Biological Psychiatry

A brief summary of the articles appearing in this issue of Biological Psychiatry

2012-02-15

Telomere length has been used as a marker of cellular aging. Wikgren et al. (pages 294–300) investigated leukocyte telomere length and hypothalamic-pituitary-adrenal (HPA) axis measurements in patients with major depressive disorder and healthy controls. They found that telomere length was shorter in patients compared with controls, and that telomere length was shorter among both patients and controls who exhibited a hypocortisolemic HPA axis profile. These findings support the concept of telomere length as a measure of stress and the idea that stress contributes to the aging process.

Child Abuse and Psychiatric Illness

Joan Kaufman — 2012-02-15

Child abuse is a nonspecific risk factor associated with an increased risk for a range of psychiatric and substance use disorders. The paper in this issue by Dannlowski et al. () adds to a growing body of literature on the mechanisms by which adverse early experiences confer vulnerability to psychiatric illness. The paper by Nikulina et al. () delineate further genetic and other factors that account for individual differences in the outcomes of adults who were abused as children.

Low Cortisol and Risk and Resilience to Stress-Related Psychiatric Disorders

Elisabeth B. Binder, Florian Holsboer — 2012-02-15

A number of both preclinical and clinical studies have investigated the long-term effects of exposure to stressful or traumatic life events on the regulation of the stress hormone system. In this issue of Biological Psychiatry, Lovallo et al. () present data from the Trier Social Stress Test (TSST), a standardized psychological stressor, performed in more than 350 healthy young adults. The authors observed that exposure to adverse life events was associated with a blunted cortisol and heart rate response to the stress task. Specifically, lower endocrine and cardiac responses were associated with separation or loss of a parent before age 15 years but not with life time exposure to physical or sexual abuse or violence. In this commentary, we will focus on the endocrine results of this study and how they may relate to risk and resilience to mood and anxiety disorders.

Memory Reconsolidation Processes and Posttraumatic Stress Disorder: Promises and Challenges of Translational Research

Jacek De̢biec — 2012-02-15

During the past decade, there was a vigorous renewal of interest in postretrieval memory processes. Numerous studies using a variety of species and learning paradigms, and targeting various brain circuitries and molecular mechanisms provided compelling evidence that established memories may be experimentally altered following their recall. Thirty years of prior research suggested the possibility of attenuating previously acquired memories following their retrieval (). This observed postretrieval plasticity was referred to as memory reconsolidation, in contrast to memory consolidation, which occurs following learning and which subserves the establishment of lasting memories. Until the publication by Nader et al. in 2000 (), amnestic agents or procedures used in reconsolidation studies were nonspecific or were applied systemically, which significantly limited conclusions that could be drawn from these studies. However, Nader et al. demonstrated the disruption of retrieved memories in a well-defined learning paradigm (auditory fear conditioning) using a well-known memory consolidation blocker (protein synthesis inhibitory anisomycin) infused into the lateral nucleus of the amygdala, a region known to be critical for acquisition and consolidation of auditory fear conditioning. Importantly, Nader et al. () showed that targeted administration of a consolidation blocker impaired the memory within few hours following learning but not later (). Subsequent studies showed that reconsolidation is not a simple repetition of consolidation (). Although features of the reconsolidation hypothesis remain to be proven, this line of research has successfully stimulated a great deal of research on postretrieval memory processes.

Limbic Scars: Long-Term Consequences of Childhood Maltreatment Revealed by Functional and Structural Magnetic Resonance Imaging

2011-11-24

Background: Childhood maltreatment represents a strong risk factor for the development of depression and posttraumatic stress disorder (PTSD) in later life. In the present study, we investigated the neurobiological underpinnings of this association. Since both depression and PTSD have been associated with increased amygdala responsiveness to negative stimuli as well as reduced hippocampal gray matter volume, we speculated that childhood maltreatment results in similar functional and structural alterations in previously maltreated but healthy adults. Methods: One hundred forty-eight healthy subjects were enrolled via public notices and newspaper announcements and were carefully screened for psychiatric disorders. Amygdala responsiveness was measured by means of functional magnetic resonance imaging and an emotional face-matching paradigm particularly designed to activate the amygdala in response to threat-related faces. Voxel-based morphometry was used to study morphological alterations. Childhood maltreatment was assessed by the 25-item Childhood Trauma Questionnaire (CTQ). Results: We observed a strong association of CTQ scores with amygdala responsiveness to threat-related facial expressions. The morphometric analysis yielded reduced gray matter volumes in the hippocampus, insula, orbitofrontal cortex, anterior cingulate gyrus, and caudate in subjects with high CTQ scores. Both of these associations were not influenced by trait anxiety, depression level, age, intelligence, education, or more recent stressful life events. Conclusions: Childhood maltreatment is associated with remarkable functional and structural changes even decades later in adulthood. These changes strongly resemble findings described in depression and PTSD. Therefore, the present results might suggest that limbic hyperresponsiveness and reduced hippocampal volumes could be mediators between the experiences of adversities during childhood and the development of emotional disorders.

Short Telomeres in Depression and the General Population Are Associated with a Hypocortisolemic State

2011-11-07

Background: The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in stress regulation, and leukocyte telomere length (TL) has been suggested to represent a cumulative measure of stress. Depression is intimately related with stress and frequently exhibits a dysregulated HPA axis. We aimed to study the relationships between TL and biological and psychological facets of stress in recurrent major depressive disorder and controls. Methods: Leukocyte TL was measured in 91 subjects with recurrent major depressive disorder and 451 control subjects. Stress was assessed from both a biological perspective, by assessing HPA axis function with a weight-adjusted very-low-dose dexamethasone suppression test (DST), and a psychological perspective, with self-report questionnaires. Results: TL was shorter among patients compared with control subjects (277 base pairs, p = .001). Overall, short TL was associated with a hypocortisolemic state (low post-DST cortisol and high percentage of cortisol reduction after the DST) among both patients and control subjects but more pronounced among patients. This state, which was overrepresented among patients, was characterized by high familial loading of affective disorders among patients (p = .001) and high C-reactive protein levels among control subjects (p = .040). TL was also inversely associated with stress measured with the Perceived Stress Questionnaire (rs = −.258, p = .003). Conclusions: Short TL is associated with depression and hypocortisolism. Because hypocortisolism has been shown to develop from chronic stress exposure, our findings corroborate the concept of TL as a cumulative measure of stress and provide novel insights into the detrimental role of stress in depressive illness and the general population.

Reorganization of Synaptic Inputs to the Hypothalamic Paraventricular Nucleus During Chronic Psychogenic Stress in Rats

Ildikó H. Miklós, Krisztina J. Kovács — 2011-12-05

Background: Chronic stress in humans precipitates hyper-reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis and triggers symptoms associated with certain forms of depression. Reorganization of neuronal networks has been implicated in development of depression, however it remained unknown how chronic exposure to psychogenic challenges affects excitatory and inhibitory inputs to corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus that govern neuroendocrine stress response. Methods: Rats (n = 32) were exposed for 21 days to chronic variable stress and their behavioral (sucrose preference) and hormonal (corticosterone) responses were followed together with electron microscopic stereologic analysis of excitatory and gamma-aminobutyric acid (GABA)-containing, inhibitory synapses on the CRH synthesizing neurons. Results: Chronic stress in rats resulted in weight loss, anhedonia, and hyperactivity of hypothalamic-pituitary-adrenocortical axis. Following 3 weeks' exposure to variable psychologic stressors the number of synapses has been doubled in the paraventricular nucleus. Asymmetrical excitatory as well as GABAergic inhibitory synaptic contacts were increased on CRH neurons; however, the excitatory/inhibitory input ratio remained constant. In response to chronic stress, we found rearrangement of inhibitory GABA-containing inputs with the increase of contacts on dendrites and decrease at the soma region of CRH neurons. Conclusions: Significant remodeling of synaptic contacts was found on CRH neurons in response to chronic stress. This morphologic plasticity might be related to the hyperactivity of the HPA axis and to development of stress-related psychopathologies such as depression.

Glucocorticoid Receptor Pathway Components Predict Posttraumatic Stress Disorder Symptom Development: A Prospective Study

2011-12-05

Background: Biological correlates of posttraumatic stress disorder (PTSD) have mostly been studied using cross-sectional or posttrauma prospective designs. Therefore, it remains largely unknown whether previously observed biological correlates of PTSD precede trauma exposure. We investigated whether glucocorticoid receptor (GR) pathway components assessed in leukocytes before military deployment represent preexisting vulnerability factors for development of PTSD symptoms. Methods: Four hundred forty-eight male soldiers were assessed before and 6 months after deployment to a combat zone. Participants were assigned to the PTSD or comparison group based on Self-Rating Inventory for PTSD scores after deployment. Logistic regression analysis was applied to predict development of a high level of PTSD symptoms based on predeployment GR number, messenger (m)RNA expression of GR target genes FKBP5, GILZ, and SGK1, plasma cortisol, and childhood trauma. We also investigated whether predeployment GR number and FKBP5 mRNA expression were associated with single nucleotide polymorphisms in the GR and FKBP5 genes, either alone or in interaction with childhood trauma. Results: Several GR pathway components predicted subsequent development of a high level of PTSD symptoms: predeployment high GR number, low FKBP5 mRNA expression, and high GILZ mRNA expression were independently associated with increased risk for a high level of PTSD symptoms. Childhood trauma also independently predicted development of a high level of PTSD symptoms. Additionally, we observed a significant interaction effect of GR haplotype BclI and childhood trauma on GR number. Conclusions: Collectively, our results indicate that predeployment GR pathway components are vulnerability factors for subsequent development of a high level of PTSD symptoms.

Site-Specific Genetic Manipulation of Amygdala Corticotropin-Releasing Factor Reveals Its Imperative Role in Mediating Behavioral Response to Challenge

Limor Regev, Michael Tsoory, Shosh Gil, Alon Chen — 2011-07-25

Background: Faulty regulation of the central extrahypothalamic corticotropin-releasing factor (CRF) expression is associated with stress-related psychopathologies including anxiety disorders and depression. Extensive pharmacological literature describes the effects of CRF agonists or antagonists' administration on anxiety-like behavior. However, the relevance of the endogenous agonist, presumed to be CRF, has never been explicitly demonstrated. Several genetic models have been used to study the role of CRF in the physiological response to stress and in stress-related disorders. Nevertheless, developmental compensatory mechanisms and lack of spatial and temporal specificity limited the interpretations of these studies. Methods: Two lentiviral-based systems were designed, generated, and used to knockdown (KD) or conditionally overexpress (OE) CRF in the central amygdala (CeA) of adult mice. Behavioral responses associated with the CeA, such as anxiety, depression and fear memory, and the plasma corticosterone levels were evaluated under both basal and stressful conditions. Results: Changing the CeA-CRF levels mildly affected anxiety-like behaviors under basal conditions. However, following exposure to an acute stressor, CeA-CRF-KD strongly attenuated stress-induced anxiety-like behaviors, whereas a short-term CeA-CRF-overexpression enhanced the stress-induced effects on these behaviors. Interestingly, a significant increase in basal corticosterone levels in the CeA-CRF-KD mice was observed, demonstrating the importance of endogenous CeA-CRF levels for basal, but not stress-induced, corticosterone levels. Conclusions: These results highlight the pivotal role of CeA CRF expression regulation in mediating adequate behavioral responses to stress and introduce these novel viral tools as a useful approach for dissecting the role of central CRF in mediating behavioral and neuroendocrine responses to stress.

Catecholamines in the Bed Nucleus of the Stria Terminalis Reciprocally Respond to Reward and Aversion

2011-11-24

Background: Traditionally, norepinephrine has been associated with stress responses, whereas dopamine has been associated with reward. Both of these catecholamines are found within the bed nucleus of the stria terminalis (BNST), a brain relay nucleus in the extended amygdala between cortical/limbic centers, and the hypothalamic-pituitary-adrenal axis. Despite this colocalization, little is known about subsecond catecholamine signaling in subregions of the BNST in response to salient stimuli. Methods: Changes in extracellular catecholamine concentration in subregions of the BNST in response to salient stimuli were measured within the rat BNST with fast-scan cyclic voltammetry at carbon-fiber microelectrodes. Results: A discrete subregional distribution of release events was observed for different catecholamines in this nucleus. In addition, rewarding and aversive tastants evoked inverse patterns of norepinephrine and dopamine release in the BNST. An aversive stimulus, quinine, activated noradrenergic signaling but inhibited dopaminergic signaling, whereas a palatable stimulus, sucrose, inhibited norepinephrine while causing dopamine release. Conclusions: This reciprocal relationship, coupled with their different time courses, can provide integration of opposing hedonic states to influence response outputs appropriate for survival.

Concussive Brain Injury Enhances Fear Learning and Excitatory Processes in the Amygdala

2011-12-12

Background: Mild traumatic brain injury (cerebral concussion) results in cognitive and emotional dysfunction. These injuries are a significant risk factor for the development of anxiety disorders, including posttraumatic stress disorder. However, because physically traumatic events typically occur in a highly emotional context, it is unknown whether traumatic brain injury itself is a cause of augmented fear and anxiety. Methods: Rats were trained with one of five fear-conditioning procedures (n = 105) 2 days after concussive brain trauma. Fear learning was assessed over subsequent days and chronic changes in fear learning and memory circuitry were assessed by measuring N-methyl-D-aspartate receptor subunits and glutamic acid decarboxylase, 67 kDa isoform protein levels in the hippocampus and basolateral amygdala complex (BLA). Results: Injured rats exhibited an overall increase in fear conditioning, regardless of whether fear was retrieved via discrete or contextual-spatial stimuli. Moreover, injured rats appeared to overgeneralize learned fear to both conditioned and novel stimuli. Although no gross histopathology was evident, injury resulted in a significant upregulation of excitatory N-methyl-D-aspartate receptors in the BLA. There was a trend toward decreased γ-aminobutyric acid-related inhibition (glutamic acid decarboxylase, 67 kDa isoform) in the BLA and hippocampus. Conclusions: These results suggest that mild traumatic brain injury predisposes the brain toward heightened fear learning during stressful postinjury events and provides a potential molecular mechanism by which this occurs. Furthermore, these data represent a novel rodent model that can help advance the neurobiological and therapeutic understanding of the comorbidity of posttraumatic stress disorder and traumatic brain injury.

Lifetime Adversity Leads to Blunted Stress Axis Reactivity: Studies from the Oklahoma Family Health Patterns Project

2011-11-24

Background: Can stressful events in early life alter the response characteristics of the human stress axis? Individual differences in stress reactivity are considered potentially important in long-term health and disease; however, little is known about the sources of these individual differences. We present evidence that adverse experience in childhood and adolescence can alter core components of the stress axis, including cortisol and heart rate reactivity. Methods: We exposed 354 healthy young adults (196 women) to public speaking and mental arithmetic stressors in the laboratory. Stress responses were indexed by self-report, heart rate, and cortisol levels relative to measures on a nonstress control day. Subjects were grouped into those who had experienced 0, 1, or 2 or more significant adverse life events, including Physical or Sexual Adversity (mugged, threatened with a weapon, experienced a break-in or robbery or raped or sexually assaulted by a relative or nonrelative) or Emotional Adversity (separation from biological mother or father for at least 6 months before age 15). Results: Experience of adversity predicted smaller heart rate and cortisol responses to the stressors in a dose-dependent fashion (0 > 1 > 2 or more events) (F values = 5.79 and 8.11, p values < .004) for both men and women. This was not explained by differences in socioeconomic status, the underlying cortisol diurnal cycle, or subjective experience during the stress procedure. Conclusions: The results indicate a long-term impact of stressful life experience on the reactivity of the human stress axis.

Child Abuse and Neglect, MAOA, and Mental Health Outcomes: A Prospective Examination

Valentina Nikulina, Cathy Spatz Widom, Linda M. Brzustowicz — 2011-10-28

Background: Studies have examined the interaction of MAOA genotype with childhood maltreatment in relation to depressive symptomatology and alcohol abuse with conflicting findings. Both high- and low-activity allele combinations have been shown to be protective for maltreated children with direction of findings varying by study methodology and participants' sex. Methods: Participants in a prospective cohort design study involving court-substantiated cases of child abuse and neglect and a matched comparison group were followed up into adulthood and interviewed (N = 802). Eighty-two percent consented to provide blood, 631 gave permission for DNA extraction and analyses, and 575 were included in the final sample. This sample included male, female, white, and nonwhite (primarily black) participants. Symptoms of dysthymia, major depression, and alcohol abuse were assessed using the National Institutes of Mental Health Diagnostic Interview Schedule-III-R. Results: Significant three-way interactions, MAOA genotype by abuse by sex, predicted dysthymic symptoms. Low-activity MAOA genotype buffered against symptoms of dysthymia in physically abused and multiply-maltreated women. Significant three-way interactions, MAOA genotype by sexual abuse by race, predicted all outcomes. Low-activity MAOA genotype buffered against symptoms of dysthymia, major depressive disorder, and alcohol abuse for sexually abused white participants. The high-activity genotype was protective in the nonwhite sexually abused group. Conclusions: This prospective study provides evidence that MAOA interacts with child maltreatment to predict mental health outcomes. Reasons for sex differences and race findings are discussed.

Gene Profiling Reveals a Role for Stress Hormones in the Molecular and Behavioral Response to Food Restriction

2011-08-22

Background: Food restriction is known to enhance learning and motivation. The neural mechanisms underlying these responses likely involve alterations in gene expression in brain regions mediating the motivation to feed. Methods: Analysis of gene expression profiles in male C57BL/6J mice using whole-genome microarrays was completed in the medial prefrontal cortex, nucleus accumbens, ventral tegmental area, and the hypothalamus following a 5-day food restriction. Quantitative polymerase chain reaction was used to validate these findings and determine the time course of expression changes. Plasma levels of the stress hormone corticosterone (CORT) were measured by enzyme-linked immunosorbent assay. Expression changes were measured in adrenalectomized animals that underwent food restriction, as well as in animals receiving daily injections of CORT. Progressive ratio responding for food, a measure of motivated behavior, was assessed after CORT treatment in restricted and fed animals. Results: Brief food restriction results in an upregulation of peripheral stress responsive genes in the mammalian brain. Time-course analysis demonstrated rapid and persistent expression changes in all four brain regions under study. Administration of CORT to nonrestricted animals was sufficient to induce a subset of the genes, and alterations in gene expression after food restriction were dependent on intact adrenal glands. CORT can increase the motivation to work for food only in the restricted state. Conclusions: These data demonstrate a central role for CORT in mediating both molecular and behavioral responses to food restriction. The stress hormone-induced alterations in gene expression described here may be relevant for both adaptive and pathological responses to stress.

Cognitive-Behavioral Stress Management Reverses Anxiety-Related Leukocyte Transcriptional Dynamics

2011-11-17

Background: Chronic threat and anxiety are associated with pro-inflammatory transcriptional profiles in circulating leukocytes, but the causal direction of that relationship has not been established. This study tested whether a cognitive-behavioral stress management (CBSM) intervention targeting negative affect and cognition might counteract anxiety-related transcriptional alterations in people confronting a major medical threat. Methods: One hundred ninety-nine women undergoing primary treatment of stage 0–III breast cancer were randomized to a 10-week CBSM protocol or an active control condition. Seventy-nine provided peripheral blood leukocyte samples for genome-wide transcriptional profiling and bioinformatic analyses at baseline, 6-month, and 12-month follow-ups. Results: Baseline negative affect was associated with >50% differential expression of 201 leukocyte transcripts, including upregulated expression of pro-inflammatory and metastasis-related genes. CBSM altered leukocyte expression of 91 genes by >50% at follow-up (group × time interaction), including downregulation of pro-inflammatory and metastasis-related genes and upregulation of type I interferon response genes. Promoter-based bioinformatic analyses implicated decreased activity of NF-κB/Rel and GATA family transcription factors and increased activity of interferon response factors and the glucocorticoid receptor as potential mediators of CBSM-induced transcriptional alterations. Conclusions: In early-stage breast cancer patients, a 10-week CBSM intervention can reverse anxiety-related upregulation of pro-inflammatory gene expression in circulating leukocytes. These findings clarify the molecular signaling pathways by which behavioral interventions can influence physical health and alter peripheral inflammatory processes that may reciprocally affect brain affective and cognitive processes.

Variations in the Promoter Region of the Serotonin Transporter Gene and Biased Attention for Emotional Information: A Meta-Analysis

2011-12-06

Background: Selective attention to negative information has been strongly implicated in the etiology and maintenance of anxiety and offered as a potential intermediate phenotype for anxiety disorders. Attention biases have been studied in relation to a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) offering equivocal findings. The present meta-analysis tested whether the extant published data support the notion that variation in the 5-HTTLPR genotype modulates selective attention to negative information. Methods: Eleven relevant samples from 10 published articles were identified through a systematic literature search (total n = 807). Relevant attention bias and 5-HTTLPR data were extracted based on specific coding rules, and Cohen's d effect size index was used to calculate all outcome measures. Publication bias was assessed using various methods. Results: Carriers of the low (SS, SLG, LGLG) transmission efficacy genotype display attentional vigilance toward negatively valenced stimuli, a pattern not found in the intermediate (SLA, LALG) and high (LALA) efficacy genotypes. This phenomenon emerges as of medium effect size. Conclusions: The meta-analysis supports the notion that allele variants of the 5-HTTLPR are associated with selective attention to negative stimuli. More studies are needed to fully establish the consistency of this effect. Future studies applying systematic attention bias modification may shed further light on the role of 5-HTTLPR in the development of anxiety disorders and in the prediction of clinical response to attention bias modification treatments.

Neural Signature of Reconsolidation Impairments by Propranolol in Humans

Lars Schwabe, Karim Nader, Oliver T. Wolf, Thomas Beaudry, Jens C. Pruessner — 2011-12-02

Background: The retrieval of consolidated memories may result in their destabilization, requiring a restabilization process called reconsolidation. During reconsolidation, memories become sensitive to psychological and pharmacological modifications again, thus providing an opportunity to alter unwanted memories. Although such reconsolidation manipulations might open the door to novel treatment approaches for psychiatric disorders such as posttraumatic stress disorder, the brain mechanisms underlying reconsolidation processes in humans are completely unknown. Here, we asked whether a β-adrenergic receptor antagonist might interfere with the reconsolidation of emotional episodic memories and what brain mechanisms are involved in these effects. Methods: Healthy participants were administered the β-adrenergic receptor antagonist propranolol or a placebo before they reactivated previously learned neutral and emotional material. Recognition memory was tested 24 hours later. Functional magnetic resonance images were collected during reactivation and recognition testing. Results: Propranolol during reactivation specifically reduced the subsequent memory for emotional pictures; memory for neutral pictures remained unaffected. This emotional memory impairment was associated with significantly increased activity in the amygdala and the hippocampus for correctly recognized pictures at test. Most interestingly, the same structures were active (but not modulated by propranolol) during memory reactivation. Memory reactivation alone or propranolol without reactivation had no effect on subsequent memory. Conclusions: Our results demonstrate how the consequences of memory reconsolidation processes are represented in the human brain, suggesting that the brain areas that are recruited during reactivation undergo changes in activity that are associated with subsequent memory recall.

Erratum to: The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) Study: Outcomes from the Acute and Continuation Phases

2012-02-15

It has been discovered that the patient flowchart was not included in Supplement 2 for “The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) Study: Outcomes from the Acute and Continuation Phases” by Keller et al., published in Biological Psychiatry (2007;62:1371–1379). The flowchart is referenced in the first sentence of the Results section, and is now printed here.

Erratum to: Catechol-O-Methyltransferase Val158Met Polymorphism Moderates Anterior Cingulate Volume in Posttraumatic Stress Disorder

2012-02-15

Errors have been discovered in “Catechol-O-Methyltransferase Val158Met Polymorphism Moderates Anterior Cingulate Volume in Posttraumatic Stress Disorder” by Schulz-Heik et al., published in Biological Psychiatry (2011;70:1091-1096).

Ifenprodil for the Treatment of Flashbacks in Female Posttraumatic Stress Disorder Patients with a History of Childhood Sexual Abuse

Akira Kishimoto, Motonori Kaneko, Yurie Gotoh, Kenji Hashimoto — 2011-11-10

A recent meta-analysis showed that a history of sexual abuse is associated with increased risk for a lifetime diagnosis of multiple psychiatric disorders, such as posttraumatic stress disorder (PTSD), anxiety disorders, depression, eating disorders, sleep disorders, and suicide attempts (). In particular, PTSD is highly prevalent among women who have experienced childhood sexual abuse. Reexperiencing the event as a flashback is a hallmark symptom of PTSD, but the precise mechanisms for flashbacks are currently unknown (). Several lines of evidence suggest that the glutamatergic system plays a role in certain behavioral manifestations common to PTSD, including dissociation and perceptual alterations (). The N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine can produce dissociative symptoms and perceptual alterations (i.e., depersonalization, derealization, altered auditory and visual acuity) akin to those observed with PTSD (). However, there are currently no standard therapeutic agents for treating flashbacks associated with PTSD.

Clinical and Cerebral Volumetric Effects of Sodium Benzoate, a d-Amino Acid Oxidase Inhibitor, in a Drug-Naïve Patient with Major Depression

Chien-Han Lai, Hsien-Yuan Lane, Guochuan Emil Tsai — 2011-12-16

Sodium benzoate, an inhibitor of d-amino acid oxidase (DAO), can prevent degradation of d-amino acid (DAA) and might be helpful for the relief of anxiety or depression symptoms (). Its therapeutic role in major depressive disorder (MDD) is still unclear. Here we present a MDD case with gray matter (GM) increases and relief of symptoms after sodium benzoate monotherapy for 6 weeks.

Editorial Board

2012-02-15

Subscribers Page

2012-02-15

Biological Psychiatry (ISSN 0006-3223) is published semimonthly by Elsevier Inc., 360 Park Avenue South, New York, NY 10010-1710. Periodicals postage paid at New York, NY and additional mailing offices.

2012-02-15

Guide for Authors

2012-02-15

Biological Psychiatry is the official journal of the Society of Biological Psychiatry. The Journal rapidly publishes reports of novel results on a broad range of topics related to the pathophysiology and treatment of major neuropsychiatric disorders. Both basic and clinical neuroscience contributions are encouraged, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Except where explicitly stated otherwise, Biological Psychiatry conforms to the guidelines set forth by the International Committee of Medical Journal Editors (ICMJE) (see Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication (April 2010): Available from http://www.ICMJE.org).

Manuscript Submission Form

2012-02-15

This form should be completed by every author and accompany every new manuscript submission. It must be fully complete and accurate, with signatures from ALL authors, before a manuscript can be finalized. Please scan the completed form(s) and attach them electronically during the submission process. If you are unable to do so, fax the completed form(s) to the Editorial Office at (214) 645-9208.

Biological Psychiatry

A brief summary of the articles appearing in this issue of Biological Psychiatry

Child Abuse and Psychiatric Illness

Low Cortisol and Risk and Resilience to Stress-Related Psychiatric Disorders

Memory Reconsolidation Processes and Posttraumatic Stress Disorder: Promises and Challenges of Translational Research

Limbic Scars: Long-Term Consequences of Childhood Maltreatment Revealed by Functional and Structural Magnetic Resonance Imaging

Short Telomeres in Depression and the General Population Are Associated with a Hypocortisolemic State

Reorganization of Synaptic Inputs to the Hypothalamic Paraventricular Nucleus During Chronic Psychogenic Stress in Rats

Glucocorticoid Receptor Pathway Components Predict Posttraumatic Stress Disorder Symptom Development: A Prospective Study

Site-Specific Genetic Manipulation of Amygdala Corticotropin-Releasing Factor Reveals Its Imperative Role in Mediating Behavioral Response to Challenge

Catecholamines in the Bed Nucleus of the Stria Terminalis Reciprocally Respond to Reward and Aversion

Concussive Brain Injury Enhances Fear Learning and Excitatory Processes in the Amygdala

Lifetime Adversity Leads to Blunted Stress Axis Reactivity: Studies from the Oklahoma Family Health Patterns Project

Child Abuse and Neglect, MAOA, and Mental Health Outcomes: A Prospective Examination

Gene Profiling Reveals a Role for Stress Hormones in the Molecular and Behavioral Response to Food Restriction

Cognitive-Behavioral Stress Management Reverses Anxiety-Related Leukocyte Transcriptional Dynamics

Variations in the Promoter Region of the Serotonin Transporter Gene and Biased Attention for Emotional Information: A Meta-Analysis

Neural Signature of Reconsolidation Impairments by Propranolol in Humans

Erratum to: The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) Study: Outcomes from the Acute and Continuation Phases

Erratum to: Catechol-O-Methyltransferase Val158Met Polymorphism Moderates Anterior Cingulate Volume in Posttraumatic Stress Disorder

Ifenprodil for the Treatment of Flashbacks in Female Posttraumatic Stress Disorder Patients with a History of Childhood Sexual Abuse

Clinical and Cerebral Volumetric Effects of Sodium Benzoate, a d-Amino Acid Oxidase Inhibitor, in a Drug-Naïve Patient with Major Depression

Editorial Board

Subscribers Page

Table of Contents

Guide for Authors

Manuscript Submission Form