The possible therapeutic impact of dietary changes on existing mental illness is largely unknown. Using a randomised controlled trial design, we aimed to investigate the efficacy of a dietary improvement program for the treatment of major depressive episodes.
We wanted to examine tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating major depressive disorder (MDD). This was a Phase 1B, double blind, randomized, placebo controlled, multiple-dose study with three cohorts. The first cohort received 40 mg q.d. (n=6) or placebo (n=2), the second cohort 40 mg b.i.d. (n=6) or placebo (n=2), and the third cohort 40 mg t.i.d. (n=6) or placebo (n=2). Twenty-four patients with MDD were recruited, with the diagnosis and severity confirmed through remote interviews. Eligible patients received NSI-189 or placebo for 28 days in an inpatient setting with assessments for safety, pharmacokinetics (PK) and efficacy. Outpatient follow-up visits were conducted until day 84 (±3). NSI-189 was relatively well tolerated at all doses, with no serious adverse effects. NSI-189 area under the curve increased in a dose-related and nearly proportional manner across the three cohorts, with a half-life of 17.4-20.5 h. The exploratory efficacy measurements, including Symptoms Of Depression Questionnaire (SDQ), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions-Improvement (CGI-I), and The Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ) showed a promising reduction in depressive and cognitive symptoms across all measures for NSI-189, with significant improvement in the SDQ and CPFQ, and a medium to large effect size for all measures. These improvements persisted during the follow-up phase. In summary, NSI-189 shows potential as a treatment for MDD in an early phase study. The main limitation of this preliminary study was the small sample size of each cohort.Molecular Psychiatry advance online publication, 8 December 2015; doi:10.1038/mp.2015.178.
A growing body of research demonstrates that individuals diagnosed with major depressive disorder (MDD) are characterized by shortened telomere length, which has been posited to underlie the association between depression and increased instances of medical illness. The temporal nature of the relation between MDD and shortened telomere length, however, is not clear. Importantly, both MDD and telomere length have been associated independently with high levels of stress, implicating dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and anomalous levels of cortisol secretion in this relation. Despite these associations, no study has assessed telomere length or its relation with HPA-axis activity in individuals at risk for depression, before the onset of disorder. In the present study, we assessed cortisol levels in response to a laboratory stressor and telomere length in 97 healthy young daughters of mothers either with recurrent episodes of depression (i.e., daughters at familial risk for depression) or with no history of psychopathology. We found that daughters of depressed mothers had shorter telomeres than did daughters of never-depressed mothers and, further, that shorter telomeres were associated with greater cortisol reactivity to stress. This study is the first to demonstrate that children at familial risk of developing MDD are characterized by accelerated biological aging, operationalized as shortened telomere length, before they had experienced an onset of depression; this may predispose them to develop not only MDD but also other age-related medical illnesses. It is critical, therefore, that we attempt to identify and distinguish genetic and environmental mechanisms that contribute to telomere shortening.Molecular Psychiatry advance online publication, 30 September 2014; doi:10.1038/mp.2014.119.
Background: Most of the literature on the association between socioeconomic status (SES) and health is focused on the protective effects of SES. However, a growing literature suggests that high SES may also operate as a vulnerability factor. Aims: Using a national sample of African American youth, this study compared the effects of perceived discrimination on major depressive disorder (MDD) based on SES. Methods: The current cross-sectional study included 810 African American youth who participated in the National Survey of American Life-Adolescent supplement. The independent variable was perceived discrimination. Lifetime, 12-month, and 30-day MDD were the dependent variables. Age and gender were covariates. Three SES indicators (subjective SES, income, and poverty index) were moderators. We used logistic regressions for data analysis. Results: Perceived discrimination was associated with higher risk of lifetime, 12-month, and 30-day MDD. Interactions were found between subjective SES and perceived discrimination on lifetime, 12-month, and 30-day MDD, suggesting a stronger effect of perceived discrimination in youth with high subjective SES. Objective measures of SES (income and poverty index) did not interact with perceived discrimination on MDD. Conclusion: While perceived discrimination is a universally harmful risk factor for MDD, its effect may depend on the SES of the individual. Findings suggest that high subjective SES may operate as a vulnerability factor for African American youth.
Sleep problems are associated with increased risk of suicide, independent of depression. This analysis explores narrative accounts of the role of sleep in relation to suicidal thoughts and behaviours.
This study examined the associations among maternal depression, mothers' emotional and material investment in their child, and children’s cognitive functioning. Middle-class Chilean mothers and children (N = 875; 52% males) were studied when children were 1, 5, 10, and 16 years (1991-2007). Results indicated that highly depressed mothers provided less emotional and material support to their child across all ages, which related to children’s lower IQ. Children with lower mental abilities at age 1 received less learning-material support at age 5, which led to mothers' higher depression at child age 10. Mothers' low support was more strongly linked to maternal depression as children got older. Findings elucidate the dynamic and enduring effects of depression on mothers' parenting and children’s development.
The factors that contribute to the development of psoriatic arthritis (PsA) among patients with psoriasis are not well known; however, systemic inflammation is believed to be important. On the basis of recent laboratory work demonstrating that major depressive disorder (MDD) is associated with increased systemic inflammation, we hypothesized that patients with psoriasis who develop MDD are at increased risk of subsequently developing PsA. We utilized The Health Improvement Network, a primary care medical records database, to identify 73,447 individuals with psoriasis. Patients were followed up to 25 years until the development of the primary outcome of PsA or the censor date. The exposure of interest was the development of MDD. Cox proportional-hazards models showed that patients with psoriasis who developed MDD were at significantly increased risk of subsequently developing PsA compared with patients who did not develop MDD, even after accounting for numerous covariates (hazard ratio 1.37, 95% confidence interval 1.05-1.80, P = 0.021). This result was maintained through numerous sensitivity analyses. These data support the hypothesis that MDD increases the risk of developing PsA among patients with psoriasis, suggesting a need for heightened prevention and management of MDD in patients with psoriasis.
Family caregivers of individuals with serious illness are at risk for depressive symptoms and depression. Hospice includes the provision of support services for family caregivers, yet evidence is limited regarding the effect of hospice use on depressive symptoms among surviving caregivers.
Curcumin, an active ingredient of Curcuma longa Linn (Zingiberaceae), has shown potential antidepressant-like activity in animal studies. The objectives of this trial were to compare the efficacy and safety of curcumin with fluoxetine in patients with major depressive disorder (MDD). Herein, 60 patients diagnosed with MDD were randomized in a 1:1:1 ratio for six weeks observer-masked treatment with fluoxetine (20 mg) and curcumin (1000 mg) individually or their combination. The primary efficacy variable was response rates according to Hamilton Depression Rating Scale, 17-item version (HAM-D17 ). The secondary efficacy variable was the mean change in HAM-D17 score after six weeks. We observed that curcumin was well tolerated by all the patients. The proportion of responders as measured by the HAM-D17 scale was higher in the combination group (77.8%) than in the fluoxetine (64.7%) and the curcumin (62.5%) groups; however, these data were not statistically significant (P = 0.58). Interestingly, the mean change in HAM-D17 score at the end of six weeks was comparable in all three groups (P = 0.77). This study provides first clinical evidence that curcumin may be used as an effective and safe modality for treatment in patients with MDD without concurrent suicidal ideation or other psychotic disorders. Copyright © 2013 John Wiley & Sons, Ltd.
Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 6 years ago
Major depressive disorder (MD) is a debilitating public mental health problem with severe societal and personal costs attached. Around one in six people will suffer from this complex disorder at some point in their lives, which has shown considerable etiological and clinical heterogeneity. Overall there remain no validated biomarkers in the youth population at large that can aid the detection of at-risk groups for depression in general and for boys and young men in particular. Using repeated measurements of two well-known correlates of MD (self-reported current depressive symptoms and early-morning cortisol), we undertook a population-based investigation to ascertain subtypes of adolescents that represent separate longitudinal phenotypes. Subsequently, we tested for differential risks for MD and other mental illnesses and cognitive differences between subtypes. Through the use of latent class analysis, we revealed a high-risk subtype (17% of the sample) demarcated by both high depressive symptoms and elevated cortisol levels. Membership of this class of individuals was associated with increased levels of impaired autobiographical memory recall in both sexes and the greatest likelihood of experiencing MD in boys only. These previously unidentified findings demonstrate at the population level a class of adolescents with a common physiological biomarker specifically for MD in boys and for a mnemonic vulnerability in both sexes. We suggest that the biobehavioral combination of high depressive symptoms and elevated morning cortisol is particularly hazardous for adolescent boys.