Neuroimaging correlates of emotional response-inhibition discriminate between young depressed adults with and without sub-threshold bipolar symptoms (Emotional Response-inhibition in Young Depressed Adults).

BACKGROUND: Many subjects with major depression (MDD) exhibit subthreshold mania symptoms (MDD+). This study investigated, for the first time, using emotional inhibition tasks, whether the neural organization of MDD+ subjects is more similar to bipolar depression (BDD) or to MDD subjects without subthreshold bipolar symptoms (MDD-). METHOD: This study included 118 medication-free young adults (15 - 30 yrs.): 20 BDD, 28 MDD+, 41 MDD- and 29 HC subjects. Participants underwent fMRI during emotional and non-emotional Go/No-go tasks during which they responded for Go stimuli and inhibited response for happy, fear, and non-emotional (gender) faces No-go stimuli. Univariate linear mixed-effects (LME) analysis for group effects and multivariate Gaussian Process Classifier (GPC) analyses were conducted. RESULTS: MDD- group compared to both the BDD and MDD+ groups, exhibited significantly lower activation in parietal, temporal and frontal regions (cluster-wise corrected p <0.05) for emotional inhibition conditions vs. non-emotional condition. GPC classification of emotional (happy + fear) vs. non-emotional response-inhibition activation pattern showed good discrimination between BDD and MDD- subjects (AUC: 0.70; balanced accuracy: 70% (corrected p = 0.018)) as well as between MDD+ and MDD- subjects (AUC: 0.72; balanced accuracy: 67% (corrected p = 0.045)) but less efficient discrimination between BDD and MDD+ groups (AUC: 0.68; balanced accuracy: 61% (corrected p = 0.273)). Notably, classification of the MDD- group was weighted for left amygdala activation pattern. LIMITATIONS: Results also need to be tested in a different independent dataset. CONCLUSION: Using an fMRI emotional Go-Nogo task, MDD- subjects can be discriminated from BDD and MDD+ subjects.

Sub-threshold bipolar disorder in medication-free young subjects with major depression: Clinical characteristics and antidepressant treatment response.

BACKGROUND: This study, for the first time, compared illness and antidepressant response characteristics of young subjects with major depression (MDD) at low (LRMDD) or high-risk (HRMDD) for developing bipolar disorder with characteristics of young bipolar (BPD) subjects and healthy controls (HC). METHODS: One hundred and six young (15-30 yr), medication-free subjects MDD subjects (HRMDD, N = 51; LRMDD, N = 55) were compared with 32 BPD (Type I: 14; Type II: 18) as well as 49 HC subjects. Baseline illness characteristics and frequency of comorbid conditions were examined using Analysis of Variance and Cochran-Armitage trend test. Additionally, in MDD subjects, the effect of open-label antidepressant treatment for up to 24 months with periodic assessments was compared between HRMDD and LRMDD groups for treatment response, remission and (hypo)mania switch while controlling for attrition. RESULTS: Significant gradation from LRMDD to HRMDD to BPD groups was found for increasing occurrence of alcohol dependence (p = 0.006), comorbid PTSD (p = 0.006), borderline personality traits (p = 0.001), and occurrence of melancholic features (p < 0.005). Antidepressant treatment response was similar between the two groups except that for the 12-month period HRMDD showed a trend for a lower response. Switch to (hypo)mania was infrequent in both groups though the HRMDD showed a higher occurrence of spikes in (hypo)mania symptoms (>25% increase in YMRS scores)(p = 0.04). CONCLUSION: Findings of the study indicate that a substantial proportion of young MDD subjects share BPD illness characteristics. These HRMDD subjects, if treated with antidepressants, need to be monitored for development of BPD. TRIAL REGISTRATION: NCT01811147.

Diagnosing and treating bipolar disorder in primary care.

Major depression often presents in patients with a history of both depression and mania, although patients may not have the insight to report manic symptoms as problematic. Distinguishing pure (unipolar) depression from bipolar depression is important for prognostic and treatment reasons. Once identified, bipolar depression can be adequately and safely treated.

Resting State Functional Connectivity of Dorsal Raphe Nucleus and Ventral Tegmental Area in Medication-Free Young Adults With Major Depression.

Background: This study has, for the first time, investigated the dorsal raphe nucleus (DRN) and ventral tegmental area (VTA) resting state whole-brain functional connectivity in medication-free young adults with major depression (MDD), at baseline and in relationship to treatment response. Method: A total of 119 subjects: 78 MDD (24 ± 4 years.) and 41 Healthy Controls (HC) (24 ± 3 years) were included in the analysis. DRN and VTA ROIs anatomical templates were used to extract resting state fluctuations and used to derive whole-brain functional connectivity. Differences between MDD and HCs were examined, as well as the correlation of baseline Hamilton Depression and Anxiety scale scores to the baseline DRN and VTA connectivity. The relationship to treatment response was examined by investigating the correlation of the percentage decrease in depression and anxiety scale scores with baseline connectivity measures. Results: There was a significant decrease (p = 0.05; cluster-wise corrected) in DRN connectivity with the prefrontal and mid-cingulate cortex in the MDD group, compared with the HC group. DRN connectivity with temporal areas, including the hippocampus and amygdala, positively correlated with baseline depression scores (p = 0.05; cluster-wise corrected). VTA connectivity with the cuneus-occipital areas correlated with a change in depression scores (p = 0.05; cluster-wise corrected). Conclusion: Our results indicate the presence of DRN-prefrontal and DRN-cingulate cortex connectivity abnormalities in young medication-free depressed subjects when compared to HCs and that the severity of depressive symptoms correlates with DRN-amygdala/hippocampus connectivity. VTA connectivity with the parietal and occipital areas is related to antidepressant treatment associated with a decrease in depressive symptoms. Future studies need to be carried out in larger and different age group populations to confirm the findings of the study.