FIRST EPISODE PSYCHOSIS: DO ANTIPSYCHOTIC DRUGS AFFECT HIPPOCAMPAL VOLUMES?

Introduction: brain abnormalities have been found in patients at their first episode of psychosis. It remains unclear whether antipsychotic drugs induce brain changes at this stage and whether such effects are dependent on drug type. To address this question I studied, in a sample of first episode psychosis patients, the volume of the hippocampus. This is a highly neuroplastic structure and it has been reported as reduced in chronic schizophrenia. Methods: I compared 76 patients at their first episode of a functional psychosis (mean age: 28.1 ± 8.4 years, 46% female; 36 schizophrenia, 27 affective psychosis and 13 other psychosis according to DSM-IV criteria) with 76 sex and age matched controls. Hippocampal volumes were manually traced using 1.5 mm coronal, 1.5T high resolution MRI images. Results: there was no difference in hippocampal volume between patients and controls. However, female patients had smaller hippocampal volume than female controls (total volume: F= 6.1, p=0.01; right-side: F=7.0, p=0.01; left-side: F=3.6, p=0.06). I did not find any correlation between cumulative dose of antipsychotic received at the time of MRI and hippocampal volumes. Female patients on treatment, but not those drug–free, had smaller hippocampal volumes than female controls (total volume: F= 4.5, p=0.01; right-side: F=4.3, p=0.02; left-side: F=3.5, p=0.04); type of antipsychotic taken did not influence the results. Discussion: these data suggest that at the time of the first psychotic episode the hippocampal structure is significantly affected in women but not in men; this may be due to a specific effect of antipsychotics in female patients. Findings could be explained by differences in the metabolism of drugs across gender, which is reflected on brain structures. Indeed, the influence of hormonal systems (such as the hypothalamic-pituitary-adrenal axis), which has been shown to influence brain volumes, might play also a role

Dialectical behaviour therapy (DBT) for forensic psychiatric patients: An Italian pilot study

Background: Several previous randomised controlled trials of dialectical behaviour therapy (DBT) since Linehan's original have shown that it has an advantage over standard care or other psychological treatments, but focus is usually on suicide-related behaviours, and little is known about its effect with offender-patients. Aims: To evaluate DBT with a group of offender-patients in the Italian high intensity therapeutic facilities—the Residenze per l'Esecuzione delle Misure di Sicurezza (REMS), established under the Italian Law 81/2014. Methods: Twenty-one male forensic psychiatric in-patients with borderline personality disorder were enrolled and randomly assigned to 12 months of standard DBT together with all the usual REMS treatments (n = 10) or usual REMS treatments alone (n = 11). All participants completed the same pretreatment and posttreatment assessments, including the Barratt Impulsiveness Scale (BIS-11), Difficulties in Emotion Regulation Scale (DERS), and Toronto Alexithymia Scale 20 (TAS-20). Results: Men receiving DBT showed a significantly greater reduction in motor impulsiveness, as measured by the BIS-11, and emotional regulation, as reflected by the DERS total score, than the controls. There were no significant differences between groups in alexithymia scores. Conclusions: Italy has innovative forensic psychiatric facilities with a new recovery–rehabilitation approach, but the ambitious goals behind these cannot be achieved by pharmacology alone. For the first time in clinical forensic settings in Italy, there has been limited access to DBT. This small pilot study suggests this is likely to help ameliorate traits associated with violent and antisocial behaviours, so a full-scale randomised controlled trial should follow

A novel SCL-90-R six-item factor identifies subjects at risk of early adverse outcomes in public mental health settings

To increase access to treatment, Italy made assessment at community mental health centers (CMHCs) independent of medical referral, resulting in increased numbers of patients to be triaged efficiently. To support this process, we evaluated SCL-90-R item-ratings to identify factors that best predicted adverse early outcomes among persons seeking first-time CMHC care in a 24-month period in Rome. A psychiatric nurse screened subjects with a brief interview and self-administered SCL-90-R and psychiatrists provided CGI ratings and ICD-9 diagnosis. Of 832 screened subjects, 32 (3.85%) were hospitalized or attempted suicide within 90 days. Six SCL-90 items (15,41,55,57,78,88) scored much higher with than without such adverse outcomes; their sum is proposed as a predictive measure (“SCL-6″). In binary multivariable logistic modeling, this factor, but not age, sex, diagnosis, or other SCL-90-derived subscales strongly predicted adverse outcomes. A ROC curve for SCL-6 reflected a strong separation between subjects with versus without adverse outcomes (AUC = 0.76). This simple screening tool may support timely identification of patients at risk of early adverse clinical outcome who require especially close follow-up

Higher cortisol levels are associated with smaller left hippocampal volume in first-episode psychosis

This study investigated the relationship between cortisol secretion and hippocampal volume in first-episode psychosis and healthy controls. Hippocampal volume was measured by magnetic resonance imaging (MRI) in 24 first-episode psychosis patients and in 18 healthy controls, together with diurnal cortisol levels. Twelve patients received a second MRI scan at 3-month follow-up. Diurnal cortisol levels were inversely correlated with left hippocampal volume in patients, both at baseline and at follow-up, while no correlation was found in controls. Our findings suggest that smaller hippocampal volume in first-episode psychosis can partly be explained by stress-related processes in the brain, as measured by cortisol hyper-secretion

Stress and inflammation reduce brain-derived neurotrophic factor expression in first-episode psychosis:a pathway to smaller hippocampal volume

BACKGROUND: Reduced brain-derived neurotrophic factor (BDNF) levels have been reported in the serum and plasma of patients with psychosis. The aim of this study was to investigate potential causes and consequences of reduced BDNF expression in these patients, by examining the association between BDNF levels and measures of stress, inflammation and hippocampal volume in first-episode psychosis. METHODS: BDNF, interleukin (IL)-6, and tumour-necrosis-factor (TNF) alpha mRNA levels were measured in leukocytes of 49 first-episode psychosis patients (DSM-IV criteria) and 30 healthy controls, recruited between January 2006 and December 2008. In the same subjects, we measured salivary cortisol levels, and collected information about psychosocial stressors (number of childhood trauma, number of recent stressors, and perceived stress). Finally, hippocampal volume was measured, using brain MRI, in a subsample of 19 patients. RESULTS: Patients had reduced BDNF (effect size d=1.3, p<0.001) and increased IL-6 (effect size d=1.1, p<0.001) and TNF-alpha (effect size d=1.7, p<0.001) gene expression levels, when compared with controls, as well as higher levels of psychosocial stressors. A linear regression analysis in patients showed that a history of childhood trauma and high levels of recent stressors predicted lower BDNF expression through an inflammation-mediated pathway (adjusted R square=0.23, p=0.009). In turn, lower BDNF expression, increased IL-6 expression, and increased cortisol levels, all significantly and independently predicted a smaller left hippocampal volume (adjusted R square=0.71, p<0.001). CONCLUSIONS: Biological changes activated by stress represent a significant factor influencing brain structure and function in first-episode psychosis, through an effect on BDNF

Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis: The role of stress and of antipsychotic treatment

First-episode psychosis (FEP) patients show hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis, but the mechanisms leading to this are still unclear. The aim of this study was to investigate the role of stress and antipsychotic treatment on diurnal cortisol levels, and on cortisol awakening response, in FEP. Recent stressful events, perceived stress and childhood trauma were collected in 50 FEP patients and 36 healthy controls using structured instruments. Salivary cortisol was obtained at awakening, at 15, 30, and 60 min after awakening, and at 12 and 8 pm. Patients experienced more recent stressful events, perceived stress and childhood trauma than controls (p < 0.001). Patients had a trend for higher diurnal cortisol levels (p=0.055), with those with less than two weeks of antipsychotics showing significantly higher cortisol levels than both patients with more than two weeks of antipsychotics (p=0.005) and controls (p=0.002). Moreover, patients showed a blunted cortisol awakening response compared with controls, irrespectively of antipsychotic treatment (p=0.049). These abnormalities in patients were not driven by the excess of stressors: diurnal cortisol levels were negatively correlated with the number of recent stressful events (r=−0.36, p=0.014), and cortisol awakening response was positively correlated with a history of sexual childhood abuse (r=0.33, p=0.033). No significant correlations were found between perceived stress or severity of symptoms and cortisol levels, either diurnal or in the awakening response. Our study shows that antipsychotics normalize diurnal cortisol hyper-secretion but not the blunted cortisol awakening response in FEP; factors other than the excess of psychosocial stress explain HPA axis abnormalities in FEP