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Biomedical subjects

B Adinoff

Publications and source records attributed to B Adinoff.

At least 19 recordsLinked to original sources

Features of cocaine dependence with concurrent alcohol abuse.

In order to assess differences between cocaine dependence alone and cocaine dependence complicated by alcohol abuse, 34 subjects who met DSM-III-R criteria for alcohol abuse and cocaine dependence (COC-ETOH group) were compared with 39 subjects who met criteria for cocaine dependence only (COC-only group) with regard to demographics, substance use, and psychopathology. There were no differences between groups in age, race, employment or socio-economic status. The baseline depression and global severity scores in the COC-ETOH group were significantly higher than in the COC-only group. The COC-ETOH group was significantly more likely to experience a paranoid psychosis with cocaine use and significantly more likely to have abused additional substances in the month prior to study entry. The COC-ETOH group also attended significantly fewer medication management sessions during the 12-week trial. There were no differences between groups in the type or frequency of Axis 1 or Axis II disorders.

Adult

Fluvoxamine treatment of alcoholic amnestic disorder.

The serotonin uptake inhibitor fluvoxamine was assessed in treatment of alcohol-induced Korsakoff's syndrome (KS) using fixed (4 weeks, 200 mg/day) or individualized (6 weeks, plasma concentration > or = 400 ng/ml) dosing in randomized placebo-controlled double-blind crossover studies. Cognitive functions and concentrations of the major cerebrospinal fluid (CSF) metabolites of serotonin (5-HIAA), norepinephrine (MHPG), and dopamine (HVA) were determined in abstinent, nondepressed KS patients (aged 45-75), at baseline and placebo (3-4 weeks), and after 3-4 (n = 10) or 6 (n = 4) weeks of fluvoxamine administration. Fluvoxamine decreased CSF 5-HIAA compared to placebo (P < 0.003) without consistent changes in HVA or MHPG. Reductions in 5-HIAA correlated with improvements on the Wechsler Memory Scale Memory Quotient (P < 0.05), independent of effects on attention/vigilance or Beck Depression Inventory scores. Reductions in 5-HIAA correlated with plasma fluvoxamine (P < 0.03) only for fluvoxamine concentrations below 450 ng/ml. These findings suggest improvement of memory consolidation and/or retrieval in patients with Korsakoff's syndrome by fluvoxamine via serotonergic mechanisms.

Aged

Double-blind study of alprazolam, diazepam, clonidine, and placebo in the alcohol withdrawal syndrome: preliminary findings.

Both a reduction in the inhibitory effects of GABA (disinhibition) and activation of the sympathetic nervous system are manifested during the alcohol withdrawal syndrome. This study was designed to explore the relative efficacy of medications that differentially affects these two biological systems: the benzodiazepines, which attenuate GABAergic disinhibition, and the alpha 2-adrenergic receptor agonists, which decrease sympathetic activation. The benzodiazepine diazepam (n = 6), the alpha 2-receptor agonist clonidine (n = 7), the benzodiazepine alprazolam (this is also purported to have alpha 2-receptor agonist properties) (n = 6), and placebo (n = 6) were evaluated in their effectiveness in decreasing signs and symptoms of alcohol withdrawal. Drug-free, alcohol-dependent patients were administered 1 of the 4 medications in a double-blind design until symptoms of withdrawal, as measured by the Clinical Instrument Withdrawal Assessment for Alcohol-Revised, were successfully treated. Alprazolam was significantly more efficacious than both clonidine and placebo in decreasing withdrawal symptoms. Diazepam was more effective than clonidine and placebo on some measures of withdrawal. Clonidine decreased systolic blood pressure significantly more than the other two active drugs and placebo, but was no more effective than placebo in decreasing other symptoms of withdrawal. Alprazolam did not significantly decrease blood pressure compared with diazepam or placebo. Despite the small sample size, these preliminary findings suggest that the efficacy of alprazolam in the treatment of alcohol withdrawal is related to its effect at the benzodiazepine receptor and not its alpha 2-receptor agonist properties.

Adult

Vagal tone decreases following intravenous diazepam.

To investigate the relationship between anxiety and parasympathetic nervous system activity, cardiac vagal tone was assessed in six healthy volunteers after the intravenous administration of the anxiolytic diazepam. Vagal tone was determined by quantifying the amplitude of respiratory sinus arrhythmia. We observed a significant dose-dependent attenuation in vagal tone, accompanied by an increase in heart rate. There was a nonstatistically significant decrease in plasma norepinephrine concentrations and subjective anxiety ratings at higher doses of diazepam. We discuss a possible role of the parasympathetic nervous system in the anxiolytic effects of the benzodiazepines.

Adult

Regional cerebral glucose utilization in chronic organic mental disorders associated with alcoholism.

Localized cerebral utilization rates for glucose (CMRglu) were determined in 10 detoxified patients with alcoholic organic mental disorders and in 7 age-equivalent normal volunteers using [18F]2-fluoro-2-deoxyglucose positron emission tomography. Although gray and white matter CMRglu were not significantly different, normalized CMRglu was increased in the left cerebellar and parietal cortical regions and decreased in the right posterior white matter and anterior temporal regions of alcoholic patients, and the pattern of regional CMRglu differed between the two groups. The results suggest functional disruption of right-sided and frontal brain regions and hyperactivity of cerebellar-cortical connections in alcoholic chronic organic mental disorders.

Aged

Mental disorders among alcoholics. Relationship to age of onset and cerebrospinal fluid neuropeptides.

Eighty-one percent of 339 alcoholics participating in a research program were found to have associated mental disorders. Alcoholics with onset of heavy drinking before 20 years of age had significantly more antisocial personality traits, drug abuse, bipolar disorder, panic disorder, suicide attempts, and paternal alcoholism than alcoholics with onset after age 20 years. Alcoholics with onset before and after 20 years of age also differed significantly from each other for cerebrospinal fluid concentrations of diazepam-binding inhibitor and somatostatin. These results support the notion that age of onset may delineate subgroups of alcoholics with significant clinical and neurochemical differences.

Adult

Personality and cerebrospinal fluid monoamine metabolites in alcoholics and controls.

Alcoholics as a group have been consistently reported to show differences from controls on various personality inventories. Moreover, neurobiologic substrates have been postulated to underlie personality dimensions. Therefore, we compared alcoholics with controls on measures of personality and investigated relationships between measures of personality and cerebrospinal fluid monoamine metabolite concentrations. The alcoholics were significantly different from controls on many personality measurements. There were significant, negative correlations between interview-derived lifetime aggression scores and cerebrospinal fluid concentrations of both the serotonin metabolite 5-hydroxyindoleacetic acid and the dopamine metabolite homovanillic acid. However, there were no significant correlations between any cerebrospinal fluid monoamine metabolite concentrations and scores on personality inventories.

3,4-Dihydroxyphenylacetic Acid

Symptoms of anxiety in inpatient alcoholics with and without DSM-III-R anxiety diagnoses.

Self- and observer-rating scales were administered to alcohol-dependent inpatients during acute withdrawal and regularly for 3 weeks. Following a structured diagnostic interview (SCID) at the end of the 3rd week of hospitalization, subjects were divided into two groups: a dual-diagnosed group (alcohol dependence and anxiety disorder) and an alcohol-only group (no other current Axis I diagnosis). The results demonstrated that the dual-diagnosed subjects experienced higher anxiety levels during and after acute alcohol withdrawal. All rating scales (i.e., Sheehan Patient Rated Anxiety Scale, Spielberger State Anxiety Inventory, Zung Rating Scale for Anxiety, and Hamilton Rating Scale for Anxiety) were analyzed to obtain the best combination of sensitivity and specificity. Taken together, the results indicate that it may be possible to identify alcoholics who require additional psychiatric evaluation early in treatment. This would allow a treatment plan which could be used to address both psychiatric and substance abuse problems.

Adult

Cerebrospinal fluid variables among alcoholics lack seasonal variation.

Seasonal influences on indices of serotonergic function, including cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), have been reported in psychiatric patients and healthy volunteers. We examined seasonal differences in CSF concentrations of 5-HIAA among 135 alcoholics admitted to a research ward who had a lumbar puncture. No significant seasonal differences were found for either CSF concentrations of 5-HIAA or CSF concentrations of other monoamine metabolites or peptides. The possible explanations for these negative findings are discussed.

Adult

Inverse relationship between CSF TRH concentrations and the TSH response to TRH in abstinent alcohol-dependent patients.

The authors performed the thyrotropin-releasing hormone (TRH) stimulation test and measured CSF concentrations of TRH in 13 abstinent alcohol-dependent subjects. They found an inverse correlation between the thyrotropin (TSH) response to TRH and endogenous CSF TRH concentrations. This finding supports the hypothesis that as the concentration of CSF TRH increases, anterior pituitary TRH receptor density decreases, resulting in a blunted TSH response to TRH stimulation.

Adult

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.

Adult

Cerebrospinal fluid thyrotropin-releasing hormone concentrations in alcoholics and normal controls.

Alterations in hypothalamic-pituitary-thyroid axis function have been reported in alcoholism. Blunting of the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) occurs in approximately 25% of alcoholic patients. Using a sensitive radioimmunoassay that allows TRH itself to be measured in cerebrospinal fluid (CSF), CSF concentrations of TRH were measured in alcoholics and normal controls. There was no significant difference in TRH concentrations between the groups. However, among the controls there was a significant correlation between CSF concentrations of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and CSF concentrations of TRH. This correlation was lacking in the alcoholics. These findings are of interest because basic neurobiological studies have reported that TRH and serotonin are co-localized in certain neurons in the rat central nervous system.

Adult

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.

Adrenocorticotropic Hormone

CSF neuropeptide Y in alcoholics and normal controls.

Neuropeptide Y is found in brain tissue. In dogs it has been shown to enhance activation of the hypothalamic-pituitary-adrenal axis by corticotropin-releasing hormone. It is localized in certain catecholamine neurons and to some extent colocalized with somatostatin. Disturbances of the central noradrenergic system may underlie some forms of alcoholism. Therefore, we compared male alcoholics and normal controls on cerebrospinal fluid (CSF) levels of neuropeptide Y. There was no significant difference between the two groups for neuropeptide Y. There was also no significant difference for CSF levels of growth hormone releasing hormone. However, there were significant positive correlations between CSF levels of neuropeptide Y and CSF levels of corticotropin-releasing hormone, somatostatin, and growth hormone releasing hormone.

Adult