Does initial use of benzodiazepines delay an adequate pharmacological treatment? A multicentre analysis in patients with psychotic and affective disorders.

It is established that delayed effective pharmacotherapy plays a significant role in the overall burden of psychiatric disorders, which are often treated with symptomatic drugs, that is benzodiazepines (BZDs), in relation to their rapid onset of action and safety, despite long-term side effects. We aimed to assess the influence of initial treatment with BZDs on the duration of untreated illness (DUI) and whether specific sociodemographic and clinical factors could influence the choice of BZDs as first treatment in 545 patients affected by schizophrenia, mood and anxiety spectrum disorders. Statistical analyses (one-way analysis of variance and χ) were carried out to compare patients who used BZDs as first treatment (BZD w/) and those who did not (BZD w/o). The overall DUI, irrespective of diagnosis, resulted in significantly longer in BZD w/ versus w/o patients, who also experienced more frequently anxious/depressive symptoms at onset. Furthermore, BZD w/ patients more frequently autonomously decided to look for treatment (mainly refering to psychologists or general practitioners) and experimented more frequently phobias, than BZD w/o ones. The present findings suggest that initial BZDs treatment may prolong the overall DUI, although their prescription seems to be influenced by specific sociodemographic and clinical factors. Further studies are needed to confirm the present findings.

A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia.

Compelling evidence supports the involvement of the endocannabinoid system (ECS) in psychosis vulnerability. We here evaluated the transcriptional regulation of ECS components in human peripheral blood mononuclear cells (PBMCs) obtained from subjects suffering from bipolar disorder, major depressive disorder and schizophrenia, focusing in particular on the effects of DNA methylation. We observed selective alterations of DNA methylation at the promoter of CNR1, the gene coding for the type-1 cannabinoid receptor, in schizophrenic patients (N=25) with no changes in any other disorder. We confirmed the regulation of CNR1 in a well-validated animal model of schizophrenia, induced by prenatal methylazoxymethanol (MAM) acetate exposure (N=7 per group) where we found, in the prefrontal cortex, a significant increase in CNR1 expression and a consistent reduction in DNA methylation at specific CpG sites of gene promoter. Overall, our findings suggest a selective dysregulation of ECS in psychosis, and highlight the evaluation of CNR1 DNA methylation levels in PBMCs as a potential biomarker for schizophrenia.

Reduced duration of untreated illness over time in patients with schizophrenia spectrum, mood and anxiety disorders.

AIMS: Psychiatric disorders represent highly impairing conditions, often underdiagnosed and undertreated, with a conspicuous duration of untreated illness (DUI). Given that social and cultural factors influence the DUI and assuming that progress in diagnosis and treatment determines a reduced latency to pharmacotherapy, we assessed and compared DUI and related variables in a large sample of psychiatric patients (n = 562) whose onset occurred within three different a priori-defined epochs. METHODS: Two temporal cut-offs were established - the year 1978, when Law 180 (redefining standards for mental care) was introduced in Italy, and the year 2000 - in order to divide patients into three subgroups: onset before 1978, onset 1978-2000 and onset after 2000. RESULTS: A significant difference in terms of age at onset, age at first diagnosis and age at first treatment was observed in patients with onset 1978-2000 and in those with onset after 2000. In addition, a significant reduction of the DUI was found across epochs (onset before 1978: 192.25 ± 184.52 months; onset 1978-2000: 77.00 ± 96.63 months; and onset after 2000: 19.00 ± 31.67 months; P < 0.001). Furthermore, the proportion of patients with onset-related stressful events, use of benzodiazepines and neurological referral was found to be significantly different between the three epochs (χ(2) = 23.4, P < 0.001; χ(2) = 9.92, P = 0.007; χ(2) = 16.50, P = 0.011). CONCLUSIONS: Present data indicate a progressive, statistically significant reduction of latency to treatment and other related changes across subsequent epochs of onset in patients with different psychiatric disorders. Future studies will assess specific changes within homogeneous diagnostic subgroups.

Assessing working memory via N-back task in euthymic bipolar I disorder patients: a review of functional magnetic resonance imaging studies.

Bipolar disorder (BD) is a chronic and highly disabling mood disorder, associated with the highest suicide rate among psychiatric disorders. Even though neurobiological bases of BD have still to be further elucidated, recent neuroimaging studies provided compelling evidence about functional correlates of cognitive deficits in BD patients, with working memory (WM) impairment being one of the most commonly reported findings. Such dysfunctions are likely to persist beyond acute phases of the illness, so they qualify as endophenotypic markers for the disorder. This review sought to synthesize, through a MEDLINE search up to December 2012, published functional magnetic resonance imaging (fMRI) studies on WM networks, conducted through N-back task in euthymic BD I patients and including a control comparison group. Eight studies meeting the search criteria were identified. Despite heterogeneity across findings, particularly in relation to task performance (i.e. accuracy and reaction time), most studies reported a loss of connectivity in BD patients' prefrontal networks, traditionally involved in WM, as well as patterns of abnormal activation in the dorso/ventrolateral prefrontal cortex, other prefrontal areas and the parietal and temporal cortex. These findings suggest the involvement of intact secondary systems in order to overcome lack of integrity across WM circuits in BD patients. Further investigation in the field is warranted.