Showing papers by "Robin M. Murray published in 2006"

Randomized Controlled Trial of the Effect on Quality of Life of Second- vs First-Generation Antipsychotic Drugs in Schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1)

Abstract: Context Second-generation (atypical) antipsychotics (SGAs) are more expensive than first-generation (typical) antipsychotics (FGAs) but are perceived to be more effective, with fewer adverse effects, and preferable to patients. Most evidence comes from short-term efficacy trials of symptoms. Objective To test the hypothesis that in people with schizophrenia requiring a change in treatment, SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs. Design A noncommercially funded, pragmatic, multisite, randomized controlled trial of antipsychotic drug classes, with blind assessments at 12, 26, and 56 weeks using intention-to-treat analysis. Setting Fourteen community psychiatric services in the English National Health Service. Participants Two hundred twenty-seven people aged 18 to 65 years withDSM-IVschizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects. Interventions Randomized prescription of either FGAs or SGAs (other than clozapine), with the choice of individual drug made by the managing psychiatrist. Main Outcome Measures Quality of Life Scale scores, symptoms, adverse effects, participant satisfaction, and costs of care. Results The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded. Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores. Participants reported no clear preference for either drug group; costs were similar. Conclusions In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result.

Incidence of schizophrenia and other psychoses in ethnic minority groups: results from the MRC AESOP study

Abstract: Background The incidence of schizophrenia in the African-Caribbean population in England is reported to be raised We sought to clarify whether (a) the rates of other psychotic disorders are increased, (b) whether psychosis is increased in other ethnic minority groups, and (c) whether particular age or gender groups are especially at risk Method We identified all people (n=568) aged 16-64 years presenting to secondary services with their first psychotic symptoms in three well-defined English areas (over a 2-year period in Southeast London and Nottingham and a 9-month period in Bristol) Standardized incidence rates and incidence rate ratios (IRR) for all major psychosis syndromes for all main ethnic groups were calculated Results We found remarkably high IRRs for both schizophrenia and manic psychosis in both African-Caribbeans (schizophrenia 9 1, manic psychosis 8 0) and Black Africans (schizophrenia 5 8, manic psychosis 6 2) in men and women IRRs in other ethnic minority groups were modestly increased as were rates for depressive psychosis and other psychoses in all minority groups These raised rates were evident in all age groups in our study Conclusions Ethnic minority groups are at increased risk for all psychotic illnesses but African- Caribbeans and Black Africans appear to be at especially high risk for both schizophrenia and mania These findings suggest that (a) either additional risk factors are operating in African- Caribbeans and Black Africans or that these factors are particularly prevalent in these groups, and that (b) such factors increase risk for schizophrenia and mania in these groups

Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: Findings from the 3-center ÆSOP study

Abstract: Context Convention suggests uniformity of incidence of schizophrenia and other psychoses; variation would have implications for their causes and biological characteristics. Objective To investigate variability in the incidence of psychotic syndromes in terms of place, ethnicity, age, and sex. Design Three-center, prospective, comprehensive survey of clinically relevant first-onset psychotic syndromes over a 2-year period (1997-1999). Census data provided the denominator. Setting Southeast London, Nottingham, and Bristol, England. Participants One million six hundred thousand person-years yielded 568 subjects aged 16 to 64 years with clinically relevant psychotic syndromes. Main Outcome Measures The World Health Organization Psychosis Screen and the Schedules for Clinical Assessment in Neuropsychiatry to classify, blind to ethnicity, all DSM-IV psychotic syndromes and the subclasses of schizophrenia, other nonaffective disorders, affective disorders, and substance-induced psychosis. Results All syndromes showed a characteristic age distribution. Schizophrenia was significantly more common in men (incidence rate ratio [IRR], 2.3 [95% confidence interval (CI), 1.7-3.1]); affective disorders occurred equally in men and women (IRR, 1.0 [95% CI, 0.7-1.3]). All psychoses were more common in the black and minority ethnic group (crude IRR, 3.6 [95% CI, 3.0-4.2]). Differences in age, sex, and study center accounted for approximately a quarter of this effect (adjusted IRR, 2.9 [95% CI, 2.4-3.5]) in each psychosis outcome. The age-sex standardized incidence rate for all psychoses was higher in Southeast London (IRR, 49.4 [95% CI, 43.6-55.3]) than Nottingham (IRR, 23.9 [95% CI, 20.6-27.2]) or Bristol (IRR, 20.4 [95% CI, 15.1-25.7]). Rates of all outcomes except affective disorders remained significantly higher in Southeast London when the model was expanded to control for ethnicity. Conclusions There is significant and independent variation of incidence of schizophrenia and other psychoses in terms of sex, age, ethnicity, and place. This confirms that environmental effects at the individual, and perhaps neighborhood level, may interact together and with genetic factors in the etiology of psychosis.

Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment.

Abstract: Objectives: To determine the clinical and costeffectiveness of different classes of antipsychotic drug treatment in people with schizophrenia responding inadequately to, or having unacceptable side-effects from, their current medication. Design: Two pragmatic, randomised controlled trials (RCTs) were undertaken. The first RCT (band 1) compared the class of older, inexpensive conventional drugs with the class of new atypical drugs in people with schizophrenic disorders, whose current antipsychotic drug treatment was being changed either because of inadequate clinical response or owing to side-effects. The second RCT (band 2) compared the new (non-clozapine) atypical drugs with clozapine in people whose medication was being changed because of poor clinical response to two or more antipsychotic drugs. Both RCTs were four-centre trials with concealed randomisation and three follow-up assessments over 1 year, blind to treatment. Setting: Adult mental health settings in England. Participants: In total, 227 participants aged 18?65 years (40% of the planned sample) were randomised to band 1 and 136 (98% of the planned sample) to band 2. Interventions: Participants were randomised to a class of drug. The managing clinician selected the individual drug within that class, except for the clozapine arm in band 2. The new atypical drugs included risperidone, olanzapine, quetiapine and amisulpride. The conventional drugs included older drugs, including depot preparations. As in routine practice, clinicians and participants were aware of the identity of the prescribed drug, but clinicians were asked to keep their participating patient on the randomised medication for at least the first 12 weeks. If the medication needed to be changed, the clinician was asked to prescribe another drug within the same class, if possible. Main outcome measures: The primary outcome was the Quality of Life Scale (QLS). Secondary clinical outcomes included symptoms [Positive and Negative Syndrome Scale (PANSS)], side-effects and participant satisfaction. Economic outcomes were costs of health and social care and a utility measure. Results: Recruitment to band 1 was less than anticipated (40%) and diminished over the trial. This appeared largely due to loss of perceived clinical equipoise (clinicians progressively becoming more convinced of the superiority of new atypicals). Good follow-up rates and a higher than expected correlation between QLS score at baseline and at follow-up meant that the sample as recruited had 75% power to detect a difference in QLS score of 5 points between the two treatment arms at 52 weeks. The recruitment to band 2 was approximately as planned. Follow-up assessments were completed at week 52 in 81% of band 1 and 87% of band 2 participants. Band 1 data showed that, on the QLS and symptom measures, those participants in the conventional arm tended towards greater improvements. This suggests that the failure to find the predicted advantage for new atypicals was not due to inadequate recruitment and statistical power in this sample. Participants reported no clear preference for either class of drug. There were no statistically significant differential outcomes for participants entering band 1 for reasons of treatment intolerance to those entering because of broadly defined treatment resistance. Net costs over the year varied widely, with a mean of �18,850 in the conventional drug group and �20,123 in the new atypical group, not a statistically significant difference. Of these costs, 2.1% and 3.8% were due to antipsychotic drug costs in the conventional and atypical group, respectively. There was a trend towards participants in the conventional drug group scoring more highly on the utility measure at 1 year. The results for band 2 showed an advantage for commencing clozapine in quality of life (QLS) at trend level (p = 0.08) and in symptoms (PANSS), which was statistically significant (p = 0.01), at 1 year. Clozapine showed approximately a 5-point advantage on PANSS total score and a trend towards having fewer total extrapyramidal side-effects. Participants reported at 12 weeks that their mental health was significantly better with clozapine than with new atypicals (p < 0.05). Net costs of care varied widely, but were higher than in band 1, with a mean of �33,800 in the clozapine group and �28,400 in the new atypical group. Of these costs, 4.0% and 3.3%, respectively, were due to antipsychotic drug costs. The increased costs in the clozapine group appeared to reflect the licensing requirement for inpatient admission for commencing the drug. There was a trend towards higher mean participant utility scores in the clozapine group. Conclusions: For band 1, there is no disadvantage in terms of quality of life and symptoms, or associated costs of care, over 1 year in commencing conventional antipsychotic drugs rather than new atypical drugs. Conventional drugs were associated with nonsignificantly better outcomes and lower costs. Drug costs represented a small proportion of the overall costs of care (<5%). For band 2, there is a statistically significant advantage in terms of symptoms but not quality of life over 1 year in commencing clozapine rather than new atypical drugs, but with increased associated costs of care. The results suggest that conventional antipsychotic drugs, which are substantially cheaper, still have a place in the treatment of patients unresponsive to, or intolerant of, current medication. Further analyses of this data set are planned and further research is recommended into areas such as current antipsychotic treatment guidance, valid measures of utility in serious mental illness, lowdose ?conventional? treatment in first episode schizophrenia, QLS validity and determinants of QLS score in schizophrenia, and into the possible financial and other mechanisms of rewarding clinician participation in trials.

Regional Brain Morphometry in Patients With Schizophrenia or Bipolar Disorder and Their Unaffected Relatives

Abstract: OBJECTIVE: Schizophrenia and psychotic bipolar disorder have a number of overlapping symptoms and risk factors, but it is not yet clear if the disorders are characterized by similar deviations in brain morphometry or whether any such deviations reflect the impact of shared susceptibility genes on brain structure. The authors used region-of-interest morphometry to volumetrically assess brain structures frequently implicated in psychotic illness in families affected with schizophrenia or psychotic bipolar disorder. METHOD: Magnetic resonance imaging brain scans were obtained from 243 subjects, comprising 42 patients with schizophrenia or schizoaffective disorder, 57 of their unaffected first-degree relatives, 38 patients with psychotic bipolar disorder, 52 of their unaffected first-degree relatives, and 54 healthy comparison subjects. Most of the families affected with schizophrenia and all of the families affected with bipolar disorder were multiply affected with the illness. Volumetric measurements of the...

Clinical and social determinants of duration of untreated psychosis in the AESOP first-episode psychosis study.

Abstract: Background Despite considerable research investigating the relationship between a long duration of untreated psychosis (DUP) and outcomes, there has been much less considering predictors of a long DUP. Aims To investigate the clinical and social determinants of DUP in a large sample of patients with a first episode of psychosis. Method All patients with a first episode of psychosis who made contact with psychiatric services over a 2-year period and were living in defined catchment areas in London and Nottingham, UK were included in the AE SOP study. Data relating to clinical and social variables and to DUP were collected from patients, relatives and case notes. Results An insidious mode of onset was associated with a substantially longer DUP compared with an acute onset, independent of other factors. Unemployment had a similar, if less strong, effect. Conversely, family involvement in help-seeking was independently associated with a shorter duration. There was weak evidence that durations were longer in London than in Nottingham. Conclusions These findings suggest that DUP is influenced both by aspects of the early clinical course and by the social context.

Heritability and Reliability of P300, P50 and Duration Mismatch Negativity

Abstract: Background Event-related potentials (ERPs) have been suggested as possible endophenotypes of schizophrenia. We investigated the test–retest reliabilities and heritabilities of three ERP components in healthy monozygotic and dizygotic twin pairs.

A dopamine transporter gene functional variant associated with cocaine abuse in a Brazilian sample

Abstract: The dopamine (DA) transporter DAT1 is a major target bound by cocaine in brain. We examined the influence of functional genetic variants in DAT1 on cocaine addiction. Repeat polymorphisms, including a 30-bp variable-number tandem repeat (VNTR) in intron 8 (Int8 VNTR) with two common alleles, were genotyped in cocaine-dependent abusers (n = 699) and in controls with no past history of drug abuse (n = 866) from Sao Paulo, Brazil. Positive association was observed with allele 3 of the Int8 VNTR and cocaine abuse (allele odds ratio = 1.2, 95% confidence interval = 1.01–1.37, P = 0.036; 3/3 homozygote odds ratio = 1.45, 95% confidence interval = 1.18–1.78, P = 0.0008). Population stratification was assessed and did not affect the results. Haplotypic analyses using additional polymorphisms indicated that the Int8 VNTR is responsible for the observed association. Functional analyses in reporter–gene constructs, demonstrated that allele 3 mediates significant (P < 0.05) but small reduced expression compared with the “protective” allele 2. This difference increased when 1 and 10 μM cocaine was added to the cell culture (≈40% reduction of the 3 allele expression versus the 2 allele). The 3 allele also demonstrated ≈3-fold-increased expression over the 2 allele in response to KCl plus forskolin challenge. We demonstrate a robust association between cocaine dependence and a VNTR allele in SLC6A3, conferring a small but detectible effect, and we show that this VNTR may be functional. This study suggests that DAT1 gene variation may play a role in cocaine dependence etiology. addiction genetics SLC6A3

Personality in Young Adults Who Are Born Preterm

Abstract: INTRODUCTION: Very preterm birth (VPT; <33 weeks' gestation) is associated with later neuromotor and cognitive impairment, reduced school performance, and psychiatric morbidity. Several follow-up studies have demonstrated increased anxiety and social rejection and reduced self-esteem in preterm children and adolescents, but few studies have examined the effects of preterm birth on adult personality. METHODS: We assessed 108 VPT individuals and 67 term-born controls at ages 18 to 19 years with the Eysenck Personality Questionnaire-Revised, short form (EPQ-RS). This questionnaire rates 3 dimensions of personality: extraversion (sociability, liveliness, sensation seeking); neuroticism (anxiety, low mood, low self-esteem); and psychoticism (coldness, aggression, predisposition to antisocial behavior). A fourth scale, "lie," which measures dissimulation, is also derived. RESULTS: VPT individuals had significantly lower extraversion scores, higher neuroticism scores, and higher lie scores than term-born controls, after controlling for age at assessment and socioeconomic status. P scores were not significantly different between the 2 groups. There was a gender difference in that the increased neuroticism and decreased extraversion scores were accounted for mainly by VPT females. Associations between EPQ-RS scores and neonatal status, adolescent behavioral ratings, and body size at 18 to 19 years were assessed by using Kendall partial correlations, correcting for age at assessment and socioeconomic status. Gestational age, indices of neonatal hypoxia, and neonatal ultrasound ratings were not correlated with EPQ-RS scores. Birth weight was weakly associated with increased lie scores. Rutter Parents' Scale score, a measure of adolescent psychopathology, was associated with an increased neuroticism score. Poor social adjustment in adolescence was associated with an increased lie score. Height and weight at 18 to 19 years were not associated with EPQ-RS, but reduced occipitofrontal circumference was associated with both decreased extraversion and increased lie scores. CONCLUSIONS: Young adults who are born VPT have different personality styles from their term-born peers. This may be associated with an increased risk of psychiatric difficulties.

Distribution of symptom dimensions across Kraepelinian divisions.

Abstract: Background Dimensional structures are established for many psychiatric diagnoses, but dimensions have not been compared between diagnostic groups. Aims To examine the structure of dimensionsin psychosis, to analyse their correlations with disease characteristics and to assess the relative contribution of dimensions v . diagnosis in explaining these characteristics. Method Factor analysis of the OPCRIT items of 191 Maudsley Family Study patients with schizophrenia, mood disorders with psychosis, schizoaffective disorder, and other psychotic illnesses, followed by regression of disease characteristics from factor scores and diagnosis. Results Five factors were identified (mania, reality distortion, depression, disorganisation, negative); all were more variable in schizophrenia than in affective psychosis. Mania was the best discriminator between schizophrenia and affective psychosis; the negative factor was strongly correlated with poor premorbid functioning, insidious onset and worse course. Dimensions explained more of the disease characteristics than did diagnosis, but the explanatory power of the latter was also high. Conclusions Kraepelinian diagnostic categories suffice for understanding illness characteristics, but the use of dimensions adds substantial information.

Violence in women with psychosis in the community: prospective study.

Abstract: Background Little is known about the determinants of violence in women with psychosis. Aims To identify predictors of violence in a community sample of women with chronic psychosis. Method The 2-year prevalence of physical assault was estimated for a sample of 304 women with psychosis. Baseline socio-demographic and clinical factors were used to identify predictors of assault. Results The 2-year prevalence of assault in the sample was 17%. Assaultive behaviour was associated with previous violence (OR=5.87,95% CI 2.42–14.25), non-violentconvictions (OR=2.63,95% CI 1.17–5.93), victimisation (OR=2.46, 95% CI1.02–5.93), African–Caribbean ethnicity (OR=2.24,95% CI1.02–4.77), cluster B personality disorder (OR=2.66, 95% CI1.11–6.38) and high levels of unmet need (OR=1.17,95% CI1.01–1.35). An interaction between African–Caribbean ethnicity and cluster B personality disorder was identified in relation to violent outcome. Violent women were found to be more costly to services. Conclusions Nearly a fifth of community-dwelling women with chronic psychosis committed assault over a period of 2 years. Six independent risk factors were found to predict violence.

Antisaccade performance in monozygotic twins discordant for schizophrenia: the Maudsley twin study.

Abstract: OBJECTIVE: Deficiency in antisaccade performance has been proposed as a schizophrenia endophenotype. METHOD: The authors assessed performance on an antisaccade task (and a prosaccade control condition) by 10 monozygotic twin pairs discordant for DSM-IV schizophrenia and 10 monozygotic healthy twin pairs matched for age, sex, and parental socioeconomic status. The authors computed antisaccade gain, latency, and error rate, as well as prosaccade gain and latency. RESULTS: The schizophrenic twins made more antisaccade reflexive errors than the nonschizophrenic co-twins and comparison twins, who did not significantly differ from each other. The nonschizophrenic members of discordant pairs performed worse than the comparison twins on antisaccade gain and latency but did not differ from their schizophrenic co-twins on these variables. There were no differences on prosaccade performance. Antisaccade errors were correlated with negative symptoms in the patients. CONCLUSIONS: Antisaccade spatial accuracy and latency deficits may serve as markers of genetic liability for schizophrenia.

The Structural Brain Correlates of Neurological Soft Signs in Healthy Individuals

Abstract: It has yet to be established whether neurological soft signs (NSS), which include poor motor coordination, sensory perceptual difficulties and difficulties in sequencing of complex motor tasks, result from specific or diffuse brain structural abnormalities. Studying the neuroanatomical basis of NSS in healthy individuals may help to identify which brain areas are specifically associated with these signs, while excluding the potential confounding effects of psychiatric and neurological disorders. We investigated the relationship between brain structure and NSS in 43 healthy individuals, using the Neurological Evaluation Scale for neurological assessment, and high resolution MRI and voxel-based methods of image analysis to investigate brain structure. Higher rates of NSS were associated with a reduction of inferior frontal gyrus, middle and superior temporal gyrus, and anterior cingulate gyrus. It is of note that in a previous study of patients with psychosis we found that an excess of NSS was associated with a reduction of similar cortical areas. Therefore, we suggest that these cortical brain structural changes represent a common neuroanatomical substrate of NSS, across healthy individuals and patients with psychosis.

Altered functional neuroanatomy of response inhibition in adolescent males who were born very preterm.

Abstract: Event-related functional magnetic resonance imaging (fMRI) was used to investigate the hypothesis that males who were born very preterm may show differences in relative strength of blood oxygen level dependent (BOLD) signals in selective brain areas during performance of a simple response inhibition task compared with term-born controls. Participants were eight males (mean gestational age at birth 28wks, [SD 2]; mean age at testing 16y, [SD 1] and 14 controls matched for sex, age (mean age 17y, [SD 1]), and IQ. A 'go-no-go' task was used to assess response selection and motor response inhibition in response to a visual stimulus. When the 'no-go' condition was contrasted with an attentional control condition, preterm participants showed reduced BOLD signal response bilaterally in the cerebellum, right caudate nucleus, and thalamus, and prefrontal areas including left inferior prefrontal and left anterior cingulate gyri. They also showed increased response mainly in temporal regions. These results suggest that despite good task performance, individuals who were born very preterm exhibit different BOLD signal responses in selective brain areas compared with controls which may underline the use of alternative strategies when challenged with motor response inhibition processing.

Neuropsychological performance at the age of 13 years and adult schizophreniform disorder: prospective birth cohort study.

Abstract: We examined neuropsychological functioning at age 13 years in adolescents who later developed schizophreniform disorder, compared with healthy controls and with adolescents diagnosed as having had a manic episode or depression or anxiety disorder. Participants were from an unselected birth cohort. Attentional, executive and motor impairments at age 13 were found in those who later fulfilled diagnostic criteria for schizophreniform disorder, suggesting that these impairments may be the earliest emerging neuropsychological impairments in schizophrenia-related disorders.

Neurological abnormalities in young adults born preterm

Abstract: Objective: Individuals born before 33 weeks’ gestation (very preterm, VPT) have an increased likelihood of neurological abnormality, impaired cognitive function, and reduced academic performance in childhood. It is currently not known whether neurological signs detected in VPT children persist into adulthood or become attenuated by maturation of the CNS. Method: We assessed 153 VPT individuals and 71 term-born controls at 17–18 years old, using a comprehensive neurological examination. This examination divides neurological signs into primary and integrative domains, the former representing the localising signs of classical neurology, and the latter representing signs requiring integration between different neural networks or systems. Integrative signs are sub-divided into three groups: sensory integration, motor confusion, and sequencing. The VPT individuals have been followed up since birth, and neonatal information is available on them, along with the results of neurological assessment at 4 and 8 years of age and neuropsychological assessment at 18 years of age. Results: The total neurology score and primary and integrative scores were significantly increased in VPT young adults compared to term-born controls. Within the integrative domain, sensory integration and motor confusion scores were significantly increased in the VPT group, but sequencing was not significantly different between the VPT and term groups. Integrative neurological abnormalities at 18 were strongly associated with reduced IQ but primary abnormalities were not. Conclusions: Neurological signs are increased in VPT adults compared to term-born controls, and are strongly associated with reduced neuropsychological function.

Exposure to obstetric complications and subsequent development of bipolar disorder: Systematic review.

Abstract: Background Research has suggested an association between obstetric complications and bipolar disorder. However, no quantitative evaluation has been made of the pooled data from existing studies. Aims To systematically review studies comparing exposure to obstetric complications in cases of bipolar disorder v. non-psychiatric controls, and in cases of bipolar disorder v. cases of other mental disorders. Method Publications were identified by computer searches of seven databases, by hand searches of reference lists and from raw data received from researchers. Results Forty-six studies were identified, of which 22 met the inclusion criteria. The pooled odds ratio for exposure to obstetric complications and subsequent development of bipolar disorder was 1.01 (95% CI 0.76–1.35) compared with healthy controls, 1.13 (95% CI 0.64–1.99) compared with cases of unipolar disorder and 0.61 (95% CI 0.39–0.95) compared with those who developed schizophrenia. Conclusions There is no robust evidence that exposure to obstetric complications increases the risk of developing bipolar disorder. However, the range of events regarded as obstetric complications and methodological inadequacies make definitive conclusions difficult.

Trends in cannabis use prior to first presentation with schizophrenia, in South-East London between 1965 and 1999.

Abstract: Background. There is evidence that cannabis use might be relevant to the aetiology of schizophrenia. We aimed to measure any change in cannabis use over time in those first presenting with schizophrenia in South-East London from 1965 to 1999, and compare this with change in use in those presenting with non-psychotic psychiatric disorders.Method. The rate of cannabis use in the year prior to first ever presentation was measured over seven time periods. Logistic regression modelling was used to determine (a) whether cannabis use changed over time, after controlling for age, sex and ethnicity, and (b) whether there was an interaction between diagnosis and time.Results. Cannabis use increased over time in both the schizophrenia group [odds ratio per time period (OR) 2·03, 95% confidence interval (CI) 1·74–2·38, p<0·0001] and the non-psychotic disorders group (OR 1·24, 95% CI 1·05–1·47, p=0·012), after controlling for age, sex and ethnicity. However, the effect of time was significantly greater in the schizophrenia group than in the non-schizophrenia group (χ2=17, p<0·0001).Conclusion. Cannabis use in the year prior to presentation with schizophrenia increased markedly between 1965 and 1999, and disproportionately so compared to increase in cannabis use in other psychiatric disorders.

Heterogeneity in Incidence Rates of Schizophrenia and Other Psychotic Syndromes

Abstract: James B. Kirkbride, MSc; Paul Fearon, PhD; Craig Morgan, PhD; Paola Dazzan, MSc, MRCPsych; Kevin Morgan, PhD;Jane Tarrant, MRCPsych; Tuhina Lloyd, MRCPsych; John Holloway, MRCPsych; Gerard Hutchinson, MRCPsych, PhD;Julian P. Leff, FRCPsych; Rosemarie M. Mallett, PhD; Glynn L. Harrison, MD; Robin M. Murray, DSc; Peter B. Jones, PhD

The Maudsley Family Study: Premorbid and Current General Intellectual Function Levels in Familial Bipolar I Disorder and Schizophrenia

Abstract: The distinction of psychosis into schizophrenia and bipolar disorder has been increasingly challenged with some evidence suggesting that the two conditions may have common etiologic and pathogenic mechanisms. We compared the premorbid and current intellectual function of bipolar patients from multiply affected families, and those of their first-degree relatives, with those of a similar series of schizophrenic subjects, as well as their relatives, and normal controls. Only schizophrenic subjects showed lower premorbid IQ, suggesting that they, but not the bipolar patients or either relative group, had suffered neurodevelopmental impairment. However, both groups of patients had comparably poor current general intellectual levels, implying that some common pathogenic process operates once illness has begun. The two groups of relatives showed distinct differences in intellectual function but we cannot exclude the possibility that these were a function of our sampling methods.

Genetic Overlap Between P300, P50, and Duration Mismatch Negativity

Abstract: Mismatch Negativity (MMN), P300, and P50 suppression event-related potential (ERP) components measure intermediate stages of information processing but little is known of how they relate to each other genetically. The present study used multivariate genetic model fitting analytic techniques in 46 monozygotic and 32 dizygotic twin pairs. P300, P50 suppression, and MMN were recorded using a 19-channel electroencephalograph (EEG). Zygosity was determined using DNA genotyping. Little evidence for either genetic or environmental association between each of the three ERP paradigms was found. This result suggests that P300, MMN, and P50 suppression serve to evaluate different brain information processing functions that may be mediated by distinct neurobiological mechanisms which in turn are influenced by different sets of genes. Within paradigm, P300 amplitude and latency shared about half of their genetic effects.

Episodic Memory Performance Predicted by the 2bp Deletion in Exon 6 of the “Alpha 7-Like” Nicotinic Receptor Subunit Gene

Abstract: Objective: There is evidence of linkage between chromosome 15q14 and the P50 auditory evoked response, a heritable neuropsychological marker associated with increased risk of schizophrenia. Chromosome 15q14 harbors the alpha-7 nicotinic receptor subunit gene (CHRNA7) and a hybrid gene of unknown function (CHRFAM7A). CHRNA7 is involved in memory formation, a core dysfunction in schizophrenia. The authors set out to determine if this locus is associated with memory dysfunction in schizophrenia. Method: A 2bp deletion in exon 6 of CHRFAM7A, which disrupts the hybrid gene and has previously been associated with P50 deficit, was genotyped in 251 individuals from the Maudsley Family Study of schizophrenia. Episodic memory function was assessed using the Wechsler Memory Scale. Results: Significant associations were identified with delayed recall and percentage retained, with the presence of the deletion predicting worse performance. Conclusions: These observations indicate that episodic memory function is a schi...

The Maudsley handbook of practical psychiatry.

Abstract: 1. The psychiatric interview with adults 2. Psychosocial assessments with adults 3. The psychiatric interview with children 4. The mental state examination 5. Neuropsychiatric assessment 6. The formulation, the summary, and progress notes 7. Special interview situations 8. Special problems 9. Treatments 10. Mental Health Law Appendix 1 The AUDIT questionnaire Appendix 2 Addenbrookes' Cognitive Examination Appendix 3 The 'SAD PERSONS' scale Appendix 4 Alcohol Withdrawal Assessment Scoring Guidelines (CIWA - Ar) Appendix 5 Antipsychotic depot injections: suggested adult doses and frequencies Appendix 6 Equivalent doses, maximum daily doses, and adverse effects of antipsychotics Appendix 7 Clozapine: management of adverse effects

Grey matter correlates of minor physical anomalies in the AeSOP first-episode psychosis study.

Abstract: Background Minor physical anomalies are more prevalent among people with psychosis. This supports a neurodevelopmental aetiology for psychotic disorders, since these anomalies and the brain are both ectodermally derived. However, little is understood about the brain regions implicated in this association. Aims To examine the relationship between minor physical anomalies and grey matter structure in a sample of patients with first-episode psychosis. Method Sixty patients underwent assessment of minor physical anomalies with the Lane scale. High-resolution magnetic resonance images and voxel-based methods of image analysis were used to investigate brain structure in these patients. Results The total anomalies score was associated with a grey matter reduction in the prefrontal cortex and precuneus and with a grey matter excess in the basal ganglia, thalamus and lingual gyrus. Conclusions Minor physical anomalies in a sample of patients with first-episode psychosis are associated with regionalgrey matter changes. These regional changes may be important in the pathogenesis of psychotic disorder.

Intellectual asymmetry and genetic liability in first-degree relatives of probands with schizophrenia

Abstract: Intellectual asymmetry with superiority of verbal skills to spatial skills frequently characterises patients with schizophrenia, but it is unclear whether this pattern also reflects genetic susceptibility to the disorder. We examined the association of a continuous measure of genetic liability to schizophrenia with Verbal-Spatial Contrast IQ (an index of intellectual asymmetry) in 108 first-degree relatives without psychosis of probands with schizophrenia. Higher genetic liability was significantly associated with greater intellectual asymmetry in favour of verbal skills. Intellectual asymmetry with a relative superiority of verbal skills to spatial skills represents a putative endophenotype of schizophrenia.