catchment areas in the UK. Population-based controls were recruited from the same areas. Data were collected on: sociodemographics; social isolation; childhood adversity; life events; minor physical anomalies; and neurological soft signs. RESULTS: Living alone (aOR = 2.26, CI = 1.21-4.23), basic level qualification (aOR = 2.89, CI = 1.08-7.74), being unemployed (aOR = 2.12, CI = 1.13-3.96), having contact with friends less than monthly (aOR = 4.24, CI = 1.62-11.14), having no close confidants (aOR = 4.71, CI = 2.08-10.68), having experienced childhood adversity (aOR = 2.57, CI = 1.02-6.44), family history of mental illness (aOR = 10.68, CI = 5.06-22.52), family history of psychosis (aOR = 12.85, CI = 5.24-31.51), and having more neurological soft signs (aOR = 1.15, CI = 1.07-1.24) were all associated with a follow-up diagnosis of PMD and schizophrenia. Few variables associated with PMD were also associated with a diagnosis of bipolar disorder. Minor physical anomalies were associated with a follow-up diagnosis of schizophrenia and bipolar disorder, but not PMD. CONCLUSIONS: Risk factors associated with PMD appear to overlap with those for schizophrenia, but less so for bipolar disorder. Future work on the differential aetiology of PMD, from other psychoses is needed to find the 'specifier' between PMD and other psychoses. Future research on aetiology in PMD, and perhaps other psychoses, should account for diagnostic change.

Diagnostic change 10 years after a first episode of psychosis.

BACKGROUND: A lack of an aetiologically based nosology classification has contributed to instability in psychiatric diagnoses over time. This study aimed to examine the diagnostic stability of psychosis diagnoses using data from an incidence sample of psychosis cases, followed up after 10 years and to examine those baseline variables which were associated with diagnostic change. METHOD: Data were examined from the ÆSOP and ÆSOP-10 studies, an incidence and follow-up study, respectively, of a population-based cohort of first-episode psychosis cases from two sites. Diagnosis was assigned using ICD-10 and DSM-IV-TR. Diagnostic change was examined using prospective and retrospective consistency. Baseline variables associated with change were examined using logistic regression and likelihood ratio tests. RESULTS: Slightly more (59.6%) cases had the same baseline and lifetime ICD-10 diagnosis compared with DSM-IV-TR (55.3%), but prospective and retrospective consistency was similar. Schizophrenia, psychotic bipolar disorder and drug-induced psychosis were more prospectively consistent than other diagnoses. A substantial number of cases with other diagnoses at baseline (ICD-10, n = 61; DSM-IV-TR, n = 76) were classified as having schizophrenia at 10 years. Many variables were associated with change to schizophrenia but few with overall change in diagnosis. CONCLUSIONS: Diagnoses other than schizophrenia should to be regarded as potentially provisional.

Reappraising the long-term course and outcome of psychotic disorders: the AESOP-10 study.

BACKGROUND: Studies of the long-term course and outcome of psychoses tend to focus on cohorts of prevalent cases. Such studies bias samples towards those with poor outcomes, which may distort our understanding of prognosis. Long-term follow-up studies of epidemiologically robust first-episode samples are rare. METHOD: AESOP-10 is a 10-year follow-up study of 557 individuals with a first episode of psychosis initially identified in two areas in the UK (South East London and Nottingham). Detailed information was collated on course and outcome in three domains (clinical, social and service use) from case records, informants and follow-up interviews. RESULTS: At follow-up, of 532 incident cases identified, at baseline 37 (7%) had died, 29 (6%) had emigrated and eight (2%) were excluded. Of the remaining 458, 412 (90%) were traced and some information on follow-up was collated for 387 (85%). Most cases (265, 77%) experienced at least one period of sustained remission; at follow-up, 141 (46%) had been symptom free for at least 2 years. A majority (208, 72%) of cases had been employed for less than 25% of the follow-up period. The median number of hospital admissions, including at first presentation, was 2 [interquartile range (IQR) 1-4]; a majority (299, 88%) were admitted a least once and a minority (21, 6%) had 10 or more admissions. Overall, outcomes were worse for those with a non-affective diagnosis, for men and for those from South East London. CONCLUSIONS: Sustained periods of symptom remission are usual following first presentation to mental health services for psychosis, including for those with a non-affective disorder; almost half recover.

The effect of the environment on symptom dimensions in the first episode of psychosis: a multilevel study.

BACKGROUND: The extent to which different symptom dimensions vary according to epidemiological factors associated with categorical definitions of first-episode psychosis (FEP) is unknown. We hypothesized that positive psychotic symptoms, including paranoid delusions and depressive symptoms, would be more prominent in more urban environments. METHOD: We collected clinical and epidemiological data on 469 people with FEP (ICD-10 F10-F33) in two centres of the Aetiology and Ethnicity in Schizophrenia and Other Psychoses (AESOP) study: Southeast London and Nottinghamshire. We used multilevel regression models to examine neighbourhood-level and between-centre differences in five symptom dimensions (reality distortion, negative symptoms, manic symptoms, depressive symptoms and disorganization) underpinning Schedules for Clinical Assessment in Neuropsychiatry (SCAN) Item Group Checklist (IGC) symptoms. Delusions of persecution and reference, along with other individual IGC symptoms, were inspected for area-level variation. RESULTS: Reality distortion [estimated effect size (EES) 0.15, 95% confidence interval (CI) 0.06-0.24] and depressive symptoms (EES 0.21, 95% CI 0.07-0.34) were elevated in people with FEP living in more urban Southeast London but disorganized symptomatology was lower (EES -0.06, 95% CI -0.10 to -0.02), after controlling for confounders. Delusions of persecution were not associated with increased neighbourhood population density [adjusted odds ratio (aOR) 1.01, 95% CI 0.83-1.23], although an effect was observed for delusions of reference (aOR 1.41, 95% CI 1.12-1.77). Hallucinatory symptoms showed consistent elevation in more densely populated neighbourhoods (aOR 1.32, 95% CI 1.09-1.61). CONCLUSIONS: In people experiencing FEP, elevated levels of reality distortion and depressive symptoms were observed in more urban, densely populated neighbourhoods. No clear association was observed for paranoid delusions; hallucinations were consistently associated with increased population density. These results suggest that urban environments may affect the syndromal presentation of psychotic disorders.

Modelling the interplay between childhood and adult adversity in pathways to psychosis: initial evidence from the AESOP study.

BACKGROUND: There is evidence that a range of socio-environmental exposures is associated with an increased risk of psychosis. However, despite the fact that such factors probably combine in complex ways to increase risk, the majority of studies have tended to consider each exposure separately. In light of this, we sought to extend previous analyses of data from the AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses) study on childhood and adult markers of disadvantage to examine how they combine to increase risk of psychosis, testing both mediation (path) models and synergistic effects. METHOD: All patients with a first episode of psychosis who made contact with psychiatric services in defined catchment areas in London and Nottingham, UK (n = 390) and a series of community controls (n = 391) were included in the AESOP study. Data relating to clinical and social variables, including parental separation and loss, education and adult disadvantage, were collected from cases and controls. RESULTS: There was evidence that the effect of separation from, but not death of, a parent in childhood on risk of psychosis was partially mediated through subsequent poor educational attainment (no qualifications), adult social disadvantage and, to a lesser degree, low self-esteem. In addition, there was strong evidence that separation from, but not death of, a parent combined synergistically with subsequent disadvantage to increase risk. These effects held for all ethnic groups in the sample. CONCLUSIONS: Exposure to childhood and adult disadvantage may combine in complex ways to push some individuals along a predominantly sociodevelopmental pathway to psychosis.

Individualized prediction of illness course at the first psychotic episode: a support vector machine MRI study.

BACKGROUND: To date, magnetic resonance imaging (MRI) has made little impact on the diagnosis and monitoring of psychoses in individual patients. In this study, we used a support vector machine (SVM) whole-brain classification approach to predict future illness course at the individual level from MRI data obtained at the first psychotic episode. METHOD: One hundred patients at their first psychotic episode and 91 healthy controls had an MRI scan. Patients were re-evaluated 6.2 years (s.d.=2.3) later, and were classified as having a continuous, episodic or intermediate illness course. Twenty-eight subjects with a continuous course were compared with 28 patients with an episodic course and with 28 healthy controls. We trained each SVM classifier independently for the following contrasts: continuous versus episodic, continuous versus healthy controls, and episodic versus healthy controls. RESULTS: At baseline, patients with a continuous course were already distinguishable, with significance above chance level, from both patients with an episodic course (p=0.004, sensitivity=71, specificity=68) and healthy individuals (p=0.01, sensitivity=71, specificity=61). Patients with an episodic course could not be distinguished from healthy individuals. When patients with an intermediate outcome were classified according to the discriminating pattern episodic versus continuous, 74% of those who did not develop other episodes were classified as episodic, and 65% of those who did develop further episodes were classified as continuous (p=0.035). CONCLUSIONS: We provide preliminary evidence of MRI application in the individualized prediction of future illness course, using a simple and automated SVM pipeline. When replicated and validated in larger groups, this could enable targeted clinical decisions based on imaging data.

The differential effect of illicit drug use on cognitive function in first-episode psychosis and healthy controls.

OBJECTIVE: Illicit drug use can result in impairment in cognitive function in healthy individuals. Individuals with a psychotic disorder also show a deficit in cognitive function. Drug use may simply contribute to the characteristic cognitive deficit found in psychosis or alternatively result in a 'double deficit'. This study aims to investigate the association between drug use and cognitive function at the first-episode of psychosis and in community-matched controls. METHOD: One hundred and seventy-seven patients at the first episode of psychosis completed a battery of neuropsychological tests. Those that had used drugs in the previous year (n = 80) were compared with those who had not used drugs in the previous year (n = 97). A subsample of the first-episode psychosis patients were compared with community-matched controls (n = 110) according to drug-use status. RESULTS: Patients with a first episode of psychosis who had used drugs performed equally to those who had not used drugs on neuropsychological tests. In contrast, healthy controls who had used drugs in the previous year performed worse on tests of executive function and working memory compared with those controls that had not used drugs. CONCLUSION: There are differential associations of illicit drug misuse with cognitive function for first-episode psychosis patients and healthy controls.

The varying impact of type, timing and frequency of exposure to childhood adversity on its association with adult psychotic disorder.

BACKGROUND: Childhood adversity has been associated with onset of psychosis in adulthood but these studies have used only general definitions of this environmental risk indicator. Therefore, we sought to explore the prevalence of more specific adverse childhood experiences amongst those with and without psychotic disorders using detailed assessments in a large epidemiological case-control sample (AESOP). METHOD: Data were collected on 182 first-presentation psychosis cases and 246 geographically matched controls in two UK centres. Information relating to the timing and frequency of exposure to different types of childhood adversity (neglect, antipathy, physical and sexual abuse, local authority care, disrupted living arrangements and lack of supportive figure) was obtained using the Childhood Experience of Care and Abuse Questionnaire. RESULTS: Psychosis cases were three times more likely to report severe physical abuse from the mother that commenced prior to 12 years of age, even after adjustment for other significant forms of adversity and demographic confounders. A non-significant trend was also evident for greater prevalence of reported severe maternal antipathy amongst those with psychosis. Associations with maternal neglect and childhood sexual abuse disappeared after adjusting for maternal physical abuse and antipathy. Paternal maltreatment and other forms of adversity were not associated with psychosis nor was there evidence of a dose-response effect. CONCLUSIONS: These findings suggest that only specific adverse childhood experiences are associated with psychotic disorders and only in a minority of cases. If replicated, this greater precision will ensure that research into the mechanisms underlying the pathway from childhood adversity to psychosis is more fruitful.

Illicit substance use and its correlates in first episode psychosis.

OBJECTIVE: To determine if substance use (particularly cannabis) is more frequent among first episode psychosis patients and associated with a more problematic clinical presentation. METHOD: All first episode psychosis (FEP) patients presenting to secondary services were recruited from London and Nottingham, over 2 years, in the Aetiology and Ethnicity of Schizophrenia and Other Psychoses study broad framework. Clinical and sociodemographic variables were assessed using a set of standardized instruments. A schedule was created to retrospectively collate substance use data from patients, relatives and clinicians. RESULTS: Five hundred and eleven FEP were identified. They used three to five times more substances than general population. Substance use was associated with poorer social adjustment and a more acute mode of onset. Cannabis use did not affect social adjustment, but was associated with a more acute mode of onset. CONCLUSION: Cannabis has a different impact on FEP than other substances. Large epidemiological studies are needed to disentangle cannabis effect.

Is the incidence of psychotic disorder in decline? Epidemiological evidence from two decades of research.

BACKGROUND: It is unclear whether the incidence of first episode psychoses is in decline. We had the opportunity to determine whether incidence had changed over a 20-year period in a single setting, and test whether this could be explained by demographic or clinical changes. METHODS: The entire population at-risk aged 16-54 in Nottingham over three time periods (1978-80, 1993-95 and 1997-99) were followed up. All participants presenting with an ICD-9/10 first episode psychosis were included. The remainder of the population at-risk formed the denominator. Standardized incidence rates were calculated at each time period with possible change over time assessed via Poisson regression. We studied six outcomes: substance-induced psychoses, schizophrenia, other non-affective psychoses, manic psychoses, depressive psychoses and all psychotic disorders combined. RESULTS: Three hundred and forty-seven participants with a first episode psychosis during 1.2 million person-years of follow-up over three time periods were identified. The incidence of non-affective or affective psychoses had not changed over time following standardization for age, sex and ethnicity. We observed a linear increase in the incidence of substance-induced psychosis, per annum, over time (incidence rate ratios: 1.15; 95% CI 1.05-1.25). This could not be explained by longitudinal changes in the age, sex and ethnic structure of the population at-risk. CONCLUSIONS: Our findings suggest psychotic disorders are not in decline, though there has been a change in the syndromal presentation of non-affective disorders, away from schizophrenia towards other non-affective psychoses. The incidence of substance-induced psychosis has increased, consistent with increases in substance toxicity over time, rather than changes in the prevalence or vulnerability to substance misuse. Increased clinical and popular awareness of substance misuse could also not be excluded.

Ethnicity, social disadvantage and psychotic-like experiences in a healthy population based sample.

OBJECTIVE: We sought to investigate the prevalence and social correlates of psychotic-like experiences in a general population sample of Black and White British subjects. METHOD: Data were collected from randomly selected community control subjects, recruited as part of the AESOP study, a three-centre population based study of first-episode psychosis. RESULTS: The proportion of subjects reporting one or more psychotic-like experience was 19% (n = 72/372). These were more common in Black Caribbean (OR 2.08) and Black African subjects (OR 4.59), compared with White British. In addition, a number of indicators of childhood and adult disadvantage were associated with psychotic-like experiences. When these variables were simultaneously entered into a regression model, Black African ethnicity, concentrated adult disadvantage, and separation from parents retained a significant effect. CONCLUSION: The higher prevalence of psychotic-like experiences in the Black Caribbean, but not Black African, group was explained by high levels of social disadvantage over the life course.

Cumulative social disadvantage, ethnicity and first-episode psychosis: a case-control study.

BACKGROUND: Numerous studies have reported high rates of psychosis in the Black Caribbean population in the UK. Recent speculation about the reasons for these high rates has focused on social factors. However, there have been few empirical studies. We sought to compare the prevalence of specific indicators of social disadvantage and isolation, and variations by ethnicity, in subjects with a first episode of psychosis and a series of healthy controls. METHOD: All cases with a first episode of psychosis who made contact with psychiatric services in defined catchment areas in London and Nottingham, UK and a series of community controls were recruited over a 3-year period. Data relating to clinical and social variables were collected from cases and controls. RESULTS: On all indicators, cases were more socially disadvantaged and isolated than controls, after controlling for potential confounders. These associations held when the sample was restricted to those with an affective diagnosis and to those with a short prodrome and short duration of untreated psychosis. There was a clear linear relationship between concentrated disadvantage and odds of psychosis. Similar patterns were evident in the two main ethnic groups, White British and Black Caribbean. However, indicators of social disadvantage and isolation were more common in Black Caribbean subjects than White British subjects. CONCLUSIONS: We found strong associations between indicators of disadvantage and psychosis. If these variables index exposure to factors that increase risk of psychosis, their greater prevalence in the Black Caribbean population may contribute to the reported high rates of psychosis in this population.

Minor physical anomalies in patients with first-episode psychosis: their frequency and diagnostic specificity.

BACKGROUND: An increased prevalence of minor physical anomalies (MPAs) has been extensively documented in schizophrenia but their specificity for the disorder remains unclear. We investigated the prevalence and the predictive power of MPAs in a large sample of first-episode psychotic patients across a range of diagnoses. METHOD: MPAs were examined in 242 subjects with first-episode psychosis (50% schizophrenia, 45% affective psychosis and 5% substance-induced psychosis) and 158 healthy controls. Categorical principal components analysis and analysis of variance were undertaken, and individual items with the highest loading were tested using the chi2 test. RESULTS: Overall facial asymmetry, assymetry of the orbital landmarks, and frankfurt horizontal significantly differentiated patients with schizophrenia and affective psychosis from controls, as did a 'V-shaped' palate, reduced palatal ridges, abnormality of the left ear surface and the shape of the left and right ears. Patients with affective psychosis had significantly lowered eye fissures compared with control subjects. CONCLUSIONS: MPAs are not specific to schizophrenia, suggesting a common developmental pathway for non-affective and affective psychoses. The topographical distribution of MPAs in this study is suggestive of an insult occurring during organogenesis in the first trimester of pregnancy.

Minor physical anomalies across ethnic groups in a first episode psychosis sample.

Minor physical anomalies (MPAs) are more prevalent amongst individuals with psychosis, supporting a neurodevelopmental model for psychotic disorders. The aim of this study was to investigate the possibility that neurodevelopmental adversity contributes to the excess of psychosis found in some ethnic groups in the UK. Subjects with first onset psychosis and healthy neighbourhood controls were enrolled in the AESOP study in South East London and Nottingham between 1997 and 1999. MPA rates were estimated in four broad ethnic groupings (White, African Caribbean, Black African and Other). Patients (n=245) had a higher mean total MPA score than healthy controls (n=158). This held true across each of the four ethnic groupings. The results of this study suggest that neurodevelopmental factors play a role in the aetiology of psychosis across all ethnic groups.

Correlations between clinical and historical variables, and cerebral structural variables in people with mild intellectual disability and schizophrenia.

The increased prevalence of schizophrenia in the population with mildly intellectual disability (ID) remains unexplained. The present study explores several possibilities by examining historical/clinical findings in relation to structural neuroimaging findings in three groups: (1) comorbid mild ID and schizophrenia; (2) schizophrenia alone; and (3) mild ID alone. Information about clinical and historical variables was obtained from 101 subjects (39 with comorbidity, 34 with schizophrenia and 28 with mild ID), out of whom 68 (23, 25 and 20, respectively) had had a cerebral magnetic resonance imaging (MRI) scan. Although a number of significant correlations exist between clinical variables and structural MRI abnormalities in all three groups, no clearly predictive inter- or between-group differences emerged. More striking was the finding that showed small amygdalo-hippocampal size to be associated with a history of central nervous system injury, especially meningitis. These findings provide support for the view that cognitive impairment and comorbid psychosis can result from a common cause, such as meningitis or obstetric complications, possibly interacting with other factors, such as family history.

Predictors of admission to a high-security hospital of people with intellectual disability with and without schizophrenia.

Admission to secure hospital facilities is a rare outcome for people with intellectual disability with or without concomitant psychosis. The present study compares people with mild intellectual disability with and without schizophrenia resident in the Scottish and Northern Irish State Hospital, Carstairs, to matched mild intellectual disability controls, also with and without schizophrenia, in the community. It is hoped that this study may identify socio-demographic, clinical or historical predictors which may lead to admission to secure hospital facilities for people with mild intellectual disability. One hundred and eight subjects were identified from two previous studies which concerned State Hospital patients and patients with intellectual disability with and without schizophrenia. Four experimental groups were derived: (1) 14 individuals with comorbid intellectual disability and schizophrenia who had been resident in the State Hospital; (2) 34 comorbid community control subjects; (3) 33 individuals with intellectual disability and no psychosis who had been resident in the State Hospital; and (4) 27 community control subjects with mild intellectual disability. The four groups were compared on a range of socio-demographic, historical and clinical variables obtained from case records and subject interviews. Relative to community controls, people with intellectual disability and no psychosis in the State Hospital are likely to be single, to have a later age of first psychiatric hospital admission, and to have a history of previous suicide attempts, alcohol abuse or drug misuse. Subjects with comorbid intellectual disability and schizophrenia in the State Hospital are more likely to be male, to have an early age of first psychiatric admission, and to have no family history of either schizophrenia or intellectual disability. Strategies aimed at addressing suicidal behaviour, alcohol and drug misuse amongst people with intellectual disability may facilitate a reduction in the number of admissions to high-security hospitals in the UK. In people with comorbid intellectual disability and schizophrenia, males with an early age of onset and no known family history are more likely to require care and treatment in a secure psychiatric setting. Such comorbid subjects may be suffering from a particular malignant form of schizophrenia, manifesting in childhood as cognitive impairment prior to the early onset of psychosis in teenage years.

Neuroanatomy of comorbid schizophrenia and learning disability: a controlled study.

BACKGROUND: Reasons for the higher frequency of schizophrenia in learning-disabled populations are uncertain. We investigated the neuroanatomical basis for this phenomenon by structural magnetic resonance imaging (MRI) in patients with learning disability and schizophrenia, learning-disabled patients, and patients with schizophrenia. METHODS: Age-matched and sex-matched patients with learning disability (20 cases), schizophrenia (25), and both disorders (23) underwent MRI scans of the brain. Whole brain areas and specific regions of interest were examined. 29 normal controls were also scanned. FINDINGS: The scans of the group with both disorders were closely similar to those of the schizophrenic group, in terms of both general structures and the structure of the amygdala-hippocampus. However, the amygdala-hippocampus was significantly smaller on both sides than that of normal controls (left 4.1 vs 4.5 cm3, p=0.011; right 4.2 vs 4.99 cm3, p<0.0001). The brains of learning-disabled patients were generally smaller than those of the other three groups, but the amygdalohippocampal complexes were larger. INTERPRETATION: In terms of brain structure, patients with comorbid learning disability and schizophrenia resemble patients with schizophrenia and not those with learning disability. We suggest that the higher frequency of schizophrenia in learning-disabled patients is due to a greater tendency of schizophrenic patients to develop cognitive deficits, and that within the learning-disabled population there may be individuals whose deficits result from undiagnosed schizophrenia.

Volumetric magnetic resonance imaging study of the brain in subjects with sex chromosome aneuploidies.

OBJECTIVES: Cognitive impairment has been reported in people with sex chromosome aneuploides (SCAs) and it has been proposed that the presence of an extra sex chromosome may have an adverse effect on neurodevelopment. This study examines the hypothesis with structural MRI of the brain. METHODS: Thirty two subjects with SCA (XXX (n=12), XYY (n=10), and XXY (n=10)) from a birth cohort study were matched groupwise for age, parental social class, and height with normal controls (13 female, 26 male). Brain MRI, measurements of IQ, and a structured psychiatric interview were performed. RESULTS: The XXX females and XXY males had significantly smaller whole brain volumes than controls of the same phenotypic sex (p=0.003 and p