Variable telomere length across post-mortem human brain regions and specific reduction in the hippocampus of major depressive disorder.

Stress can be a predisposing factor to psychiatric disorders and has been associated with decreased neurogenesis and reduced hippocampal volume especially in depression. Similarly, in white blood cells chronic psychological stress has been associated with telomere shortening and with mood disorders and schizophrenia (SZ). However, in previous post-mortem brain studies from occipital cortex and cerebellum, no difference in telomere length was observed in depression. We hypothesized that in psychiatric disorders, stress-driven accelerated cellular aging can be observed in brain regions particularly sensitive to stress. Telomere length was measured by quantitative-PCR in five brain regions (dorsolateral prefrontal cortex, hippocampus (HIPP), amygdala, nucleus accumbens and substantia nigra (SN)) in major depressive disorder (MDD), bipolar disorder, SZ and normal control subjects (N = 40, 10 subjects per group). We observed significant differences in telomere length across brain regions suggesting variable levels of cell aging, with SN and HIPP having the longest telomeres and the dorsolateral prefrontal cortex the shortest. A significant decrease (P < 0.02) in telomere length was observed specifically in the HIPP of MDD subjects even after controlling for age. In the HIPP of MDD subjects, several genes involved in neuroprotection and in stress response (FKBP5, CRH) showed altered levels of mRNA. Our results suggest the presence of hippocampal stress-mediated accelerated cellular aging in depression. Further studies are needed to investigate the cellular specificity of these findings.

Challenges contributing to disrupted transition from paediatric to adult diabetes care in young adults with type 1 diabetes.

AIM: To examine challenges contributing to disruptions in care during the transition from paediatric to adult care among young adults with Type 1 diabetes who are primarily in ethnic minority groups and have low socio-economic status. METHODS: Participants (n = 20) were newly enrolled patients in a transition clinic for young adults with Type 1 diabetes with a history of loss to medical follow-up. Participants completed qualitative semi-structured interviews detailing their transition experiences in addition to demographic, HbA1c and psychosocial measures. Descriptive statistics were completed for quantitative data, and narrative thematic analysis of interviews was used to identify common themes. A mixed-method analysis was used to identify the associations between stressors identified in interviews and clinical and psychosocial variables. RESULTS: Three categories of challenges contributing to loss to follow-up were identified: psychosocial challenges, health provider and health system challenges and developmental challenges. Participants experienced a high degree of stressful life circumstances which were associated with higher HbA1c (r = 0.60, P = 0.005), longer duration of loss to follow-up (r = 0.51, P = 0.02), greater emergency department utilization (r = 0.45, P = 0.05), and lower life satisfaction (r = -0.62, P = 0.003). CONCLUSIONS: A confluence of challenges, including stressful life circumstances, healthcare system barriers and the developmental trajectory of young adulthood, contributes to a high risk of loss to follow-up and poor health in this population of young adults with Type 1 diabetes. An integrated approach to transition addressing medical and psychosocial needs may facilitate improved follow-up and health outcomes in clinical settings.