Biomedical subjects

D S Charney

Publications and source records attributed to D S Charney.

At least 19 recordsLinked to original sources

PubMed1996

Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects.

The dopamine hypothesis of schizophrenia proposes that hyperactivity of dopaminergic transmission is associated with this illness, but direct observation of abnormalities of dopamine function in schizophrenia has remained elusive. We used a newly developed single photon emission computerized tomography method to measure amphetamine-induced dopamine release in the striatum of fifteen patients with schizophrenia and fifteen healthy controls. Amphetamine-induced dopamine release was estimated by the amphetamine-induced reduction in dopamine D2 receptor availability, measured as the binding potential of the specific D2 receptor radiotracer [123I] (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl) methyl]benzamide ([123I]IBZM). The amphetamine-induced decrease in [123I]IBZM binding potential was significantly greater in the schizophrenic group (-19.5 +/- 4.1%) compared with the control group (-7.6 +/- 2.1%). In the schizophrenic group, elevated amphetamine effect on [123I]IBZM binding potential was associated with emergence or worsening of positive psychotic symptoms. This result suggests that psychotic symptoms elicited in this experimental setting in schizophrenic patients are associated with exaggerated stimulation of dopaminergic transmission. Such an observation would be compatible with an abnormal responsiveness of dopaminergic neurons in schizophrenia.

Adult↗

PubMed1996

Effects of rapid tryptophan depletion in patients with seasonal affective disorder in remission after light therapy.

BACKGROUND: Previous studies show that rapid tryptophan depletion reverses the effects of therapy with serotonergic, but not noradrenergic, antidepressant drugs in patients with remitted nonseasonal depression. The objective of this study was to investigate the effects of rapid tryptophan depletion in patients with seasonal affective disorder (SAD) that was in clinical remission after light therapy. METHODS: Patients who met DSM-III-R criteria for recurrent major depressive episodes, seasonal (winter) pattern (equivalent to SAD), were treated with a standard course of light therapy. Ten patients with SAD in clinical remission after light therapy underwent rapid tryptophan depletion in a placebo-controlled, double-blind crossover study. Behavioral ratings and plasma tryptophan levels were obtained before and after rapid tryptophan depletion. RESULTS: Plasma total and free tryptophan levels were significantly reduced to 20% of normal levels by the rapid tryptophan depletion. The depletion session resulted in significant increases in depression scores compared with the sham control session. Six of 10 patients had a clinically significant relapse of their depression following the tryptophan depletion session. CONCLUSIONS: Rapid tryptophan depletion appears to reverse the antidepressant effect of bright light therapy in patients with SAD. This suggests that the therapeutic effects of bright light in SAD may involve a serotonergic mechanism.

Adult↗

PubMed1996

Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression.

BACKGROUND: Most hypotheses of the therapeutic mechanism of action of antidepressant drugs have focused on the role of the monoamines. We examined the effect of catecholamine depletion on antidepressant-induced remission. METHOD: The tyrosine hydroxylase inhibitor alpha-methylparatyrosine and the antihistamine diphenhydramine hydrochloride were administered, during separate test sessions, to depressed patients in remission maintained with either norepinephrine reuptake inhibitors (desipramine [n = 7] or mazindol [n = 2]) or serotonin reuptake inhibitors (fluoxetine hydrochloride [n = 9] or sertraline hydrochloride [n = 1]). Because of considerable sedation associated with alpha-methylparatyrosine testing, diphenhydramine was used as an active control rather than an inactive placebo. The effects of alpha-methylparatyrosine and diphenhydramine on depression, anxiety, and plasma catecholamine metabolites were assessed. RESULTS: alpha-Methylparatyrosine produced similar significant decreases in plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels in the treatment groups. alpha-Methylparatyrosine produced a robust increase in depressive symptoms on the Hamilton Depression Rating Scale, including depressed mood, decreased concentration, anhedonia, loss of interest, and feelings of worthlessness, helplessness, and hopelessness, in the desipramine-mazindol but not in the fluoxetine-sertraline group. Diphenhydramine had no effects on mood in either treatment group. CONCLUSIONS: The therapeutic effects of norepinephrine reuptake inhibitors, but not serotonin reuptake inhibitors, are reversed by catecholamine depletion. Considered with previous reports that serotonin depletion produces depressive relapses in patients in remission maintained with serotonin reuptake inhibitors, but not norepinephrine reuptake inhibitors, these findings suggest that antidepressants may not work via a single monoamine-related mechanism.

1-Naphthylamine↗

PubMed1996

Noradrenergic mechanisms in stress and anxiety: I. Preclinical studies.

There is considerable preclinical evidence for a relationship between noradrenergic brain systems and behaviors associated with stress and anxiety. The majority of noradrenergic neurons are located in the locus coeruleus (pons), with projections throughout the cerebral cortex and multiple subcortical areas, including hippocampus, amygdala, thalamus, and hypothalamus. This neuroanatomical formation of the noradrenergic system makes it well suited to rapidly and globally modulate brain function in response to changes in the environment, as occurs during the presentation of stressors. Stress exposure is associated with an increase in firing of the locus coeruleus and with associated increased release and turnover of norepinephrine in brain regions which receive noradrenergic innervation. Increased firing of the locus coeruleus is also associated with behavioral manifestations of fear, such as arched back and piloerection in the cat. Exposure to chronic stress results in long-term alterations in locus coeruleus firing and norepinephrine release in target brain regions of the locus coeruleus. Norepinephrine is also involved in neural mechanisms such as sensitization and fear conditioning, which are associated with stress. These findings are relevant to an understanding of psychiatric disorders, such as panic disorder and post-traumatic stress disorder (PTSD), the symptoms of which have been hypothesized to be related to alterations in noradrenergic function.

Adrenergic Fibers↗

PubMed1996

Noradrenergic mechanisms in stress and anxiety: II. Clinical studies.

Studies in animals have shown a relationship between alterations in noradrenergic brain system function and behaviors of anxiety and fear. These findings have generated the hypothesis that the symptoms seen in patients with anxiety disorders may be related to alterations in noradrenergic function. A number of clinical studies have tested this hypothesis, utilizing measures of catecholaminergic function such as heart rate and blood pressure, measurement of norepinephrine and its metabolites in urine and plasma and adrenergic receptor binding in platelets, as well as pharmacological challenge to the noradrenergic system. Acute stressors, such as public speaking, have been associated with an increase in heart rate, blood pressure, and norepinephrine and its metabolites in urine and plasma. Findings in patients with panic disorder at baseline related to heart rate, blood pressure, baseline norepinephrine and its metabolites, and platelet adrenergic receptors have been mixed, while the most consistent findings have been blunted growth hormone response to clonidine and increased 3-methoxy-4-hydroxy-phenylethylene-glucol (MHPG) and anxiety following stimulation of the noradrenergic system with yohimbine. Baseline measures of noradrenergic function in patients with posttraumatic stress disorder (PTSD) have also been mixed, while an increased heart, blood pressure and norepinephrine response to traumatic reminders, as well as increased behavioral (as well as different brain metabolic) response to yohimbine, have been found in PTSD. There are fewer studies of noradrenergic function in the other anxiety disorders, and the findings there have not been consistent. These studies provide evidence for increased noradrenergic responsiveness in panic disorder and PTSD, although there does not appear to be an alteration in baseline noradrenergic function in these patients.

Adrenergic Fibers↗

PubMed1996

Effects of alpha-methyl-para-tyrosine (AMPT) in drug-free depressed patients.

A variety of biologic studies have demonstrated abnormal regulation of the norepinephrine (NE) system in patients with major depression, suggesting a role for NE in the etiology of depression. Brain NE and dopamine levels can be rapidly reduced by blocking synthesis with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). In the current investigation, AMPT was administered to drug-free depressed patients to evaluate the effect on mood of diminished catecholamine levels. Seventeen drug-free patients meeting DSM-III-R criteria for major depressive episode were tested with AMPT and an active placebo control, diphenhydramine. Testing was accomplished in a double-blind, crossover fashion, with random assignment to test conditions. Each test included baseline evaluation, 2 days with administration of either AMPT or diphenhydramine, and a follow-up day. Diphenhydramine was used as an active control because of the significant sedation associated with AMPT. Behavioral ratings, including visual analogue scales for a variety of feeling states, the Hamilton Depression Rating Scale (HDRS), and plasma for 3-methoxy-4-hydroxyphenelethyleneglycol (MPHG) and homovanillic acid (HVA) levels, were obtained. AMPT significantly reduced plasma HVA by 70% and MHPG by 50%, but it had no significant effects on the HDRS. AMPT also significantly increased visual analogue ratings of "tired" and decreased ratings of "energetic." Diphenhydramine significantly decreased HDRS scores, but the change was small and was not clinically apparent. The lack of AMPT effects on depressed mood, in conjunction with a prior report that large reductions in plasma tryptophan do not systematically alter depressed mood, indicate that monoamine deficiency by itself is insufficient explanation of the cause of depression. The role of the noradrenergic system needs to be considered in relationship to the many other neurobiologic factors that could be involved in the pathophysiology of depression.

Adult↗

PubMed1996

Seasonal variation in neuroendocrine and mood responses to i.v. L-tryptophan in depressed patients and healthy subjects.

Seasonality of mood disorders might involve alterations in the rhythmicity of serotonin [5-HT] function. We examined seasonal effects on the neuroendocrine and mood responses to L-tryptophan (L-TRP) in depressed patients and healthy subjects. In this study, 126 drug-free patients with DSM-III-R major depression and 58 healthy subjects received in i.v. infusion of L-TRP. Serum prolactin (PRL) and plasma tryptophan levels were measured. Mood was assessed with visual analogue scales. Cosinor analysis revealed seasonal variation in peak change (delta) PRL and baseline tryptophan levels in the combined depressed and in unipolar, nonmelancholic, and nonpsychotic patients. Peak delta PRL and tryptophan levels were inversely correlated in combined depressed and unipolar patients. Seasonality was more evident in female than in male patients. These data support previous evidence that 5-HT function is abnormal in depression and further suggest a seasonal variability of such abnormalities that is absent in healthy subjects.

Adult↗

PubMed1996

The revised monoamine theory of depression: a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans.

The original hypothesis that brain monoamine systems have a primary direct role in depression has been through several modifications during the past 30 years. In order to test this hypothesis and more fully characterize the role of serotonin and catecholamines in the pathophysiology of depression and the mechanism of action of antidepressant treatments, our research group has conducted a series of studies evaluating monoamine depletion induced brief clinical relapse following different types of antidepressant treatment of depressed patients. We have also studied the effects of monoamine depletion (SD) on depressive symptoms in depressed and recovered patients off medication and in healthy controls. Relapse to serotonin depletion or to catecholamine depletion (CD) was found to be specific to the type of antidepressant treatment, i.e., patients responding to selective serotonin reuptake inhibilitors relapsed more frequently following SD than CD and patients responding to selective catecholamine reuptake inhibitors relapsed more frequently following CD than SD. Neither CD or SD increased depressive symptoms in clinically ill patients off treatment, or produced clinical depression in normal controls. However, recovered patients with a prior history of depression had a relapse with SD. Patients with obsessive compulsive disorder who improved on SSRI treatment, did not have an increase in OCD symptoms but those with prior depressive symptoms did have an increase in depressive symptoms with SD. The findings that relapse during treatment is specific to the type of treatment and type of depletion, that neither SD or CD produced an increase in clinical depression in healthy controls or depressed patients off medication, and that recovered patients off medication have a return of symptoms following SD, forces a major revision of the current monoamine theories of depression. The new hypothesis most consistent with this new data is that the monoamine systems are only modulating "other" brain neurobiologic systems which have a more primary role in depression. The modulatory or "antidepressant" function of the monoamine systems appears to be only necessary during drug induced recovery and the maintenance of recovery after a prior episode. These clinical studies point to the need for more fundamental research on the interaction of monoamine systems with other brain neurobiologic mechanisms relevant to depression.

Adrenergic Uptake Inhibitors↗

PubMed1996

Exaggerated acoustic startle reflex in Gulf War veterans with posttraumatic stress disorder.

OBJECTIVE: Exaggerated startle reflex is reputed to be one of the cardinal symptoms of posttraumatic stress disorder (PTSD). The goal of this study was to assess the magnitude of the acoustic startle reflex in Gulf War veterans with PTSD. METHOD: The eye-blink component of the startle reflex was measured in response to six blocks of pseudorandomized 40-msec white noise bursts of varying intensities (90, 96, 102, 108, and 114 dB) in 10 Gulf War veterans with PTSD, seven Gulf War veterans without PTSD, and 15 civilian subjects without PTSD. RESULTS: The magnitude of the first startle response, as well as the magnitude of startle response averaged across blocks of testing, was significantly greater in Gulf War veterans with PTSD than in veteran and civilian comparison groups. CONCLUSIONS: Consistent with some clinical studies investigating the startle response in Vietnam veterans with PTSD, this investigation provides evidence for exaggerated startle response in this disorder. Preclinical studies of shock sensitization of the startle response suggest that the higher levels of startle response seen in the PTSD subjects may reflect a sensitization of the fear/alarm response created by the stress of combat trauma.

Acoustic Stimulation↗

PubMed1996

Serotonergic and noradrenergic dysregulation in alcoholism: m-chlorophenylpiperazine and yohimbine effects in recently detoxified alcoholics and healthy comparison subjects.

OBJECTIVE: This study compared serotonergic (5-HT) and noradrenergic reactivity in recently detoxified alcoholic patients and healthy comparison subjects. METHOD: Participants were 22 male inpatients who met DSM-III-R criteria for alcohol dependence and who were abstinent for 12-26 days and 13 male healthy comparison subjects. Subjects completed 3 days of testing over 2 weeks under double-blind conditions that involved the intravenous infusions of m-chlorophenylpiperazine (mCPP), yohimbine, or a saline placebo. Drug effects on mood, physiologic responses, and plasma levels of cortisol, prolactin, and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured. RESULTS: Both mCPP and yohimbine infusion increased nervousness, vital signs, and plasma cortisol, prolactin, and MHPG levels relative to placebo Cortisol responses to mCPP were blunted in the alcoholic patients relative to the comparison subjects. Cortisol and prolactin responses to yohimbine were greater in the alcoholic patients, whereas their pulse increases after yohimbine infusion were blunted. No group differences emerged in MHPG, nervousness, or blood pressure responses to either drug. CONCLUSIONS: This study documents persistent alterations in neuroendocrine responsivity of both 5-HT and noradrenergic systems in alcoholic patients after detoxification. Blunted cortisol responses to mCPP in these recently detoxified patients may reflect reductions in 5-HT2 receptor function. The absence of altered MHPG responses to yohimbine in the alcoholic patients suggests that presynaptic noradrenergic responsivity is not persistently altered in these patients. In contrast, the enhanced cortisol responses and reduced pulse responses to yohimbine in alcoholic patients may reflect down-regulation of postsynaptic noradrenergic receptors.

Adult↗

PubMed1996

Chronic PTSD in Vietnam combat veterans: course of illness and substance abuse.

OBJECTIVE: The purpose of this study was to measure the longitudinal course of specific symptoms of posttraumatic stress disorder (PTSD) and related symptoms of alcohol and substance abuse and the effects of alcohol and substances on the symptoms of PTSD. METHOD: A structured interview for the assessment of PTSD and alcohol and substance abuse, as well as other factors such as life stressors and treatment, was administered to 61 Vietnam combat veterans with PTSD. RESULTS: Onset of symptoms typically occurred at the time of exposure to combat trauma in Vietnam and increased rapidly during the first few years after the war. Symptoms plateaued within a few years after the war, following which the disorder became chronic and unremitting. Hyperarousal symptoms such as feeling on guard and feeling easily startled developed first, followed by avoidant symptoms and finally by symptoms from the intrusive cluster. The onset of alcohol and substance abuse typically was associated with the onset of symptoms of PTSD, and the increase in use paralleled the increase of symptoms. Patients reported a tendency for alcohol, marijuana, heroin, and benzodiazepines to make PTSD symptoms better, while cocaine made symptoms in the hyperarousal category worse. There was no relationship between treatment interventions and the natural course of PTSD. CONCLUSIONS: These findings suggest that symptoms of PTSD begin soon after exposure to trauma, that hyperarousal symptoms are the first symptoms to occur, that the natural course of alcohol and substance abuse parallels that of PTSD, and that specific substances have specific effects on PTSD symptoms.

Alcoholism↗

PubMed1996

Neural mechanisms in dissociative amnesia for childhood abuse: relevance to the current controversy surrounding the "false memory syndrome".

OBJECTIVE: There is considerable controversy about delayed recall of childhood abuse. Some authors have claimed that there is a "false memory syndrome," in which therapists suggest to patients events that never actually occurred. These authors point to findings that suggest that memory traces are susceptible to modification. The purpose of this paper is to review the literature on the potential vulnerability of memory traces to modification and on the effects of stress on the neurobiology of memory. METHOD: The authors review findings on mechanisms involved in normal memory function, effects of stress on memory in normal persons, children's memory of stressful events, and alterations of memory function in psychiatric disorders. The effects of stress on specific brain regions and brain chemistry are also examined. RESULTS: Neuropeptides and neurotransmitters released during stress can modulate memory function, acting at the level of the hippocampus, amygdala, and other brain regions involved in memory. Such release may interfere with the laying down of memory traces for incidents of childhood abuse. Also, childhood abuse may result in long-term alterations in the function of these neuromodulators. CONCLUSIONS: John Nemiah pointed out several years ago that alterations in memory in the form of dissociative amnesia are an important part of exposure to traumatic stressors, such as childhood abuse. The studies reviewed here show that extreme stress has long-term effects on memory. These findings may provide a model for understanding the mechanisms involved in dissociative amnesia, as well as a rationale for phenomena such as delayed recall of childhood abuse.

Amnesia↗

PubMed1996

Preliminary evidence of an association between sensorimotor gating and distractibility in psychosis.

Impaired sensory gating and increased distractibility are key information-processing deficits in schizophrenia. This study evaluated the hypothesis that distractibility is related to reduced sensory gating. Performance on vigilance and distractibility tasks was compared to prepulse inhibition (PPI) of the acoustic startle reflex in 28 stable chronic psychotic patients. PPI significantly correlated with distractibility task score on a continuous performance test and lateralized attention on the Posner test. These results suggest that performance on tests of distractibility and lateralized attention are related to a measure of sensory gating.

Acoustic Stimulation↗

PubMed1996

[123I] beta-CIT/SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi-Parkinson's disease.

We have used in vivo single-photon emission computed tomography (SPECT) of the dopamine transporter with 2 beta-carboxymethoxy-3 beta-(4-iodophenyl)tropane ([123I] beta-CIT) to investigate striatal dopamine transporter loss in patients with early Parkinson's disease (PD). Striatal uptake of ([123I] beta-CIT was compared in eight early-PD patients with exclusively hemi-parkinsonism and eight age- and sex-matched healthy subjects. [123I] beta-CIT striatal uptake was reduced by approximately 53% contralateral and by 38% ipsilateral to the clinically symptomatic side in the hemi-PD patients, compared with the mean striatal uptake in age- and sex-matched healthy subjects. The relative reduction in [123I] beta-CIT uptake in the hemi-PD patients was greater in the putamen than in the caudate. These data demonstrate that SPECT imaging of the dopamine transporter with [123I] beta-CIT can identify patients with PD at the onset of motor symptoms and suggest that this technique also may be useful in identifying individuals with developing dopaminergic pathology before onset of motor symptoms.

Adult↗

PubMed1996

Continuous intravenous infusion of iodine-123-IBZM for SPECT determination of human brain dopamine receptor occupancy by antipsychotic agent RWJ-37796.

UNLABELLED: PET has shown that dose-dependent in vivo occupancy of dopamine receptors by antipsychotic drugs is associated with clinical response to antipsychotic agents and the production of extrapyramidal side effects. We studied the feasibility of administering [123I]IBZM as a bolus plus continuous infusion over 8 hr to achieve unchanging regional brain activity levels, and the application of [123I]IBZM continuous infusion to examine the effects of the antipsychotic agent RWJ-37796, on striatal activity in humans. METHODS: Five healthy male subjects received a bolus of [123I]IBZM followed by a continuous infusion at a bolus (mCi):infusion (mCi/hr) ratio of 6:1. Serial SPECT images were obtained every 2-3 min for a total of 8 hr with a 1-2 hr break in the scanning session. Serial venous blood samples were obtained every 30 min for the duration of the study. All five subjects achieved unchanging plasma [123I]IBZM and striatal brain-activity levels over the 300-420 min postinitiation of tracer infusion. Two subjects achieved flat brain time-activity curves later than the others, suggesting the bolus-to-infusion ratio was slightly high. An additional six healthy male subjects received a similar bolus plus constant infusion of [123I]IBZM. RWJ-37796 (0.04 mg/kg) was administered intravenously 157 +/- 13.7 min after the initiation of [123I]IBZM infusion. Serial SPECT brain images, serum prolactin and extrapyramidal side effect ratings were obtained for an additional 330 min. RESULTS: All six subjects demonstrated rapid and marked reduction of striatal activity following RWJ-37796 without return of striatal activity to baseline levels over the 5.5 hr of continued [123I]IBZM administration. Estimated receptor occupancy by RWJ-37796 was 57% +/- 5% (range 47%-67%). Prolactin was only transiently increased in all subjects by 1054% +/- 1084% over baseline. One subject experienced moderate extrapyramidal symptoms (akasthisia) during RWJ-37796 injection. CONCLUSION: SPECT imaging during continuous [123I]IBZM infusion provides a powerful within-scan method for determining both temporal binding characteristics and receptor occupancy of striatal dopamine receptors by antipsychotic agents.

Adult↗

PubMed1996

Reproducibility of iodine-123-beta-CIT SPECT brain measurement of dopamine transporters.

UNLABELLED: Iodine-123-beta-CIT has been used as a probe of monoamine transporters in human and nonhuman primates utilizing SPECT. To assess the utility of this tracer for measurement of striatal dopamine (DA) transporters in human disease, we studied the test/retest variability and reliability of SPECT measures obtained after bolus injection of [123I]beta-CIT 0-7 hr (Day 1) and 18-24 hr (Day 2) after administration. METHODS: For the Day 2 study, seven healthy humans (4 men, 3 women; aged 19-74 yr) participated in two [123I]beta-CIT SPECT scans separated by 7-14 days. Subjects were imaged at 18, 21 and 24 hr postinjection of 370 MBq (10 mCi) [123I]beta-CIT. Two outcome measures were evaluated: (a) the ratio of specific striatal (activity associated with DA transporter binding) to nondisplaceable uptake, also designated V"3 and (b) the total, specific striatal uptake (%SSU) expressed as a percentage of injected radiotracer dose. Test/retest variability associated with V"3 and total specific striatal uptakes were compared for scans acquired at 18, 21 and 24 hr with 24 hr only postinjection scans. For the Day 1 study, three of the subjects participated in two kinetic studies of [123I]beta-CIT uptake. A three-compartment model was used for determination of konBmax and binding potential (BP = Bmax/Kd) and the reproducibility of the measures assessed. RESULTS: In the Day 2 study, both outcome measures demonstrated excellent test/retest reproducibility with variability of V"3 = 6.8 +/- 6.8% and percent striatal uptake = 6.6 +/- 4.3% using data acquired from all time points. There were no significant differences in variability for the two outcome measures obtained. The intraclass correlation coefficient rho was 0.96 and 0.98 for V"3 and %SSU, respectively. Considering the 24 hr postinjection scans only, there was a nonsignificant trend toward lower test/retest variability for %SSU compared to V"3 (6.6 +/- 4.2% and 12.8 +/- 9.0%, respectively). The test/retest variability for the Day 1 kinetic modeling data showed marked differences depending on the fitting strategy and assumptions about the reversibility of [123I]beta-CIT in striatum. Using a model that assumed a low, fixed value for reversible striatal binding (k4) produced low variability (12 +/- 9%). CONCLUSION: These data suggest that SPECT imaging performed at either 0-7 hr or 18-24 hr after [123I]beta-CIT injection permits calculation of reliable and reproducible measures of dopamine transporters and supports the feasibility of using [123I]beta-CIT in serial evaluation of human neuropsychiatric disease.

Adult↗

PubMed1996

The biological basis of panic disorder.

Research over the past decade has advanced our understanding of the neuroanatomical and neurochemical substrates of anxiety disorders, including panic disorder. For example, the results of challenge studies with a variety of panicogenic agents that operate by diverse pharmacologic mechanisms have suggested a network model of panic involving dysregulation of multiple neuronal systems. Genetic analyses are consistent with a heritable predisposition, or "panic diathesis," that confers an increased susceptibility to pharmacologic challenge, even in subjects with no overt history of panic disorder. Functional imaging studies confirm preclinical investigations of the anatomical basis of anxiety and provide further evidence for a network of related brain regions mediating the genesis of anxious and fearful behaviors, including panic attacks. Taken together, this research offers a theoretical framework for the ongoing development of improved diagnostic and treatment options.

Brain↗

PubMed1995

Deficits in short-term memory in adult survivors of childhood abuse.

Exposure to stress has been associated with alterations in memory function, and we have previously shown deficits in short-term verbal memory in patients with a history of exposure to the stress of combat and the diagnosis of posttraumatic stress disorder (PTSD). Few studies of any kind have focused on adult survivors of childhood physical and sexual abuse. The purpose of this study was to investigate short-term memory function in adult survivors of childhood abuse. Adult survivors of severe childhood physical and sexual abuse (n = 21), as defined by specific criteria derived from the Early Trauma Inventory (ETI), who were presenting for psychiatric treatment were compared with healthy subjects (n = 20) matched for several variables including age, alcohol abuse, and years of education. All subjects were assessed with the Wechsler Memory Scale (WMS) Logical (verbal memory) and Figural (visual memory) components, the Verbal and Visual Selective Reminding Tests (SRT), and the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Adult survivors of childhood abuse had significantly lower scores on the WMS Logical component for immediate and delayed recall in comparison to normal subjects, with no difference in visual memory, as measured by the WMS or the SRT, or IQ, as measured by the WAIS-R. Deficits in verbal memory, as measured by the WMS, were associated with the severity of abuse, as measured by a composite score on the ETI. Our findings suggest that childhood physical and sexual abuse is associated with long-term deficits in verbal short-term memory. These findings of specific deficits in verbal (and not visual) memory, with no change in IQ, are similar to the pattern of deficits that we have previously found in patients with combat-related PTSD.

Adult↗