Hippocampus volume loss due to chronic heavy drinking.

OBJECTIVE: No clear consensus exists regarding the effect of sustained, heavy drinking on hippocampal volume. Our prior work hypothesized significantly lowered total hippocampus volumes in heavy chronically drinking alcohol-dependent (AD) subjects compared with light-drinking nondependent control subjects matched for age and gender. METHOD: Using a series of applicable exclusion criteria culled from previous published studies, we measured hippocampal volumes from MRI scan data acquired on a 3T scanner and subjected those data to automated volume analysis blind to the drinking history. RESULTS: Comparison with AD test (n=8) and non-AD control (n=8) subjects found significant lessening in total (p=0.020) and left (p=0.010) hippocampal volumes with a near-significant difference on the right (p=0.051). Linear regression demonstrated that neither total brain volume nor intracranial volume affected the hippocampus measures. CONCLUSIONS: These data support the view that heavy drinking exerts a unique and selectively injurious effect on the hippocampus. Further study in larger samples must verify this in a search for possible mechanisms of injury.

Hypercortisolism in alcohol dependence and its relation to hippocampal volume loss.

OBJECTIVE: The effects of hypercortisolism on hippocampal volume have not been studied in heavy drinkers. Prior work suggested increased hypothalamic-pituitary-adrenal activity in relation to lowered total hippocampus volume (THV) in heavy-drinking alcohol-dependent (AD) subjects. The present study hypothesized the following: (1) that chronic heavy-drinking subjects would demonstrate significantly higher salivary cortisol concentrations than light-drinking control subjects and (2) that data from the whole sample group would present an inverse relationship between cortisol concentration and THV. METHOD: In carefully selected test and control subject groups matched for age, gender, and ethnicity, we measured salivary cortisol samples at waking, waking + 30 minutes, noon, and 4 PM on the day of magnetic resonance imaging of the brain. We next compared mean cortisol concentrations between groups and assessed the statistical association between cortisol concentration and hippocampus volume measures. RESULTS: Comparison of AD test subjects (n = 8) and non-AD control subjects (n = 8) found significantly higher cortisol concentrations at both morning sampling times (mean [SD] at waking: 0.49 [0.23] vs 0.24 [0.14] microg/dl, p = .012; at waking + 30 minutes: 0.57 [0.37] vs 0.28 [0.11] microg/dl, p = 0.043). Controlling for intracranial volume, there was a significant inverse correlation between waking cortisol concentration and THV (p = .007) in the total sample group (N = 16). However, when analyzed separately, only the control group maintained a strong, inverse association (p = .025). There was no association among the heavy drinking subjects. CONCLUSIONS: These early data in a small sample support the view that chronic heavy drinking results in high salivary cortisol concentrations. What remains unclear is whether hypercortisolism exerts a selectively injurious effect that results in observed hippocampus volume loss. Further research in larger groups using more frequent, monitored sampling must address the following: (1) whether this finding can be replicated and (2) if replicated, whether the lack of an association between low hippocampal volumes and high cortisol levels may indicate an extent of injury beyond which a normal association of the two may be lost.

Cancer survival probability as a function of ego defense (adaptive) mechanisms versus depressive symptoms.

Psychological treatment studies, uncontrolled for ego defense (adaptive) styles, report conflicting survival results. The authors hypothesized that "immature" adaptive styles and frequent depression symptoms would independently predict lower survival rates. This study followed 86 consecutive, mostly late-stage, cancer outpatients for up to 5 years; their survival data were analyzed in relation to the Beck Depression Inventory and the Defense Style Questionnaire scores at study entry. Cumulative survival probability curves contrasted the extreme cases: the most (N=15) to the least (N=21) depressed, and the "immature" (N=14) to the "mature" (N=16) adaptors. Depression did not separate the groups until 30 months after diagnosis. Ego defense style separated them at 8 months; by 18 months, the "immature" survival probability had dropped to 50%, versus 87% for the "mature." At 36 months, survival probabilities were 19% and 57%, respectively. These data direct clinical attention toward ego defense mechanisms as indicators of distress and lowered survival in cancer patients. They further suggest that the maturity of adaptive mechanisms must be controlled for in behavioral-treatment trials of cancer patients.

Aripiprazole in schizophrenia with cocaine dependence: a pilot study.

The debilitation of schizophrenia (SCHZ) worsens markedly with comorbid cocaine dependence (CD) and alcohol abuse. To date, no medications have conclusively demonstrated effects against both SCHZ and CD (SCHZ + CD) simultaneously. Because of its dopamine-modulating properties, we hypothesized that aripiprazole would alleviate cocaine craving in patients with SCHZ + CD. We conducted a prospective, 8-week, open-label trial in poorly compliant SCHZ + CD subjects. Each received aripiprazole as their sole neuroleptic agent at a maximum dose of 15 mg/d. The Brief Psychiatric Rating Scale (BPRS) and the Brief Substance Craving Scale (BSCS) measured psychosis and subjective cocaine and alcohol cravings. Urine tests for cocaine provided data on actual use. Of 10 male subjects entered, 6 (60%) completed the 8-week trial. In those cases, positive urine tests dropped significantly (P < 0.001) after 2 weeks, when aripiprazole had reached steady state. Mean cocaine craving scores declined significantly (P = 0.026) as did mean alcohol craving scores (P = 0.006). Declining psychosis scores were associated with declining cocaine craving (r = 0.87, P < 0.01) and alcohol craving (r = 0.88, P < 0.01), respectively. This experience suggests possible aripiprazole effects in lowering both desire for and the use of cocaine in comorbid SCHZ subjects. These data suggest double-blind, randomized, comparison study in this severely ill, comorbid patient group.

Reduction of affective lability and alcohol use following traumatic brain injury: a clinical pilot study of anti-convulsant medications.

OBJECTIVE: A large and under-recognized sub-set of patients suffer both traumatic brain injury (TBI) and alcohol dependence (ADep). This group appears to use alcohol to self-treat affective and anxiety lability following TBI, resulting in new ADep or worsened prior ADep. This study hypothesized that treatment of such patients with mood-stabilizing medications would relieve post-TBI emotional dysregulation and facilitate reduction in alcohol use. DESIGN: This study reported retrospective medical record data from outpatients in the Substance Abuse Treatment Programme who were treated for labile mood. Medications followed clinical indication and were given in non-blind fashion. METHOD: Subjects included 18 patients who (1) complained of debilitating affective lability following TBI, (2) described drinking alcohol to ease lability symptoms, (3) met DSM-IV criteria for current ADep and (4) were treated with a mood stabilizing medication. RESULTS: During 6 weeks of treatment, 16 (89%) achieved abstinence from alcohol. All but two (14/16 or 88%) also showed improvement in their affective and anxiety symptoms. CONCLUSIONS: These preliminary data are limited by the retrospective collection, clinical impression and non-blinded trial. Nonetheless, the results suggest further investigation of anti-convulsants as potentially useful agents in co-morbid emotional lability and ADep following TBI.

Disulfiram therapy in patients with hepatitis C: a 12-month, controlled, follow-up study.

OBJECTIVE: Although abstinence slows liver injury in alcoholic Hepatitis C (HCV) infected patients, few clinicians prescribe disulfiram because of concern over its hepatotoxic effect. Finding no controlled studies on this effect, we investigated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) patterns in seropositive (HCV[+]) and seronegative (HCV[-]) patients who received supervised disulfiram over 12 months. METHOD: We recorded retrospective aminotransferase measurements from medical records of 26 HCV(+) and 20 HCV(-) cases receiving 1500 mg disulfiram weekly in divided doses. Within groups, paired mean AST and ALT levels at 3, 6, 9 and 12 months were compared with baseline; between groups, nonpaired mean comparisons were used. RESULTS: There were no statistically or clinically significant elevations for the HCV(+) group at any time point. Between-group means were identical at all time points. CONCLUSIONS: Although sample size and retrospective design invite replication, the data suggest that disulfiram may be useful for HCV(+) alcohol-dependent patients in slowing hepatic injury by eliminating alcohol use and thereby removing the purported alcohol-HCV hepatotoxic synergy. It may also help to establish the abstinence criteria necessary to qualify for antiviral treatment. If disulfiram is used in HCV treatment, AST and ALT must be monitored closely.

Developing a brief monitoring procedure for alcohol-dependent liver graft recipients.

To address the occurrence of deaths in later postoperative years among alcohol-dependent liver graft recipients, the authors developed the Brief Active Focused Follow-Up protocol as an instrument for monitoring alcohol use following liver transplant. In this preliminary study, patient receptiveness to its use was tested and its ability to identify patient drinking was noted. Alcohol-dependent liver transplant recipients (N=24) and alcohol-dependent nontransplant patients (N=25) were asked to rate their receptiveness to the Brief Active Focused Follow-Up in three areas. Subjects used a five-point scale for which 5 indicated the highest positive response. Liver transplant recipients responded positively to the Brief Active Focused Follow-Up, with mean responses of 4.92, 4.08, and 4.63 with regard to clarity, usefulness, and ease of completion, respectively. Nontransplant subjects responded similarly, with mean responses of 4.88, 4.12, and 4.52. The two groups were not significantly different in their receptiveness to the Brief Active Focused Follow-Up interview. The Brief Active Focused Follow-Up identified alcohol use within the last 30 days: 8% (N=2 of 24) in the transplant group, and 56% (N=14 of 25) in the nontransplant group. These results suggest that 1) this manualized, brief monitoring technique is well received by alcohol-dependent liver transplant patients, and 2) the Brief Active Focused Follow-Up's "user friendliness" makes it a potentially appropriate instrument for long-term monitoring of alcohol use among alcohol-dependent liver graft recipients.

Adherence to court-ordered disulfiram at fifteen months: a naturalistic study.

Previously, we observed that the presence of a court-mandate doubled adherence to supervised disulfiram treatment over voluntary supervised disulfiram treatment during the initial twelve weeks. To assess persistence, we conducted a naturalistic followup study of adherence at 15 months in 19 voluntary and 17 court-ordered patients from the original groups. Treatment adherence, measured by the percentage of completed disulfiram clinic visits during the study period, was significantly higher in court-ordered subjects: 61.0% vs. 18.2% in the voluntary group (p<.0001). The data suggest that court assistance can exert a significant effect in maintaining adherence. Factors mediating adherence, as well as the effects of adherence on behavior change and abstinence, must be determined through prospective, controlled study.