Characterizing the spectrum of distress symptoms in midlife women with perimenopausal depression.

Background: Perimenopausal onset depression (PO-MDD) is a common cause of distress and functional impairment, though efforts to describe its clinical symptomatology have been limited. We aimed to characterize affective and anxiety symptoms associated with PO-MDD, and to identify clinical correlates of distress, including anxiety, temperament and climacteric symptoms.

Methods: Baseline data from unmedicated women, ages 44-55, with PO-MDD (n = 49) and without PO-MDD (controls; n = 37) in the late-perimenopause (STRAW -1 criteria) recruited for two studies examining estrogen's effect on brain activation were included.

Effects of combined estrogen and bazedoxifene (CEB) on depressive symptoms in perimenopause.

Background: Perimenopause is characterized by ovarian hormone fluctuation and associated with elevated risk for depression. Perimenopausal-onset major depression (PO-MDD) can be alleviated with estrogen treatment. However, due to potential risk for breast and uterine cancer, traditional hormone treatments may not be suitable for some.

Differential sensitivity: not more or less.

Although posited as an explanation for reproductive endocrine-related mood disorders, differential hormone sensitivity is an elusive concept. In this editorial, we define differential sensitivity, embed it in current understanding of the generation of brain states and discuss its practical utility.

Esr1-Dependent Signaling and Transcriptional Maturation in the Medial Preoptic Area of the Hypothalamus Shapes the Development of Mating Behavior during Adolescence.

Mating and other behaviors emerge during adolescence through the coordinated actions of steroid hormone signaling throughout the nervous system and periphery. In this study, we investigated the transcriptional dynamics of the medial preoptic area (MPOA), a critical region for reproductive behavior, using single-cell RNA sequencing (scRNAseq) and hybridization techniques in male and female mice throughout adolescence development. Our findings reveal that estrogen receptor 1 (Esr1) plays a pivotal role in the transcriptional maturation of GABAergic neurons within the MPOA during adolescence.

Cortisol and ACTH response to Dex/CRH testing and 24-hour urine free cortisol levels in women with and without premenstrual dysphoric disorder.

Hyperactive and hyperreactive HPA axis functions are frequently reported in depressive disorders, particularly in major depression. However, research into HPA axis function in women with premenstrual dysphoric disorder (PMDD), which is also classified as a depressive disorder, has shown inconsistent results. This study aimed to characterize the HPA axis in women with PMDD using the combined dexamethasone suppression and CRH stimulation (Dex/CRH) test, alongside measurements of 24-hour urine free cortisol (UFC).

GABA-ergic Modulators: New Therapeutic Approaches to Premenstrual Dysphoric Disorder.

Premenstrual dysphoric disorder (PMDD) is characterized by the predictable onset of mood and physical symptoms secondary to gonadal steroid fluctuation during the luteal phase of the menstrual cycle. Although menstrual-related affective dysfunction is responsible for considerable functional impairment and reduction in quality of life worldwide, currently approved treatments for PMDD are suboptimal in their effectiveness. Research over the past two decades has suggested that the interaction between allopregnanolone, a neurosteroid derivative of progesterone, and the gamma-aminobutyric acid (GABA) system represents an important relationship underlying symptom genesis in reproductive-related mood disorders, including PMDD.

Temporal dynamics of neurobehavioral hormone sensitivity in a scaled-down experimental model of early pregnancy and parturition.

The hormonal changes of pregnancy and parturition can trigger robust changes in affective state, particularly among patients with a history of postpartum depression. However, more work is needed to elucidate the temporal dynamics of symptom emergence. The current study explored how quickly hormone-sensitive (HS+) individuals can be differentiated from hormone-insensitive (HS-) controls in the context of a tightly controlled experimental hormone manipulation, and which symptoms demonstrate the most rapid, consistent, and largest response during this protocol.

Divergent Transcriptomic Effects of Allopregnanolone in Postpartum Depression.

Brexanolone, a formulation of the neurosteroid allopregnanolone (ALLO), is approved for treating postpartum depression (PPD) and is being investigated for therapeutic efficacy across numerous neuropsychiatric disorders. Given ALLO's beneficial effects on mood in women with PPD compared to healthy control women, we sought to characterize and compare the cellular response to ALLO in women with ( = 9) or without ( = 10, i.e.

Epigenetic aging and PTSD outcomes in the immediate aftermath of trauma.

Background: Psychological trauma exposure and posttraumatic stress disorder (PTSD) have been associated with advanced epigenetic age. However, whether epigenetic aging measured at the time of trauma predicts the subsequent development of PTSD outcomes is unknown. Moreover, the neural substrates underlying posttraumatic outcomes associated with epigenetic aging are unclear.

Intrinsically dysregulated cellular stress signaling genes and gene networks in postpartum depression.

Postpartum depression (PPD) is a leading cause of morbidity and mortality among women. Clinically, the administration and withdrawal of supraphysiologic estradiol and progesterone (E2 + P) can cause affective symptom reoccurrence in women with a history of PPD, but not matched controls. To investigate the cellular basis underlying this differential affective response, lymphoblastoid cell lines (LCLs) were derived from women with and without past PPD and compared transcriptomically in hormone conditions mimicking pregnancy and parturition: supraphysiologic E2 + P-addback; supraphysiologic E2 + P-withdrawal; and no added E2 + P (Baseline).

Baseline anxiety-sensitivity to estradiol fluctuations predicts anxiety symptom response to transdermal estradiol treatment in perimenopausal women - A randomized clinical trial.

Background: The menopausal transition (perimenopause) is associated with an increased risk of major depression, characterized by anxiety and anhedonia phenotypes. Greater estradiol (E2) variability predicts the development of perimenopausal depression, especially within the context of stressful life events (SLEs). While transdermal E2 (TE2) reduces perimenopausal depressive symptoms, the mechanisms underlying TE2 efficacy and predictors of TE2 treatment response remain unknown.

Methods for characterizing ovarian and adrenal hormone variability and mood relationships in peripubertal females.

Peripubertal females are at elevated risk for developing affective illness compared to males, yet biological mechanisms underlying this sex disparity are poorly understood. Female risk for depression remains elevated across a woman's reproductive lifespan, implicating reproductive hormones. A sensitivity to normal hormone variability during reproductive transition events (e.

Transcriptome-wide association study for postpartum depression implicates altered B-cell activation and insulin resistance.

Postpartum depression (PPD) affects 1 in 7 women and has negative mental health consequences for both mother and child. However, the precise biological mechanisms behind the disorder are unknown. Therefore, we performed the largest transcriptome-wide association study (TWAS) for PPD (482 cases, 859 controls) to date using RNA-sequencing in whole blood and deconvoluted cell types.

Autonomic and Depression Symptoms in Parkinson's Disease: Clinical Evidence for Overlapping Physiology.

Background: Autonomic dysfunction and depression are common non-motor symptoms of Parkinson's disease (PD) that confer poorer prognosis. These PD symptoms may have overlapping pathophysiologic underpinnings.

Objective: To investigate associations between autonomic and depression symptoms in early PD, and their evolution over time.

In search of sex-related mediators of affective illness.

Sex differences in the rates of affective disorders have been recognized for decades. Studies of physiologic sex-related differences in animals and humans, however, have generally yielded little in terms of explaining these differences. Furthermore, the significance of these findings is difficult to interpret given the dynamic, integrative, and highly context-dependent nature of human physiology.

Reward-Based Decision-Making Engages Distinct Modes of Cross-Frequency Coupling.

Prefrontal cortex exerts control over sensory and motor systems via cross-frequency coupling. However, it is unknown whether these signals play a role in reward-based decision-making and whether such dynamic network configuration is altered in a major depressive episode. We recruited men and women with and without depression to perform a streamlined version of the Expenditure of Effort for Reward Task during recording of electroencephalography.

Reduction in Left Frontal Alpha Oscillations by Transcranial Alternating Current Stimulation in Major Depressive Disorder Is Context Dependent in a Randomized Clinical Trial.

Background: Left frontal alpha oscillations are associated with decreased approach motivation and have been proposed as a target for noninvasive brain stimulation for the treatment of depression and anhedonia. Indeed, transcranial alternating current stimulation (tACS) at the alpha frequency reduced left frontal alpha power and was associated with a higher response rate than placebo stimulation in patients with major depressive disorder (MDD) in a recent double-blind, placebo-controlled clinical trial.

Methods: In this current study, we aimed to replicate successful target engagement by delineating the effects of a single session of bifrontal tACS at the individualized alpha frequency (IAF-tACS) on alpha oscillations in patients with MDD.