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

Abstract

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.

Resting State Functional Connectivity Biomarkers of Treatment Response in Mood Disorders: A Review

“…In a separate study of young adults treated with selective serotonin reuptake inhibitors for unipolar depression, RSFC between ventral tegmental area and cuneus-occipital areas correlated with symptom improvement ( 117 ).…”

Is there any difference in the fractional amplitude of low-frequency fluctuations between first episode major depressive disorder patients and subclinical depressive subjects?

“…Apart from the PFC, we observed decreased fALFF in the left cuneus in MDD subjects compared with that in SD subjects. The cuneus is a part of the visual recognition circuit [43], and its dysfunctional connectivity has been a target of antidepressant treatment effects [44]. MDD patients also exhibit decreased gray matter volume in the cuneus [45].…”

Ketamine—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms

“…More recently, the use of ketamine in treating various psychiatric disorders has regained momentum. Apart from ketamine’s use as a rapid-acting antidepressant drug—which will be more thoroughly discussed in the subsequent section—its use as a novel pharmacotherapeutic intervention for the treatment of post-traumatic stress disorder (PTSD) [ 62 ] and substance use disorders [ 63 ] has also been explored.…”

“…In this context, mystical-type experiences mediated by the psychoactive profile of the drug have been suggested to be important [ 86 ]. At present, evidence for the use of ketamine in this context is only beginning to emerge, and further research is needed to properly evaluate its effectiveness and safety in treating substance use disorders [ 63 ].…”