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A positron emission tomography study of memories of childhood abuse in borderline personality disorder

Schmahl, Christian G; Vermetten, Eric; Elzinga, Bernet M; Bremner, J Douglas
BACKGROUND: Borderline personality disorder (BPD) is a common psychiatric disorder, which is linked to early stressors in many cases; however, the impact of traumatic events in the etiology of BPD is still unclear. This pilot study was conducted to measure the neural correlates of recall of traumatic memories in women with and without BPD. METHODS: Twenty women with a history of childhood physical or sexual abuse underwent measurement of brain blood flow with positron emission tomography imaging while they listened to scripts describing neutral and personal traumatic abuse events. Brain blood flow during exposure to trauma and neutral scripts was compared between women with and without BPD. RESULTS: Memories of trauma were associated with increases in blood flow in right dorsolateral prefrontal cortex (Brodmann's area [BA] 44 and 45) and with decreased blood flow in left dorsolateral prefrontal cortex (BA 44 and 45) in women without BPD. There was also increased blood flow in right anterior cingulate (BA 24) and left orbitofrontal cortex (BA 11) in women without BPD. Women with BPD failed to activate anterior cingulate gyrus and orbitofrontal cortex. Also, no blood flow changes were seen in dorsolateral prefrontal gyrus in women with BPD. CONCLUSIONS: Dysfunction of dorsolateral and medial prefrontal cortex, including anterior cingulate, seems to be correlated with the recall of traumatic memories in women with BPD. These brain areas might mediate trauma-related symptoms, such as dissociation or affective instability, in patients with BPD.
PMID: 15039006
ISSN: 0006-3223
CID: 1470682

Deficits in hippocampal and anterior cingulate functioning during verbal declarative memory encoding in midlife major depression

Bremner, J Douglas; Vythilingam, Meena; Vermetten, Eric; Vaccarino, Viola; Charney, Dennis S
OBJECTIVE: Prior studies showed that subjects with major depression have deficits in hippocampal-based verbal declarative memory (e.g., recall of a paragraph) and in hippocampal and prefrontal cortical functioning and structure. The purpose of the present study was to assess hippocampal and prefrontal functioning during performance of a verbal declarative memory task in subjects with midlife major depression. METHOD: Subjects with midlife major depression (N=18) and healthy subjects (N=9) underwent positron emission tomography imaging during a control task and verbal encoding of a paragraph. RESULTS: During the verbal memory encoding task the comparison subjects, but not the subjects with depression, activated the right hippocampus and prefrontal cortex (anterior cingulate), as well as the cuneus and cerebellum. CONCLUSIONS: These results are consistent with a failure of hippocampal and anterior cingulate activation in depression, and they support the hypothesis of deficits in hippocampal and anterior cingulate functioning in depression.
PMID: 15056509
ISSN: 0002-953x
CID: 1470672

Neural correlates of the classic color and emotional stroop in women with abuse-related posttraumatic stress disorder

Bremner, J Douglas; Vermetten, Eric; Vythilingam, Meena; Afzal, Nadeem; Schmahl, Christian; Elzinga, Bernet; Charney, Dennis S
BACKGROUND: The anterior cingulate and medial prefrontal cortex play an important role in the inhibition of responses, as measured by the Stroop task, as well as in emotional regulation. Dysfunction of the anterior cingulate/medial prefrontal cortex has been implicated in posttraumatic stress disorder (PTSD). The purpose of this study was to use the Stroop task as a probe of anterior cingulate function in PTSD. METHODS: Women with early childhood sexual abuse-related PTSD (n = 12) and women with abuse but without PTSD (n = 9) underwent positron emission tomographic measurement of cerebral blood flow during exposure to control, color Stroop, and emotional Stroop conditions. RESULTS: Women with abuse with PTSD (but not abused non-PTSD women) had a relative decrease in anterior cingulate blood flow during exposure to the emotional (but not color) classic Stroop task. During the color Stroop there were also relatively greater increases in blood flow in non-PTSD compared with PTSD women in right visual association cortex, cuneus, and right inferior parietal lobule. CONCLUSIONS: These findings add further evidence for dysfunction of a network of brain regions, including anterior cingulate and visual and parietal cortex, in abuse-related PTSD.
PMID: 15013830
ISSN: 0006-3223
CID: 1470692

In reactie op glucocorticoid hypothesis

Vermetten, Eric; Greuze, E; De Kloet, C
ORIGINAL:0009549
ISSN: 0024-8576
CID: 1479162

Disordered sleep in post-traumatic stress disorder : clinical presentation, research findings and implications for treatment

Chapter by: Greuze, Elbert; Vermetten, Eric
in: Sleep psychiatry by Golbin, Alexander Z; Kravitz, Howard M; Keith, Louis G [Eds]
London ; New York : Taylor & Francis, 2004
pp. ?-?
ISBN: 9781842141458
CID: 1479482

General concepts of sleep in relation to psychiatry

Chapter by: Vermetten, Eric; Greuze, Elbert; Mertens, Joost
in: Sleep psychiatry by Golbin, Alexander Z; Kravitz, Howard M; Keith, Louis G [Eds]
London ; New York : Taylor & Francis, 2004
pp. ?-?
ISBN: 9781842141458
CID: 1479492

Posttraumatische Stress Stoornis

Chapter by: Elzinga, Bernet; Vermetten, Eric; Hovens, Hnas
in: Handboek neurobiologische psychiatrie by Hovens, J. E.; Loonen, A; Timmerman, Leo [Eds]
Leusden : De Tijdstroom, 2004
pp. 269-285
ISBN: 9789058980496
CID: 1518612

Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder

Vermetten, Eric; Vythilingam, Meena; Southwick, Steven M; Charney, Dennis S; Bremner, J Douglas
BACKGROUND: Animal studies have shown that stress is associated with damage to the hippocampus, inhibition of neurogenesis, and deficits in hippocampal-based memory dysfunction. Studies in patients with posttraumatic stress disorder (PTSD) found deficits in hippocampal-based declarative verbal memory and smaller hippocampal volume, as measured with magnetic resonance imaging (MRI). Recent preclinical evidence has shown that selective serotonin reuptake inhibitors promote neurogenesis and reverse the effects of stress on hippocampal atrophy. This study assessed the effects of long-term treatment with paroxetine on hippocampal volume and declarative memory performance in PTSD. METHODS: Declarative memory was assessed with the Wechsler Memory Scale-Revised and Selective Reminding Test before and after 9-12 months of treatment with paroxetine in PTSD. Hippocampal volume was measured with MRI. Of the 28 patients who started the protocol, 23 completed the full course of treatment and neuropsychological testing. Twenty patients were able to complete MRI imaging. RESULTS: Patients with PTSD showed a significant improvement in PTSD symptoms with treatment. Treatment resulted in significant improvements in verbal declarative memory and a 4.6% increase in mean hippocampal volume. CONCLUSIONS: These findings suggest that long-term treatment with paroxetine is associated with improvement of verbal declarative memory deficits and an increase in hippocampal volume in PTSD.
PMCID:3233762
PMID: 14512209
ISSN: 0006-3223
CID: 1470712

Higher cortisol levels following exposure to traumatic reminders in abuse-related PTSD

Elzinga, Bernet M; Schmahl, Christian G; Vermetten, Eric; van Dyck, Richard; Bremner, J Douglas
Animal studies have found that prior stressful events can result in increased reactivity in the HPA-axis. However, baseline function of the HPA-axis has typically been normal or decreased in post-traumatic stress disorder (PTSD). The first purpose of this study was to assess cortisol responsivity to traumatic reminders in women with PTSD related to childhood abuse. The second aim was to assess the relationship between stress-induced cortisol levels and neutral and emotional memory. Salivary cortisol levels were measured before, during and after exposure to personalized trauma scripts in abused women with (N=12) and without current PTSD (N=12). Memory for neutral and emotional material was assessed immediately after trauma scripts exposure and 3 days later. PTSD patients had 122% higher cortisol levels during script exposure, 69% higher cortisol levels during recovery, and 60% higher levels in the period leading up to the script exposure compared to controls. PTSD symptoms were highly predictive of cortisol levels during trauma script exposure (r=0.70), but not during periods of rest. Both in PTSD patients and controls, memory consolidation after the trauma scripts was impaired relative to baseline (P<0.001), with no differences between the two groups on memory performance. There was no association between memory performance and cortisol levels. These results are consistent with higher cortisol levels following exposure to traumatic stressors in PTSD.
PMID: 12838270
ISSN: 0006-3223
CID: 1470722

Cortisol response to a cognitive stress challenge in posttraumatic stress disorder (PTSD) related to childhood abuse

Bremner, J D; Vythilingam, M; Vermetten, E; Adil, J; Khan, S; Nazeer, A; Afzal, N; McGlashan, T; Elzinga, B; Anderson, G M; Heninger, G; Southwick, S M; Charney, D S
Preclinical studies show that animals with a history of chronic stress exposure have increased hypothalamic-pituitary-adrenal (HPA) axis reactivity following reexposure to stress. Patients with posttraumatic stress disorder (PTSD) have been found to have normal or decreased function of the HPA axis, however no studies have looked at the HPA response to stress in PTSD. The purpose of this study was to assess cortisol responsivity to a stressful cognitive challenge in patients with PTSD related to childhood abuse. Salivary cortisol levels, as well as heart rate and blood pressure, were measured before and after a stressful cognitive challenge in patients with abuse-related PTSD (N=23) and healthy comparison subjects (N=18). PTSD patients had 61% higher group mean cortisol levels in the time period leading up to the cognitive challenge, and 46% higher cortisol levels during the time period of the cognitive challenge, compared to controls. Both PTSD patients and controls had a similar 66-68% increase in cortisol levels from their own baseline with the cognitive challenge. Following the cognitive challenge, cortisol levels fell in both groups and were similar in PTSD and control groups. PTSD patients appeared to have an increased cortisol response in anticipation of a cognitive challenge relative to controls. Although cortisol has been found to be low at baseline, there does not appear to be an impairment in cortisol response to stressors in PTSD.
PMID: 12812861
ISSN: 0306-4530
CID: 1470732