MIR137 polygenic risk for schizophrenia and ephrin-regulated pathway: Role in lateral ventricles and corpus callosum volume.

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods. Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning.

Parental education and youth suicidal behaviours: a systematic review and meta-analysis.

AIMS: Lower parental education has been linked to adverse youth mental health outcomes. However, the relationship between parental education and youth suicidal behaviours remains unclear. We explored the association between parental education and youth suicidal ideation and attempts, and examined whether sociocultural contexts moderate such associations. METHODS: We conducted a systematic review and meta-analysis with a systematic literature search in PubMed, PsycINFO, Medline and Embase from 1900 to December 2020 for studies with participants aged 0-18, and provided quantitative data on the association between parental education and youth suicidal ideation and attempts (death included). Only articles published in English in peer-reviewed journals were considered. Two authors independently assessed eligibility of the articles. One author extracted data [e.g. number of cases and non-cases in each parental education level, effect sizes in forms of odds ratios (ORs) or beta coefficients]. We then calculated pooled ORs using a random-effects model and used moderator analysis to investigate heterogeneity. RESULTS: We included a total of 59 articles (63 study samples, totalling 2 738 374 subjects) in the meta-analysis. Lower parental education was associated with youth suicidal attempts [OR = 1.12, 95% Confidence Interval (CI) = 1.04-1.21] but not with suicidal ideation (OR = 1.05, 95% CI = 0.98-1.12). Geographical region and country income level moderated the associations. Lower parental education was associated with an increased risk of youth suicidal attempts in Northern America (OR = 1.26, 95% CI = 1.10-1.45), but with a decreased risk in Eastern and South-Eastern Asia (OR = 0.72, 95% CI = 0.54-0.96). An association of lower parental education and increased risk of youth suicidal ideation was present in high- income countries (HICs) (OR = 1.14, 95% CI = 1.05-1.25), and absent in low- and middle-income countries (LMICs) (OR = 0.91, 95% CI = 0.77-1.08). CONCLUSIONS: The association between youth suicidal behaviours and parental education seems to differ across geographical and economical contexts, suggesting that cultural, psychosocial or biological factors may play a role in explaining this association. Although there was high heterogeneity in the studies reviewed, this evidence suggests that the role of familial sociodemographic characteristics in youth suicidality may not be universal. This highlights the need to consider cultural, as well as familial factors in the clinical assessment and management of youth's suicidal behaviours in our increasingly multicultural societies, as well as in developing prevention and intervention strategies for youth suicide.

Classification of first-episode psychosis using cortical thickness: A large multicenter MRI study.

Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, multi-site analysis of cortical thickness comparing parcellations and vertex-wise approaches. By leveraging the multi-site nature of the study, we further investigated how different demographical and site-dependent variables affected predictions. Finally, we assessed relationships between predictions and clinical variables. 428 subjects (147 females, mean age 27.14) with FEP and 448 (230 females, mean age 27.06) healthy controls were enrolled in 8 centers by the ClassiFEP group. All subjects underwent a structural MRI and were clinically assessed. Cortical thickness parcellation (68 areas) and full cortical maps (20,484 vertices) were extracted. Linear Support Vector Machine was used for classification within a repeated nested cross-validation framework. Vertex-wise thickness maps outperformed parcellation-based methods with a balanced accuracy of 66.2% and an Area Under the Curve of 72%. By stratifying our sample for MRI scanner, we increased generalizability across sites. Temporal brain areas resulted as the most influential in the classification. The predictive decision scores significantly correlated with age at onset, duration of treatment, and positive symptoms. In conclusion, although far from the threshold of clinical relevance, temporal cortical thickness proved to classify between FEP subjects and healthy individuals. The assessment of site-dependent variables permitted an increase in the across-site generalizability, thus attempting to address an important machine learning limitation.

Air pollution and trajectories of adolescent conduct problems: the roles of ethnicity and racism; evidence from the DASH longitudinal study.

PURPOSE: No known UK empirical research has investigated prospective associations between ambient air pollutants and conduct problems in adolescence. Ethnic minority children are disproportionately exposed to structural factors that could moderate any observed relationships. This prospective study examined whether exposure to PM2.5 and NO2 concentrations is associated with conduct problems in adolescence, and whether racism or ethnicity moderate such associations. METHODS: Longitudinal associations between annual mean estimated PM2.5 and NO2 concentrations at the residential address and trajectories of conduct problems, and the potential influence of racism and ethnicity were examined school-based sample of 4775 participants (2002-2003 to 2005-2006) in London, using growth curve models. RESULTS: Overall, in the fully adjusted model, exposure to lower concentrations of PM2.5 and NO2 was associated with a decrease in conduct problems during adolescence, while exposure to higher concentrations was associated with a flattened trajectory of conduct symptoms. Racism amplified the effect of PM2.5 (ß = 0.05 (95% CI 0.01 to 0.10, p < 0.01)) on adolescent trajectories of conduct problems over time. At higher concentrations of PM2.5, there was a divergence of trajectories of adolescent conduct problems between ethnic minority groups, with White British and Black Caribbean adolescents experiencing an increase in conduct problems over time. CONCLUSION: These findings suggest that the intersections between air pollution, ethnicity, and racism are important influences on the development of conduct problems in adolescence.

The influence of risk factors on the onset and outcome of psychosis: What we learned from the GAP study.

The GAP multidisciplinary study carried out in South London, recruited 410 first episode of psychosis patients and 370 controls; the aim was to elucidate the multiple genetic and environmental factors influencing the onset and outcome of psychosis. The study demonstrated the risk increasing effect of adversity in childhood (especially parental loss, abuse, and bullying) on onset of psychosis especially positive symptoms. Adverse life events more proximal to onset, being from an ethnic minority, and cannabis use also played important roles; indeed, one quarter of new cases of psychosis could be attributed to use of high potency cannabis. The "jumping to conclusions" bias appeared to mediate the effect of lower IQ on vulnerability to psychosis. We confirmed that environmental factors operate on the background of polygenic risk, and that genetic and environment act together to push individuals over the threshold for manifesting the clinical disorder. The study demonstrated how biological pathways involved in the stress response (HPA axis and immune system) provide important mechanisms linking social risk factors to the development of psychotic symptoms. Further evidence implicating an immune/inflammatory component to psychosis came from our finding of complement dysregulation in FEP. Patients also showed an upregulation of the antimicrobial alpha-defensins, as well as differences in expression patterns of genes involved in NF-κB signaling and Cytokine Production. Being of African origin not only increased risk of onset but also of a more difficult course of illness. The malign effect of childhood adversity predicted a poorer outcome as did continued use of high potency cannabis.

Response to initial antipsychotic treatment in first episode psychosis is related to anterior cingulate glutamate levels: a multicentre 1H-MRS study (OPTiMiSE).

Conventional antipsychotic medication is ineffective in around a third of patients with schizophrenia, and the nature of the therapeutic response is unpredictable. We investigated whether response to antipsychotics is related to brain glutamate levels prior to treatment. Proton magnetic resonance spectroscopy was used to measure glutamate levels (Glu/Cr) in the anterior cingulate cortex (ACC) and in the thalamus in antipsychotic-naive or minimally medicated patients with first episode psychosis (FEP, n = 71) and healthy volunteers (n = 60), at three sites. Following scanning, patients were treated with amisulpride for 4 weeks (n = 65), then 1H-MRS was repeated (n = 46). Remission status was defined in terms of Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores. Higher levels of Glu/Cr in the ACC were associated with more severe symptoms at presentation and a lower likelihood of being in remission at 4 weeks (P < 0.05). There were longitudinal reductions in Glu/Cr in both the ACC and thalamus over the treatment period (P < 0.05), but these changes were not associated with the therapeutic response. There were no differences in baseline Glu/Cr between patients and controls. These results extend previous evidence linking higher levels of ACC glutamate with a poor antipsychotic response by showing that the association is evident before the initiation of treatment.

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.

Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors.

BACKGROUND: We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors. METHOD: The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance. RESULTS: From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset. CONCLUSIONS: The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

Sexual dysfunction and central obesity in patients with first episode psychosis.

BACKGROUND: In recent years the association between sexual dysfunction (SD) and obesity in the general population has drawn major attention. Although sexual dysfunction is common in psychosis, its relationship with weight gain and obesity remains unclear. AIMS: To investigate the association between sexual dysfunction and obesity in a cohort of patients with first episode psychosis. METHOD: Sexual function was assessed in a cohort of patients with first episode psychosis using the Sexual Function Questionnaire (SFQ). Anthropometric measures, including weight, BMI, waist, waist-hip ratio were investigated. Additionally, leptin and testosterone were investigated in male patients. RESULTS: A total of 116 patients (61 males and 55 females) were included. Of these 59% of males and 67.3% of females showed sexual dysfunction (SD) according to the SFQ. In males, higher SFQ scores were significantly correlated with higher BMI (Std. ß=0.36, P=0.01), higher leptin levels (Std. ß=0.34, P=0.02), higher waist-hip ratio (Std. ß=0.32, P=0.04) and lower testosterone levels (Std. ß=-0.44, P=0.002). In contrast, in females, SFQ scores were not associated with any of these factors. CONCLUSIONS: While sexual dysfunction is present in both female and male patients with their first episode of psychosis, only in males is sexual dysfunction associated with increased BMI and waist-hip ratio. The association between SD, BMI, low levels of testosterone and high levels of leptin suggest that policies that lead to healthier diets and more active lifestyles can be beneficial at least, to male patients.

Further evidence of a cumulative effect of social disadvantage on risk of psychosis.

BACKGROUND: A growing body of evidence suggests that indicators of social disadvantage are associated with an increased risk of psychosis. However, only a few studies have specifically looked at cumulative effects and long-term associations. The aims of this study are: To compare the prevalence of specific indicators of social disadvantage at, and prior to, first contact with psychiatric services in patients suffering their first episode of psychosis and in a control sample. To explore long-term associations, cumulative effects, and direction of effects. METHOD: We collected information on social disadvantage from 332 patients and from 301 controls recruited from the local population in South London. Three indicators of social disadvantage in childhood and six indicators of social disadvantage in adulthood were analysed. RESULTS: Across all the domains considered, cases were more likely to report social disadvantage than were controls. Compared with controls, cases were approximately two times more likely to have had a parent die and approximately three times more likely to have experienced a long-term separation from one parent before the age of 17 years. Cases were also more likely than controls to report two or more indicators of adult social disadvantage, not only at first contact with psychiatric services [odds ratio (OR) 9.5], but also at onset of psychosis (OR 8.5), 1 year pre-onset (OR 4.5), and 5 years pre-onset (OR 2.9). CONCLUSIONS: Greater numbers of indicators of current and long-term exposure are associated with progressively greater odds of psychosis. There is some evidence that social disadvantage tends to cluster and accumulate.

Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses.

BACKGROUND: Clozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated. METHOD: This is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not. RESULTS: Seventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25-4.94] compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44-9.56); and patients of male gender (OR 3.13 95% CI 1.35-7.23). CONCLUSIONS: For the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.

Psychological processes underlying the association between childhood trauma and psychosis in daily life: an experience sampling study.

BACKGROUND: Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis. METHOD: We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire. RESULTS: Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all p FWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation. CONCLUSIONS: Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.

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.

Impact of childhood adversities on specific symptom dimensions in first-episode psychosis.

BACKGROUND: The relationship between childhood adversity (CA) and psychotic disorder is well documented. As the adequacy of the current categorical diagnosis of psychosis is being increasingly questioned, we explored independent associations between different types of CA and specific psychotic symptom dimensions in a well-characterized sample of first-episode psychosis (FEP) patients. METHOD: This study involved 236 FEP cases aged 18-65 years who presented for the first time to psychiatric services in South London, UK. Psychopathology was assessed with the Positive and Negative Syndrome Scale and confirmatory factor analysis was used to evaluate the statistical fit of the Wallwork/Fortgang five-factor model of psychosis. CA prior to 17 years of age (physical abuse, sexual abuse, parental separation, parental death, and being taken into care) was retrospectively assessed using the Childhood Experience of Care and Abuse Questionnaire. RESULTS: Childhood sexual abuse [ß = 0.96, 95% confidence interval (CI) 0.40-1.52], childhood physical abuse (ß = 0.48, 95% CI 0.03-0.93) and parental separation (ß = 0.60, 95% CI 0.10-1.11) showed significant associations with the positive dimension; while being taken into care was associated with the excited dimension (ß = 0.36, 95% CI 0.08-0.65), independent of the other types of CA. No significant associations were found between parental death and any of the symptom dimensions. CONCLUSIONS: A degree of specificity was found in the relationships between different types of CA and psychosis symptom dimensions in adulthood, suggesting that distinct pathways may be involved in the CA-psychosis association. These potentially different routes to developing psychosis merit further empirical and theoretical exploration.

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.

Effect of high-potency cannabis on corpus callosum microstructure.

BACKGROUND: The use of cannabis with higher Δ9-tetrahydrocannabinol content has been associated with greater risk, and earlier onset, of psychosis. However, the effect of cannabis potency on brain morphology has never been explored. Here, we investigated whether cannabis potency and pattern of use are associated with changes in corpus callosum (CC) microstructural organization, in patients with first-episode psychosis (FEP) and individuals without psychosis, cannabis users and non-users. METHOD: The CC of 56 FEP (37 cannabis users) and 43 individuals without psychosis (22 cannabis users) was virtually dissected and segmented using diffusion tensor imaging tractography. The diffusion index of fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity was calculated for each segment. RESULTS: Across the whole sample, users of high-potency cannabis had higher total CC MD and higher total CC AD than both low-potency users and those who never used (p = 0.005 and p = 0.004, respectively). Daily users also had higher total CC MD and higher total CC AD than both occasional users and those who never used (p = 0.001 and p < 0.001, respectively). However, there was no effect of group (patient/individuals without psychosis) or group x potency interaction for either potency or frequency of use. The within-group analysis showed in fact that the effects of potency and frequency were similar in FEP users and in users without psychosis. CONCLUSIONS: Frequent use of high-potency cannabis is associated with disturbed callosal microstructural organization in individuals with and without psychosis. Since high-potency preparations are now replacing traditional herbal drugs in many European countries, raising awareness about the risks of high-potency cannabis is crucial.

Differences in cannabis-related experiences between patients with a first episode of psychosis and controls.

BACKGROUND: Many studies have reported that cannabis use increases the risk of a first episode of psychosis (FEP). However, only a few studies have investigated the nature of cannabis-related experiences in FEP patients, and none has examined whether these experiences are similar in FEP and general populations. The aim of this study was to explore differences in self-reported cannabis experiences between FEP and non-psychotic populations. METHOD: A total of 252 subjects, who met International Classification of Diseases (ICD)-10 criteria for FEP, and 217 controls who reported cannabis use were selected from the Genetics and Psychosis (GAP) study. The Medical Research Council Social Schedule and the Cannabis Experience Questionnaire were used to collect sociodemographic data and cannabis use information, respectively. RESULTS: Both 'bad' and 'enjoyable' experiences were more commonly reported by FEP subjects than controls. Principal components factor analysis identified four components which explained 62.3% of the variance. Linear regression analysis on the whole sample showed that the type of cannabis used and beliefs about the effect of cannabis on health all contributed to determining the intensity and frequency of experiences. Linear regression analysis on FEP subjects showed that the duration of cannabis use and amount of money spent on cannabis were strongly related to the intensity and frequency of enjoyable experiences in this population. CONCLUSIONS: These results suggest a higher sensitivity to cannabis effects among people who have suffered their first psychotic episode; this hypersensitivity results in them reporting both more 'bad' and 'enjoyable' experiences. The greater enjoyment experienced may provide an explanation of why FEP patients are more likely to use cannabis and to continue to use it despite experiencing an exacerbation of their psychotic symptoms.

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.