Gianluca Rosso

Serum levels of brain-derived neurotrophic factor in drug-naïve obsessive-compulsive patients: A case-control study

BACKGROUND There is lack of data regarding BDNF serum levels in patients with obsessive-compulsive disorder (OCD). The aims of the present study were: 1) to assess the serum BDNF content in a sample of drug-naïve patients with OCD and 2) to assess whether putative alterations in peripheral BDNF may be associated to OCD severity and clinical characteristics. METHODS Twenty-four drug-naïve patients with a principal diagnosis of OCD were recruited. In parallel, a control group of 24 unrelated volunteers matched for gender and age was enrolled. Serum BDNF levels were measured by ELISA method. RESULTS The results showed that BDNF levels were decreased in OCD patients when compared to controls (36.90+/-6.42 ng/ml versus 41.59+/-7.82 ng/ml; p=0.043). No correlations were evidenced between serum BDNF content and the severity of OCD symptoms measured as Y-BOCS scores or other clinical variables. LIMITATIONS The choice of drug-naïve patients with obsessive-compulsive disorder had limited the size of the sample and excluded the recruitment of patients with a severe symptomatology. CONCLUSIONS Our findings reveal for the first time in OCD patients a decrease in serum BDNF levels. These data corroborate the hypothesis of a dysfunction in the neurotrophin expression in the OCD pathogenetic mechanism and provide the rationale for further investigations directed to the identification of novel biomarkers and new therapeutic strategies for antiobsessional treatments.

Brief dynamic therapy combined with pharmacotherapy in the treatment of major depressive disorder: Long-term results

BACKGROUND There is a paucity of controlled trials examining the efficacy of brief dynamic psychotherapy (BDT) in the treatment of major depressive disorder, especially in a long-term perspective. The aim of the present study is to evaluate recurrence rates in unipolar major depressed patients who are responsive to acute phase combined treatment with BDT plus pharmacotherapy in comparison with patients initially treated with pharmacotherapy alone. METHODS Subjects for this study were 92 patients who met criteria for remission at the end of a 6-month acute treatment phase for major depressive disorder, single episode, with combined therapy (BDT plus pharmacotherapy) versus pharmacotherapy alone. 41 (64.1%) subjects were remitters to combined treatment and 51 (61.4%) were remitters to antidepressants alone. The study included a 6-month continuation treatment trial with pharmacotherapy and a following perspective, naturalistic 48-month follow-up (without any treatment). RESULTS Patients who received combined treatment, in comparison with those who were treated with pharmacotherapy alone, show a significant lower rate of recurrences of depressive episodes at 48-months naturalistic follow up (27.5% in comparison with 46.9%: chi(2)=3.525; df=1; p=.048). LIMITATIONS Inclusion and exclusion criteria may limit the generalizability of the results. Furthermore it may be unclear whether the effect is attributable to BDT per se as opposed to extra time with a therapist. CONCLUSIONS The significant lower recurrence rates in a 48-month follow-up in the group of patients treated with the addition of BDT to medication in the acute phase support the view of the advantage in the long-term outcome of adding psychotherapeutic intervention to pharmacotherapy in the acute therapy of unipolar major depression.

Peripheral whole blood microRNA alterations in major depression and bipolar disorder

Major depression (MD) and bipolar disorder (BD) are severe and potentially life-threating mood disorders whose etiology is to date not completely understood. MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein synthesis post-transcriptionally by base-pairing to target gene mRNAs. Growing evidence indicated that miRNAs might play a key role in the pathogenesis of neuropsychiatric disorders and in the action of psychotropic drugs. On these bases, in this study we evaluated the expression levels of 1733 mature miRNAs annotated in miRBase v.17, through a microarray technique, in the blood of 20 MD and 20 BD patients and 20 healthy controls, in order to identify putative miRNA signatures associated with mood disorders. We found that 5 miRNAs (hsa-let-7a-5p, hsa-let-7d-5p, hsa-let-7f-5p, hsa-miR-24-3p and hsa-miR-425-3p) were specifically altered in MD patients and 5 (hsa-miR-140-3p, hsa-miR-30d-5p, hsa-miR-330-5p, hsa-miR-378a-5p and hsa-miR-21-3p) in BD patients, whereas 2 miRNAs (hsa-miR-330-3p and hsa-miR-345-5p) were dysregulated in both the diseases. The bioinformatic prediction of the genes targeted by the altered miRNAs revealed the possible involvement of neural pathways relevant for psychiatric disorders. In conclusion, the observed results indicate a dysregulation of miRNA blood expression in mood disorders and could indicate new avenues for a better understanding of their pathogenetic mechanisms. The identified alterations may represent potential peripheral biomarkers to be complemented with other clinical and biological features for the improvement of diagnostic accuracy.

Age-specific prevalence of metabolic syndrome in Italian patients with bipolar disorder

Aim:  Metabolic syndrome (MetS) is highly prevalent in patients with bipolar disorder (BD). Little research has evaluated the risk profile of MetS and cardiovascular disease in different gender and age groups in these patients. Our aim is to evaluate the prevalence of MetS in Italian patients with BD stratified by gender and age, and to determine the correlates of MetS.

No Effect of Adding Brief Dynamic Therapy to Pharmacotherapy in the Treatment of Obsessive-Compulsive Disorder with Concurrent Major Depression

Background: Until now no studies have investigated the benefits of adding brief dynamic therapy (BDT) to medication in obsessive-compulsive disorder (OCD), while a number of recent investigations have demonstrated the efficacy of supplemental BDT among patients with major depressive disorders (MDD). The objective of the present study was to explore the efficacy of BDT combined with pharmacotherapy in comparison with pharmacotherapy alone in the treatment of OCD with concurrent MDD. Methods: A 12-month randomized clinical trial compared a standard selective serotonin reuptake inhibitor treatment with (n = 27) or without (n = 30) supplemental BDT in patients with OCD and concurrent MDD. Supplemental BDT was added during the first 16-week trial; all patients continued to be treated with only pharmacotherapy in the following continuation phase. The primary efficacy assessments were the Yale-Brown Obsessive Compulsive Scale and the 17-item Hamilton Rating Scale for Depression; the secondary efficacy measures included the Clinical Global Impression scale and the Global Assessment of Functioning. The data analysis was conducted on the ‘intent-to-treat (ITT) efficacy patient sample’. Results: Fifty patients completed the study. No difference between the 2 treatment groups was found at any point by any assessment method in the ITT study sample. Conclusions: Supplemental BDT in the treatment of patients with OCD with concurrent MDD who are receiving effective medication has no significant clinical effect on both obsessive and depressive symptoms.

Combined Brief Dynamic Therapy and Pharmacotherapy in the Treatment of Major Depressive Disorder: A Pilot Study

Background: The relative efficacy of supplemental psychotherapy in the treatment of depression is still a matter of debate. Moreover, the superiority of brief dynamic therapy (BDT) over supportive psychotherapies is not well established. The aim of this study is to compare the efficacy of BDT added to medication with that of brief supportive psychotherapy (BSP) added to medication in the treatment of major depressive disorder. Method: A 12-month randomized clinical trial compared BDT (n = 18) with BSP (n = 17) combined with antidepressants in outpatients with major depressive disorder. Both psychotherapies were added during the first 6 months of the trial; all patients continued to be treated with only pharmacotherapy (paroxetine or citalopram) in the following 6-month continuation phase. Efficacy was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety and the Clinical Global Impression (CGI). The data analysis was conducted on two samples: the per-protocol (PP) sample and the observed-cases (OC) sample. Results: Thirty-two patients completed the study. Although at the end of the combined therapies (T2) no differences emerged between the two treatment approaches, the group of patients treated with BDT showed a further clinical improvement at the end of the study (T3): a significant reduction in symptomatology emerged on the HAM-D (PP sample: F = 75.154, p = 0.03; OC sample: F = 67.149, p = 0.022) and on the CGI total scores (PP sample: F = 78.527, p = 0.016; OC sample: F = 74.104, p = 0.007). The difference in remission rates on the HAM-D (75 vs. 12.5% at T3) is statistically significant favoring BDT. Conclusions: BDT combined with antidepressants is preferable to supportive psychotherapy combined with medication in the treatment of outpatients with major depression.

A randomized, single-blind, comparison of duloxetine with bupropion in the treatment of SSRI-resistant major depression

INTRODUCTION For patients who continue to experience depressive symptoms despite an adequate antidepressant SSRI trial, across-class switch is considered one of the best treatment options. The goal of the present work was to compare in terms of efficacy two different dual-action compounds, duloxetine and bupropion, in patients who failed to respond in two consecutive antidepressant trials with SSRIs. METHODS The patients were allocated randomly to duloxetine (120 mg daily) or bupropion extended release (300 mg daily). The intended medication period was 6 weeks. The primary measure of efficacy was depressive symptoms severity. RESULTS A total of 49 participants were randomly assigned to duloxetine 120 mg (n=27) or bupropion 300 mg (n=22). The ITT efficacy patient sample consisted of 46 patients. Relatively high response and remission rates in treatment groups were found: from 60 to 70% of patients responded to treatment, and approximately 30 to 40% were in remission by the endpoint (week 6). No statistically significant difference emerged between the two groups at any post-baseline assessment, neither on mean scores of rating scales nor on qualitative efficacy measures. LIMITS Limitations of the study are the lack of a placebo arm, difficult to include owing to ethical reasons, and the relatively small size of the sample. CONCLUSIONS These preliminary results seem to support the hypothesis that in patients unresponsive to SSRIs the administration of antidepressants with different mechanisms of action is an effective switching strategy. Further studies are needed in light of the challenge posed by resistant depression.

Lithium prophylaxis during pregnancy and the postpartum period in women with lithium-responsive bipolar I disorder

The aim of this study was to evaluate the efficacy of lithium prophylaxis during the peripartum period in women with lithium-responsive bipolar I disorder. Seventeen lithium-treated patients were selected and underwent preconception counseling that included both a psychiatric and an obstetric evaluation. Treatment was continued with flexible-doses of lithium combined with supportive psychotherapy throughout the pregnancy and the postpartum period. The results support the prophylaxis efficacy of lithium in lithium-responder bipolar women who have a high risk of severe peripartum recurrences.

Glucose metabolism alterations in patients with bipolar disorder

Patients with bipolar disorder (BD) are more frequently affected by metabolic syndrome (MetS) than the general population, but the neurobiological correlates underlying such association are still not clarified and few studies in BD have evaluated the role of regulators of lipid and glucose metabolism. The present study was aimed to investigate putative alterations in markers linked to metabolic dysfunctions as C-peptide, Ghrelin, GIP, GLP-1, Glucagon, Insulin, Leptin, PAI-1 (total), Resistin and Visfatin in a sample of BD patients compared to controls. Furthermore, associations between changes of metabolic markers and relevant clinical features, such as severity of symptomatology, number and type of past mood episodes, drug treatments and presence/absence of metabolic alterations (MetS, diabetes and cardiovascular disease) were analyzed. A total of 57 patients with BD and 49 healthy controls were recruited. The main results showed lower serum levels of Glucagon, GLP-1, Ghrelin, and higher levels of GIP in BD patients as compared to controls (p = 0.018 for Ghrelin; p < 0.0001 for Glucagon; p < 0.0001 for GLP-1; p < 0.0001 for GIP). Further, Glucagon and GLP-1 levels were significantly associated with the number of past mood episodes. These findings support the hypothesis that alterations in Glucagon, GLP-1, GIP and Ghrelin might be involved in BD pathogenesis and might represent useful biomarkers for the development of preventive and personalized therapies in this disorder.

Admixture analysis of age at symptom onset and age at disorder onset in a large sample of patients with obsessive-compulsive disorder.

BACKGROUND A number of studies tested for the presence of different homogeneous subgroups of obsessive-compulsive disorder (OCD) patients depending on the age at onset (AAO). However, none of the various thresholds of AAO have been validated. No study examined whether age at symptoms onset (ASO) and age at disorder onset (ADO) each define specific and diverse OCD subgroups. METHODS We used normal distribution mixture analysis in a sample of 483 OCD patients to test whether we could identify subgroups of patients according to the AAO. We tested whether ASO and ADO had different distributions and identified different subgroups of OCD patients, and whether clinical correlates had similar patterns of associations with patients subgroups identified with ASO or ADO. RESULTS The mixture analysis showed a trimodal distribution for ASO (mean ASO: 6.9 years for the early onset, 14.99 years for the intermediate onset, and 27.7 years for the late onset component), and confirmed a bimodal distribution for ADO (mean ADO: 18.0 and 29.5 years). Significant differences in the clinical profile of the subgroups emerged, particularly when identified using ASO. LIMITATIONS Limitations of our study are the retrospective investigation of AAO, and the fact that our sample may not represent the OCD population, as we enrolled patients referring to a tertiary center specialized in the treatment of OCD. Our findings need to be confirmed in community samples. Another limitation is the lack of information on medication status at enrollment. CONCLUSIONS Age at symptom onset and ADO showed distinct patterns of distributions. Similarly, phenotypic delineation was specific for ASO and ADO identified subgroups. Accurate clinical and biological profiling of ADO and ASO subgroups might show distinct genetic liabilities, ultimately leading to better nosological models and possibly to improved treatment decision making of OCD patients.