Gut-Brain Axis: Role of Microbiome, Metabolomics, Hormones, and Stress in Mental Health Disorders.

The influence of gut microbiome, metabolites, omics, hormones, and stress on general and mental health is increasingly being recognized. Ancient cultures recognized the importance of diet and gut health on the overall health of an individual. Western science and modern scientific methods are beginning to unravel the foundations and mechanisms behind some of the ancient beliefs and customs.

An exploratory study on lipidomic profiles in a cohort of individuals with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) can develop after trauma exposure. Some studies report that women develop PTSD at twice the rate of men, despite greater trauma exposure in men. Lipids and their metabolites (lipidome) regulate a myriad of key biological processes and pathways such as membrane integrity, oxidative stress, and neuroinflammation in the brain by maintaining neuronal connectivity and homeostasis.

Tumor Suppressor MicroRNAs in Clinical and Preclinical Trials for Neurological Disorders.

Cancers and neurological disorders are two major types of diseases in humans. We developed the concept called the "Aberrant Cell Cycle Disease (ACCD)" due to the accumulating evidence that shows that two different diseases share the common mechanism of aberrant cell cycle re-entry. The aberrant cell cycle re-entry is manifested as kinase/oncoprotein activation and tumor suppressor (TS) inactivation, which are associated with both tumor growth in cancers and neuronal death in neurological disorders.

The lipidome of posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) can develop after trauma exposure. Some studies report that women develop PTSD at twice the rate of men, despite greater trauma exposure in men. Lipids and their metabolites (lipidome) regulate a myriad of key biological processes and pathways such as membrane integrity, oxidative stress, and neuroinflammation in the brain by maintaining neuronal connectivity and homeostasis.

The Middle-Out Approach to reconceptualizing, assessing, and analyzing traumatic stress reactions.

Alternative models of traumatic stress and broader psychopathology have been proposed to address issues of heterogeneity, comorbidity, clinical utility, and equitable representation. However, systematic and practical methods and guidelines to organize and apply these models remain scarce. The Middle-Out Approach is a novel, integrative, contextually informed framework for organizing and applying existing empirical methods to evaluate current and alternative traumatic stress reactions.

Military Sexual Trauma and Menopause Symptoms Among Midlife Women Veterans.

Background: Sexual assault and/or sexual harassment during military service (military sexual trauma (MST)) can have medical and mental health consequences. Most MST research has focused on reproductive-aged women, and little is known about the long-term impact of MST on menopause and aging-related health.

Objective: Examine associations of MST with menopause and mental health outcomes in midlife women Veterans.

Lifetime history of interpersonal partner violence is associated with insomnia among midlife women veterans.

Objective: Over a third of women in the United States report a lifetime history of intimate partner violence. Although a recent review found that intimate partner violence is related to poor subjective sleep, the majority of studies involved reproductive-aged women and used suboptimal measures of interpersonal violence and/or insomnia. We examined the relationship between lifetime intimate partner violence and current clinical insomnia in a cross-sectional sample of midlife women veterans.

Impact of hormonal contraceptives on sex differences in fear conditioning and fear extinction in PTSD.

Sex differences in the neurobiological mechanisms involved in fear conditioning and extinction have been suggested to contribute to differential vulnerability for the development of posttraumatic stress disorder (PTSD) in women compared with men. Reproductive hormones, such as estradiol, have been shown to facilitate fear conditioning and extinction learning and may explain some of these differences. However, the effect of commonly used hormonal contraceptives on the neurobiological mechanisms of fear conditioning and extinction is poorly understood.

Comparing Heart Rate Analytical Methods to Examine Engagement During Imaginal Prolonged Exposure Therapy: Multicase Study.

Objective: As mobile health technologies proliferate, their use during exposure-based therapies has the potential to illuminate treatment mechanisms. The primary purpose of this study was to examine three approaches to using continuously collected physiological data of patients with posttraumatic stress disorder during prolonged exposure (PE) therapy, in an effort to examine physiological markers of treatment response.

Methods: Photoplethysmogram-measured heart rates from three non-Hispanic White male veterans, during clinic-based PE therapy sessions, were analyzed to assess three potential therapeutic mechanisms: emotional engagement (examined via correlation analysis between self-reported peak distress ratings and objectively measured peak heart rate in the minute prior to distress ratings), initial emotion activation (examined through time to peak heart rate and peak self-reported distress), and extinction processes within and between therapy sessions (examined via multilevel modeling of within- and between-person changes in heart rate over time and across imaginal PE therapy sessions).

Veterans Health Administration Screening for Military Sexual Trauma May Not Capture Over Half of Cases Among Midlife Women Veterans.

Background: Approximately 1 in 3 women veterans endorse military sexual trauma (MST) during Veterans Health Administration (VHA) screening. Higher rates have been reported in anonymous surveys.

Objective: We compared MST identified by VHA screening to survey-reported MST within the same sample and identified participant characteristics associated with discordant responses.

Racial/ethnic disparities in the diagnosis and management of menopause symptoms among midlife women veterans.

Objective: Racial/ethnic disparities in menopause symptoms and hormone therapy management remain understudied among women served by the Veteran's Health Administration, despite the unique racial/ethnic diversity of this population. Thus, we determined racial/ethnic disparities in medical record-documented menopause symptoms and prescribed menopausal hormone therapy among women veterans.

Methods: We conducted cross-sectional analyses of national Veteran's Health Administration electronic health record data from 2014 to 2015.

Randomized controlled experimental study of hydrocortisone and D-cycloserine effects on fear extinction in PTSD.

Fear extinction underlies prolonged exposure, one of the most well-studied treatments for posttraumatic stress disorder (PTSD). There has been increased interest in exploring pharmacological agents to enhance fear extinction learning in humans and their potential as adjuncts to PE. The objective of such adjuncts is to augment the clinical impact of PE on the durability and magnitude of symptom reduction.

The relationship of fear-potentiated startle and polysomnography-measured sleep in trauma-exposed men and women with and without PTSD: testing REM sleep effects and exploring the roles of an integrative measure of sleep, PTSD symptoms, and biological sex.

Study Objectives: Published research indicates that sleep is involved in emotional information processing. Using a fear-potentiated startle (FPS) and nap sleep protocol, we examined the relationship of emotional learning with REM sleep (REMS) in trauma-exposed participants. We also explored the roles of posttraumatic stress disorder (PTSD) symptoms, biological sex, and an integrative measure of polysomnography-measured (PSG) sleep in the learning-sleep relationship.

Ventromedial and insular cortical volume moderates the relationship between BDNF Val66Met and threat sensitivity.

While the BDNF Val66Met polymorphism has been linked to various trauma and anxiety - related psychiatric disorders, limited focus has been on the neural structures that might modulate its relationship with objective measures of threat sensitivity. Therefore, we assessed whether there was an interaction of Val66Met polymorphism with brain area volumes previously associated with anxiety and PTSD, such as the ventromedial prefrontal cortex (vmPFC), insular cortex (IC), and dorsal and ventral anterior cingulate cortices (dACC and vACC), in predicting fear-potentiated psychophysiological response in a clinical sample of Veterans. 110 participants engaged in a fear-potentiated acoustic startle paradigm and provided genetic and imaging data.

Impulsivity as a multifactorial construct and its relationship to PTSD severity and threat sensitivity.

Changes to the DSM-5's conceptualization of posttraumatic stress disorder (PTSD) highlight the importance of impulsivity within the context of PTSD-related arousal dysregulation. While the relationship between PTSD and threat sensitivity is well defined, how they relate to impulsivity remains understudied. We examined the relationship between PTSD symptom severity, threat sensitivity, and impulsivity.

Acute cognitive effects of the hypocretin receptor antagonist almorexant relative to zolpidem and placebo: a randomized clinical trial.

Study Objectives: Hypnotic medications can adversely affect behavior during unanticipated awakenings during the night. Animals treated with the hypocretin (Hcrt) receptor antagonist almorexant (ALM) have less acute cognitive impairment compared to the GABAA receptor modulator zolpidem (ZOL). This study aimed to determine whether ALM produces less acute cognitive impairment than ZOL in human subjects.

Validation of sleep measurement in a multisensor consumer grade wearable device in healthy young adults.

Study Objectives: Our objective was to examine the ability of a consumer-grade wearable device (Basis B1) with accelerometer and heart rate technology to assess sleep patterns compared with polysomnography (PSG) and research-grade actigraphy in healthy adults.

Methods: Eighteen adults underwent consecutive nights of sleep monitoring using Basis B1, actigraphy, and PSG; 40 nights were used in analyses. Discrepancies in gross sleep parameters and epoch-by-epoch agreements in sleep/wake classification were assessed.

Work by day and sleep by night, do not sleep too little or too much: Effects of sleep duration, time of day and circadian synchrony on flanker-task performance in internet brain-game users from teens to advanced age.

Research elucidating the effects of sleep and circadian rhythm on cognitive performance is advancing, yet many important questions remain. Using flanker-task performance scores from a large internet sample (N = 48,881) with repeated measures of cognitive performance and linked prior-night self-reported sleep duration, we analysed the relationship between sleep duration, time of day of task performance, and chronotype synchrony with performance in participants aged 15-80 years. Results indicate a performance peak at 7 hr habitual sleep duration, and point to a variable effect of deviation from habitual sleep duration depending on users' habitual sleep duration and age.

Gender Differences in Threat Biases: Trauma Type Matters in Posttraumatic Stress Disorder.

Women are diagnosed with posttraumatic stress disorder (PTSD) at twice the rate of men. This gender difference may be related to differences in PTSD experiences (e.g.

Psychophysiological treatment outcomes: Corticotropin-releasing factor type 1 receptor antagonist increases inhibition of fear-potentiated startle in PTSD patients.

After exposure to a traumatic event, a subset of people develop post-traumatic stress disorder (PTSD). One of the key deficits in PTSD is regulation of fear, and impaired inhibition of fear-potentiated startle (FPS) has been identified as a potential physiological biomarker specific to PTSD. As part of a larger clinical trial, this study investigated the effects of a CRF receptor 1 antagonist, GSK561679, on inhibition of fear-potentiated startle during a conditional discrimination fear-conditioning paradigm, termed AX+/BX-.

Child abuse interacts with hippocampal and corpus callosum volume on psychophysiological response to startling auditory stimuli in a sample of veterans.

Child abuse (CA), which is linked to posttraumatic stress disorder (PTSD), has been associated with a reduction in both hippocampal and corpus callosum (CC) volume. However, few studies have explored these relationships on psychophysiological variables related to trauma exposure. Therefore, we assessed whether the interaction between CA and hippocampal and CC volume were associated with enhanced fear potentiated psychophysiological response patterns in a sample of Veterans.

Altered overnight levels of pro-inflammatory cytokines in men and women with posttraumatic stress disorder.

Background: Posttraumatic stress disorder (PTSD) is associated with disturbed sleep and elevated levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Studies in animals and healthy humans have also shown that disrupted sleep elevates pro-inflammatory cytokines, including IL-6 and TNF-α. A better understanding of overnight cytokine levels and sleep might shed light on possible mechanisms for elevated inflammation in PTSD.

Gender Differences in Cardiovascular Risk Related to Diabetes and Posttraumatic Stress Disorder.

Objectives: To examine relationships between posttraumatic stress disorder (PTSD), diabetes, and cardiovascular disease (CVD) among older men and women.

Methods: In a national retrospective cohort study of Veterans aged ≥55 (n=2,789,264, 6% female), associations between PTSD and diabetes (2008-2011) and incident CVD (2012-2015) were assessed with gender-stratified Fine-Gray proportional hazard models, adjusted for demographics and medical comorbidities.

Results: Incident CVD was observed in 22% of men and 12% of women, and related to PTSD (men HR=1.