Pathological gambling. A psychobiological study.

We investigated psychobiological substrates of pathological gambling by measuring levels of norepinephrine, monoamine metabolites, and peptides in cerebrospinal fluid, plasma, and urine. Pathological gamblers had a significantly higher centrally produced fraction of cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenylglycol as well as significantly greater urinary outputs of norepinephrine than controls. These results suggest that pathological gamblers may have a functional disturbance of the noradrenergic system. This system has been postulated to underlie sensation-seeking behaviors, aspects of which are thought to be abnormal among pathological gamblers.

Hypothalamic-pituitary-adrenal axis functioning and cerebrospinal fluid corticotropin releasing hormone and corticotropin levels in alcoholics after recent and long-term abstinence.

We assessed the plasma corticotropin (adrenocorticotropic hormone) and cortisol responses to ovine corticotropin releasing hormone (oCRH) and the cerebrospinal fluid levels of CRH and corticotropin in alcoholics at various durations of abstinence and compared these variables with age-equivalent controls. Alcoholics who were tested at 1 week of abstinence (n = 11) demonstrated a significantly attenuated corticotropin response to oCRH compared with their response at 3 weeks of abstinence. Nine of these alcoholic patients demonstrated a significantly blunted corticotropin response at both 1 and 3 weeks of abstinence compared with controls (n = 15). A markedly exaggerated corticotropin response to oCRH, associated with tachycardia, was exhibited by 2 alcoholics at both 1 and 3 weeks of abstinence. Alcoholics who were abstinent greater than 3 weeks did not differ in their response to oCRH compared with controls. Controls demonstrated a significant inverse correlation between baseline cortisol levels and the cortisol response to oCRH. This correlation was not evident in any of the alcoholic groups, including those patients who were abstinent greater than 6 months. There was a positive correlation between cerebrospinal fluid concentrations of CRH and corticotropin in all patient groups. These findings indicated that alcoholics have significantly altered hypothalamic-pituitary-adrenal axis functioning up to 3 weeks following the cessation of drinking, with a more subtle impairment present for greater than 6 months following abstinence.

Disturbances of hypothalamic-pituitary-adrenal axis functioning during ethanol withdrawal in six men.

OBJECTIVE: Excessive exposure to glucocorticoids can have neurotoxic effects. The behavioral, cognitive, and neurochemical changes observed following the cessation of heavy drinking, therefore, may be associated with disturbances of the hypothalamic-pituitary-adrenal (HPA) axis. To investigate HPA axis disturbances during the ethanol withdrawal syndrome, the authors examined diurnal changes in plasma cortisol in six alcohol-dependent men following the abrupt discontinuation of alcohol intake. METHOD: Plasma cortisol concentrations were quantified every 30 minutes for 24 hours in the early stage (1 day after cessation) and the middle to late stage (3 days after cessation) of the ethanol withdrawal syndrome as well as after the resolution of acute symptoms (8 days or more after cessation). RESULTS: Plasma cortisol concentrations were almost twice as high during acute withdrawal as they were following recovery. The duration of the cortisol diurnal cycle on the first day of withdrawal was negatively correlated with the severity of withdrawal. CONCLUSIONS: There is a marked activation of the HPA axis associated with the ethanol withdrawal syndrome. The authors hypothesize that this activation may account for some of the signs and symptoms of acute and subacute withdrawal. They discuss the potential long-term physiological effects of the episodic increases in cortisol associated with repeated episodes of ethanol withdrawal. The alterations in cortisol rhythmicity during early withdrawal may also have clinical implications.

Experience-dependent neuropsychological recovery and the treatment of alcoholism.

Accumulating research has shown that some cognitive deficits in recently abstinent alcoholics (e.g., cognitive flexibility, acquisition of novel skills) improve only with remediation in contrast to the spontaneous, time-dependent rebound seen for other tasks. In principle, this facilitated or experience-dependent recovery should enhance acquisition of the content of alcoholism treatment programs, but this relationship has yet to be tested empirically; previous research assessed recovery using only neuropsychological tasks presented by an experimenter. The current investigation focused on treatment-relevant remediation (acquisition of the content of a relapse-prevention [RP] program) using tasks administered by self-guided workbooks. Four groups of male alcoholics received pre- and posttesting. Between the two testing sessions, the groups received neuropsychological remediation tasks (n = 15), ecologically relevant tasks (n = 15), attention-placebo tasks (n = 16), or no intervention (n = 15). Results showed that exposure to both types of remediation produced significant cognitive recovery, with skills transferring to posttest neuropsychological measures and RP acquisition. Hence, cognitive remediation may facilitate alcoholism treatment.

Empirical modeling of an alcohol expectancy memory network using multidimensional scaling.

Risk-related antecedent variables can be linked to later alcohol consumption by memory processes, and alcohol expectancies may be one relevant memory content. To advance research in this area, it would be useful to apply current memory models such as semantic network theory to explain drinking decision processes. We used multidimensional scaling (MDS) to empirically model a preliminary alcohol expectancy semantic network, from which a theoretical account of drinking decision making was generated. Subanalyses (PREFMAP) showed how individuals with differing alcohol consumption histories may have had different association pathways within the expectancy network. These pathways may have, in turn influenced future drinking levels and behaviors while the person was under the influence of alcohol. All individuals associated positive/prosocial effects with drinking, but heavier drinkers indicated arousing effects as their highest probability associates, whereas light drinkers expected sedation. An important early step in this MDS modeling process is the determination of iso-meaning expectancy adjective groups, which correspond to theoretical network nodes.

Alcohol expectancies and male sexuality: review and implications for sex therapy.

Psychological expectancies regarding the use of alcohol may often be more powerful than pharmacological effects. Studies focusing on alcohol expectancies and the male sexual response are reviewed. Males who believe they consumed alcohol show increased arousal to deviant stimuli (rape, violent erotica) compared to males who are told to expect no alcohol. Sex guilt may mediate these effects. This research, and widely held cultural beliefs that portray alcohol as an aphrodisiac, may lead many males to employ alcohol as a "cure" for sexual dysfunctions. Suggestions are included to enable sex therapists to uncover and dispel these myths in their male clients.

Influence of thiamine deficiency on the response to ethanol in two inbred rat strains.

We investigated whether thiamine deficiency (TD), a frequent concomitant of chronic alcoholism, differentially modifies the response to ethanol in two inbred rat strains with highly different genetic susceptibilities to development of TD encephalopathy. Ethanol-induced (3 g/kg i.p.) behavioral impairment and hypothermia were studied after 2, 5 and 7 weeks of TD and after 6 weeks of repletion on normal diet. Controls of the M520/N (TD-sensitive) strain metabolized ethanol more rapidly, had a greater liver to body weight ratio, greater total body water, earlier and lower peak blood ethanol concentrations (BEC), diminished area under the BEC curve and lesser behavioral impairment and hypothermia (even at equivalent BEC values) than those of the F344/N (TD-resistant) strain. In both strains, TD resulted in reduced ethanol metabolic rate and liver to body weight ratio and equivalent ethanol-induced hypothermia and behavioral impairment at lower BEC. Lower and delayed peak BEC and unchanged area under the BEC curve suggest an increased volume of ethanol distribution during TD. Recovery appeared complete after 6 weeks of normal diet. Both strains lost an equivalent proportion of body weight during TD but M520/N rats had lesser decrements in ethanol metabolic rate, had greater reductions in liver weight, peak BEC and baseline body temperature and developed overt encephalopathy whereas F344/N rats did not. Therefore, in the chronic alcoholic, TD may modify ethanol's effects via pharmacokinetic and pharmacodynamic mechanisms. Relatively high ethanol tolerance of the strain with a genetic predisposition to TD encephalopathy is consistent with the hypothesized role of this avitaminosis in the pharmacogenetics of alcoholism.

Treatment of alcoholic organic brain syndrome with the serotonin reuptake inhibitor fluvoxamine: a preliminary study.

The chronic effects of fluvoxamine (200 mg per day for 4 weeks) were studied in ten alcoholic organic brain syndrome patients in a double-blind cross-over design. Complete neuropsychological evaluation was performed as well as measurement of neurochemical changes in CSF. Fluvoxamine produced a small but significant improvement in memory performance. An analysis of fluvoxamine minus placebo difference scores showed a significant correlation between memory functioning and CSF 5HIAA levels. Alcohol amnestic syndrome patients who had the highest blood levels of fluvoxamine demonstrated the largest changes in CSF 5HIAA and improvement in memory performance under fluvoxamine. These findings implicate a role of serotonergic mechanisms in alcoholic organic brain syndrome and suggest that with individual titration of the drug dose, fluvoxamine might be a clinically useful agent in the treatment of this syndrome.