Brain-derived neurotrophic factor association with amygdala response in major depressive disorder

Background: Brain-derived neurotrophic factor (BDNF) has an essential role in synaptic plasticity and neurogenesis. BDNF mediates amygdala-dependent learning for both aversive and appetitive emotional memories. The expression of BDNF in limbic regions is posited to contribute the development of depression, and amygdala responsivity is a potential marker of depressive state. Methods: The present study examined the relationship between platelet BDNF levels and amygdala volume and function in major depressive disorder (MDD). Participants were 23 MDD (mean age 38.9 years) and 23 healthy controls (mean age 38.8 years). All participants were recruited from the community. MDD participants were in a current depressive episode of moderate severity and medication-free. Amygdala responses were acquired during a functional MRI task of implicit emotional processing with sad facial expressions. Results: Significant correlation was observed between platelet BDNF levels and left amygdala responses, but no significant correlations were found with right amygdala responses or with amygdala volumes. Limitations: Interactions with neuroprotective as well as neurotoxic metabolites in the kyneurenine pathway were not examined. Conclusions: Relationship between BDNF levels and amygdala responsivity to emotionally salient stimuli in MDD could reflect the importance of BDNF in amygdala-dependent learning with clinical implications for potential pathways for treatment

Number of risk genotypes is a risk factor for major depressive disorder: a case control study

BACKGROUND: The objective of the study was to determine the genetic basis of Major Depressive Disorder, and the capacity to respond to antidepressant treatment. An association study of 21 candidate polymorphisms relevant to monoamine function and the mechanism of antidepressant response was conducted in 3 phenotypically distinct samples: a group with chronic or recurrent depression unable to respond to antidepressants (non-responders) (n = 58), a group capable of symptomatic improvement with or without treatment (responders) (n = 39), and volunteer controls (n = 85). The responders and non-responders constituted a larger group of depressed subjects. METHODS: A candidate gene approach was employed to asses the genetics basis of Major Depressive Disorder. The genotypic frequencies of selected polymorphisms were compared between the controls and depressed subjects. To asses the genetics basis of the capacity to respond to antidepressant treatment, the responders were compared to the non-responders. Candidate genes were chosen based on functional studies and proximity to whole genome linkage findings in the literature. Risk genotypes were identified by previous functional studies and association studies. RESULTS: A statistically significant difference in genotype frequency for the SLC6A4 intron 2 VNTR was detected between the subjects with a history of depression and controls (p = 0.004). Surprisingly, a statistically significant difference was detected between responders and non-responders for the DRD4 exon III VNTR genotype frequencies (p = 0.009). Furthermore, a difference between the controls and depressed subjects as well as between the controls and non-responders was detected for the number and distribution of risk genotypes in each group. CONCLUSION: An association between several monoamine-related genes and Major Depressive Disorder is supported. The data suggest that the two depressive phenotypes are genetically different, inferring that the genetic basis for the capacity to respond to standard antidepressant treatment, and the genetic susceptibility to Major Depressive Disorder may be independent. In addition, a proof of concept is provided demonstrating that the number of risk genotypes may be an indication of susceptibility of major depressive disorder and the severity of the disorder

Impact of non-remission of depression on costs and resource utilization: from the COmorbidities and symptoms of DEpression (CODE) study

<p>To determine the economic impact of sustained non-remission of depression on the total annual all-cause healthcare costs of patients with a history of depression.</p> <p>Adults with ≥2 claims with depression diagnosis codes from the HealthCore Integrated Research Database were invited to participate in this retrospective/prospective fixed-cohort repeated-measures study. Patients with scores >5 at initial survey and 6 month assessment on the Quick Inventory of Depressive Symptomatology (QIDS-SR) were considered to be in ‘sustained non-remission’, while those with scores ≤5 at both assessments were considered to be in ‘sustained remission’. Patients also completed self-report instruments to assess pain, fatigue, anxiety, sleep difficulty, and other health and wellness domains. Survey data were linked to patient claims (12 month pre- and post-initial-survey periods). After adjusting for demographic and clinical characteristics using propensity scores, post-survey costs and resource utilization were compared between remission and non-remission groups using non-parametric bootstrapping methods.</p> <p>Of the 640 patients who met inclusion criteria, 140 (21.9%) were in sustained remission and 348 (54.5%) never achieved remission. Using propensity-score adjusted costs, sustained non-remission of depression was associated with higher annual healthcare expenditures of >$2300 per patient ($14,627 vs. $12,313, <i>p</i> = 0.0010) compared to remitted patients. Higher costs were associated with greater resource utilization and increased medication use. Non-remitters were prescribed more medications than remitters, including antidepressants and second-generation antipsychotics. Although length of antidepressant exposure over 12 months was similar, remitters were more likely to be adherent to antidepressants. Non-remission was associated with anxiety, pain, fatigue, sleep disruption, diabetes, anemia, obesity, and heavy drinking.</p> <p>Failing to achieve remission of depression was associated with increased costs and greater resource utilization. Clinicians should strive to achieve sustained remission in patients with depression. Study limitations included reliance on claims data for initial identification of cohort and high rate of attrition in the analytic sample.</p

Linkage disequilibrium mapping of the chromosome 6q21-22.31 bipolar I disorder susceptibility locus.

We previously reported genome-wide significant evidence for linkage between chromosome 6q and bipolar I disorder (BPI) by performing a meta-analysis of original genotype data from 11 genome scan linkage studies. We now present follow-up linkage disequilibrium mapping of the linked region utilizing 3,047 single nucleotide polymorphism (SNP) markers in a case-control sample (N = 530 cases, 534 controls) and family-based sample (N = 256 nuclear families, 1,301 individuals). The strongest single SNP result (rs6938431, P = 6.72 x 10(-5)) was observed in the case-control sample, near the solute carrier family 22, member 16 gene (SLC22A16). In a replication study, we genotyped 151 SNPs in an independent sample (N = 622 cases, 1,181 controls) and observed further evidence of association between variants at SLC22A16 and BPI. Although consistent evidence of association with any single variant was not seen across samples, SNP-wise and gene-based test results in the three samples provided convergent evidence for association with SLC22A16, a carnitine transporter, implicating this gene as a novel candidate for BPI risk. Further studies in larger samples are warranted to clarify which, if any, genes in the 6q region confer risk for bipolar disorder