Correlation between emotion dysregulation and mood symptoms of bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Emotion dysregulation (ED) is a transdiagnostic construct characterized by difficulties regulating intense emotions. People with bipolar disorder (BD) are more likely to show ED and use maladaptive emotion regulation strategies than adaptive ones. However, little is known about whether ED in BD is a trait or it is rather an epiphenomenon of mood symptoms. METHODS: We conducted a systematic review and meta-analysis of the evidence across major literature databases reporting correlations between measures of emotion regulation (overall ED and different emotion regulation strategies) and measures of depressive and (hypo)manic symptoms in BD from inception until April 12th, 2022. RESULTS: Fourteen studies involving 1371 individuals with BD were included in the qualitative synthesis, of which 11 reported quantitative information and were included in the meta-analysis. ED and maladaptive strategies were significantly higher during periods with more severe mood symptoms, especially depressive ones, while adaptive strategies were lower. CONCLUSION: ED significantly correlates with BD symptomatology, and it mainly occurs during mood alterations. ED may be a target for specific psychotherapeutic and pharmacological treatments, according to precision psychiatry. However, further studies are needed, including patients with mood episodes and longitudinal design, to provide more robust evidence and explore the causal direction of the associations.

Clinical features in co-occuring obsessive-compulsive disorder and bipolar disorder: A systematic review and meta-analysis.

Obsessive-compulsive disorder (OCD) frequently co-occurs with various psychiatric conditions and may impact as many as one-fifth of individuals diagnosed with bipolar disorder (BD). Despite the expanding body of literature on the coexistence of OCD and BD, there is a notable lack of comprehensive data pertaining to the distinct features of obsessive-compulsive symptoms that define this comorbidity. To bridge this knowledge gap, we conducted a systematic search of PubMed/MEDLINE, Scopus, EMBASE, and PsycINFO until August 7th, 2023. We performed random-effects meta-analyses to compare individuals with both OCD and BD to those with OCD in terms of OCD symptomatology as well as the specific categories of obsessions and compulsions. Out of the 10,393 records initially screened, 17 studies were ultimately incorporated into the qualitative assessment, with 15 of them being included in the quantitative analysis. Individuals with OCD and BD experienced fewer lifetime contamination obsessions (OR=0.71; 95 %CI=0.53, 0.95; p = 0.021) and more sexual obsessions (OR=1.77; 95 %CI=1.03, 3.04; p = 0.04) compared to individuals with OCD without BD. No significant difference was observed for other types of obsessions or compulsions or for the severity of OCD symptoms, although BD type may play a role according to meta-regression analyses. The detection of the presence of sexual or contamination obsessions through a detailed interview may be the focus of clinical attention when assessing OCD in the context of comorbid BD. Sub-phenotyping complex clinical presentation of comorbid psychiatric disorders can aid in making more informed decisions when choosing an appropriate treatment approach.

Pharmacological treatments for psychotic depression: a systematic review and network meta-analysis.

BACKGROUND: There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network meta-analysis to assess and compare the efficacy and safety of pharmacological treatments for psychotic depression. METHODS: In this systematic review and network meta-analysis, we searched ClinicalTrials.gov, CENTRAL, Embase, PsycINFO, PubMed, Scopus, and Web of Science from inception to Nov 23, 2023 for randomised controlled trials published in any language that assessed pharmacological treatments for individuals of any age with a diagnosis of a major depressive episode with psychotic features, in the context of major depressive disorder or bipolar disorder in any setting. We excluded continuation or maintenance trials. We screened the study titles and abstracts identified, and we extracted data from relevant studies after full-text review. If full data were not available, we requested data from study authors twice. We analysed treatments for individual drugs (or drug combinations) and by grouping them on the basis of mechanisms of action. The primary outcomes were response rate (ie, the proportion of participants who responded to treatment) and acceptability (ie, the proportion who discontinued treatment for any reason). We calculated risk ratios and did separate frequentist network meta-analyses by using random-effects models. The risk of bias of individual studies was assessed with the Cochrane risk-of-bias tool and the confidence in the evidence with the Confidence-In-Network-Meta-Analysis (CINeMA). This study was registered with PROSPERO, CRD42023392926. FINDINGS: Of 6313 reports identified, 16 randomised controlled trials were included in the systematic review, and 14 were included in the network meta-analyses. The 16 trials included 1161 people with psychotic depression (mean age 50·5 years [SD 11·4]). 516 (44·4%) participants were female and 422 (36·3%) were male; sex data were not available for the other 223 (19·2%). 489 (42·1%) participants were White, 47 (4·0%) were African American, and 12 (1·0%) were Asian; race or ethnicity data were not available for the other 613 (52·8%). Only the combination of fluoxetine plus olanzapine was associated with a higher proportion of participants with a treatment response compared with placebo (risk ratio 1·91 [95% CI 1·27-2·85]), with no differences in terms of safety outcomes compared with placebo. When treatments were grouped by mechanism of action, the combination of a selective serotonin reuptake inhibitor with a second-generation antipsychotic was associated with a higher proportion of treatment responses than was placebo (1·89 [1·17-3·04]), with no differences in terms of safety outcomes. In head-to-head comparisons of active treatments, a significantly higher proportion of participants had a response to amitriptyline plus perphenazine (3·61 [1·23-10·56]) and amoxapine (3·14 [1·01-9·80]) than to perphenazine, and to fluoxetine plus olanzapine compared with olanzapine alone (1·60 [1·09-2·34]). Venlafaxine, venlafaxine plus quetiapine (2·25 [1·09-4·63]), and imipramine (1·95 [1·01-3·79]) were also associated with a higher proportion of treatment responses overall. In head-to-head comparisons grouped by mechanism of action, antipsychotic plus antidepressant combinations consistently outperformed monotherapies from either drug class in terms of the proportion of participants with treatment responses. Heterogeneity was low. No high-risk instances were identified in the bias assessment for our primary outcomes. INTERPRETATION: According to the available evidence, the combination of a selective serotonin reuptake inhibitor and a second-generation antipsychotic-and particularly of fluoxetine and olanzapine-could be the optimal treatment choice for psychotic depression. These findings should be taken into account in the development of clinical practice guidelines. However, these conclusions should be interpreted cautiously in view of the low number of included studies and the limitations of these studies. FUNDING: None.

Clinical insights into the cross-link between mood disorders and type 2 diabetes: A review of longitudinal studies and Mendelian randomisation analyses.

Mood disorders and type 2 diabetes mellitus (T2DM) are prevalent conditions that often co-occur. We reviewed the available evidence from longitudinal and Mendelian randomisation (MR) studies on the relationship between major depressive disorder (MDD), bipolar disorder and T2DM. The clinical implications of this comorbidity on the course of either condition and the impact of antidepressants, mood stabilisers, and antidiabetic drugs were examined. Consistent evidence indicates a bidirectional association between mood disorders and T2DM. T2DM leads to more severe depression, whereas depression is associated with more complications and higher mortality in T2DM. MR studies demonstrated a causal effect of MDD on T2DM in Europeans, while a suggestive causal association in the opposite direction was found in East Asians. Antidepressants, but not lithium, were associated with a higher T2DM risk in the long-term, but confounders cannot be excluded. Some oral antidiabetics, such as pioglitazone and liraglutide, may be effective on depressive and cognitive symptoms. Studies in multi-ethnic populations, with a more careful assessment of confounders and appropriate power, would be important.

Differences in facial emotion recognition between bipolar disorder and other clinical populations: A systematic review and meta-analysis.

Facial emotion (or expression) recognition (FER) is a domain of affective cognition impaired across various psychiatric conditions, including bipolar disorder (BD). We conducted a systematic review and meta-analysis searching for eligible articles published from inception to April 26, 2023, in PubMed/MEDLINE, Scopus, EMBASE, and PsycINFO to examine whether and to what extent FER would differ between people with BD and those with other mental disorders. Thirty-three studies comparing 1506 BD patients with 1973 clinical controls were included in the present systematic review, and twenty-six of them were analyzed in random-effects meta-analyses exploring the discrepancies in discriminating or identifying emotional stimuli at a general and specific level. Individuals with BD were more accurate in identifying each type of emotion during a FER task compared to individuals diagnosed with schizophrenia (SCZ) (SMD = 0.27; p-value = 0.006), with specific differences in the perception of anger (SMD = 0.46; p-value = 1.19e-06), fear (SMD = 0.38; p-value = 8.2e-04), and sadness (SMD = 0.33; p-value = 0.026). In contrast, BD patients were less accurate than individuals with major depressive disorder (MDD) in identifying each type of emotion (SMD = -0.24; p-value = 0.014), but these differences were more specific for sad emotional stimuli (SMD = -0.31; p-value = 0.009). No significant differences were observed when BD was compared with children and adolescents diagnosed with attention-deficit/hyperactivity disorder. FER emerges as a potential integrative instrument for guiding diagnosis by enabling discrimination between BD and SCZ or MDD. Enhancing the standardization of adopted tasks could further enhance the accuracy of this tool, leveraging FER potential as a therapeutic target.

The Mixed Tendency in Bipolar Disorder: An Operational Proposal for the Integration of Mixed Episodes in Predominant Polarity.

Predominant Polarity (PP) is an established specifier of Bipolar Disorder (BD), holding significant clinical implications. Nevertheless, there exists no consensus on how to incorporate mixed states into PP, leaving patients prone to mixed recurrences that are unclassified. In a comprehensive study involving 701 euthymic BD patients, we sought to redefine PP by introducing a novel metric, the "mixed tendency", and establish a practical threshold to identify patients with a "mixed phenotype". Furthermore, we investigated potential associations between the mixed phenotype and specific PP categories. Our findings revealed that the mixed tendency correlated significantly with early BD type I, lifetime suicide attempts, self-aggressive behaviour, and lifetime number of affective episodes (>5). Using a ROC curve analysis, we determined an optimal cut-off point for the mixed tendency at 0.228, suggesting that patients with ~25% of lifetime mixed episodes relative to total affective episodes should be identified as having a mixed phenotype. Notably, the mixed phenotype was positively associated with undetermined PP and negatively with manic and depressive PP. This study introduces a promising approach to incorporating mixed episodes into the PP definition, potentially enabling tailored interventions for patients with a substantial history of mixed episodes. However, further research in large, longitudinal cohorts is essential to validate these findings.

Dissecting pain processing in adolescents with Non-Suicidal Self Injury: Could suicide risk lurk among the electrodes?

BACKGROUND: Although non-suicidal self-injury (NSSI) disorder is highly prevalent in adolescents, its relationship with pain system function and suicidality is still controversial. The present study was designed to assess the function of the nociceptive afferent pathways and the endogenous pain modulation in adolescent patients with NSSI and to longitudinally register any suicide attempt, describe its frequency and find a possible association between suicide, neurophysiological measures and psychological measures. METHODS: We enrolled 30 adolescents suffering from NSSI and 20 age- and gender-matched healthy controls. Patients underwent a comprehensive psychological evaluation. Each participant underwent thermal pain thresholds of the quantitative sensory testing, laser-evoked potential recording to study the ascending nociceptive pathway and the conditioned pain modulation testing to test the endogenous pain modulation. RESULTS: We found that patients with NSSI had a reduced amplitude of the N2 component of laser-evoked potentials and an abnormal conditioned pain modulation. The amplitude of the N2 was associated with suicidal risk. CONCLUSIONS: The deficit of the endogenous pain modulation likely depends on a saturation due to continuous pain solicitation. The strong association of a reduced amplitude of the N2 component with suicide suggests that it may serve as a possible biomarker in self-harming adolescents. SIGNIFICANCE: The present study identifies the N2 component of laser-evoked potentials as a possible neurophysiological biomarker of suicidal risk in patients with non-suicidal self-injury, therefore, raising the possibility for a non-invasive test to identify subjects at higher risk of suicide among self-harming patients.