Identification of a GABAergic neural circuit governing leptin signaling deficiency-induced obesity.

The hormone leptin is known to robustly suppress food intake by acting upon the leptin receptor (LepR) signaling system residing within the agouti-related protein (AgRP) neurons of the hypothalamus. However, clinical studies indicate that leptin is undesirable as a therapeutic regiment for obesity, which is at least partly attributed to the poorly understood complex secondary structure and key signaling mechanism of the leptin-responsive neural circuit. Here, we show that the LepR-expressing portal neurons send GABAergic projections to a cohort of α3-GABAA receptor expressing neurons within the dorsomedial hypothalamic nucleus (DMH) for the control of leptin-mediated obesity phenotype. We identified the DMH as a key brain region that contributes to the regulation of leptin-mediated feeding. Acute activation of the GABAergic AgRP-DMH circuit promoted food intake and glucose intolerance, while activation of post-synaptic MC4R neurons in the DMH elicited exactly opposite phenotypes. Rapid deletion of LepR from AgRP neurons caused an obesity phenotype which can be rescued by blockage of GABAA receptor in the DMH. Consistent with behavioral results, these DMH neurons displayed suppressed neural activities in response to hunger or hyperglycemia. Furthermore, we identified that α3-GABAA receptor signaling within the DMH exerts potent bi-directional regulation of the central effects of leptin on feeding and body weight. Together, our results demonstrate a novel GABAergic neural circuit governing leptin-mediated feeding and energy balance via a unique α3-GABAA signaling within the secondary leptin-responsive neural circuit, constituting a new avenue for therapeutic interventions in the treatment of obesity and associated comorbidities.

Emotion regulation accounts for associations between mindfulness and depression across and within diagnostic categories.

BACKGROUND: Previous research shows that mindfulness and emotion regulation (ER) are highly related to each other. Preliminary evidence in small clinical populations show that ER may partially account for the relationship between mindfulness and depressive symptoms. The present study aimed to investigate which diagnostic categories were associated with depressive symptoms after controlling for ER in a heterogeneous sample of treatment-seeking patients. METHODS: A large sample of psychiatric outpatients (N = 911) completed the Structured Clinical Interview for DSM-IV (SCID), Five Facet Mindfulness Questionnaire (FFMQ), Difficulties in Emotion Regulation Scale (DERS), and Clinically Useful Depression Outcome Scale (CUDOS). Partial correlations were conducted to evaluate to what degree the relationship between depression scores and facets of mindfulness were accounted for by ER scores. RESULTS: When controlling for baseline mindfulness, the relationship between emotion dysregulation and depression symptoms remained significant for all data points; however, when controlling for baseline emotion dysregulation, the association between mindfulness and depression was not significant in the majority of cases. Nonjudging was most resistant to this result. CONCLUSIONS: Although mindfulness is negatively associated with depressive symptoms, this association may be better accounted for by emotion dysregulation.

"I Learned to Let Go of My Pain". The Effects of Mindfulness Meditation on Adolescents with Chronic Pain: An Analysis of Participants' Treatment Experience.

Chronic pain can lead to significant negative outcomes across many areas of life. Recently, mindfulness-based interventions (MBIs) have been identified as potentially effective tools for improved pain management among adolescents living with pain. This study aimed to explore the experience of adolescents who participated in an eight-week mindfulness group adapted for adolescents with chronic pain (MBI-A), and obtain their feedback and suggestions on group structure and content. A mixed method design was used employing qualitative data from focus groups and data from a satisfaction questionnaire. Focus group data were transcribed and analyzed using inductive simple descriptive content analysis. Of the total participants (n = 21), 90% (n = 19) provided feedback by completing satisfaction questionnaires and seventeen (n = 17) of those also participated across two focus groups. Analysis of the focus group transcripts uncovered six themes: mindfulness skills, supportive environment, group exercises (likes and dislikes), empowerment, program expectations, and logistics. Participants reported positive experiences in the MBI-A program, including support received from peers and mindfulness skills, including present moment awareness, pain acceptance, and emotion regulation. Group members suggested increasing the number of sessions and being clearer at outset regarding a focus on reduction of emotional suffering rather than physical pain.