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Childhood trauma associated with smaller hippocampal volume in women with major depression
Vythilingam, Meena; Heim, Christine; Newport, Jeffrey; Miller, Andrew H; Anderson, Eric; Bronen, Richard; Brummer, Marijn; Staib, Lawrence; Vermetten, Eric; Charney, Dennis S; Nemeroff, Charles B; Bremner, J Douglas
OBJECTIVE: Smaller hippocampal volume has been reported only in some but not all studies of unipolar major depressive disorder. Severe stress early in life has also been associated with smaller hippocampal volume and with persistent changes in the hypothalamic-pituitary-adrenal axis. However, prior hippocampal morphometric studies in depressed patients have neither reported nor controlled for a history of early childhood trauma. In this study, the volumes of the hippocampus and of control brain regions were measured in depressed women with and without childhood abuse and in healthy nonabused comparison subjects. METHOD: Study participants were 32 women with current unipolar major depressive disorder-21 with a history of prepubertal physical and/or sexual abuse and 11 without a history of prepubertal abuse-and 14 healthy nonabused female volunteers. The volumes of the whole hippocampus, temporal lobe, and whole brain were measured on coronal MRI scans by a single rater who was blind to the subjects' diagnoses. RESULTS: The depressed subjects with childhood abuse had an 18% smaller mean left hippocampal volume than the nonabused depressed subjects and a 15% smaller mean left hippocampal volume than the healthy subjects. Right hippocampal volume was similar across the three groups. The right and left hippocampal volumes in the depressed women without abuse were similar to those in the healthy subjects. CONCLUSIONS: A smaller hippocampal volume in adult women with major depressive disorder was observed exclusively in those who had a history of severe and prolonged physical and/or sexual abuse in childhood. An unreported history of childhood abuse in depressed subjects could in part explain the inconsistencies in hippocampal volume findings in prior studies in major depressive disorder.
PMCID:3230324
PMID: 12450959
ISSN: 0002-953x
CID: 1470802
Comorbidity of obsessive-compulsive disorder and depression: prevalence, symptom severity, and treatment effect
Overbeek, Thea; Schruers, Koen; Vermetten, Eric; Griez, Eric
BACKGROUND: The goal of this study was to investigate the co-occurrence of depressive disorders in obsessive-compulsive disorder (OCD) and the effect of these disorders on combined pharmacologic and behavioral treatment for OCD. METHOD: A retrospective chart analysis was performed on baseline ratings of 120 OCD patients and posttreatment ratings of 72 of these patients. For depressive symptoms, the Montgomery-Asberg Depression Rating Scale and the Self-Rating Depression Scale were applied; for obsessive-compulsive symptoms, the Yale-Brown Obsessive Compulsive Scale and the Maudsley Obsessive Compulsive Inventory were used; and for general anxiety symptoms, the Self-Rating Anxiety Scale, the Clinical Anxiety Scale, and the State-Trait Anxiety Inventory were given. RESULTS: One third of the OCD patients in our sample were found to be depressed. Symptom severity on OCD symptoms at baseline did not differ between depressed and nondepressed OCD patients; on general anxiety symptoms, the comorbid group was more severely affected. Both depressed and nondepressed OCD patients responded well to treatment, as reflected in assessments for depressive, obsessive-compulsive, and general anxiety symptoms. However, comorbid depression had a negative effect on treatment: depressed OCD patients showed less improvement than nondepressed OCD patients on most scales. CONCLUSION: Depression frequently accompanies OCD and appears to affect treatment outcome negatively. While both groups of patients improved with combination treatment, the OCD-alone group had more improvement than the group that had comorbid depression.
PMID: 12523869
ISSN: 0160-6689
CID: 1470812
Hippocampal volume in patients with major depression without childhood trauma [Meeting Abstract]
Vythilingam, M; Vermetten, E; Anderson, E; Norris, S; Staib, L; Bronen, R; Charney, DS; Bremner, JD
ISI:000174980400097
ISSN: 0006-3223
CID: 1507132
Neural correlates of memory for emotional words in abuserelated PTSD [Meeting Abstract]
Bremner, JD; Vythilingam, M; Vermetten, E; McGlashan, T; Southwick, SM; Charney, DS
ISI:000174980400037
ISSN: 0006-3223
CID: 1507122
Cortisol, memory and the hippocampus in PTSD and DID [Meeting Abstract]
Vermetten, E; Loewenstein, RJ; Zdunek, C; Wilson, K; Bremner, JD
ISI:000174980400409
ISSN: 0006-3223
CID: 1507142
Increased cortisol reactivity in response to traumatic reminders in posttraumatic stress disorder (PTSD) [Meeting Abstract]
Elzinga, B; Schmahl, C; Vermetten, E; van Dyck, R; Bremner, JD
ISI:000174980400535
ISSN: 0006-3223
CID: 1507152
Reduced volume of orbitofrontal cortex in major depression
Bremner, J Douglas; Vythilingam, Meena; Vermetten, Eric; Nazeer, Ahsan; Adil, Jahangir; Khan, Sarfraz; Staib, Lawrence H; Charney, Dennis S
BACKGROUND: Functional neuroimaging studies have implicated dysfunction of orbitofrontal cortex in the symptoms of depression, and a recent postmortem study of depressed patients found reduced density of neurons and glia in this area. The purpose of this study was to measure volume of orbitofrontal cortex and other frontal cortical subregions in patients with major depression. METHODS: Magnetic resonance imaging was used to measure volume of the orbitofrontal cortex and other frontal cortical regions in patients with major depression in remission (n = 15) and comparison subjects (n = 20). RESULTS: Patients with depression had a statistically significant 32% smaller medial orbitofrontal (gyrus rectus) cortical volume, without smaller volumes of other frontal regions including anterior cingulate Brodmann's area 24 (subgenual gyrus), anterior cingulate Brodmann's area 32, subcallosal gyrus (Brodmann's area 25), or whole brain volume. The findings were significant after statistically controlling for brain size. CONCLUSIONS: These findings are consistent with smaller orbitofrontal cortical volume in depression.
PMID: 11958777
ISSN: 0006-3223
CID: 1470822
Circuits and systems in stress. II. Applications to neurobiology and treatment in posttraumatic stress disorder
Vermetten, Eric; Bremner, J Douglas
This paper follows the preclinical work on the effects of stress on neurobiological and neuroendocrine systems and provides a comprehensive working model for understanding the pathophysiology of posttraumatic stress disorder (PTSD). Studies of the neurobiology of PTSD in clinical populations are reviewed. Specific brain areas that play an important role in a variety of types of memory are also preferentially affected by stress, including hippocampus, amygdala, medial prefrontal cortex, and cingulate. This review indicates the involvement of these brain systems in the stress response, and in learning and memory. Affected systems in the neural circuitry of PTSD are reviewed (hypothalamic-pituitary-adrenal axis (HPA-axis), catecholaminergic and serotonergic systems, endogenous benzodiazepines, neuropeptides, hypothalamic-pituitary-thyroid axis (HPT-axis), and neuro-immunological alterations) as well as changes found with structural and functional neuroimaging methods. Converging evidence has emphasized the role of early-life trauma in the development of PTSD and other trauma-related disorders. Current and new targets for systems that play a role in the neural circuitry of PTSD are discussed. This material provides a basis for understanding the psychopathology of stress-related disorders, in particular PTSD.
PMID: 12203669
ISSN: 1091-4269
CID: 1470832
Circuits and systems in stress. I. Preclinical studies
Vermetten, Eric; Bremner, J Douglas
This paper reviews the preclinical literature related to the effects of stress on neurobiological and neuroendocrine systems. Preclinical studies of stress provide a comprehensive model for understanding neurobiological alterations in post-traumatic stress disorder (PTSD). The pathophysiology of stress reflects long-standing changes in biological stress response systems and in systems involved in stress responsivity, learning, and memory. The neural circuitry involved includes systems mediating hypothalamic-pituitary-adrenal (HPA) axis, norepinephrine (locus coeruleus), and benzodiazepine, serotonergic, dopaminergic, neuropeptide, and central amino acid systems. These systems interact with brain structures involved in memory, including hippocampus, amygdala, and prefrontal cortex. Stress responses are of vital importance in living organisms; however excessive and/or repeated stress can lead to long-lasting alterations in these circuits and systems involved in stress responsiveness. Intensity and duration of the stressor, and timing of the stressor in life, have strong impact in this respect.
PMID: 12001181
ISSN: 1091-4269
CID: 1470842
Ethics, culture, and psychiatry international perspectives. [Book Review]
Vermetten, E
ISI:000179215600011
ISSN: 1091-4269
CID: 1470922