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Background: Prenatal maternal stress is increasingly recognized as a risk factor for offspring mental health challenges. DNA methylation may be a mechanism, but few studies directly tested mediation. These few integrative studies are reviewed along with studies from three research areas: prenatal maternal stress and child mental health, prenatal maternal stress and child DNA methylation, and child mental health and DNA methylation.Methods: We conducted a narrative review of articles in each research area and the few published integrative studies to evaluate the state of knowledge.Results: Prenatal maternal stress was related to greater offspring internalizing and externalizing symptoms and to greater offspring peripheral DNA methylation of the NR3C1 gene. Youth mental health problems were also related to NR3C1 hypermethylation while epigenome-wide studies identified genes involved in nervous system development. Integrative studies focused on infant outcomes and did not detect significant mediation by DNA methylation though methodological considerations may partially explain these null results.Limitations: Operationalization of prenatal maternal stress and child mental health varied greatly. The few published integrative studies did not report conclusive evidence of mediation by DNA methylation.Conclusions: DNA methylation likely mediates the association between prenatal maternal stress and child mental health. This conclusion still needs to be tested in a larger number of integrative studies. Key empirical and statistical considerations for future research are discussed. Understanding the consequences of prenatal maternal stress and its pathways of influence will help prevention and intervention efforts and ultimately promote well-being for both mothers and children. [ABSTRACT FROM AUTHOR]

Abstract: Background: It has frequently been demonstrated that experimental lowering of serotonin (5-HT) neurotransmission by acute tryptophan depletion (ATD) induces a transient depressed mood in 50–60% of patients treated with a selective serotonin reuptake inhibitor (SSRI) who are in remission from depression. In unmedicated depressed patients, ATD has no immediate effect on symptoms. The effects in currently depressed medicated patients have not been investigated. Methods: Fourteen currently depressed patients (seven patients treated with a selective serotonin–noradrenalin reuptake inhibitor (SSNRI); seven other treatment, non-SSNRI) received ATD in a double-blind, crossover design. Different strengths of the ATD mixture (aimed at 50% and 90% reduction of tryptophan) were used on separate days. Psychiatric symptoms were assessed at both sessions prior to, at +6.5 h, and at +24 h after ATD. Results: The ATD mixtures induced the expected reductions of plasma tryptophan levels. Full but not partial depletion improved mood and other psychiatric symptoms at +24 h in patients who received SSNRI treatment, as indicated by clinical ratings and self-report. Subjective sleep quality also improved. Conclusions: The effects of ATD on psychiatric symptoms in currently depressed patients are remarkably different from the results in recently remitted SSRI-treated patients. ATD in currently depressed patients treated with serotonergic antidepressants possibly provides important information about the mechanism of action of SSRIs. [Copyright &y& Elsevier]

Background: Subthreshold depression is highly prevalent in adolescence, but compared to major depressive disorder, the clinical impact is under-researched. The aim of this review was to compare subthreshold depression and major depressive disorder in adolescents by reviewing available literature on epidemiology, risk factors, illness trajectories, brain anatomy and function, genetics, and treatment response.Methods: We conducted a scoping review of papers on subthreshold depression and major depressive disorder in adolescence published in English. Studies in adults were included when research in adolescence was not available.Results: We found that individuals with subthreshold depression were similar to individuals with major depressive disorder in several regards, including female/male ratio, onset, functional impairment, comorbidity, health care utilization, suicidal ideation, genetic predisposition, brain alterations, and treatment response. Further, subthreshold depression was about two times more common than major depressive disorder.Limitations: The definition of subthreshold depression is highly variable across studies. Adolescent-specific data are limited in the areas of neurobiology and treatment.Conclusions: The findings of the current review support the idea that subthreshold depression is of clinical importance and provide evidence for a spectrum, versus categorical model, for depressive symptomatology. Given the frequency of subthreshold depression escalating to major depressive disorder, a greater recognition and awareness of the significance of subthreshold depression in research, clinical practice and policy-making may facilitate the development and application of early prevention and intervention. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of sadness, the prevailing mood in major depression (MD), in a prospective, well-documented community sample followed since birth. Methods: The children, comprising 136 children (65 boys and 71 girls) of mothers with varying levels of depressive symptomatology, were scanned – using a 1.5-Tesla system – while they watched 5 blocks of both sad and neutral film excerpts. Following scanning, they rated the emotions they experienced, and if they identified sadness, they were also asked to rate its intensity. Results: In children whose mothers exhibited higher depressive symptomatology, compared to children whose mothers displayed lower depressive symptomatology, altered neural responses to sad film excerpts were noted in brain regions known to be involved in sadness and MD, notably the insula, anterior cingulate cortex and caudate nucleus, even though the children did not differ in current mood. Limitations: Whether this represents genetic vulnerability or a consequence of exposure to maternal depressive symptoms at a young age is unknown. Discussion: The results are consistent with the results of studies in healthy adults and MD patients. The present study suggests that an altered pattern of regional brain responses to sad stimuli, is already present in childhood and might represent vulnerability for MD later in life. [Copyright &y& Elsevier]