P.0399 Differential subcortical volume in patients with major depressive disorder and healthy controls depending on patterns of adverse childhood experiences

Background Depression is recognized globally as a leading cause of disability. Early-life adverse childhood experiences (ACEs) have been shown to have robust associations with poor mental health during adulthood. These effects may be cumulative, whereby a greater number of ACEs are progressively associated with worse outcomes. This study aimed to estimate the associations between ACEs and adult depression and suicidal ideation in a cross-sectional, population-based study of adults in Uganda. Methods and findings Between 2016 and 2018, research assistants visited the homes of 1,626 adult residents of Nyakabare Parish, a rural area in southwestern Uganda. ACEs were assessed using a modified version of the Adverse Childhood Experiences-International Questionnaire, and depression symptom severity and suicidal ideation were assessed using the Hopkins Symptom Checklist for Depression (HSCL-D). We applied a validated algorithm to determine major depressive disorder diagnoses. Overall, 1,458 participants (90%) had experienced at least one ACE, 159 participants (10%) met criteria for major depressive disorder, and 28 participants (1.7%) reported suicidal ideation. We fitted regression models to estimate the associations between cumulative number of ACEs and depression symptom severity (linear regression model) and major depressive disorder and suicidal ideation (Poisson regression models). In multivariable regression models adjusted for age, sex, primary school completion, marital status, self-reported HIV status, and household asset wealth, the cumulative number of ACEs was associated with greater depression symptom severity (b = 0.050; 95% confidence interval [CI], 0.039–0.061, p < 0.001) and increased risk for major depressive disorder (adjusted relative risk [ARR] = 1.190; 95% CI, 1.109–1.276; p < 0.001) and suicidal ideation (ARR = 1.146; 95% CI, 1.001–1.311; p = 0.048). We assessed the robustness of our findings by probing for nonlinearities and conducting analyses stratified by age. The limitations of the study include the reliance on retrospective self-report as well as the focus on ACEs that occurred within the household. Conclusions In this whole-population, cross-sectional study of adults in rural Uganda, the cumulative number of ACEs had statistically significant associations with depression symptom severity, major depressive disorder, and suicidal ideation. These findings highlight the importance of developing and implementing policies and programs that safeguard children, promote mental health, and prevent trajectories toward psychosocial disability.

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Association between CSF hypocretin-1 levels, vigilance regulation and intracortical EEG-frequency power in patients with major depressive disorder and healthy controls

Pharmacopsychiatry ◽

10.1055/s-0031-1292542 ◽

2011 ◽

Vol 44 (06) ◽

Author(s):

FM Schmidt ◽

S Olbrich ◽

U Hegerl ◽

P Schönknecht

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Healthy Controls ◽

Major Depressive ◽

Frequency Power ◽

Hypocretin 1

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Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications

Translational Psychiatry ◽

10.1038/s41398-021-01377-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nicolas Salvetat ◽

Fabrice Chimienti ◽

Christopher Cayzac ◽

Benjamin Dubuc ◽

Francisco Checa-Robles ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Rna Editing ◽

Whole Blood ◽

Healthy Controls ◽

Major Depressive ◽

Suicide Attempters ◽

Blood Samples ◽

Depressed Patients ◽

The Brain

AbstractMental health issues, including major depressive disorder, which can lead to suicidal behavior, are considered by the World Health Organization as a major threat to global health. Alterations in neurotransmitter signaling, e.g., serotonin and glutamate, or inflammatory response have been linked to both MDD and suicide. Phosphodiesterase 8A (PDE8A) gene expression is significantly decreased in the temporal cortex of major depressive disorder (MDD) patients. PDE8A specifically hydrolyzes adenosine 3′,5′-cyclic monophosphate (cAMP), which is a key second messenger involved in inflammation, cognition, and chronic antidepressant treatment. Moreover, alterations of RNA editing in PDE8A mRNA has been described in the brain of depressed suicide decedents. Here, we investigated PDE8A A-to-I RNA editing-related modifications in whole blood of depressed patients and suicide attempters compared to age-matched and sex-matched healthy controls. We report significant alterations of RNA editing of PDE8A in the blood of depressed patients and suicide attempters with major depression, for which the suicide attempt took place during the last month before sample collection. The reported RNA editing modifications in whole blood were similar to the changes observed in the brain of suicide decedents. Furthermore, analysis and combinations of different edited isoforms allowed us to discriminate between suicide attempters and control groups. Altogether, our results identify PDE8A as an immune response-related marker whose RNA editing modifications translate from brain to blood, suggesting that monitoring RNA editing in PDE8A in blood samples could help to evaluate depressive state and suicide risk.

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