Euthymic Patients with Bipolar Disorder Show Decreased Reward Learning in a Probabilistic Reward Task

Background: Bipolar disorder (BPD) features cycling mood states ranging from depression to mania with intermittent phases of euthymia. Bipolar disorder subjects often show excessive goal-directed and pleasure-seeking behavior during manic episodes and reduced hedonic capacity during depressive episodes, indicating that BPD might involve altered reward processing. Our goal was to test the hypothesis that BPD is characterized by impairments in adjusting behavior as a function of prior reinforcement history, particularly in the presence of residual anhedonic symptoms. Methods: Eighteen medicated BPD subjects and 25 demographically matched comparison subjects performed a probabilistic reward task. To identify putative dysfunctions in reward processing irrespective of mood state, primary analyses focused on euthymic BPD subjects (n = 13). With signal-detection methodologies, response bias toward a more frequently rewarded stimulus was used to objectively assess the participants' propensity to modulate behavior as a function of reinforcement history. Results: Relative to comparison subjects, euthymic BPD subjects showed a reduced and delayed acquisition of response bias toward the more frequently rewarded stimulus, which was partially due to increased sensitivity to single rewards of the disadvantageous stimulus. Analyses considering the entire BPD sample revealed that reduced reward learning correlated with self-reported anhedonic symptoms, even after adjusting for residual manic and anxious symptoms and general distress. Conclusions: The present study provides preliminary evidence indicating that BPD, even during euthymic states, is characterized by dysfunctional reward learning in situations requiring integration of reinforcement information over time and thus offers initial insights about the potential source of dysfunctional reward processing in this disorder.Psycholog

Comparative efficacy and acceptability of psychosocial interventions for individuals with cocaine and amphetamine addiction: A systematic review and network meta-analysis.

BACKGROUND: Clinical guidelines recommend psychosocial interventions for cocaine and/or amphetamine addiction as first-line treatment, but it is still unclear which intervention, if any, should be offered first. We aimed to estimate the comparative effectiveness of all available psychosocial interventions (alone or in combination) for the short- and long-term treatment of people with cocaine and/or amphetamine addiction. METHODS AND FINDINGS: We searched published and unpublished randomised controlled trials (RCTs) comparing any structured psychosocial intervention against an active control or treatment as usual (TAU) for the treatment of cocaine and/or amphetamine addiction in adults. Primary outcome measures were efficacy (proportion of patients in abstinence, assessed by urinalysis) and acceptability (proportion of patients who dropped out due to any cause) at the end of treatment, but we also measured the acute (12 weeks) and long-term (longest duration of study follow-up) effects of the interventions and the longest duration of abstinence. Odds ratios (ORs) and standardised mean differences were estimated using pairwise and network meta-analysis with random effects. The risk of bias of the included studies was assessed with the Cochrane tool, and the strength of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We followed the PRISMA for Network Meta-Analyses (PRISMA-NMA) guidelines, and the protocol was registered in PROSPERO (CRD 42017042900). We included 50 RCTs evaluating 12 psychosocial interventions or TAU in 6,942 participants. The strength of evidence ranged from high to very low. Compared to TAU, contingency management (CM) plus community reinforcement approach was the only intervention that increased the number of abstinent patients at the end of treatment (OR 2.84, 95% CI 1.24-6.51, P = 0.013), and also at 12 weeks (OR 7.60, 95% CI 2.03-28.37, P = 0.002) and at longest follow-up (OR 3.08, 95% CI 1.33-7.17, P = 0.008). At the end of treatment, CM plus community reinforcement approach had the highest number of statistically significant results in head-to-head comparisons, being more efficacious than cognitive behavioural therapy (CBT) (OR 2.44, 95% CI 1.02-5.88, P = 0.045), non-contingent rewards (OR 3.31, 95% CI 1.32-8.28, P = 0.010), and 12-step programme plus non-contingent rewards (OR 4.07, 95% CI 1.13-14.69, P = 0.031). CM plus community reinforcement approach was also associated with fewer dropouts than TAU, both at 12 weeks and the end of treatment (OR 3.92, P < 0.001, and 3.63, P < 0.001, respectively). At the longest follow-up, community reinforcement approach was more effective than non-contingent rewards, supportive-expressive psychodynamic therapy, TAU, and 12-step programme (OR ranging between 2.71, P = 0.026, and 4.58, P = 0.001), but the combination of community reinforcement approach with CM was superior also to CBT alone, CM alone, CM plus CBT, and 12-step programme plus non-contingent rewards (ORs between 2.50, P = 0.039, and 5.22, P < 0.001). The main limitations of our study were the quality of included studies and the lack of blinding, which may have increased the risk of performance bias. However, our analyses were based on objective outcomes, which are less likely to be biased. CONCLUSIONS: To our knowledge, this network meta-analysis is the most comprehensive synthesis of data for psychosocial interventions in individuals with cocaine and/or amphetamine addiction. Our findings provide the best evidence base currently available to guide decision-making about psychosocial interventions for individuals with cocaine and/or amphetamine addiction and should inform patients, clinicians, and policy-maker

Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder

<p>Abstract</p> <p>Background</p> <p>The MAOA uVNTR polymorphism has been documented to affect the MAOA gene at the transcriptional level and is associated with aggressive impulsive behaviors, depression associated with suicide (depressed suicide), and major depressive disorder (MDD). We hypothesized that the uVNTR polymorphism confers vulnerability to MDD, suicide or both. The aim of this study was to explore the association between the MAOA uVNTR and depressed suicide, using multiple controls.</p> <p>Methods</p> <p>Four different groups were included: 432 community controls, 385 patients with MDD who had not attempted suicide, 96 community subjects without mental disorders who had attempted suicide, and 109 patients with MDD who had attempted suicide. The MAOA uVNTR polymorphism was genotyped by a PCR technique. The symptom profiles and personal characteristics in each group were also compared.</p> <p>Results</p> <p>The MAOA 4R allele was more frequent in males with MDD than in male community controls (χ²= 4.182, p = 0.041). Logistic regression analysis showed that, among the depressed subjects, those younger in age, more neurotic or who smoked had an increased risk of suicide (β = -0.04, p = 0.002; β = 0.15, p = 0.017; β = 0.79, p = 0.031, respectively). Moreover, among those who had attempted suicide, those younger in age, with more paternal overprotection, and more somatic symptoms were more likely to be in the MDD group than in the community group (β = -0.11, p < 0.001; β = 0.15, p = 0.026; β = 1.11, p < 0.001). Structural equation modeling (SEM) showed that nongenetic factors, such as age, paternal overprotection, and somatic symptoms, were associated with MDD, whereas depressed suicide were associated with severity of depression, personality traits, age, marital status, and inversely associated with anxiety symptoms. However, depression did not affect suicidal behavior in the community group.</p> <p>Conclusion</p> <p>The MAOA 4R allele is associated with enhanced vulnerability to suicide in depressed males, but not in community subjects. The MAOA 4R allele affects vulnerability to suicide through the mediating factor of depressive symptoms. Further large-scale studies are needed to verify the psychopathology of the relationships among MAOA uVNTR polymorphism, symptom profiles, and suicidal behavior.</p

Sub-threshold depression and antidepressants use in a community sample: searching anxiety and finding bipolar disorder

<p>Abstract</p> <p>Background</p> <p>To determine the use of antidepressants (ADs) in people with sub-threshold depression (SD); the lifetime prevalence of mania and hypomania in SD and the link between ADs use, bipolarity and anxiety disorders in SD.</p> <p>Methods</p> <p>Study design: community survey. Study population: samples randomly drawn, after stratification from the adult population of municipal records. Sample size: 4999 people from seven areas within six Italian regions. Tools: Questionnaire on psychotropic drug consumption, prescription; Structured Clinical Interview NP for DSM-IV modified (ANTAS); Hamilton Depression Rating Scale (HAM-D); Mood Disorder Questionnaire (MDQ); Short Form Health Survey (SF-12). SD definition: HAM-D > 10 without lifetime diagnosis of Depressive Episode (DE).</p> <p>Results</p> <p>SD point prevalence is 5.0%. The lifetime prevalence of mania and hypomania episodes in SD is 7.3%. Benzodiazepines (BDZ) consumption in SD is 24.1%, followed by ADs (19.7%). In SD, positive for MDQ and comorbidity with Panic Disorder (PD) or Generalized Anxiety Disorders (GAD) are associated with ADs use, whereas the association between a positive MDQ and ADs use, without a diagnosis of PD or GAD, is not significant. Only in people with DE the well-being (SF-12) is higher among those using first-line antidepressants compared to those not using any medication. In people with SD no significant differences were found in terms of SF-12 score according to drug use.</p> <p>Conclusions</p> <p>This study suggests caution in prescribing ADs to people with SD. In people with concomitant anxiety disorders and SD, it should be mandatory to perform a well-designed assessment and evaluate the presence of previous manic or hypomanic symptoms prior to prescribing ADs.</p

Convergent functional genomic studies of omega-3 fatty acids in stress reactivity, bipolar disorder and alcoholism

Omega-3 fatty acids have been proposed as an adjuvant treatment option in psychiatric disorders. Given their other health benefits and their relative lack of toxicity, teratogenicity and side effects, they may be particularly useful in children and in females of child-bearing age, especially during pregnancy and postpartum. A comprehensive mechanistic understanding of their effects is needed. Here we report translational studies demonstrating the phenotypic normalization and gene expression effects of dietary omega-3 fatty acids, specifically docosahexaenoic acid (DHA), in a stress-reactive knockout mouse model of bipolar disorder and co-morbid alcoholism, using a bioinformatic convergent functional genomics approach integrating animal model and human data to prioritize disease-relevant genes. Additionally, to validate at a behavioral level the novel observed effects on decreasing alcohol consumption, we also tested the effects of DHA in an independent animal model, alcohol-preferring (P) rats, a well-established animal model of alcoholism. Our studies uncover sex differences, brain region-specific effects and blood biomarkers that may underpin the effects of DHA. Of note, DHA modulates some of the same genes targeted by current psychotropic medications, as well as increases myelin-related gene expression. Myelin-related gene expression decrease is a common, if nonspecific, denominator of neuropsychiatric disorders. In conclusion, our work supports the potential utility of omega-3 fatty acids, specifically DHA, for a spectrum of psychiatric disorders such as stress disorders, bipolar disorder, alcoholism and beyond