Faculty Bibliography

Brain imaging studies have mapped out the neural circuitry of posttraumatic stress disorder (PTSD), implicating brain areas sensitive to stress such as the hippocampus. Animal studies show that antidepressants promote hippocampal neurogenesis and block the effects of stress on the hippocampus. We found that treatment of PTSD patients for a year with the serotonin reuptake inhibitor (SSRI) paroxetine resulted in a 5% increase in hippocampal volume and a 35% improvement in verbal declarative memory function. Patients subjectively reported an improvement in cognition and work performance. These studies are consistent with the idea that antidepressants have a beneficial effect on hippocampal function in PTSD patients.

Alterations in the hypothalamic-pituitary-adrenal (HPA) axis and hippocampal-based memory have been associated with posttraumatic stress disorder (PTSD), and the administration of exogenous glucocorticoids has been shown to result in a transient verbal declarative memory impairment in healthy human subjects. The purpose of this study was to assess the effects of the glucocorticoid dexamethasone on verbal declarative memory function in patients with PTSD. Forty-two men and women with (n=14) and without (n=28) PTSD received placebo or dexamethasone (1 and 2 mg on two successive days) in a double-blind, randomized fashion. Declarative memory was assessed with paragraph recall at baseline (day 1) and day 3. There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall related to a relative detrimental effect of dexamethasone on memory function in healthy subjects, but not those with PTSD. These findings are consistent with an altered sensitivity of declarative memory function in PTSD to regulation by glucocorticoids, possibly explainable by alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory.

Several studies have shown deficits in verbal declarative memory function in posttraumatic stress disorder (PTSD). Most of these studies have been performed in men with combat-related PTSD compared with healthy subjects; relatively little is known about memory function in women with abuse-related PTSD, or whether these effects are specific to PTSD or are a nonspecific outcome of exposure to early abuse. The purpose of this study was to assess declarative memory function in women with and without a history of early childhood sexual abuse and PTSD. Forty-three women with and without a history of early childhood sexual abuse and PTSD underwent neuropsychological testing with subtests of the Wechsler Memory Scale--Revised for measurement of verbal and visual memory and subtests of the Wechsler Adult Intelligence Scale for measurement of IQ, and behavioral ratings of PTSD and other psychiatric symptoms. Abused women with PTSD had deficits in verbal declarative memory as measured with the subtests of the Wechsler Memory Scale--Revised compared with women with early abuse without PTSD and nonabused women without PTSD. There were no significant differences in IQ. These findings suggest that early abuse with PTSD is associated with deficits in verbal declarative memory, and that these effects are not related to the nonspecific effects of childhood abuse.

BACKGROUND: Depression has been linked to stress, memory deficits, and hypercortisolemia. However, the relationships between depression, hippocampal structure and function, and cortisol levels are unclear and the effects of antidepressant treatment on the measures are not well studied. METHODS: Whole hippocampal volume, performance on verbal and visual declarative memory function and cortisol status was evaluated in 38 subjects with major depressive disorder (MDD) and 33 healthy subjects. All measures were repeated in a subgroup (n = 22) of depressed patients after successful selective serotonin reuptake inhibitor (SSRI) treatment. RESULTS: Hippocampal volume was not significantly different between patients with untreated MMD and healthy subjects, after controlling for whole brain volume, age and gender. However, depressed subjects had significantly greater deficits in delayed memory and percent retention on the verbal portion of the Wechsler Memory Scale-Revised (WMS-R) compared with healthy subjects, without significant differences in visual memory, attention, vigilance, or distractibility. Baseline plasma or urinary free cortisol (UFC) was not related to either hippocampal volume or memory deficits. Successful treatment with antidepressants did not change hippocampal volume but did result in a significant improvement in memory function and a reduction in UFC excretion. CONCLUSIONS: Medication-free nonelderly depressed outpatients without alcohol dependence or adverse experiences in childhood had normal hippocampal volume. Focal declarative memory deficits in depression supported localized hippocampal dysfunction in depressed patients. Treatment with antidepressants significantly improved memory and depression but did not alter hippocampal volume, suggesting that antidepressants may improve hippocampal function in the absence of detectable structural changes.

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.