Biomedical subjects

J Douglas Bremner

Publications and source records attributed to J Douglas Bremner.

At least 19 recordsLinked to original sources

PubMed2006

Effects of antidepressant treatment on neural correlates of emotional and neutral declarative verbal memory in depression.

BACKGROUND: Multiple studies have documented deficits in verbal declarative memory function in depression that improve with resolution of symptoms; imaging studies show deficits in anterior cingulate function in depression, a brain area that mediates memory. No studies to date have examined neural correlates of emotionally valenced declarative memory using affectively negative (sad) verbal material that is clinically relevant to understanding depression. Also no studies have examined the effects of treatment on neural correlates of verbal declarative memory. The purpose of this study was to examine the effects of treatment with antidepressants on verbal declarative memory in patients with depression. METHODS: Subjects with (N=18) and without (N=9) mid-life major depression underwent positron emission tomography (PET) imaging during verbal declarative memory tasks with both neutral paragraph encoding compared to a control condition, and emotional (sad) word pair retrieval compared to a control condition. Imaging was repeated in 13 subjects with depression after treatment with antidepressants. RESULTS: Patients with untreated depression had a failure of anterior cingulate activation relative to controls during retrieval of emotional word pairs. Antidepressant treatment resulted in increased anterior cingulate function compared to the untreated baseline for both neutral and emotional declarative memory. LIMITATIONS: Limitations include a small sample size and variety of antidepressants used. CONCLUSIONS: These results are consistent with alterations in anterior cingulate function that are reversible with treatment in patients with depression. These findings may have implications for understanding the mechanism of action of antidepressants in the treatment of depression.

Adult↗

PubMed2006

The impact of the 1991 Gulf War on the mind and brain: findings from neuropsychological and neuroimaging research.

Many veterans of the 1991 Gulf War (GW) have complained of somatic and cognitive symptoms that may be neurological in nature. However, whether or not changes in brain function are associated with GW service continues to be debated. Studies of GW veterans using objective, performance-based neuropsychological measures have yielded inconsistent findings, with those indicating deficits among GW veterans typically revealing only relatively mild levels of neuropsychological impairment. Further, performances on objective neuropsychological tasks show little correspondence to subjective perceptions of cognitive functioning. Although preliminary magnetic resonance spectroscopy (MRS) studies demonstrate reduced N-acetylaspartate-to-creatine (NAA/Cr) ratio in select brain regions among GW veterans who report health concerns, this work requires further replication with larger, more representative samples. There is no evidence from neuroimaging studies of a non-specific effect of GW service or of changes in brain structure or function related to health status when conventional radiological methods are used. Owing to the paucity of objective exposure, baseline health data, and the now significant time elapsed since the GW, aetiological issues may never be fully resolved. Therefore, research addressing clinical management of GW veterans with neuropsychological dysfunction and neuroimaging abnormalities may prove more fruitful than exclusive focus on aetiology.

Brain↗

PubMed2006

Smaller volume of anterior cingulate cortex in abuse-related posttraumatic stress disorder.

OBJECTIVE: The anterior cingulate cortex (ACC) plays an important role in emotion, and studies in animals have shown changes in ACC structure with early life stress. The purpose of this study was to measure volume of the ACC in PTSD. METHOD: Magnetic resonance imaging (MRI) was used to measure ACC volume in 8 subjects with abuse-related PTSD and 13 healthy subjects without PTSD. ACC volume included Brodmann's area [BA] 24 and 32. RESULTS: Right ACC volume in PTSD patients was significantly smaller than in non-PTSD subjects. CONCLUSION: These results are consistent with smaller ACC volume in PTSD.

Adult↗

PubMed2006

The intellectual performance of traumatized children and adolescents with or without posttraumatic stress disorder.

This study compared the Wechsler Intelligence Scale for Children-III (WISC-III) scores of traumatized youth with posttraumatic stress disorder (PTSD) to the scores of trauma-exposed and nonexposed comparison groups without PTSD. All groups were free of additional major childhood psychiatric disorders. The PTSD group scored significantly lower than the comparison groups on verbal subtests, but not on performance subtests. The scores of the trauma-exposed PTSD negatives and nontrauma exposed controls were not significantly different. Accordingly, PTSD and not a history of trauma exposure in the absence of PTSD was associated with lower verbal IQ.

Adolescent↗

PubMed2006

Surfing the net for medical information about psychological trauma: an empirical study of the quality and accuracy of trauma-related websites.

Psychological trauma is a major public-health problem, and trauma victims frequently turn to the Internet for medical information related to trauma. The Internet has many advantages for trauma victims, including low cost, privacy, use of access, and reduced direct social interactions. However, there are no regulations on what is posted on the Internet, or by whom, and little is known about the quality of information currently available related to the topic of psychological trauma. The purpose of this study was to evaluate the quality of Internet sites related to the topic of psychological trauma. The top 20 hits for searches on Google, AllTheWeb, and Yahoo were tabulated, using search words of 'psychological trauma', 'stress', 'PTSD', and 'trauma'. From these searches, a list of 94 unique unsponsored hits that represented accessible websites was generated. Fourteen sites were unrelated or only peripherally related, and eight were related but were not comprehensively evaluated because they represented brochures, online book sales, etc. Seventy-two websites underwent evaluation of the content, design, disclosure, ease of use, and other factors based on published guidelines for medical information sites. Forty-two per cent of sites had inaccurate information, 82% did not provide a source of their information, and 41% did not use a mental-health professional in the development of the content. Ratings of content (e.g. accuracy, reliability, etc.) were 4 (2 SD) on a scale of 1 - 10, with 10 being the best. There were similar ratings for the other variables assessed. These findings suggest that although abundant, websites providing information about psychological trauma are often not useful, and can sometimes provide inaccurate and potentially harmful information to consumers of medical information.

Empirical Research↗

PubMed2006

Hippocampal and amygdalar volumes in dissociative identity disorder.

OBJECTIVE: Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. METHOD: The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. RESULTS: Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. CONCLUSIONS: The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects.

Adult↗

PubMed2006

The relationship between cognitive and brain changes in posttraumatic stress disorder.

Preclinical studies show that stress is associated with changes in structure of the hippocampus, a brain area that plays a critical role in memory, inhibition of neurogenesis, and memory deficits. Studies in animals showed that both serotonin reuptake inhibitors (SSRIs) and the epilepsy medication phenytoin (dilantin) block the effects of stress on the hippocampus. Imaging studies in posttraumatic stress disorder (PTSD) have found smaller volume of the hippocampus as measured with magnetic resonance imaging (MRI) in patients with PTSD related to both combat and childhood abuse. These patients were also found to have deficits in memory on neuropsychological testing. Functional imaging studies using positron emission tomography (PET) found decreased hippocampal activation with memory tasks. In an initial study, we found that a year of treatment with paroxetine led to a 5% increase in hippocampal volume and a 35% increase in memory function. A second study showed that phenytoin was efficacious for symptoms of PTSD and led to a significant 6% increase in both right hippocampal and right whole brain volume, with no significant change in memory. These studies suggest that medications may counteract the effects of stress on the brain in patients with PTSD.

Brain↗

PubMed2006

Alterations in stress reactivity after long-term treatment with paroxetine in women with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is typically accompanied by both acute and chronic alterations in the stress response. These alterations have mostly been described in individuals under baseline conditions, but studies have also used a challenge model to assess the role of the hypothalamic-pituitary-adrenal (HPA) axis in the stress response. The purpose of this article was to assess the effect of long-term treatment with the selective reuptake inhibitor (SSRI), paroxetine, on stress reactivity in patients with PTSD. We assessed diurnal salivary cortisol and urinary cortisol as well as cortisol, heart rate, and behavioral responses to a standardized cognitive stress challenge, in 13 female patients with chronic PTSD before and after 12 months of paroxetine treatment. Treatment resulted in a significant decrease in PTSD symptoms. Twenty-four-hour urinary cortisol was lower compared to base line after successful treatment. Treatment resulted in a decrease of salivary cortisol levels on all time points on a diurnal curve. Despite similar stress perception, cortisol response to the cognitive stress challenge resulted in a 26.5% relative decrease in stress-induced salivary cortisol with treatment. These results suggest that successful treatment with SSRI in chronic PTSD is associated with a trend for a decrease in baseline diurnal cortisol and with reduced cortisol reactivity to stress.

Adult↗

PubMed2006

Stress and brain atrophy.

Studies in animals showed that stress is associated with changes in hippocampal function and structure, an effect mediated through decreased neurogenesis, increased glucocorticoids, and/or decreased brain derived neurotrophic factor. Antidepressants and some anticonvulsants block the effects of stress and/or promote neurogenesis in animal studies. Patients with posttraumatic stress disorder (PTSD) have been shown to have smaller hippocampal volume on magnetic resonance imaging and deficits in hippocampal-based memory. Symptom activation is associated with decreased anterior cingulate and medial prefrontal function, which is proposed as the neural correlate of a failure of extinction seen in these patients. Treatment with antidepressants and phenytoin reverse hippocampal volume reduction and memory deficits in PTSD patients, suggesting that these agents may promote neurogenesis in humans.

Animals↗

PubMed2005

The enduring effects of abuse and related adverse experiences in childhood. A convergence of evidence from neurobiology and epidemiology.

BACKGROUND: Childhood maltreatment has been linked to a variety of changes in brain structure and function and stress-responsive neurobiological systems. Epidemiological studies have documented the impact of childhood maltreatment on health and emotional well-being. METHODS: After a brief review of the neurobiology of childhood trauma, we use the Adverse Childhood Experiences (ACE) Study as an epidemiological "case example" of the convergence between epidemiologic and neurobiological evidence of the effects of childhood trauma. The ACE Study included 17,337 adult HMO members and assessed 8 adverse childhood experiences (ACEs) including abuse, witnessing domestic violence, and serious household dysfunction. We used the number of ACEs (ACE score) as a measure of cumulative childhood stress and hypothesized a "dose-response" relationship of the ACE score to 18 selected outcomes and to the total number of these outcomes (comorbidity). RESULTS: Based upon logistic regression analysis, the risk of every outcome in the affective, somatic, substance abuse, memory, sexual,and aggression-related domains increased in a graded fashion as the ACE score increased (P <0.001). The mean number of comorbid outcomes tripled across the range of the ACE score. CONCLUSIONS: The graded relationship of the ACE score to 18 different outcomes in multiple domains theoretically parallels the cumulative exposure of the developing brain to the stress response with resulting impairment in multiple brain structures and functions.

Adult↗

PubMed2005

Posttraumatic stress disorder: a state-of-the-science review.

This article reviews the state-of-the-art research in posttraumatic stress disorder (PTSD) from several perspectives: (1) Sex differences: PTSD is more frequent among women, who tend to have different types of precipitating traumas and higher rates of comorbid panic disorder and agoraphobia than do men. (2) Risk and resilience: The presence of Group C symptoms after exposure to a disaster or act of terrorism may predict the development of PTSD as well as comorbid diagnoses. (3) Impact of trauma in early life: Persistent increases in CRF concentration are associated with early life trauma and PTSD, and may be reversed with paroxetine treatment. (4) Imaging studies: Intriguing findings in treated and untreated depressed patients may serve as a paradigm of failed brain adaptation to chronic emotional stress and anxiety disorders. (5) Neural circuits and memory: Hippocampal volume appears to be selectively decreased and hippocampal function impaired among PTSD patients. (6) Cognitive behavioral approaches: Prolonged exposure therapy, a readily disseminated treatment modality, is effective in modifying the negative cognitions that are frequent among PTSD patients. In the future, it would be useful to assess the validity of the PTSD construct, elucidate genetic and experiential contributing factors (and their complex interrelationships), clarify the mechanisms of action for different treatments used in PTSD, discover ways to predict which treatments (or treatment combinations) will be successful for a given individual, develop an operational definition of remission in PTSD, and explore ways to disseminate effective evidence-based treatments for this condition.

Adaptation, Psychological↗

PubMed2005

Neuroimaging in borderline personality disorder.

Neuroimaging has become one of the most important methods in the investigation of the neurobiological underpinnings of borderline personality disorder. Structural and functional imaging studies have revealed dysfunction in different brain regions which seem to contribute to borderline symptomatology. This review presents relevant studies using different methodologies: volumetry of limbic and prefrontal regions, investigations of brain metabolism under resting conditions, studies of serotonergic neurotransmission, and challenge studies using emotional, stressful, and sensory stimuli. Dysfunction in a frontolimbic network is suggested to mediate much, if not all of the borderline symptomatology.

Borderline Personality Disorder↗

PubMed2005

Mood disorders in the medically ill: scientific review and recommendations.

OBJECTIVE: The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research. DATA SOURCES: Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors. STUDY SELECTION/DATA EXTRACTION: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed. CONCLUSIONS: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Smaller head of the hippocampus in Gulf War-related posttraumatic stress disorder.

Reductions in hippocampal volume and impairment in short-term verbal memory have been reported in Vietnam combat veterans with posttraumatic stress disorder (PTSD) and in women with abuse-related PTSD. The present investigation evaluated hippocampal volume and memory in Gulf War veterans. This research is timely given the ongoing war in Iraq and the anticipated high rates of PTSD among returning combat soldiers. Fourteen veterans with PTSD related to traumatic experiences during the Gulf War (1990-1991), 23 deployed veterans without PTSD, 22 non-deployed reservists and 29 healthy civilians were studied. Volumes of the hippocampus, temporal lobe, and whole brain were measured on coronal MRI scans, and hippocampal mediated memory function was evaluated. The head of the hippocampus was the only subregion that was significantly smaller in Gulf War veterans with PTSD than in healthy civilians. Deployed veterans with PTSD, deployed veterans without PTSD, and non-deployed reservists had significantly smaller whole hippocampal volume and lower scores on immediate and delayed verbal and visual retrieval compared with healthy civilians.

Adult↗

PubMed2005

Stress-induced cortisol elevations are associated with impaired delayed, but not immediate recall.

Glucocorticoids are known to modulate memory functions, with elevated cortisol levels being associated with impaired declarative memory. This specific effect has been shown in several studies using pharmacological doses of cortisol. The present study was designed to assess the effects of stress-induced cortisol elevations on (1) the type of memory processing (encoding, consolidation and retrieval), and (2) on the emotional valence of the material under study. Sixteen healthy females were presented neutral and emotional material (words and paragraphs) before and after a stress challenge. Declarative memory was tested immediately after presentation and 24 h later (delayed recall). Delayed, but not immediate recall of the information presented after the stress challenge was significantly reduced compared with delayed recall of information presented before the stress challenge. In line with this, strong negative correlations were found for delayed recall of words and spatial memory presented after the challenge with post-stress cortisol levels, whereas no significant correlations were found between cortisol levels and delayed recall at day 1. These results suggest that stress-induced cortisol specifically affects long-term consolidation of declarative memories. These findings may have implications for understanding the effects of traumatic stress on memory functioning in patients with stress-related psychiatric disorders.

Adolescent↗

PubMed2005

Stress model for research into preterm delivery among black women.

The disparity between black and white infant mortality rates increased over the last decade, despite overall improvement in infant survival. Because most black infant deaths are related to preterm delivery, the discovery of the cause of premature birth in general and excess premature birth for black infants in particular is of paramount importance for reproductive health research. Substantial theoretic support exists for maternal stress as a risk factor for preterm birth. Traumatic events early in life may sensitize the adult to contemporary stresses and increase her vulnerability to stress-induced neuroendocrine or infection/inflammatory pathways to early parturition. In addition, an individual may prematurely age as a result of cumulative stress or a major traumatic event. This "stress age," which is synonymous with the concept of weathering and similar to the concept of allostatic load, may affect parturition through chronic conditions (such as hypertension) and in poorly understood pathophysiologic mechanisms that are related to increased chronologic age. One potential measure of stress age is maternal serum dehydroepiandrosterone sulfate. Maternal stress is a potential explanatory factor for excess preterm delivery among black women because of their exposure to racism-associated stress. However, few studies have addressed this question, and results are mixed. Future etiologic research must take into account the complexities of the measurement of stress age and past and current exposures to stress, which includes internalized racism and interpersonal racism.

Black People↗

PubMed2005

Magnetic resonance imaging (MRI) measurement of hippocampal volume in posttraumatic stress disorder: a meta-analysis.

BACKGROUND: Studies in animals showed that the hippocampus, a brain area involved in learning and memory, is sensitive to stress. Although several MRI studies showed smaller hippocampal volume in adults with chronic PTSD, others did not show significant differences from controls. These studies are typified by small sample sizes which may limit the ability to show significant differences. We therefore performed a meta-analytic study of all of these studies to clarify the role of hippocampal structural changes in subjects with PTSD. METHODS: Nine studies with a total of 133 adult subjects with chronic PTSD, 148 healthy controls, and 53 traumatized controls were included in the meta-analysis. RESULTS: There was significantly smaller volume in both right and left hippocampi in adult subjects with chronic PTSD in comparison with both healthy controls and traumatized controls. CONCLUSION: These findings are consistent with smaller hippocampal volume in adult subjects with chronic PTSD.

Adult↗

PubMed2005

Carbon-11 HOMADAM: a novel PET radiotracer for imaging serotonin transporters.

UNLABELLED: Carbon-11-labeled N,N-dimethyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine (HOMADAM) was synthesized as a new serotonin transporter (SERT) imaging agent. METHODS: Carbon-11 was introduced into HOMADAM by preparation of N-methyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine followed by alkylation with carbon-11 iodomethane. Binding affinities of HOMADAM and the radiolabeling substrate, N-methyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine, were determined in cDNA transfected cells expressing human SERT, dopamine transporters (DAT) and norepinephrine transporters NET using [3H]citalopram, [(125)I]RTI-55 and [3H]nisoxetine, respectively. MicroPET brain imaging was performed in monkeys. Arterial plasma metabolites of HOMADAM were analyzed in a rhesus monkey by high-performance liquid chromatography (HPLC). RESULTS: HOMADAM displayed high affinity for the SERT (Ki = 0.6 nM). N-methyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine displayed moderate affinity for the SERT (Ki = 15.11 nM). The affinities of HOMADAM for the DAT and NET were 2000- and 253-fold lower, respectively, than for the SERT. [11C]HOMADAM was prepared from [11C]iodomethane in approximately 25% radiochemical yield (decay-corrected to end of bombardment). MicroPET brain imaging studies in monkeys demonstrated that [11C]HOMADAM uptake was selectively localized in the midbrain, thalamus, pons, caudate, putamen and medulla. The midbrain-to-cerebellum, pons-to-cerebellum, thalamus-to-cerebellum and putamen-to-cerebellum ratios at 85 min were 4.2, 2.8, 2.3 and 2.0, respectively. HOMADAM binding achieved quasi-equilibrium at 45 min. Radioactivity in the SERT-rich regions of monkey brain was displaceable with R,S-citalopram. Radioactivity in the DAT-rich regions of monkey brain was not displaceable with the DAT ligand RTI-113. Radioactivity in the SERT-rich regions of monkey brain was displaceable with the R,S-reboxetine, a NET ligand with a high nanomolar affinity for SERT. Arterial plasma metabolites of HOMADAM were analyzed in a rhesus monkey by HPLC and displayed a single peak that corresponded to unmetabolized HOMADAM. CONCLUSION: HOMADAM is an excellent candidate for PET primate imaging of brain SERTs.

Animals↗