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Abstract: Background: A history of childhood symptoms of inattention–hyperactivity is often reported in first episode psychosis (FEP) as is cannabis use. In the general population childhood ADHD predicts future cannabis use but the relationship has not been tested in FEP. Method: Parents of patients with a first episode of psychosis (n=75) retrospectively assessed their affected child for symptoms of early-life disorders, namely, attention deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD) using the Child Behaviour Checklist (CBCL). Assessments were made prospectively of cannabis use over two years following a FEP and of SCID diagnosis of cannabis-use disorder. Results: Childhood hyperactivity–inattention symptoms predicted inability to maintain abstinence from cannabis following treatment (Wald=8.4, p=.004) and lifetime cannabis-use diagnosis (Wald=5.3, p=.022) in a logistic regression controlling for relevant covariates including symptoms of CD and ODD from ages 12 to 18. When the symptom of inattention was considered in place of the hyperactivity–inattention syndrome it predicted cannabis-use diagnosis (Wald=6.4, p=.011) and persistent abstinence from cannabis (Wald=5.3, p=.021). Symptoms of CD and ODD did not predict cannabis use when hyperactivity–inattention symptoms were controlled for. Conclusions: Symptoms of childhood inattention–hyperactivity predict subsequent cannabis use in FEP. [Copyright &y& Elsevier]

Summary: Early life adversity has been associated with an increased risk for the development of mental health problems, including psychotic disorders, perhaps mediated by a changed regulation of the Hypothalamic Pituitary Adrenal (HPA) axis. Aim of the present study was to confirm our previous finding of an attenuated cortisol awakening response (CAR) in men with first episode psychosis (FEP) and to explore a possible link between a blunted CAR and early adversity as indicated by perceived parental bonding. Fifty-eight patients (38 men, 20 women; mean age 23.25±3.86) with a FEP and 33 healthy community controls (16 men, 17 women; mean age 22.91±3.64) participated in the study. Saliva samples for assessment of the CAR were collected immediately, 30 and 60min after awakening. Complete cortisol samples were available in a reduced sample of 56 patients (37 men) and 30 controls (13 men). Parental bonding during the first 16 years of life was assessed retrospectively with the Parental Bonding Inventory. Results showed a significantly blunted CAR in male compared to female patients, confirming our previously reported findings. We also found a lower CAR in the total FEP group compared to controls, which failed to reach significance after controlling for time of awakening. A significantly lower percentage of patients than controls reported optimal maternal parenting. Within the patient group, significantly fewer male than female patients reported optimal maternal and paternal parenting. Only in patients, unfavorable paternal parenting was related to a blunted CAR. Dysregulation of the HPA axis in male patients might be a consequence of non-optimal parenting and contribute to the less favorable course of psychosis in men compared to women. [ABSTRACT FROM AUTHOR]

Objective: Early life adversity is suspected to play an important role for onset and course of psychosis, but its relationship with longer-term clinical outcome is not entirely clear. In this longitudinal study, we investigated the impact of childhood trauma (CT) on positive and negative symptom remission in first episode psychosis (FEP) patients over two years.Methods: A total of 210 FEP patients were assessed with the Childhood Trauma Questionnaire. Patients reporting moderate to severe trauma (CT; N = 114; 54.3%) were compared to those without trauma (N-CT; N = 96; 45.7%). Positive (PSR) and negative symptom remission (NSR) were determined monthly over 24 months following established criteria using the Scale for Assessment of Positive Symptoms and the Scale for Assessment of Negative Symptoms. Global Functioning was evaluated at baseline and 24 months of follow-up.Results: Compared to N-CT patients, CT patients had achieved significantly lower rates of PSR at 12 months and significantly lower rates of NSR at 24 months. A dose-response relationship was observed between the number of trauma categories fulfilled and the number of patients not achieving PSR and NSR at these time points. Higher trauma scores were significantly associated with poor functioning and higher positive and negative symptom severity at 24 months, but not at baseline and 12 months of follow-up.Conclusion: Differential effects of CT on clinical outcome may not be apparent at psychosis onset, but only become evident through poor symptomatic remission and general functioning over time. Targeted diagnostic and therapeutic efforts after illness onset might limit these detrimental consequences. [ABSTRACT FROM AUTHOR]

• First episode psychosis patients show reduced baseline cortisol levels during the TSST. • Cortisol increase following the TSST is intact in first episode psychosis patients. • Lower cortisol levels during the TSST are associated with poor self-esteem and active coping skills. • Cortisol non-responders to the TSST had experienced more physical neglect during childhood. Psychosis has been associated with abnormalities in hypothalamic-pituitary-adrenal axis functioning, which may emerge through heightened stress sensitivity following early life adversity – ultimately resulting in illness onset and progression. The present study assessed cortisol levels during an established psychosocial stress task and their association with current stress perception, putative protective factors and adverse childhood experiences in patients with a first episode of psychosis (FEP). A total of 100 volunteers participated in the study, 57 of whom were patients with a FEP (mean age 23.9 ± 3.8) and 43 healthy community controls (mean age 23.2 ± 3.9). Salivary cortisol, heart rate and blood pressure were measured at eight time points before and after the Trier Social Stress Test. Subjective stress and protective factors were assessed with the Perceived Stress Scale, the Self-Esteem Rating Scale and the Brief COPE. Early life adversity was assessed with the Childhood Trauma Questionnaire. Patients compared to controls showed significantly lower cortisol levels (F = 7.38; p =.008) throughout the afternoon testing period, but no difference in the cortisol response to the TSST. Heart rate was elevated and protective factors were lower in patients compared to controls. Attenuated cortisol levels were associated with higher levels of perceived stress, poor protective factors and more physical neglect during childhood. Our results suggest that attenuated baseline cortisol levels and not a blunted response during an acute stress task might be an indicator of heightened stress vulnerability and poor resilience in psychosis. The possible influence of childhood adversity and antipsychotic medication is discussed. [ABSTRACT FROM AUTHOR]

Early life adversity is associated with increased risk for psychosis onset and poor clinical outcome. Male compared to female patients often show a more severe course of psychotic illness. The aim of the present study was to investigate gender differences in childhood trauma (CT) and their impact on symptomatic and functional outcome following psychosis onset. The study included 210 patients (144 men, 66 women) diagnosed with a first-episode of psychosis (FEP). Early adversity was assessed with the Childhood Trauma Questionnaire. Psychotic symptoms and general functioning were rated with the Brief Psychiatric Rating Scale and Global Assessment of Functioning scale at baseline, 12 and 24 months of follow-up in an established early intervention service. Male patients reported higher rates of physical or emotional neglect, whereas female patients indicated significantly higher rates of emotional abuse. More severe CT was related to higher levels of depression in women and to negative symptoms in men. Distinct CT effects were observed on positive and negative symptom severity and global functioning in male patients at 24 months. Emotional abuse was the strongest predictor of depression in both genders. In male patients only, emotional abuse predicted positive symptom severity and impaired global functioning, whereas emotional neglect predicted more severe negative symptoms. Our results suggest differences in CT experiences in male and female FEP patients, with a more pronounced impact on longer-term outcome in male patients. The findings support the notion that sex differences in stress vulnerability account for the relatively poor illness course in male psychosis patients. [ABSTRACT FROM AUTHOR]

Elevated rates of cigarette smoking are observed prior to the onset of psychosis and remain stable early in the illness. Cannabis use frequently co-occurs with cigarette smoking and is independently associated with distinct clinical outcomes. However, past research has not controlled for cannabis use in cigarette smokers with first episode psychosis (FEP), limiting conclusions on the unique relationship of cigarette smoking to the demographic and clinical profiles of these patients. The present study therefore aimed to: (1) Determine the prevalence and patterns of cigarette smoking and its co-use with cannabis in FEP, and (2) Examine the demographic, clinical, cognitive, and functional characteristics associated with cigarette smoking status, after adjusting for frequency of cannabis use. Patients entering specialized treatment for FEP ( N = 140) were divided into groups according to their current smoking status: 66 non-smokers (0 cigarettes/day), 47 light/moderate smokers (1–19 cigarettes/day; M = 9.81, SD = 3.93), and 27 heavy smokers (≥20 cigarettes/day; M = 26.39, SD = 6.31). The prevalence of cigarette smoking was 53% and smoking status was highly associated with frequency of cannabis use. After adjusting for cannabis use, significant between-group differences emerged. Heavy smokers were older at program entry and had a later age of onset of psychosis than light/moderate and non-smokers. Non-smokers had more education, better neurocognitive performance, and higher levels of functioning than light/moderate and heavy smokers. Prospective, longitudinal studies are needed to better understand the clinical significance of tobacco use and factors that contribute to the initiation and continuation of smoking behaviours in FEP. [ABSTRACT FROM AUTHOR]

Introduction: Aripiprazole has been associated with a low prevalence of metabolic side effects as compared to other second generation antipsychotic (SGA) medications mostly in patients with long standing illness. The purpose of the present study was to assess specifically the effectiveness and safety of aripiprazole as a first choice for antipsychotic therapy for young patients presenting with a previously untreated first episode of a psychotic disorder (FEP).Methods: Seventy-three patients presenting with a FEP and with minimal prior exposure to antipsychotic medications were recruited to be part of an open label naturalistic outcome study using aripiprazole as the first choice of antipsychotic medication. Data on positive, negative and total symptom severity including general psychopathological symptoms, level of functioning and metabolic indices were collected prospectively over a one-year period.Results: As compared to baseline, patients treated with aripiprazole (mean dose 9.6mg) improved significantly on measures of positive (p<0.001), negative (p<0.001) and total severity-general psychopathology symptoms (p<0.001) and level of functioning (p<0.001). Seventy two percent of the participants achieved positive symptom remission and 50% achieved total remission (positive and negative) at one year of follow up. Unlike reports on patients with longer standing illness, significant weight gain (p<0.001) was observed, with 44% of participants experiencing >7% increase in body weight.Conclusion: FEP patients starting treatment with aripiprazole improved on symptoms and social and occupational functioning. Aripiprazole was well tolerated except for a significant weight gain. [ABSTRACT FROM AUTHOR]

Abstract: Background: Single nucleotide polymorphisms in TCF4 gene have been consistently associated with schizophrenia in genome wide association studies, including the C allele of rs9960767. However, its exact role in modulating the schizophrenia phenotype is not known. Aims: To comprehensively investigate the relationship between rs9960767 risk allele (C) of TCF4 and cognitive performance in patients with first episode psychosis (FEP). Methods: 173 patients with FEP received a comprehensive neurocognitive evaluation and were genotyped for rs9960767. Carriers of the risk allele (CA/CC) were compared to non-carriers (AA) using Multivariate Analysis of Covariance MANCOVA. Ethnicity, negative symptoms and substance abuse were included as covariates. Results: Carriers of the risk allele had a statistically significant lower performance in the cognitive domain of Reasoning/Problem-Solving compared to non-carriers (F1,172 =4.4, p=.038). There were no significant genotype effects on the other cognitive domains or general cognition. This effect on the Reasoning/Problem-Solving domain remained significant even when controlling for IQ (F1,172 =4.3, p=.039). Conclusions: rs9960767 (C) of TCF4 appears to be associated with neurocognitive deficits in the Reasoning/Problem-Solving cognitive domain, in patients with FEP. A confirmation of this finding in a larger sample and including other TCF4 polymorphisms will be needed to gain further validity of this result. [Copyright &y& Elsevier]

Abstract: Stress-vulnerability models of schizophrenia regard psychosocial stress as an important factor in the onset and aggravation of psychotic symptoms, but such research in the early phases of psychosis is limited. Protective factors against the effects of stress might be the key to understanding some inconclusive findings and to the development of optimal psychosocial interventions. The present study compared self-reported levels of stress, self-esteem, social support and active coping in 32 patients with a first episode of psychosis (FEP), 30 individuals at ultra-high risk for psychosis (UHR) and 30 healthy controls. Associations with symptoms of psychosis were assessed in both patient groups. Individuals at UHR reported significantly higher stress levels compared to FEP patients. Both patient groups showed lower self-esteem compared to controls, and the UHR group reported lower social support and active coping than controls. These group differences could not be explained by age and dose of antipsychotic medication in the FEP group. In the UHR group, higher stress levels and lower self-esteem were associated with more severe positive and depressive symptoms on the Brief Psychiatric Rating Scale. Multiple regression analyses revealed that stress was the only significant predictor for both symptom measures and that the relationship was not moderated by self-esteem. Our findings show that individuals at UHR for psychosis experience high levels of psychosocial stress and marked deficits in protective factors. The results suggest that psychosocial interventions targeted at reducing stress levels and improving resilience in this population may be beneficial in improving outcomes. [Copyright &y& Elsevier]

Abstract: Determining reliable markers of clinical outcome for psychosis is essential to adjust intervention efforts. White matter alterations exist prior to psychosis onset but its association with clinical outcome in the very early phase of psychosis is currently unknown. In the present study, white matter was assessed by diffusion tensor imaging (DTI) in patients with first episode psychosis (FEP) and healthy controls. Forty-four FEP patients and 30 matched healthy controls completed a DTI scan. The patient group was split in poor (n =24) and good (n =20) outcome subgroups based on 6-month clinical data. DTI tractography was used to estimate fractional anisotropy (FA) in the three main tracts connecting frontal and temporal regions (i.e. the cingulum, the superior longitudinal fasciculus and the uncinate fasciculus). The analyses showed selective FA reductions in both the uncinate and the superior longitudinal fasciculi, but not in the cingulum, when comparing FEP patients to healthy controls. FEP subgroup analyses revealed greater white matter changes in these tracts in patients with poor outcome as compared to patients with good outcome. These findings confirm that abnormal fronto-temporal connectivity contributes to the physiopathology of FEP and constitutes an early marker of clinical short-term outcome. [Copyright &y& Elsevier]

Summary: A dysregulation of the hypothalamus–pituitary–adrenal (HPA) axis has been suggested as a factor in the etiology and exacerbation of psychosis, but has not been reported consistently. Sex differences are apparent in many aspects of psychotic disorders and may explain some of the equivocation associated with the regulation of the HPA axis in the illness. The present study compared the cortisol response to awakening (CRA) in 27 patients (16 men and 11 women) with recent onset of psychosis (within the past 2 years) and 40 age and gender matched controls. Within the patient group, we also assessed the relationship between the CRA and positive and negative symptoms of psychosis, anxiety and depression. The CRA in patients was not significantly different from controls. However, within the patient group, we observed a significant sex difference, with a blunted cortisol response to awakening in men but not in women (F =7.26; p <0.002). This difference could not be explained by differences between male and female patients in awakening time, medication, or diagnosis of schizophrenia vs. affective psychosis. Cortisol levels were not related to symptom measures. Our findings demonstrate a dysregulation of the HPA axis in male patients with recent onset of psychosis. This sex specificity might be related to and explain in part the unfavorable course of the illness observed in men. [Copyright &y& Elsevier]