Carter GC, Cantrell RA, Zarotsky V et al.Comprehensive review of factors implicated in the heterogeneity of response in depression. Depress Anxiety 29:340-354

Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.
Depression and Anxiety (Impact Factor: 4.41). 04/2012; 29(4):340-54. DOI: 10.1002/da.21918
Source: PubMed


Heterogeneity in overall response and outcomes to pharmacological treatment has been reported in several depression studies but with few sources that integrate these results. The goal of this study was to review the literature and attempt to identify nongenetic factors potentially predictive of overall response to depression treatments.
A comprehensive review of the literature from the last 10 years was performed using three key databases (PubMed, EMBASE, and Cochrane). All relevant studies that met the inclusion criteria were selected and scored for their levels of evidence using the NICE scoring method. A subjective assessment of the strength of evidence for each factor was performed using predefined criteria.
Our broad search yielded 76 articles relevant to treatment heterogeneity. Sociodemographic factors, disease characteristics, and comorbidities were the most heavily researched areas. Some of the factors associated with more favorable overall response include being married, other social support, and low levels of baseline depressive symptoms. Evidence relating to baseline disease severity as a factor predictive of antidepressant response was particularly convincing among the factors reviewed. The presence of comorbid anxiety and pain contributed to worse antidepressant treatment outcomes.
Several factors either predictive of or associated with overall response to antidepressant treatment have been identified. Inclusion of factors predictive of response in the design of future trials may help tailor treatments to depression patients presenting to the average clinical practice, resulting in improved outcomes.

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    • "The other SNP examined in our study, rs2072621, was associated with a fourfold increased risk of depression comorbid with anxiety, but for women with depression in the absence of anxiety, there was no significant association . High levels of anxiety in depression have been associated with higher suicide risk, longer duration of illness, and greater likelihood of treatment nonresponse (Lenze 2003) and these mixed states may constitute a specific diagnostic entity relatively common among older people (Wolitzky-Taylor et al. 2010; Carter et al. 2012). While this is an intronic nonsynonymous SNP, it could still influence gene splicing and thus has the potential to be a functional variant. "
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    ABSTRACT: IntroductionDespite the explosion in genetic association studies over the last decade, clearly identified genetic risk factors for depression remain scarce and replication studies are becoming increasingly important. G-protein-coupled receptor 50 (GPR50) has been implicated in psychiatric disorders in a small number of studies, although not consistently.Methods Data were obtained from 1010 elderly men and women from the prospective population-based ESPRIT study. Logistic regression and survival models were used to determine whether three common GPR50 polymorphisms were associated with depression prevalence or the incidence of depression over 12-years. The analyses were adjusted for a range of covariates such as comorbidity and cholesterol levels, to determine independent associations.ResultsAll three variants showed some evidence of an association with late-life depression in women, although these were not consistent across outcomes, the overall effect sizes were relatively small, and most would not remain significant after correction for multiple testing. Women heterozygous for rs13440581, had a 1.6-fold increased risk of baseline depression, while the odds of depression comorbid with anxiety were increased fourfold for women homozygous for the minor allele of rs2072621. When depressed women at baseline were excluded from the analysis, however, neither variant was associated with the 12-year incidence of depression. In contrast, rs561077 was associated with a 1.8-fold increased risk of incident depression specifically. No significant associations were observed in men.DiscussionOur results thus provide only weak support for the involvement of GPR50 variants in late-life depression, which appear specific to certain subgroups of depressed individuals (i.e., women and those with more severe forms of depression).
    Full-text · Article · Feb 2015 · Brain and Behavior
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    • "Hence, experiences of social disconnection are processed as a survival threat, thus constituting a risk for physical and psychiatric diseases [20] [21]. For example, low social support predicts high risk for both a first episode of major depression and recurrence [22] [23] [24] [25]. Interestingly, using social network analysis, a study showed that people with looser ties have higher depression scores and the tendency to cut any remaining ties that they have left. "
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    ABSTRACT: Social cognition refers to the brain mechanisms by which we process social information about other humans and ourselves. Alterations in interpersonal and social functioning are common in major depressive disorder, though only poorly addressed by current pharmacotherapies. Further standardized tests, such as depression ratings or neuropsychologic tests, used in routine practice provide very little information on social skills, schemas, attributions, stereotypes and judgments related to social interactions. In this article, we review recent literature on how healthy human brains process social decisions and how these processes are altered in major depressive disorder. We especially focus on interactive paradigms (e.g., game theory based tasks) that can reproduce daily life situations in laboratory settings. The evidences we review, together with the rich literature on the protective role of social networks in handling stress, have implications for developing more ecologically-valid biomarkers and interventions in order to optimize functional recovery in depressive disorders
    Full-text · Article · Dec 2013 · Translational Neuroscience
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    • "Marital status (being married or cohabitating) has been found in this study to serve a protective factor from psychological stress (K-10 ≥28) and this finding is consistent with the findings of other studies [39,40]. Being married or cohabitating provides social support thereby reducing the levels of psychological distress [40]. In contrast to some studies [11,13] but in agreement with other studies [41], we did not find a significant association between gender and psychological distress. "
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    ABSTRACT: Psychological distress has been rarely investigated among tuberculosis patients in low-resource settings despite the fact that mental ill health has far-reaching consequences for the health outcome of tuberculosis (TB) patients. In this study, we assessed the prevalence and predictors of psychological distress as a proxy for common mental disorders among tuberculosis (TB) patients in South Africa, where over 60 % of the TB patients are co-infected with HIV. We interviewed 4900 tuberculosis public primary care patients within one month of initiation of anti-tuberculosis treatment for the presence of psychological distress using the Kessler-10 item scale (K-10), and identified predictors of distress using multiple logistic regressions. The Kessler scale contains items associated with anxiety and depression. Data on socio-demographic variables, health status, alcohol and tobacco use and adherence to anti-TB drugs and anti-retroviral therapy (ART) were collected using a structured questionnaire. Using a cut off score of ≥28 and ≥16 on the K-10, 32.9 % and 81 % of tuberculosis patients had symptoms of distress, respectively. In multivariable analysis older age (OR = 1.52; 95 % CI = 1.24-1.85), lower formal education (OR = 0.77; 95 % CI = 0.65-0.91), poverty (OR = 1.90; 95 % CI = 1.57-2.31) and not married, separated, divorced or widowed (OR = 0.74; 95 % CI = 0.62-0.87) were associated with psychological distress (K-10 ≥28), and older age (OR = 1.30; 95 % CI = 1.00-1.69), lower formal education (OR = 0.55; 95 % CI = 0.42-0.71), poverty (OR = 2.02; 95 % CI = 1.50-2.70) and being HIV positive (OR = 1.44; 95 % CI = 1.19-1.74) were associated with psychological distress (K-10 ≥16). In the final model mental illness co-morbidity (hazardous or harmful alcohol use) and non-adherence to anti-TB medication and/or antiretroviral therapy were not associated with psychological distress. The study found high rates of psychological distress among tuberculosis patients. Improved training of providers in screening for psychological distress, appropriate referral to relevant health practitioners and providing comprehensive treatment for patients with TB who are co-infected with HIV is essential to improve their health outcomes. It is also important that structural interventions are promoted in order to improve the financial status of this group of patients.
    Full-text · Article · Jul 2012 · BMC Psychiatry
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