Faculty Bibliography

The behavioral and psychophysiological alterations during recall in patients with trauma disorders often resemble phenomena that are seen in hypnosis. In studies of emotional recall as well as in neuroimaging studies of hypnotic processes similar brain structures are involved: thalamus, hippocampus, amygdala, medial prefrontal cortex, anterior cingulate cortex. This paper focuses on cross-correlations in traumatic recall and hypnotic responses and reviews correlations between the involvement of brain structures in traumatic recall and processes that are involved in hypnotic responsiveness. To further improve uniformity of results of brain imaging specifically for traumatic recall studies, attention is needed for standardization of hypnotic variables, isolation of the emotional process of interest (state),and assessment of trait-related differences.

BACKGROUND: Major depression has been associated with hypercortisolemia in a subset of patients with depression. Administration of exogenous cortisol and other glucocorticoids to healthy human subjects has been observed to result in a transient impairment in verbal declarative memory function. The purpose of this study was to assess the effects of the glucocorticoid, dexamethasone, on verbal declarative memory function in patients with untreated unipolar major depressive disorder (MDD). METHODS: Fifty two men and women with (n = 28) and without (n = 24) MDD received placebo or dexamethasone (1 mg and 2 mg on 2 successive days) in a double-blind, randomized fashion. Declarative memory was assessed with paragraph recall at baseline (day 1) and day 3. RESULTS: There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall. In the healthy subjects, memory improved from baseline to day 3 with placebo and was unchanged with dexamethasone, whereas in MDD patients memory function showed a pattern of decreasing with placebo and improving with dexamethasone from baseline to day 3. CONCLUSIONS: These findings are consistent with an altered sensitivity of declarative memory function in MDD to regulation by glucocorticoids. Possible explanations of the findings include alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory, or differential sensitivity to dexamethasone-induced reductions in cortisol, in patients with MDD.

Borderline personality disorder (BPD) is a highly prevalent and disabling condition linked to early stressors including traumatic abuse and abandonment. While much work has addressed traumatic events in childhood, little is known about the biological sequelae of BPD including how this disorder may be differentiated from other stress-related disorders such as posttraumatic stress disorder (PTSD). The purpose of this study was to investigate psychophysiological effects of different types of stressful reminders in BPD and in PTSD. Psychophysiological measures including heart rate, skin conductance responses, systolic and diastolic blood pressure in response to standardized neutral scripts, and personalized scripts of traumatic and abandonment situations were compared among subjects with BPD, PTSD and controls, all with a reported history of sexual and/or physical abuse before age 18. Significant script by diagnosis interactions were found for skin conductance and systolic blood pressure. No significant effects were found for diastolic blood pressure or heart rate. In the PTSD group the greatest systolic blood pressure responses were to traumatic scripts, whereas patients with BPD showed a tendency towards greater skin conductance responses to abandonment scripts. Our findings reveal only partially different psychophysiological responses to traumatic and abandonment scripts in PTSD and BPD. A divergence in pathophysiology in these two disorders is suggested that may be linked to childhood trauma. However, this interpretation must be tested in a larger population.

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.

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.

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.