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 hypersecretion but not the blunted cortisol awakening response in FEP; factors other than the excess of psychosocial stress explain HPA axis abnormalities in FEP.

Antipsychotic treatment potentially contributes to the brain structural changes observed in psychosis. Future research should take into account these potential effects, and use adequate sample sizes, to allow improved interpretation of neuroimaging findings in these disorders.

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.

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.

No abstract

We evaluated the long-term antidepressant safety and response of adjunctive pramipexole, a D2-D3 dopamine agonist, in the course of drug-resistant depression. Twenty-three patients with treatment-resistant major depressive episode (MDE) were followed up after a 16-week pramipexole add-on trial. Pramipexole was added to current treatment with TCA or SSRI, at increasing doses from 0.375-1.500 mg/day. The LIFE scale was administered at baseline of the acute trial, at Weeks 16, 32, and 48. Patients were analyzed for sustained remission (score=<2 at LIFE for at least 8 weeks) and recurrence (after remission score > =3 at LIFE for at least 2 weeks) of depression. Of 23 patients, 12 had major depression and 11 had bipolar depression (16 women; mean age=52.8 years). Mean age of onset and median duration of current MDE were 35.1 years and 6 months, respectively; all subjects had at least two prior MDEs. Mean pramipexole dose was 0.990 mg/day. Median duration of follow-up was 28 weeks. Mean baseline MADRS and CGI-S scores were 33.7+/-8.4 (sd) and 4.6+/-0.8, respectively. Median time to sustained remission from baseline was 10 weeks and overall 60.9% (14/23) of subjects recovered within Week 22. Recurrence of depression occurred in 35.7% (5/14) of remitters after Week 24 and within Week 28 from remission. Although there were no sleep attacks, two cases of hypomania and one case of psychotic mania occurred at Weeks 22, 24, and 30, respectively. Pramipexole augmentation of antidepressant treatment was relatively safe and presumably effective in the long-term course of treatment resistant depression.

These pilot data suggest that, in selected cases of TRD, ropinirole augmentation of antidepressants is effective and relatively well tolerated.

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.