Thomas Neylan | University of California, San Francisco (original) (raw)

Papers by Thomas Neylan

Psychoneuroendocrinology, 2015

Posttraumatic stress disorder (PTSD) is associated with an increased risk of cardiovascular disea... more Posttraumatic stress disorder (PTSD) is associated with an increased risk of cardiovascular disease and several other chronic illnesses. Alterations in the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis in PTSD might contribute to these associations but findings regarding SNS and HPA activity in PTSD are heterogeneous. We measured 24-h urinary catecholamines and cortisol in a large cohort of adult outpatients recruited from 2 Veterans Affairs medical centers. 24-h urinary norepinephrine, epinephrine, dopamine and cortisol were measured by tandem mass spectrometry. Lifetime and current PTSD were assessed with the Clinician Administered PTSD Scale using DSM-IV-TR criteria. Out of 613 participants, 199 (32.5%) had current PTSD, 100 (16.3%) had lifetime but not current PTSD, and 314 (51.2%) never had PTSD. Patients with current PTSD had significantly higher norepinephrine secretion compared to those without PTSD. Patients in the lifetime PTSD group ex...

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, Jan 15, 2014

Physical inactivity is linked to health outcomes such as obesity, diabetes, and psychiatric disor... more Physical inactivity is linked to health outcomes such as obesity, diabetes, and psychiatric disorders. Sleep disturbance has been linked to the same adverse outcomes. We examine the influence of sleep on physical activity as a novel approach to understand these relationships. Specifically, our objective was to determine whether low sleep quality predicts low physical activity in posttraumatic stress disorder (PTSD), a disorder associated with sleep disturbance, physical inactivity, and poor health outcomes. We used data from the Mind Your Heart Study, a prospective cohort study of 736 outpatients recruited from two Department of Veterans Affairs (VA) medical centers. We assessed PTSD with the Clinician Administered PTSD Scale, sleep quality using an item from the Pittsburgh Sleep Quality Index, and physical activity by self-report at baseline and again one year later. Hierarchical multiple regression models and structural equation modeling were used to examine the relationships amon...

The Psychiatric quarterly, 2002

Advances in psychopharmacology of PTSD are presented, focusing on antidepressants, adrenergic age... more Advances in psychopharmacology of PTSD are presented, focusing on antidepressants, adrenergic agents, antianxiety agents, and mood stabilizers. Treatment recommendations are related to recent advances in the understanding of the biology of PTSD. Pharmacotherapy of PTSD in children and adolescents is discussed, including recommended dose ranges. Recommendations are specified for pharmacotherapy of trauma survivors in the immediate aftermath of traumatic exposure, and for those with acute and chronic posttraumatic stress disorders.

Psychiatry research, Jan 28, 2010

Police work is one of the most stressful occupations. Previous research has indicated that work s... more Police work is one of the most stressful occupations. Previous research has indicated that work stress and trauma exposure may place individuals at heightened risk for the development of depression symptomatology. This prospective longitudinal study was designed to examine predictors of depression symptoms in police service. Participants comprised 119 healthy police recruits from an ongoing prospective study. They completed baseline measures of depression symptoms, childhood trauma exposure, neuroticism, and self-worth during academy training. Follow-up measures of depression symptoms, PTSD symptoms, critical incident exposure, negative life events, and routine work environment stress were assessed after 12 months of police service. Hierarchical linear regression analysis was conducted to examine predictors of current levels of depression symptoms, controlling for baseline depression symptoms and current PTSD symptoms. Greater childhood trauma exposure, lower self-worth during train...

Psychiatry Research-neuroimaging, 2008

Magnetic resonance spectroscopic imaging (MRSI) studies suggest hippocampal abnormalities in post... more Magnetic resonance spectroscopic imaging (MRSI) studies suggest hippocampal abnormalities in posttraumatic stress disorder (PTSD), whereas findings of volume deficits in the hippocampus, as revealed with magnetic resonance imaging (MRI), have been inconsistent. Co-morbidities of PTSD, notably alcohol abuse, may have contributed to the inconsistency. The objective was to determine whether volumetric and metabolic abnormalities in the hippocampus and other brain

A (CgA) is co-released with catecholamines and peptides and has a wide distribution in the brain.... more A (CgA) is co-released with catecholamines and peptides and has a wide distribution in the brain. Chromogranin A provides a measure of tonic arousal. CSF CgA-like immunoreactivity (CgA-LI) was studied in 42 drug-free male schizophrenic patients. 33 of these patients were first studied during chronic haloperidol maintenance treatment. Withdrawal from haloperidol maintenance treatment was associated with a significant increase in CSF CgA-LI, particularly in the patients who did not relapse. Contrary to expectation CSF CgA-LI was higher in drug-free patients who slept longer the night before the lumbar puncture. Significant relationships were observed between CSF CgA-LI and CSF homovanillic acid, acetylcholinesterase, neuropeptide Y-L1 and 5-hydroxs -indole acetic acid, but not with CSF norepinephrine or 3-methoxy-4-hydroxyphenylglycol. Ventricular brain ratios correlated negatively with CSF CgA-LI levels.

Studies that have conducted quantitative analysis of the sleep electroencephalogram (EEG) have de... more Studies that have conducted quantitative analysis of the sleep electroencephalogram (EEG) have demonstrated decreased delta sleep in PTSD. Elevations in both hypothalamic (neurohormonal) and extrahypothalamic (neurotransmitter) corticotropin releasing factor (CRF) release is associated with decreased delta sleep activity. We present data from several studies examining the effect of metyrapone administration on the sleep EEG in PTSD and control subjects. Plasma ACTH, cortisol, and 11-deoxycorticol were obtained the morning following polysomnographic sleep recordings before and after metyrapone administration. Delta sleep was measured by period amplitude analysis. The results demonstrate: a) decreased delta sleep in male subjects with PTSD; b) metyrapone administration resulted in an activation of the sleep EEG and a robust decrease in quantitative delta sleep; c) the sleep and endocrine (increase in ACTH) responses to metyrapone were significantly decreased in PTSD in two different study samples; and d) the metyrapone-related disruption to sleep in both samples was predicted by the increase in ACTH measured the following morning. These findings strongly suggest that the delta sleep response to metyrapone is a measure of the brain response to a hypothalamic CRF challenge. The attenuated delta sleep and endocrine response to metyrapone challenge in PTSD is consistent with a model of enhanced negative feedback regulation or downregulation of CRF receptors in an environment of chronically increased CRF activity.

CSF diazepam-binding inhibitor-like immunoreactivity (DBI-LI) and polysomnography were studied in... more CSF diazepam-binding inhibitor-like immunoreactivity (DBI-LI) and polysomnography were studied in 28 drug-free male schizophrenic (DSM-III-R) patients. They underwent a three-night polysomnography evaluation and a lumbar puncture. CSF DBI-LI correlated positively with REM latency, the REM latency/2d nonREM period ratio and stage-4% sleep, and negatively with stage-1% sleep. CSF DBI-LI did not correlate significantly with duration of sleep or sleep latency. CSF DBI-LI during haloperidol treatment did not correlate significantly with sleep EEG measures. The results of this first study of the relationship between endogenous DBI and sleep in humans suggest that physiological effects of DBI other than interactions with the BZD/GABAA receptor complex may explain its positive effects on sleep. However, the absence of similar sleep data in normal subjects precludes us from establishing a specific relationship between DBI and sleep in schizophrenia.

Conflict and health, 2014

Without effective treatment, PTSD and depression can cause persistent disability in disaster-affe... more Without effective treatment, PTSD and depression can cause persistent disability in disaster-affected populations. Our objective was to test the efficacy of Interpersonal Psychotherapy (IPT) delivered by trained local personnel compared with treatment as usual (TAU) for Posttraumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) among adults affected by the Sichuan 2008 earthquake. A small randomized controlled trial of IPT + TAU versus TAU alone was delivered by local mental health personnel in Shifang, China. Between July 2011 and January 2012, 49 adults ≥ 18 years with PTSD, MDD or both were enrolled and randomized to 12 weekly sessions of IPT + TAU (27) or TAU (22) alone x 12 weeks. IPT was then offered to the TAU group. Unblinded follow up assessments were conducted at three and six months. IPT was a 12 session, weekly one hour treatment delivered by local personnel who were trained and supervised in IPT. TAU was continuation of prescribed psychotropic medication (...

European journal of psychotraumatology, 2014

Posttraumatic stress disorder (PTSD) and other deployment-related outcomes originate from a compl... more Posttraumatic stress disorder (PTSD) and other deployment-related outcomes originate from a complex interplay between constellations of changes in DNA, environmental traumatic exposures, and other biological risk factors. These factors affect not only individual genes or bio-molecules but also the entire biological networks that in turn increase or decrease the risk of illness or affect illness severity. This review focuses on recent developments in the field of systems biology which use multidimensional data to discover biological networks affected by combat exposure and post-deployment disease states. By integrating large-scale, high-dimensional molecular, physiological, clinical, and behavioral data, the molecular networks that directly respond to perturbations that can lead to PTSD can be identified and causally associated with PTSD, providing a path to identify key drivers. Reprogrammed neural progenitor cells from fibroblasts from PTSD patients could be established as an in vi...

Psychoneuroendocrinology, 2015

Inflammation may reduce hippocampal volume by blocking neurogenesis and promoting neurodegenerati... more Inflammation may reduce hippocampal volume by blocking neurogenesis and promoting neurodegeneration. Posttraumatic stress disorder (PTSD) has been linked with both elevated inflammation and reduced hippocampal volume. However, few studies have examined associations between inflammatory markers and hippocampal volume, and none have examined these associations in the context of PTSD. We measured levels of the inflammatory markers interleukin-6 (IL-6) and soluble receptor II for tumor necrosis factor (sTNF-RII) as well as hippocampal volume in 246 Gulf War veterans with and without current and past PTSD as assessed with the Clinician Administered PTSD Scale (CAPS). Enzyme-linked immunosorbent assays were used to measure inflammatory markers, and 1.5Tesla magnetic resonance imaging (MRI) and Freesurfer version 4.5 were used to quantify hippocampal volume. Hierarchical linear regression and analysis of covariance models were used to examine if hippocampal volume and PTSD status would be associated with elevated levels of IL-6 and sTNF-RII. Increased sTNF-RII, but not IL-6, was significantly associated with reduced hippocampal volume (β=-0.14, p=0.01). The relationship between sTNF-RII and hippocampal volume was independent of potential confounds and covariates, including PTSD status. Although we observed no PTSD diagnosis-related differences in either IL-6 or sTNF-RII, higher PTSD severity was associated with significantly increased sTNF-RII (β=0.24, p=0.04) and reduced IL-6 levels (β=-0.24, p=0.04). Our results indicate that specific inflammatory proteins may be associated with brain structure and function as indexed by hippocampal volume and PTSD symptoms.

Expert Review of Neurotherapeutics, 2007

Studies and treatments for the symptomatic menopausal woman with sleep complaints have been revie... more Studies and treatments for the symptomatic menopausal woman with sleep complaints have been reviewed elsewhere. This article, as part of the clinical review series on the comorbid symptomatic menopausal woman, aims to examine the evidence for diagnosis and treatment of women who present with distressing sleep symptoms that they attribute to menopause. The etiology of these symptoms may be a psychiatric disorder, a pre- or co-existing problem with sleep, or a dynamic interaction among one of these and/or a symptomatic menopause. The relationship between sleep disturbance and cognitive complaints, mood problems, fatigue and low energy will be reviewed. The new research on sleep, clinical consequences of insomnia of various types, the impact of sleep disturbance on morbidity and functioning--in the context of the midlife woman in the menopausal transition--will be explored along with the evidence for different treatment strategies for these sleep problems.

order was assessed using the Computerized Diagnostic Interview Schedule for DSM-IV. Cardiac funct... more order was assessed using the Computerized Diagnostic Interview Schedule for DSM-IV. Cardiac function was measured using left ventricular ejection fraction, tread- mill exercise capacity, and inducible ischemia on stress echocardiography. Disease-specific health status was as- sessed using the symptom burden, physical limitation, and quality of life subscales of the Seattle Angina Ques- tionnaire. We used ordinal logistic regression to evalu-

Alzheimer's & Dementia, 2014

Posttraumatic stress disorder (PTSD) is associated with smaller volumes of the hippocampus, as ha... more Posttraumatic stress disorder (PTSD) is associated with smaller volumes of the hippocampus, as has been demonstrated by meta-analyses. Proposed mechanistic relationships are reviewed briefly, including the hypothesis that sleep disturbances mediate the effects of PTSD on hippocampal volume. Evidence for this includes findings that insomnia and restricted sleep are associated with changes in hippocampal cell regulation and impairments in cognition. We present results of a new study of 187 subjects in whom neither PTSD nor poor sleep was associated with lower hippocampal volume. We outline a broad research agenda centered on the hypothesis that sleep changes mediate the relationship between PTSD and hippocampal volume.

Alzheimer's & dementia : the journal of the Alzheimer's Association, 2014

Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems re... more Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just...

Psychoneuroendocrinology, 2006

Psychoneuroendocrinology, 2014

Posttraumatic stress disorder (PTSD) is associated with a 2-4 fold increased risk of developing T... more Posttraumatic stress disorder (PTSD) is associated with a 2-4 fold increased risk of developing Type 2 diabetes mellitus. However, detailed assessments of glucose metabolism and insulin secretion in a study designed to minimize confounders are lacking. Furthermore, few studies examine potential mechanisms involved. We analyzed data from a case-control study of medically healthy, medication-free adults to determine whether individuals with PTSD had abnormal glucose or insulin response to oral glucose tolerance test (OGTT) compared to controls. Secondarily, we assessed potential mediators such as sleep, cortisol and adiponectin. Data was analyzed from 92 age and gender-matched subjects (44 PTSD, 48 controls). Chronic PTSD was diagnosed using the Structured Clinical Interview for DSM-IV and Clinician Administered PTSD Scale. Subjects underwent 75-g OGTT, actigraphy and sleep diary (to quantify sleep duration), polysomnography (to assess slow wave sleep [SWS] and delta power), and overn...

Biological psychiatry, Jan 15, 2015

Posttraumatic stress disorder (PTSD) is associated with endocrine and immune abnormalities that c... more Posttraumatic stress disorder (PTSD) is associated with endocrine and immune abnormalities that could increase risk for autoimmune disorders. However, little is known about the risk for autoimmune disorders among individuals with PTSD. We conducted a retrospective cohort study of 666,269 Iraq and Afghanistan veterans under age 55 who were enrolled in the Department of Veterans Affairs health care system between October 7, 2001, and March 31, 2011. Generalized linear models were used to examine if PTSD, other psychiatric disorders, and military sexual trauma exposure increased risk for autoimmune disorders, including thyroiditis, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and lupus erythematosus, adjusting for age, gender, race, and primary care visits. PTSD was diagnosed in 203,766 veterans (30.6%), and psychiatric disorders other than PTSD were diagnosed in an additional 129,704 veterans (19.5%). Veterans diagnosed with PTSD had significantly higher adjus...

Journal of psychiatric research, 2014

Heterogeneity in glucocorticoid response to experimental stress conditions has shown to different... more Heterogeneity in glucocorticoid response to experimental stress conditions has shown to differentiate individuals with healthy from maladaptive real-life stress responses in a number of distinct domains. However, it is not known if this heterogeneity influences the risk for developing stress related disorders or if it is a biological consequence of the stress response itself. Determining if glucocorticoid response to stress induction prospectively predicts psychological vulnerability to significant real life stressors can adjudicate this issue. To test this relationship, salivary cortisol as well as catecholamine responses to a laboratory stressor during academy training were examined as predictors of empirically identified distress trajectories through the subsequent 4 years of active duty among urban police officers routinely exposed to potentially traumatic events and routine life stressors (N = 234). During training, officers were exposed to a video vignette of police officers e...

Psychiatry research, Jan 13, 2014

Abnormality in the "fear circuitry" has been known as a major neural characteristic of ... more Abnormality in the "fear circuitry" has been known as a major neural characteristic of posttraumatic stress disorder (PTSD). Recent studies also revealed decreased functional connectivity in the default mode network in PTSD. The present study aims to investigate, in war-zone-related PTSD, the spontaneous activity and functional connectivity of the amygdala and the precuneus, which are two representative brain regions of the two networks, respectively. Two groups of 52 male US Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) veterans (PTSD vs. controls), well matched on age and ethnicity, were clinically assessed and then studied in a resting state functional magnetic resonance imaging (fMRI) procedure. Functional connectivity analysis was conducted on the resting state fMRI data with the amygdala and precuneus as seeds. Compared with controls, veterans with PTSD had lower functional connectivity in the default mode network, as well as lower amygdala-front...

Psychoneuroendocrinology, 2015

Posttraumatic stress disorder (PTSD) is associated with an increased risk of cardiovascular disea... more Posttraumatic stress disorder (PTSD) is associated with an increased risk of cardiovascular disease and several other chronic illnesses. Alterations in the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis in PTSD might contribute to these associations but findings regarding SNS and HPA activity in PTSD are heterogeneous. We measured 24-h urinary catecholamines and cortisol in a large cohort of adult outpatients recruited from 2 Veterans Affairs medical centers. 24-h urinary norepinephrine, epinephrine, dopamine and cortisol were measured by tandem mass spectrometry. Lifetime and current PTSD were assessed with the Clinician Administered PTSD Scale using DSM-IV-TR criteria. Out of 613 participants, 199 (32.5%) had current PTSD, 100 (16.3%) had lifetime but not current PTSD, and 314 (51.2%) never had PTSD. Patients with current PTSD had significantly higher norepinephrine secretion compared to those without PTSD. Patients in the lifetime PTSD group ex...

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, Jan 15, 2014

Physical inactivity is linked to health outcomes such as obesity, diabetes, and psychiatric disor... more Physical inactivity is linked to health outcomes such as obesity, diabetes, and psychiatric disorders. Sleep disturbance has been linked to the same adverse outcomes. We examine the influence of sleep on physical activity as a novel approach to understand these relationships. Specifically, our objective was to determine whether low sleep quality predicts low physical activity in posttraumatic stress disorder (PTSD), a disorder associated with sleep disturbance, physical inactivity, and poor health outcomes. We used data from the Mind Your Heart Study, a prospective cohort study of 736 outpatients recruited from two Department of Veterans Affairs (VA) medical centers. We assessed PTSD with the Clinician Administered PTSD Scale, sleep quality using an item from the Pittsburgh Sleep Quality Index, and physical activity by self-report at baseline and again one year later. Hierarchical multiple regression models and structural equation modeling were used to examine the relationships amon...

The Psychiatric quarterly, 2002

Advances in psychopharmacology of PTSD are presented, focusing on antidepressants, adrenergic age... more Advances in psychopharmacology of PTSD are presented, focusing on antidepressants, adrenergic agents, antianxiety agents, and mood stabilizers. Treatment recommendations are related to recent advances in the understanding of the biology of PTSD. Pharmacotherapy of PTSD in children and adolescents is discussed, including recommended dose ranges. Recommendations are specified for pharmacotherapy of trauma survivors in the immediate aftermath of traumatic exposure, and for those with acute and chronic posttraumatic stress disorders.

Psychiatry research, Jan 28, 2010

Police work is one of the most stressful occupations. Previous research has indicated that work s... more Police work is one of the most stressful occupations. Previous research has indicated that work stress and trauma exposure may place individuals at heightened risk for the development of depression symptomatology. This prospective longitudinal study was designed to examine predictors of depression symptoms in police service. Participants comprised 119 healthy police recruits from an ongoing prospective study. They completed baseline measures of depression symptoms, childhood trauma exposure, neuroticism, and self-worth during academy training. Follow-up measures of depression symptoms, PTSD symptoms, critical incident exposure, negative life events, and routine work environment stress were assessed after 12 months of police service. Hierarchical linear regression analysis was conducted to examine predictors of current levels of depression symptoms, controlling for baseline depression symptoms and current PTSD symptoms. Greater childhood trauma exposure, lower self-worth during train...

Psychiatry Research-neuroimaging, 2008

Magnetic resonance spectroscopic imaging (MRSI) studies suggest hippocampal abnormalities in post... more Magnetic resonance spectroscopic imaging (MRSI) studies suggest hippocampal abnormalities in posttraumatic stress disorder (PTSD), whereas findings of volume deficits in the hippocampus, as revealed with magnetic resonance imaging (MRI), have been inconsistent. Co-morbidities of PTSD, notably alcohol abuse, may have contributed to the inconsistency. The objective was to determine whether volumetric and metabolic abnormalities in the hippocampus and other brain

A (CgA) is co-released with catecholamines and peptides and has a wide distribution in the brain.... more A (CgA) is co-released with catecholamines and peptides and has a wide distribution in the brain. Chromogranin A provides a measure of tonic arousal. CSF CgA-like immunoreactivity (CgA-LI) was studied in 42 drug-free male schizophrenic patients. 33 of these patients were first studied during chronic haloperidol maintenance treatment. Withdrawal from haloperidol maintenance treatment was associated with a significant increase in CSF CgA-LI, particularly in the patients who did not relapse. Contrary to expectation CSF CgA-LI was higher in drug-free patients who slept longer the night before the lumbar puncture. Significant relationships were observed between CSF CgA-LI and CSF homovanillic acid, acetylcholinesterase, neuropeptide Y-L1 and 5-hydroxs -indole acetic acid, but not with CSF norepinephrine or 3-methoxy-4-hydroxyphenylglycol. Ventricular brain ratios correlated negatively with CSF CgA-LI levels.

Studies that have conducted quantitative analysis of the sleep electroencephalogram (EEG) have de... more Studies that have conducted quantitative analysis of the sleep electroencephalogram (EEG) have demonstrated decreased delta sleep in PTSD. Elevations in both hypothalamic (neurohormonal) and extrahypothalamic (neurotransmitter) corticotropin releasing factor (CRF) release is associated with decreased delta sleep activity. We present data from several studies examining the effect of metyrapone administration on the sleep EEG in PTSD and control subjects. Plasma ACTH, cortisol, and 11-deoxycorticol were obtained the morning following polysomnographic sleep recordings before and after metyrapone administration. Delta sleep was measured by period amplitude analysis. The results demonstrate: a) decreased delta sleep in male subjects with PTSD; b) metyrapone administration resulted in an activation of the sleep EEG and a robust decrease in quantitative delta sleep; c) the sleep and endocrine (increase in ACTH) responses to metyrapone were significantly decreased in PTSD in two different study samples; and d) the metyrapone-related disruption to sleep in both samples was predicted by the increase in ACTH measured the following morning. These findings strongly suggest that the delta sleep response to metyrapone is a measure of the brain response to a hypothalamic CRF challenge. The attenuated delta sleep and endocrine response to metyrapone challenge in PTSD is consistent with a model of enhanced negative feedback regulation or downregulation of CRF receptors in an environment of chronically increased CRF activity.

CSF diazepam-binding inhibitor-like immunoreactivity (DBI-LI) and polysomnography were studied in... more CSF diazepam-binding inhibitor-like immunoreactivity (DBI-LI) and polysomnography were studied in 28 drug-free male schizophrenic (DSM-III-R) patients. They underwent a three-night polysomnography evaluation and a lumbar puncture. CSF DBI-LI correlated positively with REM latency, the REM latency/2d nonREM period ratio and stage-4% sleep, and negatively with stage-1% sleep. CSF DBI-LI did not correlate significantly with duration of sleep or sleep latency. CSF DBI-LI during haloperidol treatment did not correlate significantly with sleep EEG measures. The results of this first study of the relationship between endogenous DBI and sleep in humans suggest that physiological effects of DBI other than interactions with the BZD/GABAA receptor complex may explain its positive effects on sleep. However, the absence of similar sleep data in normal subjects precludes us from establishing a specific relationship between DBI and sleep in schizophrenia.

Conflict and health, 2014

Without effective treatment, PTSD and depression can cause persistent disability in disaster-affe... more Without effective treatment, PTSD and depression can cause persistent disability in disaster-affected populations. Our objective was to test the efficacy of Interpersonal Psychotherapy (IPT) delivered by trained local personnel compared with treatment as usual (TAU) for Posttraumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) among adults affected by the Sichuan 2008 earthquake. A small randomized controlled trial of IPT + TAU versus TAU alone was delivered by local mental health personnel in Shifang, China. Between July 2011 and January 2012, 49 adults ≥ 18 years with PTSD, MDD or both were enrolled and randomized to 12 weekly sessions of IPT + TAU (27) or TAU (22) alone x 12 weeks. IPT was then offered to the TAU group. Unblinded follow up assessments were conducted at three and six months. IPT was a 12 session, weekly one hour treatment delivered by local personnel who were trained and supervised in IPT. TAU was continuation of prescribed psychotropic medication (...

European journal of psychotraumatology, 2014

Posttraumatic stress disorder (PTSD) and other deployment-related outcomes originate from a compl... more Posttraumatic stress disorder (PTSD) and other deployment-related outcomes originate from a complex interplay between constellations of changes in DNA, environmental traumatic exposures, and other biological risk factors. These factors affect not only individual genes or bio-molecules but also the entire biological networks that in turn increase or decrease the risk of illness or affect illness severity. This review focuses on recent developments in the field of systems biology which use multidimensional data to discover biological networks affected by combat exposure and post-deployment disease states. By integrating large-scale, high-dimensional molecular, physiological, clinical, and behavioral data, the molecular networks that directly respond to perturbations that can lead to PTSD can be identified and causally associated with PTSD, providing a path to identify key drivers. Reprogrammed neural progenitor cells from fibroblasts from PTSD patients could be established as an in vi...

Psychoneuroendocrinology, 2015

Inflammation may reduce hippocampal volume by blocking neurogenesis and promoting neurodegenerati... more Inflammation may reduce hippocampal volume by blocking neurogenesis and promoting neurodegeneration. Posttraumatic stress disorder (PTSD) has been linked with both elevated inflammation and reduced hippocampal volume. However, few studies have examined associations between inflammatory markers and hippocampal volume, and none have examined these associations in the context of PTSD. We measured levels of the inflammatory markers interleukin-6 (IL-6) and soluble receptor II for tumor necrosis factor (sTNF-RII) as well as hippocampal volume in 246 Gulf War veterans with and without current and past PTSD as assessed with the Clinician Administered PTSD Scale (CAPS). Enzyme-linked immunosorbent assays were used to measure inflammatory markers, and 1.5Tesla magnetic resonance imaging (MRI) and Freesurfer version 4.5 were used to quantify hippocampal volume. Hierarchical linear regression and analysis of covariance models were used to examine if hippocampal volume and PTSD status would be associated with elevated levels of IL-6 and sTNF-RII. Increased sTNF-RII, but not IL-6, was significantly associated with reduced hippocampal volume (β=-0.14, p=0.01). The relationship between sTNF-RII and hippocampal volume was independent of potential confounds and covariates, including PTSD status. Although we observed no PTSD diagnosis-related differences in either IL-6 or sTNF-RII, higher PTSD severity was associated with significantly increased sTNF-RII (β=0.24, p=0.04) and reduced IL-6 levels (β=-0.24, p=0.04). Our results indicate that specific inflammatory proteins may be associated with brain structure and function as indexed by hippocampal volume and PTSD symptoms.

Expert Review of Neurotherapeutics, 2007

Studies and treatments for the symptomatic menopausal woman with sleep complaints have been revie... more Studies and treatments for the symptomatic menopausal woman with sleep complaints have been reviewed elsewhere. This article, as part of the clinical review series on the comorbid symptomatic menopausal woman, aims to examine the evidence for diagnosis and treatment of women who present with distressing sleep symptoms that they attribute to menopause. The etiology of these symptoms may be a psychiatric disorder, a pre- or co-existing problem with sleep, or a dynamic interaction among one of these and/or a symptomatic menopause. The relationship between sleep disturbance and cognitive complaints, mood problems, fatigue and low energy will be reviewed. The new research on sleep, clinical consequences of insomnia of various types, the impact of sleep disturbance on morbidity and functioning--in the context of the midlife woman in the menopausal transition--will be explored along with the evidence for different treatment strategies for these sleep problems.

order was assessed using the Computerized Diagnostic Interview Schedule for DSM-IV. Cardiac funct... more order was assessed using the Computerized Diagnostic Interview Schedule for DSM-IV. Cardiac function was measured using left ventricular ejection fraction, tread- mill exercise capacity, and inducible ischemia on stress echocardiography. Disease-specific health status was as- sessed using the symptom burden, physical limitation, and quality of life subscales of the Seattle Angina Ques- tionnaire. We used ordinal logistic regression to evalu-

Alzheimer's & Dementia, 2014

Posttraumatic stress disorder (PTSD) is associated with smaller volumes of the hippocampus, as ha... more Posttraumatic stress disorder (PTSD) is associated with smaller volumes of the hippocampus, as has been demonstrated by meta-analyses. Proposed mechanistic relationships are reviewed briefly, including the hypothesis that sleep disturbances mediate the effects of PTSD on hippocampal volume. Evidence for this includes findings that insomnia and restricted sleep are associated with changes in hippocampal cell regulation and impairments in cognition. We present results of a new study of 187 subjects in whom neither PTSD nor poor sleep was associated with lower hippocampal volume. We outline a broad research agenda centered on the hypothesis that sleep changes mediate the relationship between PTSD and hippocampal volume.

Alzheimer's & dementia : the journal of the Alzheimer's Association, 2014

Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems re... more Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just...

Psychoneuroendocrinology, 2006

Psychoneuroendocrinology, 2014

Posttraumatic stress disorder (PTSD) is associated with a 2-4 fold increased risk of developing T... more Posttraumatic stress disorder (PTSD) is associated with a 2-4 fold increased risk of developing Type 2 diabetes mellitus. However, detailed assessments of glucose metabolism and insulin secretion in a study designed to minimize confounders are lacking. Furthermore, few studies examine potential mechanisms involved. We analyzed data from a case-control study of medically healthy, medication-free adults to determine whether individuals with PTSD had abnormal glucose or insulin response to oral glucose tolerance test (OGTT) compared to controls. Secondarily, we assessed potential mediators such as sleep, cortisol and adiponectin. Data was analyzed from 92 age and gender-matched subjects (44 PTSD, 48 controls). Chronic PTSD was diagnosed using the Structured Clinical Interview for DSM-IV and Clinician Administered PTSD Scale. Subjects underwent 75-g OGTT, actigraphy and sleep diary (to quantify sleep duration), polysomnography (to assess slow wave sleep [SWS] and delta power), and overn...

Biological psychiatry, Jan 15, 2015

Posttraumatic stress disorder (PTSD) is associated with endocrine and immune abnormalities that c... more Posttraumatic stress disorder (PTSD) is associated with endocrine and immune abnormalities that could increase risk for autoimmune disorders. However, little is known about the risk for autoimmune disorders among individuals with PTSD. We conducted a retrospective cohort study of 666,269 Iraq and Afghanistan veterans under age 55 who were enrolled in the Department of Veterans Affairs health care system between October 7, 2001, and March 31, 2011. Generalized linear models were used to examine if PTSD, other psychiatric disorders, and military sexual trauma exposure increased risk for autoimmune disorders, including thyroiditis, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and lupus erythematosus, adjusting for age, gender, race, and primary care visits. PTSD was diagnosed in 203,766 veterans (30.6%), and psychiatric disorders other than PTSD were diagnosed in an additional 129,704 veterans (19.5%). Veterans diagnosed with PTSD had significantly higher adjus...

Journal of psychiatric research, 2014

Heterogeneity in glucocorticoid response to experimental stress conditions has shown to different... more Heterogeneity in glucocorticoid response to experimental stress conditions has shown to differentiate individuals with healthy from maladaptive real-life stress responses in a number of distinct domains. However, it is not known if this heterogeneity influences the risk for developing stress related disorders or if it is a biological consequence of the stress response itself. Determining if glucocorticoid response to stress induction prospectively predicts psychological vulnerability to significant real life stressors can adjudicate this issue. To test this relationship, salivary cortisol as well as catecholamine responses to a laboratory stressor during academy training were examined as predictors of empirically identified distress trajectories through the subsequent 4 years of active duty among urban police officers routinely exposed to potentially traumatic events and routine life stressors (N = 234). During training, officers were exposed to a video vignette of police officers e...

Psychiatry research, Jan 13, 2014

Abnormality in the "fear circuitry" has been known as a major neural characteristic of ... more Abnormality in the "fear circuitry" has been known as a major neural characteristic of posttraumatic stress disorder (PTSD). Recent studies also revealed decreased functional connectivity in the default mode network in PTSD. The present study aims to investigate, in war-zone-related PTSD, the spontaneous activity and functional connectivity of the amygdala and the precuneus, which are two representative brain regions of the two networks, respectively. Two groups of 52 male US Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) veterans (PTSD vs. controls), well matched on age and ethnicity, were clinically assessed and then studied in a resting state functional magnetic resonance imaging (fMRI) procedure. Functional connectivity analysis was conducted on the resting state fMRI data with the amygdala and precuneus as seeds. Compared with controls, veterans with PTSD had lower functional connectivity in the default mode network, as well as lower amygdala-front...