Endocrinological studies in alcoholics during withdrawal and after abstinence

Several endocrine parameters were assessed in 35 alcoholic inpatients after admission to hospital, and 17 of the 35 were retested after several weeks of sobriety. No difference was found in clonidine-stimulated growth hormone (GH) secretion between male alcoholics and male healthy controls, but significant positive correlations of GH secretion and alcohol content in expired breath on admission and gamma-GT values after abstinence were observed. Nonsuppression in the dexamethasone suppression test was found in 17% of the patients on admission, which seemed to be due to alcohol withdrawal. Postdexamethasone cortisol levels were significantly positively correlated with the "apathic syndrome" (r = 0.40; p less than or equal to 0.05). About one-third of the patients showed a blunted response in the TRH-test both on admission and after abstinence. No significant influence of alcohol intake, withdrawal or familial disposition on prolactin values could be detected. The results of the TRH test and the DST point to similar endocrinological patterns in alcoholics as in depressive patients and thus support the hypothesis of a link between alcoholism and depression.     

Event-related potentials in chronic alcoholics during withdrawal and abstinence

Twenty-one chronic alcoholics were submitted to an "oddball" auditory event-related potentials (ERP) paradigm and to the Wechsler Memory Scale (WMS) after four weeks' abstinence. Eight of these patients were also submitted to the same ERP procedure and to two WMS items (digit span and associations) during a minor withdrawal state in the first days of hospitalization. Alcoholics showed reduced N1-P3 and N2-P3 amplitudes as compared to control subjects. Three alcoholics showed a P3 latency that exceeded the age-corrected control range (2 SE). There was no correlation between neuropsychological performances and electrophysiological measures, but the three subjects with abnormal P3 latencies had lower WMS scores. During withdrawal, greater N1-P2 amplitudes and shorter P3 latencies were observed as well as poorer performances on the two WMS items. The results are discussed in view of the possible contributions of ERPs in the understanding of the effects of chronic alcohol intake and alcohol withdrawal on CNS functions.     

Significant reversibility of alcoholic brain shrinkage within 3 weeks of abstinence

Chronic alcoholism is often associated with brain shrinkage or atrophy. During recent years, it has been demonstrated that this shrinkage is, at least in part, reversible when abstinence is maintained. There are different hypotheses concerning the mechanisms for this reversibility, but many questions are still open. Especially the time conditions for these reversible changes are subject of discussion. Twenty-eight male patients with severe alcohol dependence were investigated in a computed tomographic study at the beginning of abstinence and 3 weeks later. Planimetric evaluation of 5 selected slices revealed a significant decrease in liquor areas and an increase of brain volume. The densitometric analysis showed an increase in brain tissue density. In a multiple regression approach it was shown that the reversibility was mostly influenced by the age of the patients. Our results support neither the hypothesis of an increase in brain water as the most important principle for reversibility in alcoholic brain shrinkage nor the hypothesis of augmented dendritic growth. Other mechanisms like reduced (during chronic intoxication) and normalized (during abstinence) cerebral hemoperfusion have to be considered as possible mechanisms for the reversibility of alcoholic brain shrinkage.     

Short-term cognition deficits during early alcohol withdrawal are associated with elevated plasma homocysteine levels in patients with alcoholism

Summary. Higher plasma homocysteine levels have been found in actively drinking alcoholics as well as in early abstinent patients. Furthermore, elevated homocysteine levels are associated with cognitive decline in dementia and in healthy elderly people. The aim of this prospective study was to investigate a possible association between homocysteine serum levels and clinically well known cognitive deficits during alcohol withdrawal. We examined 89 patients (67 men, 22 women) during early withdrawal treatment. Cognitive function was assessed using the c.I.-Test. Patients with cognitive deficits showed significantly higher homocysteine serum levels (Mann-Whitney-U, p = 0.004) than patients without cognitive deficits, while the difference in blood alcohol concentration was not significant. Using logistic regression analysis, cognitive deficits were best predicted by high homocysteine serum levels (Wald χ² = 4.071, OR = 1.043, 95% CI 1.001–1.086, p<0.05), which was confirmed by Receiver Operating Curves (AUC = 0.68, 95% CI = 0.57–0.79, p = 0.004). The present results show first evidence of an association between elevated plasma homocysteine levels in alcoholics and cognition deficits in patients undergoing alcohol withdrawal.     

Normalization of regional cerebral blood flow in alcoholics during the first 7 weeks of abstinence

Twenty-two institutionalized alcoholics were studied after 1, 3, 5 and 7 weeks of abstinence with measurements of the regional cerebral blood flow (rCBF), psychometric testing and clinical ratings. Twenty-two healthy volunteers served as age-matched controls. Mean rCBF was significantly reduced in the alcoholics at all measurements compared to the controls. The older alcoholics (median cut) showed a 9% increase of rCBF from the 1st to the 7th week (P less than 0.01). The mean rCBF in these alcoholics also increased more in the right than in the left hemisphere (P less than 0.05) during the investigation. The differences between the alcoholics and the controls were most pronounced in the right frontal lobe. The mean flow changes were correlated to improvement in clinical state. Right hemisphere and frontal lobe flow decreases were more accentuated in older alcoholics.     

Plasma opioids in alcoholics after acute alcohol consumption and withdrawal

Beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) plasma concentrations were examined in ten chronic alcohol abusers, eight men and two women aged 25-56 years with histories of continuously elevated ethanol consumption dating from 5-30 years. Plasma levels of the two peptides were measured after acute alcohol consumption and then after 3, 6 and 9 days of forced abstinence, during chlordiazepoxide treatment. Beta-EP and beta-LPH concentrations were normal on all four occasions. A reduced sensitivity of opioid receptors to acute alcohol administration due to chronic alcohol consumption is suggested.     

AMP-rated psychopathology in chronic alcoholics

Summary In a group of 39 alcoholics within a withdrawal process, the psychical situation was rated using AMP scales (Angst et al. 1969). Cluster analysis of the items rendered the following five-cluster solution: (1) aggressive-depressive patients, (2) less impaired persons, (3) slowed persons with diminished contact, (4) emotionally inadequate persons, (5) appealing depressive persons. These results are discussed with respect to other data from clinical history and diagnostic findings.Supported by Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 115, Teilprojekt C21     

Heart rate variability of chronic alcoholics in withdrawal and abstinence

Measurement of heart rate variability was performed in 106 healthy volunteers and 31 alcoholics. The mean momentary arrhythmia (MMA) of normal individuals showed an exponential decrease with increasing age. Cardiac autonomic neuropathy was found in 5 of 31 alcoholics. In agreement with the concept of hyperexcitability the withdrawing alcoholics had a significant increase in heart rate and decrease in MMA compared to later measurements. The result suggests that the diagnosis of autonomic alcoholic neuropathy may be reliable only after at least a one week period of abstinence from alcohol.     

Electrolyte changes and acid base balance after alcohol withdrawal

70 chronic alcoholics in the withdrawal state, 45 with convulsions and 25 controls without convulsive seizures, were tested with respect to electrolyte changes and acid base balance in serum or blood and cerebrospinal fluid (CSF). It was of special interest to note that there was a partial independence between magnesium levels in serum and CSF. Thus the serum level has only a limited liability as to magnesium depletion suggested to be responsible for seizure precipitation. In the seizure group a slightly but significantly lower magnesium, potassium and calcium in CSF and a significant decrease of potassium and calcium in serum were revealed. In the nonzeizure controls a similar decrease of magnesium in serum and potassium in CSF was observed while serum potassium and calcium in CSF and serum remained in low normal range. In both groups there was a prominent respiratory alkalosis. The role of magnesium depression for seizure precipitation is discussed with respect to the concomitant changes of other electrolytes and acid base disturbances.     

Involvement of plasma atrial natriuretic peptide in protracted alcohol withdrawal

OBJECTIVE: Atrial natriuretic peptide (ANP) has been shown to inhibit the effects of corticotrophin releasing hormone, corticotrophin and cortisol, and to influence affective and anxiety symptoms in man. We tested the hypothesis of whether ANP is associated with endocrine and psychopathological disturbances during acute alcohol withdrawal. METHOD: ANP and cortisol plasma concentrations were studied in alcoholics during in-patient detoxification and in healthy controls. Additionally, craving, depressive mood and anxiety were assessed. RESULTS: Although mean ANP levels increased significantly in alcoholics between days 1 and 14, they remained diminished compared to controls. Separating a subgroup of alcoholics with a decrease of ANP levels during withdrawal, these individuals revealed significantly elevated scores for mean and maximum craving and a trend to an elevated self-rated anxiety on day 14. CONCLUSION: We suggest that a dysregulation of ANP plasma levels during alcohol withdrawal may contribute to symptoms of protracted withdrawal such as craving and anxiety.     

CSF dopamine turnover and positive schizophrenic symptoms after withdrawal of long-term neuroleptic treatment

Dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured in cerebrospinal fluid (CSF) of 14 schizophrenic inpatients before and 2 weeks after withdrawal of long-term neuroleptic medication. Total neuroleptic-like activity (NLA) in serum was determined at the same times. DA and its metabolites (DOPAC and HVA) were significantly reduced after neuroleptic discontinuation. NLA was substantially diminished. The decrease in DA and DOPAC was positively correlated with positive symptoms of postwithdrawal deterioration, and low prewithdrawal DOPAC level predicted severe relapse. These results are compatible with the hypothesis linking an overregulated central DA system to the positive symptoms of schizophrenia.     

Cerebral glucose metabolism during opioid withdrawal following methylnaloxonium injection into the locus coeruleus

Previous studies have demonstrated a widespread stimulation of regional cerebral metabolic rate(s) for glucose (rCMRglc) in morphine-dependent rats subjected to opioid withdrawal precipitated by systemic injection of naloxone. Nonetheless, many of the behavioral signs of opioid withdrawal are produced by intracerebral injections of an opioid antagonist, methylnaloxonium (MN), into the locus coeruleus (LC). The purpose of the present work was to determine the extent to which cerebral metabolic alterations in opioid withdrawal could be initiated by a local action in LC. Intracerebral injections of MN into LC increased rCMRglc in morphine-dependent rats, and the anatomical distribution of this effect was similar to that produced by systemic injections of naloxone. The present data support the view that LC is a major substrate of opioid withdrawal in the brain, and they suggest that LC plays an important role in changing rCMRglc during opioid withdrawal induced by systemic naloxone administration.     

Cause-specific mortality risk among male alcoholics residing in the Osaka metropolitan area

We evaluated the mortality risk among 306 male alcoholics living in Osaka, Japan, at the time of initial diagnosis between 1972 and 1983, with regard to the cause of death, length of time from diagnosis, and participation in an alcohol abstinence self-help group. By the closing date on 1 March 1992, 110 of the 306 alcoholics had died, yielding an observed-to-expected (O/E) ratio of 4.5 [95% confidence interval (CI) = 3.7-5.4]. The alcoholics had significantly elevated mortality risks from all malignant neoplasms (O/E = 2.1, 95%CI = 1.2-3.3), esophageal cancer (O/E = 8.4, 95%CI = 1.7-24.5), diseases of the circulatory system (O/E = 4.4, 95%CI = 3.0-6.2), liver cirrhosis (O/E = 15.9, 95%CI = 10.2-23.6), diseases of the genitourinary system (O/E = 6.3, 95%CI = 1.3-18.5), and external death (O/E = 10.3, 95%CI = 6.3-15.8). The mortality risk from all causes still remained significantly high beyond the tenth year following initial diagnosis (O/E = 2.6, 95%CI = 1.0-6.2). The mortality risks from liver cirrhosis and external death (such as suicide) were highest within the first year following diagnosis, and were still high beyond the tenth year. A significantly high mortality risk from diseases of the circulatory system was observed between the first and ninth years, and the mortality risk from all malignant neoplasms was significantly elevated beyond 10 years following diagnosis. Alcoholics who did not join a self-help group soon after the initial institutional treatment had different cause-specific and time-specific mortality risks from those who did join a self-help group. These findings show the importance of long-term clinical follow-up of male alcoholics, taking into consideration the cause-specific mortality.     

Circadian variation in plasma 5-hydroxyindoleacetic acid level during and after alcohol withdrawal: phase advances in alcoholic patients compared with normal subjects

Alcohol withdrawal symptoms in 19 male alcoholics were objectively evaluated and classified and circadian variation in their plasma 5-hydroxyindoleacetic acid (5-HIAA) concentrations was determined at 3 different intervals after cessation of drinking. Circadian variations in plasma 5-HIAA level exhibited phase advances in alcoholic patients compared with normal controls and were different depending on the severity of alcohol withdrawal symptoms. Plasma 5-HIAA in patients with delirium tremens showed significantly higher levels during the abstention period, possibly suggesting peculiarity in their serotonergic metabolism.     

Alcoholism-associated hyperhomocysteinemia and previous withdrawal seizures.

BACKGROUND: Higher homocysteine levels were found in actively drinking alcoholics as well as in early abstinent patients. Furthermore, it has been shown that high homocysteine levels predicted first-onset alcohol withdrawal seizures. The aim of the present study was to determine plasma homocysteine levels in actively drinking alcoholics and patients with early abstinence in order to evaluate whether there is an additional association between elevated plasma homocysteine levels and a history of alcohol withdrawal seizures. METHODS: Two groups of patients with an established diagnosis of alcohol dependence were studied. Group A comprised 56 consecutively admitted alcoholics who had been abstinent from alcohol between 24 to 72 hours before hospitalization. Group B consisted of 144 consecutively recruited alcoholics who were admitted - acutely intoxicated - for withdrawal treatment. Furthermore, groups were divided into two subgroups: patients with and without a history of alcohol withdrawal seizures. RESULTS: Alcoholics of GROUP B with a history of withdrawal seizures had significantly (p<.0001) higher homocysteine levels than actively drinking patients without seizures in their history: 42.0 micromol/l (SD 26.4) versus 22.5 micromol/l (SD 11.4). Using a logistic regression analysis, history withdrawal seizures in Group B but not in Group A patients were best predicted by a high homocysteine level at admission (Wald chi2=15.5, p<.0001; odds ratio 1.11, 95% CI 1.05-1.20). CONCLUSIONS: Homocysteine levels on admission may be a useful screening method to identify actively drinking patients with a higher risk of alcohol withdrawal seizures.     

Neuroleptic withdrawal in chronic schizophrenia: CT and endocrine variables relating to psychopathology

The psychopathology of 36 chronic, schizophrenic patients who had been on maintenance neuroleptics was rated during neuroleptic therapy and after 12 days of neuroleptic withdrawal. At both times, hormonal serum levels were also determined. Moreover, in 27 of these patients, ventricle-brain ratio, maximal width of the third ventricle, and sulcal widening were measured on computed tomography (CT). Neuroleptic withdrawal resulted in individually different psychopathological changes: 7 patients improved, 11 worsened. Within the whole group, thought disorder deteriorated, and anergia improved. Levels of cortisol and beta-endorphin increased; those of prolactin and norepinephrine decreased. The majority of patients showed ventricular enlargement, which was marginally related to reduced thought disorder. CT and endocrine variables were slightly related to psychopathology or psychopathological effects of neuroleptic withdrawal.     

Sexual adjustment of male alcoholics

This study set out to describe the sexual attitudes and behaviour of 50 hospitalized alcoholic men by comparing them with a sample of the general population, matched in age and social class. This control sample was identified by random selection from a company register, and subjects were recruited into the study with the assistance of a trade union. All subjects completed the same assessment by semi-structured interview and the Eysenck Inventory of Attitudes to Sex. A method of scoring this questionnaire was derived, and comparison between samples showed the alcoholics differed from the controls only in describing less sexual satisfaction and not in other sexual attitudes. This difference probably arose from their greater interest in sex, loss of erectile potency and lack of a sexual partner.     

Clonidine treatment of neonatal narcotic abstinence syndrome

Clonidine hydrochloride, an alpha 2-adrenergic agonists, was used to treat seven infants who were passively addicted to narcotics because of maternal methadone maintenance. In six of seven infants, the major symptoms of narcotic withdrawal were ameliorated after a total daily oral dose of 3-4 micrograms/kg/day was achieved. One infant failed to respond. No toxic side effects of clonidine were observed at the dosage level used. The results of this pilot study suggest that clonidine may be a safe therapeutic agent for the treatment of neonatal narcotic abstinence syndrome (NNAS). Clonidine treatment of NNAS remains strictly investigational at this time. The relative efficacy and safety of clonidine versus other currently used drug regimens for NNAS also remains to be determined.     

Platelet aggregation and plasma lipoproteins in alcoholics during alcohol withdrawal

Platelet aggregation, platelet lipid composition and plasma lipoprotein concentrations were measured each week in a group of seventeen alcoholics, without overt liver disease, for one month, following acute, total alcohol withdrawal. The platelets were initially hypoaggregable but, within 1-2 weeks of cessation of drinking, they became hyperaggregable and then gradually returned towards normal values. Hyperaggregability could not be explained by increases in either the cholesterol or the arachidonic acid content of the platelets. Plasma very-low-density lipoprotein cholesterol levels remained high throughout the study, but the initially raised levels of high-density lipoprotein (HDL) cholesterol fell by 26%. Low-density lipoprotein (LDL) cholesterol concentration rose by 10% after two weeks of withdrawal but then returned to about the starting level. The resulting changes in the plasma LDL-cholesterol:HDL-cholesterol ratio, which had increased by more than 50% after two weeks of abstinence, essentially paralleled the time course of enhanced platelet reactivity in all but four of the alcoholics. These findings suggest that alterations in plasma lipoprotein concentrations during acute alcohol withdrawal may be a contributory factor to the haemostatic disorders present in such patients.     

Elevated tryptophan levels in post-withdrawal alcoholics

Changes in serotonin function and disturbances in tryptophan availability have been implicated in many psychiatric disorders, including alcoholism. In the present study we took serum free tryptophan samples from 31 healthy volunteer controls and from 42 DSM-III-R alcohol-dependent subjects who had abstained from alcohol for at least 2.5 weeks (range 2.5-104 weeks). We also measured the basal serum Cortisol level at 09.00 hours for the same subjects and controls. There was a significant increase in the serum tryptophan level of the alcoholic subjects, by 43.7 μmol l^-1 (range 29-63 μmol l^-1), regardless of age of onset of alcoholism, family history of alcoholism or sociopathic traits, compared to the controls (33.0 μmol l^-1, range 19-60 μmol l^-1). There was also an increase in the basal serum Cortisol level in the alcoholic subjects compared to the controls, but this was not related to the increase in tryptophan levels. These findings indicate a disturbance in serotonin precursor availability in post-withdrawal alcoholics, and contribute to the evidence for involvement of the serotonin system in alcoholism.