Giovanni B. Cassano

Efficacy of ECT in depression: A meta-analytic review

Summary: This study analyzed the efficacy of electroconvulsive therapy (ECT) in depression by means a meta-analytic review of randomized controlled trials that compared ECT with simulated ECT or placebo or antidepressant drugs and by a complementary meta-analytic review of nonrandomized controlled trials that compared ECT with antidepressants drugs. The review revealed a significant superiority of ECT in all comparisons: ECT versus simulated ECT, ECT versus placebo, ECT versus antidepressants in general, ECT versus TCAs and ECT versus MAOIs. The nonrandomized controlled trials also revealed a significant statistical difference in favor of ECT when confronted with antidepressants drugs. Data analyzed suggest that ECT is a valid therapeutic tool for treatment of depression, including severe and resistant forms.

Prevalence and burden of bipolar disorders in European countries

A literature search, supplemented by an expert survey and selected reanalyses of existing data from epidemiological studies was performed to determine the prevalence and associated burden of bipolar I and II disorder in EU countries. Only studies using established diagnostic instruments based on DSM-III-R or DSM-IV, or ICD-10 criteria were considered. Fourteen studies from a total of 10 countries were identified. The majority of studies reported 12-month estimates of approximately 1% (range 0.5-1.1%), with little evidence of a gender difference. The cumulative lifetime incidence (two prospective-longitudinal studies) is slightly higher (1.5-2%); and when the wider range of bipolar spectrum disorders is considered estimates increased to approximately 6%. Few studies have reported separate estimates for bipolar I and II disorders. Age of first onset of bipolar disorder is most frequently reported in late adolescence and early adulthood. A high degree of concurrent and sequential comorbidity with other mental disorders and physical illnesses is common. Most studies suggest equally high or even higher levels of impairments and disabilities of bipolar disorders as compared to major depression and schizophrenia. Few data are available on treatment and health care utilization.

Prevalence of anxiety disorders comorbidity in bipolar depression, unipolar depression and dysthymia

Eighty-seven patients with current episode of depression were assessed by the SCID-P and subdivided in bipolar depressives (N = 24), unipolar depressives (n = 38) and dysthymics (n = 25). Anxiety disorders comorbidity in these three groups was investigated by means of the SCID-P. Panic disorder comorbidity was found in 36.8% of bipolar depressives, 31.4% of unipolar depressives and 13% of dysthymics. Prevalence of obsessive-compulsive disorder was 21.1% in bipolars, 14.3% in unipolars and 8.7% in dysthymics. Generalized anxiety disorder resulted in being much more associated with dysthymia (65.2%) than with bipolar (31.6%) or unipolar depression (37.1%). Social phobia comorbidity was exhibited mainly by unipolars (11.4%), while no cases were detected in the bipolar group. Odds ratios revealed that generalized anxiety disorder is significantly more likely to co-occur with dysthymia. Panic disorder showed a higher trend to be associated with bipolar and unipolar depression. Social phobia was more frequent among unipolar depression.

Oxytocin receptor polymorphisms and adult attachment style in patients with depression

Much evidence of an association between specific attachment styles and depression prompted us to investigate, in depressive disorders, the potential role of polymorphisms within the gene encoding the receptor of the main neurohormone involved in attachment processes, oxytocin. For this purpose, two single nucleotide polymorphisms (SNPs), 6930G>A (rs53576) and 9073G>A (rs2254298), within the oxytocin receptor gene (OXTR), were studied in a cohort of 185 patients with major depression (50.3%) or bipolar I or II disorders (49.7%) and 192 matched healthy controls. A positive association between the GG genotype of OXTR SNPs (6930G>A or 9073G>A) and unipolar depression was demonstrated. In this group, GG individuals showed high scores on Attachment Style Questionnaire factors that have been previously associated with depression. Moreover, the GG genotype was also associated with high levels of adult separation anxiety. These findings support the involvement of the oxytocinergic system in the mechanisms that underlie depression and specific adult attachment styles.

From the third month of pregnancy to 1 year postpartum. Prevalence, incidence, recurrence, and new onset of depression. Results from the Perinatal Depression―Research & Screening Unit study

OBJECTIVE Perinatal depression is a particular challenge to clinicians, and its prevalence estimates are difficult to compare across studies. Furthermore, to our knowledge, there are no studies that systematically assessed the incidence of perinatal depression. The aim of this study is to estimate the prevalence, incidence, recurrence, and new onset of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, minor and major depression (mMD) in an unselected population of women recruited at the third month of pregnancy and followed up until the 12th month postpartum. METHOD One thousand sixty-six pregnant women were recruited. Minor and major depression was assessed in a naturalistic, longitudinal study. The Edinburgh Postnatal Depression Scale and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Disorders were administered at different time points during pregnancy and in the postpartum period. RESULTS The period prevalence of mMD was 12.4% in pregnancy and 9.6% in the postpartum period. The cumulative incidence of mMD in pregnancy and in the postpartum period was 2.2% and 6.8%, respectively. Thirty-two (7.3%) women had their first episode in the perinatal period: 1.6% had a new onset of depression during pregnancy, 5.7% in the postpartum period. CONCLUSIONS Our postpartum prevalence figures, which are lower than those reported in the literature, may reflect treatment during the study, suggesting that casting a multiprofessional network around women in need of support may be potentially useful for reducing the effects of this disorder on the mother and the newborn child. Furthermore, our results indicate that women with a history of depression have a 2-fold risk of developing mMD in the perinatal period.

Distribution and cellular localization of the serotonin type 2C receptor messenger RNA in human brain

The regional and cellular distribution of serotonin type 2C receptor messenger RNA was investigated in autopsy samples of human brain by in situ hybridization histochemistry. The main sites of serotonin receptor type 2C messenger RNA expression were the choroid plexus, cerebral cortex, hippocampus, amygdala, some components of the basal ganglia, the substantia nigra, the substantia innominata and the ventromedial hypothalamus, suggesting that this receptor might be involved in the regulation of different brain functions. Interestingly, in all regions examined, the serotonin type 2C receptor messenger RNA was always restricted to subpopulations of cells, suggesting a specific role, perhaps determined by regionality. A comparison of the in situ hybridization results with those previously obtained by means of radioligand binding experiments suggested that in most of the areas analysed the serotonin type 2C receptors were located at axon terminals.

Significant Linkage on Chromosome 10p in Families with Bulimia Nervosa

Bulimia nervosa (BN) is strongly familial, and additive genetic effects appear to contribute substantially to the observed familiality. In turn, behavioral components of BN, such as self-induced vomiting, are reliably measured and heritable. To identify regions of the genome harboring genetic variants conferring susceptibility to BN, we conducted a linkage analysis of multiplex families with eating disorders that were identified through a proband with BN. Linkage analysis of the entire sample of 308 families yielded a double peak, with the highest nonparametric multipoint maximum LOD score (MLS), of 2.92, on chromosome 10. Given the high heritability of self-induced vomiting and the reliability with which it can be measured, we performed linkage analysis in a subset (n=133) of families in which at least two affected relatives reported a symptom pattern that included self-induced vomiting. The highest MLS (3.39) observed was on chromosome 10, between markers D10S1430 and D10S1423. These results provide evidence of the presence of a susceptibility locus for BN on chromosome 10p. Using simulations, we demonstrate that both of these scores, 2.92 and 3.39, meet the widely accepted criterion for genomewide significance. Another region on 14q meets the criterion for genomewide suggestive linkage, with MLSs of 1.97 (full sample) and 1.75 (subset) at 62 centimorgans from p-ter.

The manic-depressive mixed state: familial, temperamental and psychopathologic characteristics in 108 female inpatients.

SummaryData on 108 hospitalized bipolar I women were analyzed to characterize those whose course was marked with at least one mixed episode (i.e. an episode with concomitant manic and depressed features) on the basis of various anamnestic and cross-sectional clinical features in comparison with those without mixed episodes. Our data revealed a later age of appearance of the first mixed episode in the course of bipolar illness with a tendency to recur true to type; greater prevalence of mood incongruent psychotic features; lower frequency of hyperthymic temperament; and familial depressive, rather than bipolar, disorders. These characteristics tend to identify the mixed state as a distinct longitudinal pattern of manic-depressive illness.

Gender-related differences in body dysmorphic disorder (Dysmorphophobia)

Body Dysmorphic Disorder (BDD), which consists of pathological preoccupations with defects in different body parts, has been systematically studied only in the last decade. We hypothesized that gender would differentially influence the localization of the preoccupations as well as the extent and type of comorbidity with other psychiatric disorders. With the use of a specially constructed semistructured interview, we evaluated 58 consecutive outpatients with DSM-III-R BDD (women = 41.4%, men = 58.6%). Women had significantly more preoccupations with breast and legs, checking in the mirror and camouflaging, as well as lifetime comorbidity with panic, generalized anxiety, and bulimia. Men had significantly higher preoccupations with genitals, height, excessive body hair, as well as higher lifetime comorbidity with bipolar disorder. Although BDD is almost never found without comorbidity, it does appear to be an autonomous syndrome, and gender tends to influence the nature and extent of this comorbidity.

Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression.

An eight-week double-blind, multicentre study was performed to evaluate the efficacy and safety of sertraline vs. fluoxetine in the treatment of major depression (DSM-III-R). There were 108 out-patients, from nine Italian centres, entered into the study, of whom 88 were evaluable (48 sertraline, 40 fluoxetine). The final mean daily dose of sertraline was 72 mg and for fluoxetine it was 28 mg. Both treatment groups showed a statistically significant improvement from baseline at one week, and this was maintained until the end of treatment for all of the following measures: Hamilton Rating Scales for Depression and Anxiety, the Montgomery Asberg Depression Rating Scale, Clinical Global Impressions Scale, Zung Self-Rating Scale for Anxiety and the Leeds Sleep Evaluation Questionnaire. Although there was a numerical advantage for sertraline on several efficacy measures, there was no statistically significant difference found between the treatment groups. The incidence of adverse events was similar for both treatments; 40.4% for sertraline and 39.3% for fluoxetine. However, adverse events were generally rated by patients as of lower severity in the sertraline group. In addition, for the fluoxetine group, there was a higher incidence of agitation, anxiety and insomnia than for sertraline. Sertraline was considered to be better tolerated than fluoxetine overall, since only 9.6% of sertraline-treated patients discontinued treatment due to therapy failure whereas in the fluoxetine-treated group this figure was 19.6%. By contrast, 13.5% of sertraline-treated patients discontinued prematurely because of clinical improvement, compared with 10.7% of fluoxetine-treated patients.