COMT but Not 5HTTLPR Gene Is Associated with Depression in First-Episode Psychosis: The Role of Stressful Life Events.

Serotonergic and dopaminergic systems are involved in the regulation of mood and reactivity to psychological stress. This study explores, in a sample of first episode psychosis (FEP) patients, whether more severe depressive symptoms were found in those who: (1) experienced a major stressful event in the 6 months preceding illness onset; and (2) were homozygous for the COMT Val158 allele or carrying the S allele of 5-HTTLPR. A total of 186 FEP patients recruited were assessed using the Hamilton Rating Scale for Depression (HAMD) for depressive symptoms. Stressful life events (SLEs) were collected by the List of Events Scale. The genotypes of 5-HTTLPR, rs25531, and COMT Val158 Met were performed. It has been found that higher levels of depression is associated with the presence of SLEs (p = 0.019) and with COMT Val158 allele homozygosity (p = 0.029), but not with carrying the S allele of 5-HTTLPR. The COMT gene moderates the association between depression and SLEs as Val158 allele homozygote patients experiencing SLEs had the highest level of depressive symptoms compared to the others (p = 0.002). The present study provides initial evidence for an effect of the COMT Val158 homozygosity and severe stressful life events on the severity of depressive symptoms in first episode psychosis.

Childhood adversity, symptoms, and cortisol in first episode psychosis: a cross-sectional, secondary, observational analysis of a subsample of FEP patients.

BACKGROUND: Although it has been proposed that childhood adversities (CAs) may affect the hypothalamic-pituitary-adrenal (HPA) axis activity and psychotic symptoms severity, these associations have not been fully confirmed in first-episode psychosis (FEP). This study explored the association between CA, cortisol and psychotic symptoms in FEP patients. METHODS: 81 FEP patients were enrolled. CAs were evaluated by the Childhood Experience of Care and Abuse Questionnaire and a semi-structured interview. Psychotic symptoms were evaluated by the Positive and Negative Syndrome Scale. Cortisol level was collected using saliva samples. ANCOVA and partial correlation analyses were run. RESULTS: FEP patients with childhood abuse reported severe positive symptoms than those without CA. FEP patients with at least one CA had higher levels of cortisol awaking, cortisol at 12 a.m., and cortisol at 8 p.m. Morning cortisol levels were negatively correlated with the severity of negative symptoms and positively correlated with the severity of general psychopathology. Evening cortisol levels were positively correlated with severity of general psychopathology. CONCLUSION: FEP patients with CAs, compared with those without CA, might report more severe positive symptoms and higher cortisol, even though these findings as prone to bias due to the small sample size, and should be seen in the larger perspective of conflicting evidence in the field.

Dietary habits and physical activity in first-episode psychosis patients treated in community services. Effect on early anthropometric and cardio-metabolic alterations.

People with psychosis often develop metabolic and cardiovascular disorders, due to several factors including unhealthy lifestyle and antipsychotic treatment. This study aims to evaluate in a sample of first episode psychosis (FEP) patients lifestyle factors, with a specific emphasis on dietary habits and physical activity, and cardio-metabolic and anthropometric profile at illness onset and at 9 months. Moreover, this study aims to evaluate the impact of lifestyle factors on short term changes in cardio-metabolic and anthropometric profile. A 9-month follow-up study was conducted on a sample of 96 FEP patients recruited within the context of the GET UP program. Standardised assessments of dietary habits (EPIC) and physical activity (IPAQ) were retrospectively performed at 9 months; cardiovascular measures (blood pressure, heart rate), metabolic parameters (glucose, cholesterol, triglycerides), BMI and antipsychotic treatment were assessed at illness onset and at 9 months. We found that most FEP patients (60%) displayed poor dietary habits, as defined in terms of adherence to the Mediterranean diet. A significant increase for both BMI and cholesterol levels was found in the overall sample over 9 months. However, when considering the effect of lifestyle factors, BMI and total cholesterol were specifically raised in patients with low adherence to Mediterranean diet. The association with antipsychotic medication was found for SGA only, with a significant increase in both BMI and total cholesterol overtime. Our findings confirm the need to implement specific and early strategies to promote healthy lifestyle in people with FEP, since metabolic alterations occur within the first months of treatment.

No association between NRG1 and ErbB4 genes and psychopathological symptoms of schizophrenia.

Neuregulin 1 (NRG1) and v-erb-a erythroblastic leukemia viral oncogene homolog 4 (ErbB4) have been extensively studied in schizophrenia susceptibility because of their pivotal role in key neurodevelopmental processes. One of the reasons for the inconsistencies in results could be the fact that the phenotype investigated has mostly the diagnosis of schizophrenia per se, which is widely heterogeneous, both clinically and biologically. In the present study we tested, in a large cohort of 461 schizophrenia patients recruited in Scotland, whether several SNPs in NRG1 and/or ErbB4 are associated with schizophrenia symptom dimensions as evaluated by the Positive and Negative Syndrome Scale (PANSS). We then followed up nominally significant results in a second cohort of 439 schizophrenia subjects recruited in Germany. Using linear regression, we observed two different groups of polymorphisms in NRG1 gene: one showing a nominal association with higher scores of the PANSS positive dimension and the other one with higher scores of the PANSS negative dimension. Regarding ErbB4, a small cluster located in the 5' end of the gene was detected, showing nominal association mainly with negative, general and total dimensions of the PANSS. These findings suggest that some regions of NRG1 and ErbB4 are functionally involved in biological processes that underlie some of the phenotypic manifestations of schizophrenia. Because of the lack of significant association after correction for multiple testing, our analyses should be considered as exploratory and hypothesis generating for future studies.

Positive symptoms in first-episode psychosis patients experiencing low maternal care and stressful life events: a pilot study to explore the role of the COMT gene.

COMT Val(158)Met moderates the effect of stress on psychotic symptoms. Exposure to stress is also associated with mesolimbic dopamine release in individuals experiencing low maternal care. We therefore test the hypothesis that recent stressful life events are associated with more severe positive symptoms (associated with mesolimbic dopamine release) in first-episode psychosis (FEP) patients who experienced low maternal care during childhood. We hypothesized that COMT Val(158)Met moderates this association. A total of 149 FEP patients recruited within the Psychosis Incident Cohort Outcome Study (PICOS) participated in the present study. Maternal care was assessed by the Parental Bonding Instrument (PBI), stressful life events were collected by the List of Events Scale and positive symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). We found that low maternal care and recent stressful life events were associated with higher level of positive symptoms at the onset (analysis of variance [ANOVA], p = 0.012), and that patients who were also homozygotes for the COMT Val(158) allele had the highest level of positive symptoms (ANOVA, p = 0.024). Low maternal care and severe stressful life events may contribute to a symptomatology characterized by more severe positive symptoms at the onset, possibly due to an increased mesolimbic dopamine release. Homozygosity for the COMT Val(158) allele seems to confer a biological predisposition to the stress-related hyperactivity of the mesolimbic dopaminergic system. The data imply that the mesolimbic dopaminergic system is involved in the mediation/modulation of the effect of stressful events on the vulnerability for psychosis.

The role of experienced and anticipated discrimination in the lives of people with first-episode psychosis.

OBJECTIVE: This study aimed to describe patterns of experienced and anticipated discrimination in a sample of persons experiencing a first episode of psychosis and to explore associations with clinical and psychosocial variables. METHODS: This cross-sectional survey was conducted within the context of the Psychosis Incident Cohort Outcome Study, a multisite naturalistic study examining first-episode patients treated in public psychiatric services in the Veneto Region of Italy. The Discrimination and Stigma Scale was used to assess experienced and anticipated discrimination. RESULTS: Ninety-seven patients were interviewed. Experiences of discrimination were common in relationships with family members (43%), making friends (32%), relationships with neighbors (25%), keeping a job (25%), finding a job (24%), and intimate relationships (23%). In regard to anticipated discrimination, 37% had stopped seeking a close relationship and 34% had stopped looking for work, 58% felt the need to conceal their diagnosis, and 37% reported that other people avoided them. In regression analysis, a higher number of functioning needs together with higher anticipated discrimination were associated with a higher level of experienced discrimination. A higher level of experienced discrimination and greater illness awareness were associated with more anticipated discrimination. CONCLUSIONS: First-episode patients reported experiencing discrimination in several key life areas. Anticipated discrimination further limited their access to life opportunities. Patients' awareness of the negative consequences of symptoms and disabilities led them to more easily perceive discrimination.

First-contact incidence of psychosis in north-eastern Italy: influence of age, gender, immigration and socioeconomic deprivation.

BACKGROUND: Considerable variations in the incidence of psychosis have been observed across countries, in terms of age, gender, immigration status, urbanicity and socioeconomic deprivation. AIMS: To evaluate the incidence rate of first-episode psychosis in a large area of north-eastern Italy and the distribution of the above-mentioned risk factors in individuals with psychoses. METHOD: Epidemiologically based survey. Over a 3-year period individuals with psychosis on first contact with services were identified and diagnosed according to ICD-10 criteria. RESULTS: In total, 558 individuals with first-episode psychosis were identified during 3,077,555 person-years at risk. The annual incidence rate per 100,000 was 18.1 for all psychoses, 14.3 for non-affective psychoses and 3.8 for affective psychoses. The rate for all psychoses was higher in young people aged 20-29 (incidence rate ratio (IRR) = 4.18, 95% CI 2.77-6.30), immigrants (IRR = 2.26, 95% CI 1.85-2.75) and those living in the most deprived areas (IRR = 2.09, 95% CI 1.54-2.85). CONCLUSIONS: The incidence rate in our study area was lower than that found in other European and North American studies and provides new insights into the factors that may increase and/or decrease risk for developing psychosis.

The impact of cannabis use on age of onset and clinical characteristics in first-episode psychotic patients. Data from the Psychosis Incident Cohort Outcome Study (PICOS).

Cannabis use is frequent among first-episode psychosis (FEP) patients and has been associated with several clinical features. This study aimed in an FEP sample to determine whether cannabis use is associated with (1) a higher level of positive symptoms, a lower level of depression and a better premorbid adjustment, (2) an earlier age of onset, and a better premorbid IQ. The study was conducted within the framework of the Psychosis Incident Cohort Outcome Study (PICOS), a multisite collaborative research on FEP patients who attended the psychiatric services in Veneto Region, Italy. Standardized instruments were used to collect sociodemographic, clinical, and drug use data. A total of 555 FEP patients met the inclusion criteria, 517 of whom received an ICD-10 diagnosis of psychosis; 397 (55% males; mean age: 32 yrs ± 9.5) were assessed. Out of these, 311 patients agreed to be interviewed on drug and alcohol misuse; 20.3% was positive for drug misuse: cannabis (19.0%), cocaine (3.9%), and hallucinogens (3.9%). Cannabis use was not associated with a higher level of positive symptoms, but correlated with less severe depressive symptoms. No relationship was observed between premorbid adjustment or IQ and cannabis use. FEP patients who used cannabis had an earlier age of onset than abstinent patients, even after adjusting for gender and diagnosis. Our results suggest a possible causal role of cannabis in triggering psychosis in certain vulnerable subjects. Particular attention must be paid to this behaviour, because reducing cannabis use can delay or prevent some cases of psychosis.

Predictors of anxiety and depression in hematopoietic stem cell transplant patients during protective isolation.

OBJECTIVE: To examine in a sample of hematopoietic stem cell transplant patients assessed throughout protective isolation (i) levels of anxiety and depression and (ii) pre-isolation factors (socio-demographics, biomedical variables and personality traits), which might predict higher levels of anxiety and depression during isolation. METHODS: The study used a longitudinal prospective design. Anxiety and depression were assessed in 107 participants by the State-Trait Anxiety Inventory and Self-rating Depression Scale at admission and weekly at fixed time points throughout isolation. Among pre-isolation factors, patients' psychological status was evaluated by the Cognitive Behavioral Assessment (2.0). Predictors were explored by random-effects models. RESULTS: One-tenth of the patients suffered from clinically significant anxiety and depressive symptoms at admission. Although the percentage of depressed patients increased more than twofold after 2 weeks of isolation, that of anxious patients did not significantly change over time. Female gender, higher anxiety and obsessive-compulsive symptoms, intratensive personality traits and lower performance status predicted higher depression during isolation. CONCLUSIONS: Anxiety and depression represent a relevant problem for hematopoietic stem cell transplant patients during isolation. Early detection of predictors, such as anxiety levels, obsessive-compulsive symptoms and performance status, could help prevent depression via targeted psychological intervention.

Is neuregulin 1 involved in determining cerebral volumes in schizophrenia? Preliminary results showing a decrease in superior temporal gyrus volume.

BACKGROUND/AIMS: Reduced left superior temporal gyrus (STG) volume is one of the most replicated imaging findings in schizophrenia. However, it remains unclear whether genes play any role in our understanding of such structural alteration. It has been proposed that Neuregulin 1 (NRG1) might be a promising gene involved in schizophrenia, because of its role in neurodevelopment and neuroplasticity. In this study, the association between NRG1 and STG anatomy in patients with schizophrenia was explored for the first time. METHODS: We investigated a 1-year treated prevalence cohort of patients with schizophrenia in contact with the South Verona Community-Based Mental Health Service. A blood sample was collected for DNA extraction and brain structure was assessed with an MRI scan. A total of 27 subjects with schizophrenia underwent both assessments and were included in the study. RESULTS: We investigated the association between the polymorphism SNP8NRG222662 (rs4623364) of NRG1 and volume of the STG. We found that patients homozygous for the C allele had reduced left STG gray and white matter volumes in comparison to those homozygous for the G allele (p < 0.01 and p < 0.001, respectively). CONCLUSIONS: This exploratory study suggests that NRG1 may be involved in determining STG size in schizophrenia, and may play a role in the neurogenetic basis of the language disturbances seen in this disorder. However, due to our small sample size, the results should be regarded as preliminary and replicated in a larger sample.

Effect of COMT genotype on aggressive behaviour in a community cohort of schizophrenic patients.

Although the etiology of aggression is multifactorial, many studies have associated the Val158Met polymorphism of the COMT with aggression in schizophrenia. This study tests the hypothesis that Met/Met patients display more episodes of aggression and violent behaviour than Val/Val patients in a 6 year follow-up cohort of subjects with schizophrenia in contact with the South-Verona Community-based Mental Health Service. Out of the 141 subjects with an ICD-10 SCAN-confirmed diagnosis of schizophrenia, 115 completed both baseline and follow-up assessments (81.6% of the baseline cohort). Of these, 80 subjects (70%) were genotyped and rated for aggression using the Overt Aggression Scale. Met/Met homozygous patients had higher aggressive behaviour compared to Val/Val homozygous subjects. Antipsychotic dosage, alcohol and drug abuse were taken into account as confounders. The Met/Met genotype of COMT may have an effect on aggressive behaviour in schizophrenia because norepinephrine is less effectively inactivated.

Influence of perceived organisational factors on job burnout: survey of community mental health staff.

BACKGROUND: Staff burnout is a critical issue for mental healthcare delivery, as it can lead to decreased work performance and, ultimately, to poorer treatment outcomes. AIMS: To explore the relative weight of job-related characteristics and perceived organisational factors in predicting burnout in staff working in community-based psychiatric services. METHOD: A representative sample of 2000 mental health staff working in the Veneto region, Italy, participated. Burnout and perceived organisational factors were assessed by using the Organizational Checkup Survey. RESULTS: Overall, high levels of job distress affected nearly two-thirds of the psychiatric staff and one in five staff members suffered from burnout. Psychiatrists and social workers reported the highest levels of burnout, and support workers and psychologists, the lowest. Burnout was mostly predicted by a higher frequency of face-to-face interaction with users, longer tenure in mental healthcare, weak work group cohesion and perceived unfairness. CONCLUSIONS: Improving the workplace atmosphere within psychiatric services should be one of the most important targets in staff burnout prevention strategies. The potential benefits of such programmes may, in turn, have a favourable impact on patient outcomes.

Association study of dysbindin gene with clinical and outcome measures in a representative cohort of Italian schizophrenic patients.

There is evidence suggesting that Dysbindin (DTNBP1) is a susceptibility gene for schizophrenia in Caucasian, Chinese, and Japanese populations. We sought to determine if dysbindin was associated with schizophrenia and its symptoms in a representative group of schizophrenic patients from a Community-Based Mental Health Service (CMHS) in Verona, Italy. A prevalence cohort of schizophrenic patients (n = 141) was assessed at baseline and then 3 and 6 years later. Eighty patients and 106 healthy controls were genotyped for polymorphisms in dysbindin. We tested if diagnosis, clinical symptoms as measured by the Brief Psychiatric Rating Scale (BPRS), and functioning as measured by the Global Assessment of Functioning Scale (GAF), were associated with the presence of certain dysbindin polymorphisms. Finally, using the longitudinal clinical data, we tested if patients carrying dysbindin high-risk haplotypes had a more unfavorable longitudinal clinical outcome. A trend towards statistical association (P = 0.058) between schizophrenia and rs2619538 was found. Using GENECOUNTING software, we found that rs2619538-P1583 (P = 0.048), P1320-P1757 (P = 0.034), and rs2619538-P1583-P1578 (P = 0.040) haplotypes occurred more often in cases compared to controls before correction for multiple testing. The rs2619538-P1583 haplotype was more likely to be transmitted to subjects with more severe and persistent psychopathology. These preliminary results are compatible with the view that DTNBP1 is a susceptibility factor for schizophrenia, and is associated with worse psychopathology.