Altered Reward Processing in the Orbitofrontal Cortex and Hippocampus in Healthy First-Degree Relatives of Patients With Depression.

Altered reward processing in the orbitofrontal cortex and hippocampus in healthy first-degree relatives of patients with depression.

Psychol Med. 2013 Jul 19; 1-13
Macoveanu J, Knorr U, Skimminge A, Søndergaard MG, Jørgensen A, Fauerholdt-Jepsen M, Paulson OB, Knudsen GM, Siebner HR, Kessing LV

Healthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing. Method In a two-step functional magnetic resonance imaging (fMRI) investigation, we first evaluated whether positive and negative monetary outcomes were differentially processed by rMD+ individuals compared to healthy first-degree relatives of control probands (rMD-). Second, in a double-blinded placebo-controlled randomized trial we investigated whether a 4-week intervention with the selective serotonergic reuptake inhibitor (SSRI) escitalopram had a normalizing effect on behavior and brain responses of the rMD+ individuals.Negative outcomes increased the probability of risk-averse choices in the subsequent trial in rMD+ but not in rMD- individuals. The orbitofrontal cortex (OFC) displayed a stronger neural response when subjects missed a large reward after a low-risk choice in the rMD+ group compared to the rMD- group. The enhanced orbitofrontal response to negative outcomes was reversed following escitalopram intervention compared to placebo. Conversely, for positive outcomes, the left hippocampus showed attenuated response to high wins in the rMD+ compared to the rMD- group. The SSRI intervention reinforced the hippocampal response to large wins. A subsequent structural analysis revealed that the abnormal neural responses were not accounted for by changes in gray matter density in rMD+ individuals.Our study in first-degree relatives of depressive patients showed abnormal brain responses to aversive and rewarding outcomes in regions known to be dysfunctional in depression. We further confirmed the reversal of these aberrant activations with SSRI intervention. HubMed – depression

Persistence of chronic major depression: A national prospective study.

J Affect Disord. 2013 Jul 15;
Garcia-Toro M, Rubio JM, Gili M, Roca M, Jin CJ, Liu SM, Bastianoni C, Blanco C

Chronic major depressive disorder (CMDD) is highly prevalent and associated with high personal and societal cost. Identifying risk factors for persistence and remission of CMDD may help in developing more effective treatment and prevention interventions.Prospective cohort study of individuals participating in the National Epidemiologic Survey on Alcohol and Related Conditions (Wave 1; n=43,093) and its 3-year follow-up (Wave 2; n=34,653) who met a diagnosis of CMDD at the Wave 1 assessment.Among the 504 respondents who met criteria for present CMDD at Wave 1, only 63 (11.52%) of them continued to meet criteria of CMDD. A history of childhood sexual abuse, earlier onset of MDD, presence of comorbidity and a history of treatment-seeking for depression predicted persistence of CMDD three years after the baseline evaluation.Our sample is limited to adults, our follow-up period was only three-years and the diagnosis of CMDD at baseline was retrospective.CMDD shows high rates of remission within three years of baseline assessment, although some specific risk factors predict a persistent course. Given the high personal and societal cost associated with CMDD, there is a need to develop and disseminate effective interventions for CMDD. HubMed – depression

Combined dexamethasone suppression-corticotrophin-releasing hormone stimulation test in medication-free major depression and healthy volunteers.

J Affect Disord. 2013 Jul 15;
Sher L, Oquendo MA, Burke AK, Cooper TB, John Mann J

The hypothalamic-pituitary-adrenal (HPA) axis is dysfunctional in a subgroup of mood disorders.We compared cortisol and adrenocorticotropic hormone (ACTH) responses in major depression and healthy volunteers to the combined dexamethasone suppression-corticotrophin-releasing hormone stimulation (DEX-CRH) test. Unlike other published studies, the study patients were medication-free and the healthy volunteers did not have first-degree relatives with a mood or psychotic disorder. Demographics, DSM-IV diagnoses and other clinical parameters were evaluated in major depressive disorder (MDD) and healthy control groups. Participants received an oral dose of 1.5mg dexamethasone at 11pm the day before CRH administration. On the following day, at 3pm, 100µg of ovine CRH was infused. Blood samples for determination of cortisol and ACTH were collected every 15min from 3pm to 4:15pm. Cortisol and ACTH responses were calculated as areas under the curve.Controlling for age, baseline (i.e., post-dexamethasone) ACTH levels were higher in depressed patients compared to controls (p=0.01). There was a trend for higher ACTH responses in depressed patients compared to the control group (p=0.08). In depressed patients, cortisol and ACTH responses correlated positively with age, duration of illness and number of hospitalizations.Because of the cross-sectional study design we can only evaluate the nature of potential HPA axis disturbances that were present in patients when they are acutely depressed.Feedback inhibition of ACTH secretion by cortisol is compromised in MDD, and this is independent of an age effect on the HPA axis function. HubMed – depression