Bipolar Disorder: an impossible diagnosis.

Following the recent debates on the discrepancy between the predominant weight of bipolar disorder (BPD) in the clinical reality and its relatively low prevalence figures emerging from epidemiological surveys, the present paper contends the ability of current operational diagnostic system to properly detect the clinical entity of bipolar disorder.As an episode of mania/hypomania is the necessary requirement for a diagnosis of bipolar disorder to be made, in this editorial we maintain that: a) the most severe forms of mania, characterized by cloudy consciousness, mood incongruent delusions, and physical symptoms are likely to escape DSM IV criteria, that are shaped around hypomania or mild mania; b) the impossibility to diagnose mania when this occurs during antidepressant treatments impedes diagnosing those cases whose natural illness pattern is Depression followed by Mania (known as DMI pattern); c) given that approximately 50% of cases have their onset of BPD with affective episodes other than mania/hypomania any prevalence figure necessarily underestimates BPD; d) the sub-threshold forms of BPD, well described in the concept of Bipolar Spectrum, are beyond the possibility to be recognized using operational diagnoses in spite of their utmost clinical relevance.

The Imperial College Cambridge Manchester (ICCAM) platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part A: Study description.

Drug and alcohol dependence are global problems with substantial societal costs. There are few treatments for relapse prevention and therefore a pressing need for further study of brain mechanisms underpinning relapse circuitry. The Imperial College Cambridge Manchester (ICCAM) platform study is an experimental medicine approach to this problem: using functional magnetic resonance imaging (fMRI) techniques and selective pharmacological tools, it aims to explore the neuropharmacology of putative relapse pathways in cocaine, alcohol, opiate dependent, and healthy individuals to inform future drug development. Addiction studies typically involve small samples because of recruitment difficulties and attrition. We established the platform in three centres to assess the feasibility of a multisite approach to address these issues. Pharmacological modulation of reward, impulsivity and emotional reactivity were investigated in a monetary incentive delay task, an inhibitory control task, and an evocative images task, using selective antagonists for µ-opioid, dopamine D3 receptor (DRD3) and neurokinin 1 (NK1) receptors (naltrexone, GSK598809, vofopitant/aprepitant), in a placebo-controlled, randomised, crossover design. In two years, 609 scans were performed, with 155 individuals scanned at baseline. Attrition was low and the majority of individuals were sufficiently motivated to complete all five sessions (n=87). We describe herein the study design, main aims, recruitment numbers, sample characteristics, and explain the test hypotheses and anticipated study outputs.

Plasma clomipramine levels in adult patients with obsessive-compulsive disorder.

The aim of this study was to explore the possible relationship between plasma clomipramine and its major metabolite (N-desmethylclomipramine) levels and related parameters, and clinical features in patients with obsessive-compulsive disorder (OCD). Twenty-six outpatients (13 men, 13 women), suffering from OCD were consecutively enrolled in this study. The severity of OCD was assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The measurements were taken after 4 weeks and 6 months from the beginning of the treatment. The drug levels were measured by a high-performance liquid chromatography method developed by us. The correlations between biological and clinical parameters were analyzed by means of Spearman's correlation coefficient. The Mann-Whitney test was used for comparing biological and clinical variables between men and women. The results showed that clomipramine levels were related to the doses at the two assessment times. A significant and positive correlation was detected at the beginning between the N-desmethylclomipramine ratio and the Y-BOCS total score; however, this was true only for men, where the similar correlations were measured also with the Y-BOCS subscale. After 6 months of clomipramine, men showed a significant improvement of the compulsions. These findings would highlight the potential impact of assessing clomipramine plasma levels and their relationships with specific symptoms, as well as the influence of the sex on the drug response.

Cognitive impairment in major depression.

In the past decade, a growing bulk of evidence has accumulated to suggest that patients suffering from major depression (MD) present some cognitive disturbances, such as impairment in attention, working memory, and executive function, including cognitive inhibition, problem- and task-planning. If the results of short-term memory assessment in depressed patients are equivocal, a general consensus exists that memory problems are secondary to attentional dysfunctions, and reflect the inability to concentrate. Moreover, both unipolar and bipolar patients show evidence of impaired verbal learning that has been commonly interpreted as reflecting an inability to transfer information from short-term to long-term storage. According to some authors, there would be a gender-related as well age-related specificity of some disturbances. Depressed patients also show impairments of executive functions and their recent exploration through brain imaging techniques has recently permitted to formulate some general hypotheses on the possible involvement of different brain areas in MD.

Agoraphobia between panic and phobias: clinical epidemiology from the Sesto Fiorentino Study.

In the last few decades, there has been a long debate on the existence of agoraphobia (AG) without a history of panic attacks (PAs). In the present study, the problem of the relationships between AG and PAs is addressed trough a reevaluation of the cases who had been diagnosed with AG in the community survey of Sesto Fiorentino. Forty-one of the 75 subjects who met the criterion of AG in the Sesto Fiorentino Study were reinterviewed by experienced clinical psychiatrists. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and the Composite International Diagnostic Interview were used to make the diagnoses. The Mobility Inventory for Agoraphobia (MIA) and a specific adjunctive question, "why do/did you avoid?", were used to compare AG subjects with or without PD. Of the 41 subjects with a lifetime history of AG, 12 cases had original diagnosis of AG without PAs and the remaining 29 had PD with AG. After the reassessment, in 10 cases, the criteria for the diagnosis of AG without PAs were confirmed, totaling a lifetime prevalence of 0.4% (confidence interval, 0.2-0.8). Agoraphobia subjects with and without PAs were comparable as regard to sex, age, age of onset, duration of illness, family history for anxiety or mood disorders, MIA scores, number, and type of situations avoided. Thus, AG seems to exist also in absence of a history of PAs, and the one-way relationship between the occurrence of PAs and a following development of AG, postulated by DSM-IV, should be reconsidered for the future classifications.