Sex-specific disease-associated modules for depression

Duman, Ronald S.

doi:10.1038/nm.4391

Cited by 10 publications

(7 citation statements)

References 11 publications

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“…Females had two-to three-fold higher rates of depression than males, as previously reported ( 61), of which several explanations have been offered: (1) Sexual dimorphism at the transcriptional level mediates gender-specific stress susceptibility (62). (2) Gender-related differences in neurotransmitter, endocrine, and metabolic systems result in differences in mood susceptibility (61). Our results from the stratified analyses revealed that, as we hypothesized, females had higher odds of probable LLD than males in the older population who were classified at the same IMCPR grade.…”

Section: Discussionsupporting

confidence: 58%

The Effect of Individual Musculoskeletal Conditions on Depression: Updated Insights From an Irish Longitudinal Study on Aging

et al. 2021

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Few longitudinal studies have systematically investigated whether or how individual musculoskeletal conditions (IMCs) convey risks for negative psychological health outcomes, and approaches to assess such risk in the older population are lacking. In this Irish nationally representative longitudinal prospective study of 6,715 individuals aged 50 and above, machine learning algorithms and various models, including mediation models, were employed to elaborate the underlying mechanisms of IMCs leading to depression and to develop an IMC-induced negative psychological risk (IMCPR) classification approach. Resultantly, arthritis [odds ratio (95% confidence interval): 2.233 (1.700–2.927)], osteoporosis [1.681 (1.133–2.421)], and musculoskeletal chronic pain [MCP, 2.404 (1.838–3.151)] were found to increase the risk of depression after 2 years, while fracture and joint replacement did not. Interestingly, mediation models further demonstrated that arthritis per se did not increase the risk of depression; such risk was augmented only when arthritis-induced restrictions of activities (ARA) existed [proportion of mediation: 316.3% (ARA of usual), 213.3% (ARA of social and leisure), and 251.3% (ARA of sleep)]. The random forest algorithm attested that osteoarthritis, not rheumatoid arthritis, contributed the most to depressive symptoms. Moreover, bone mineral density was negatively associated with depressive symptoms. Systemic pain contributed the most to the increased risk of depression, followed by back, knee, hip, and foot pain (mean Gini-Index: 3.778, 2.442, 1.980, 1.438, and 0.879, respectively). Based on the aforementioned findings, the IMCPR classification approach was developed using an interpretable machine learning model, which stratifies participants into three grades. Among the IMCPR grades, patients with a grade of “severe” had higher odds of depression than those with a “mild” [odds ratio (95% confidence interval): 4.055 (2.907–5.498)] or “moderate” [3.584 (2.101–5.883)] grade. Females with a “severe” grade had higher odds of depression by 334.0% relative to those with a “mild” grade, while males had a relative risk of 258.4%. In conclusion, the present data provide systematic insights into the IMC-induced depression risk and updated the related clinical knowledge. Furthermore, the IMCPR classification approach could be used as an effective tool to evaluate this risk.

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Section: Discussionsupporting

confidence: 58%

The Effect of Individual Musculoskeletal Conditions on Depression: Updated Insights From an Irish Longitudinal Study on Aging

et al. 2021

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“…Nevertheless, our preliminary evidence is new in the literature. If reproduced on larger samples, the parahippocampal deactivation that we observed in MDD females during response inhibition might either contribute to and/or result from the female-specific symptomatology (4,13,120) characterized by detrimentally high stress levels (4,13,75,132).…”

Section: Diagnosis By Sex Modulation Of Fmri Activationsmentioning

confidence: 76%

“…Some studies also reported a correlation between deficits in this area and illness severity ( 72 – 74 ). Therefore, the increased GM deficits in the orbitofrontal cortex observed in adult-onset MDD females may explain the higher rates of internalizing problems and rumination often observed in the female sex, which could also be explained by the presence of different illness-related genes that in turn contribute to the different symptomatology observed in males and females with MDD ( 14 , 75 – 77 ).…”

Section: Discussionmentioning

confidence: 99%

Sexual Dimorphism in the Brain Correlates of Adult-Onset Depression: A Pilot Structural and Functional 3T MRI Study

et al. 2022

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Major Depressive Disorder (MDD) is a disabling illness affecting more than 5% of the elderly population. Higher female prevalence and sex-specific symptomatology have been observed, suggesting that biologically-determined dimensions might affect the disease onset and outcome. Rumination and executive dysfunction characterize adult-onset MDD, but sex differences in these domains and in the related brain mechanisms are still largely unexplored. The present pilot study aimed to explore any interactions between adult-onset MDD and sex on brain morphology and brain function during a Go/No-Go paradigm. We hypothesized to detect diagnosis by sex effects on brain regions involved in self-referential processes and cognitive control. Twenty-four subjects, 12 healthy (HC) (mean age 68.7 y, 7 females and 5 males) and 12 affected by adult-onset MDD (mean age 66.5 y, 5 females and 7 males), underwent clinical evaluations and a 3T magnetic resonance imaging (MRI) session. Diagnosis and diagnosis by sex effects were assessed on regional gray matter (GM) volumes and task-related functional MRI (fMRI) activations. The GM volume analyses showed diagnosis effects in left mid frontal cortex (p < 0.01), and diagnosis by sex effects in orbitofrontal, olfactory, and calcarine regions (p < 0.05). The Go/No-Go fMRI analyses showed MDD effects on fMRI activations in left precuneus and right lingual gyrus, and diagnosis by sex effects on fMRI activations in right parahippocampal gyrus and right calcarine cortex (p < 0.001, ≥ 40 voxels). Our exploratory results suggest the presence of sex-specific brain correlates of adult-onset MDD–especially in regions involved in attention processing and in the brain default mode–potentially supporting cognitive and symptom differences between sexes.

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“…Studies have revealed that women are more likely to experience depression during times of hormonal flux postpartum and during perimenopausal periods ( Ahokas et al, 2001 ; Parker and Brotchie, 2004 ). Circulating sex hormones and differences in inflammatory, neurotrophic, and serotonergic responses to unfavorable events between sexes have been suggested as important factors in the pathophysiology of gender-specific depression ( Bangasser and Valentino, 2014 ; Duman, 2017 ; Labonté et al, 2017 ). Therefore, a better understanding of the gender-specific pathophysiology of depression could help reveal novel and gender-specific therapeutic targets or approaches.…”

Section: Prospect Of Tcm In Depression Treatmentmentioning

confidence: 99%

Challenge and Prospect of Traditional Chinese Medicine in Depression Treatment

Zhang

Cheng

2019

Front. Neurosci.

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Current medication for depression is inadequate and far from ideal. Development of novel antidepressant drugs is a pressing task. The discovery of ketamine and related agents represents a new era in drug discovery for the rapid treatment of depression. Due to potential neurotoxicity, short-lasting efficacy, the limitation of a single target approach, and a limited role in depression prevention of these agents, additional approaches or drugs that exert synergy and compatibility, with the rapid-acting agents are required for better treatment of depression. Traditional Chinese Medicine (TCM) is a systems medicine and its clinical experience and integrated theory for diagnosis and treatment provides an alternative method of novel drug discovery in depression treatment. In TCM, there are numerous claimed effective antidepressant formulas, but comprehensive research and evidence-based clinical studies are required for their acceptance as a treatment. In this essay, we review current attempts in the discovery of new agents, TCM drug formulation, and TCM treatment of depression, and discuss the challenges and opportunities of TCM in the new era of antidepressant discovery. TCM could provide an important resource in the discovery of novel agents, assistance of the rapid-acting antidepressants, development of new agents for female patients, and the prevention of depression at its early stages. The study of depression in conjunction with TCM therefore not only provides an opportunity to scientifically evaluate the benefits and risks of TCM, but also accelerates the development of novel antidepressant agents by combining the principle of modern molecular medicine with the ideas of empirical systems medicine.

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Sex-specific disease-associated modules for depression

Abstract: A recent study reveals sexually dimorphic disease-associated gene-expression modules and hub genes in postmortem brains from female and male individuals with depression. These modules are conserved in mouse models of depression.

Cited by 10 publications

References 11 publications

The Effect of Individual Musculoskeletal Conditions on Depression: Updated Insights From an Irish Longitudinal Study on Aging

The Effect of Individual Musculoskeletal Conditions on Depression: Updated Insights From an Irish Longitudinal Study on Aging

Sexual Dimorphism in the Brain Correlates of Adult-Onset Depression: A Pilot Structural and Functional 3T MRI Study

Challenge and Prospect of Traditional Chinese Medicine in Depression Treatment

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