Elevated prolactin serum levels and history of alcohol withdrawal seizures

BACKGROUND: Prolactin has been discussed to be useful for differential diagnosis in epilepsia. Aim of the present study was to investigate the association between prolactin serum levels and previous alcohol withdrawal seizures. METHODS: We assessed 118 male patients admitted for detoxification treatment. Previous withdrawal seizures were recorded and prolactin serum levels were measured using an enzymatic immunoassay. RESULTS: Patients with a history of alcohol withdrawal seizures had significantly higher prolactin levels (17.8 ng/ml, SD=12.1) than patients without previous seizures (13.0 ng/ml, SD=8.1, p<0.05). Logistic regression revealed significant predictive qualities for prolactin serum levels (B=0.05, Wald=5.30, p=0.021, OR=1.06, 95%CI=1.01-1.11). CONCLUSIONS: The present findings show an association between elevated prolactin serum levels and a history of withdrawal seizures. Hence, the results suggest that prolactin elevation at admission may be a clinical marker for an increased risk of withdrawal seizures.     

The TTTAn aromatase (CYP19A1) polymorphism is associated with compulsive craving of male patients during alcohol withdrawal

Alcoholism is associated with alterations of the hypothalamus-pituitary-gonadal hormone axis. We recently reported a leptin-mediated relation between the CAGn polymorphism of the androgen receptor and craving during alcohol withdrawal. This study investigated whether the TTTAn polymorphism of the aromatase (CYP19A1) is equally linked to craving. An association between TTTAn and compulsive craving (p=0.029) was revealed in our sample of 118 male alcohol addicts at day of hospital admission. Genotype-dependent subgroups showed differences in that the patients with short alleles suffered from lower compulsive craving during withdrawal than those with the longer alleles (p=0.027). The additional inclusion of leptin revealed no further significant association in the present study. Our finding is a further step on the way to elucidate the genesis of craving for alcohol with its extensive underlying interactions of different genetic and non-genetic factors. Future investigations should enrol women and consider sex hormone levels for further clarification of the observed TTTAn-craving relationship.     

Decreased galanin serum levels are associated with alcohol-craving during withdrawal

Background

The hypothalamic galanin expression has been associated with increased intake of carbohydrates and fats in preclinical studies. The appetite stimulating effect of galanin is thought to underlie the positive association between alcohol consumption and hypothalamic galanin expression observed in preclinical studies.

Methods

In this pilot study we investigated alterations in galanin serum levels (33 male patients) in alcohol-dependent patients during alcohol withdrawal (days 1, 7 and 14) in comparison to healthy controls (19 male controls). In order to assess the putative association between appetite regulation, galanin serum levels and alcohol consumption we additionally investigated the serum levels of insulin, glucose and triglycerides.

Results

The galanin serum levels on day 1 of alcohol withdrawal were significantly reduced in the alcohol-dependent patients (T = − 3.302, p = 0.002) and increased significantly from day 1 to day 14 of alcohol withdrawal (F = 6.437, p = 0.002). We found a significant negative association between the galanin serum levels and alcohol craving measured by the Obsessive Compulsive Drinking Scale (OCDS) (r=−0.449, p=0.009) and the obsessive subscale of the OCDS (r = − 0.521, p = 0.002) on day 1 of alcohol withdrawal. There was no association between the galanin serum levels and the parameters of energy homeostasis (triglycerides, cholesterol, insulin, and glucose) investigated.

Conclusions

Acute alcohol withdrawal was associated with decreased galanin serum levels in this pilot study. There was no association between the galanin serum levels and the parameters of energy homeostasis. Further research of galanin serum levels in active drinkers will be necessary to clarify the putative association between galanin serum levels, appetite regulation and alcohol consumption.     

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.     

Evidence of an association of leptin serum levels and craving in alcohol dependence

Recent studies have described an association of leptin serum levels and craving in alcohol dependent patients. The aim of the present study was to investigate a large patients' sample using a power-based statistical analysis. We included 156 male and 33 female patients suffering from alcohol dependence admitted for detoxification treatment. Leptin serum levels were measured using a commercial ELISA kit. The Obsessive Compulsive Drinking Scale (OCDS) was used to assess alcohol craving at admission. For both genders Spearman's correlation revealed significant results. These findings could be confirmed using multiple linear regression models (males: r=1.881, t=4.338, p<0.001; females: r=6.160, t=5.793, p<0.001) with a power of 1.00. In contrast to previous results describing an association only in female patients, this power-based analysis shows that leptin is associated with alcohol craving in both genders.     

Genetics of Lesch's typology of alcoholism

It is widely accepted that dopamine and serotonin (5-HT) neurotransmission can be critically involved in the development of alcohol abuse and alcohol dependence. Lesch's typology of alcoholism has been gaining increasing popularity as it qualitatively differentiates patients into different treatment response subgroups. The aim of the present study was to evaluate a possible genetic background of Lesch's typology with special emphasis placed on dopamine- and serotonin-related genes. 122 alcoholics (the mean age: 35+/-9 years) were investigated. According to Lesch's typology, 58 patients were of type I, 36 patients of type II, 11 patients of type III, and 17 patients of type IV. Alcohol drinking and family history was assessed by means of a structured interview, based on the Semi-Structured Assessment for the Genetics of Alcoholism. 150 control subjects without psychiatric disorders were also recruited. The control group was ethnically-, age- and gender-matched to the patients. The DRD2 TaqIA, exon 8, and promoter -141C ins/del polymorphisms as well as COMT Val158Met, 5HTT 44 bp del in promoter, and DAT 40 bp VNTR polymorphisms were detected by means of PCR. No significant differences were observed when the whole group of alcoholics and the controls were compared. Similarly, there were no differences between either the Lesch type I or type II alcoholics and the control subjects. No significant differences were observed between type I and type II alcoholics. Alleles frequencies were not calculated for the Lesch type III and type IV alcoholics since the number of patients was too small. The present results argue against any major role of the investigated polymorphisms in either Lesch type I or type II alcoholism. More comprehensive studies are needed to define the role of the investigated polymorphisms in Lesch type III and type IV alcoholism.     

NGF plasma levels increase due to alcohol intoxication and decrease during withdrawal

Recent studies show that alcohol dependence is associated with alterations in plasma levels of nerve growth factor (NGF). The aim of this study was to further elucidate reported alterations in NGF plasma levels during alcohol intoxication and withdrawal. Therefore, we assessed NGF plasma levels by enzyme-linked immunosorbent assay (ELISA) on admission (day 0) and day 7 of alcohol withdrawal in male alcohol dependent patients (n=75) in comparison to healthy controls (n=44). We found significant higher (U=1005.0, p<0.001) NGF plasma levels in the alcohol-dependent patients. Subgroup analysis showed significant higher (U=-2.934, p=0.003) NGF plasma levels in patients suffering from acute alcohol intoxication (group A) than in early abstinent patients (group B). From day 0 to day 7 of alcohol withdrawal NGF plasma levels decreased significantly in both groups (group A: Z=-3.118, p=0.002, group B: Z=-2.103, p=0.035). Our results suggest that acute alcohol intoxication is associated with an increase in NGF plasma levels, which decrease during alcohol withdrawal. These results suggest that NGF plasma levels increase as part of a regulation mechanism that counteracts alcohol intoxication.     

Leptin: a modulator of alcohol craving?

BACKGROUND: Leptin has been shown to regulate food intake and energy expenditure. Because leptin acts via regulation of appetite, we studied the hypothesis that suggests leptin modulates craving for alcohol as well. METHODS: We studied leptin plasma concentrations (RIA) both in alcoholic subjects during inpatient detoxification (day 1: n = 78, day 14: n = 60) and in healthy control subjects (n = 30). To rule out interference with the activation of the HPA axis during alcohol withdrawal, we also evaluated cortisol plasma levels (RIA). RESULTS: We found plasma leptin and cortisol elevated at onset of withdrawal, decreasing significantly up to day 14. Leptin (and the body-mass corrected ratio leptin/BMI) was highly correlated with self-rated craving. No correlations of craving with cortisol and BMI were observed. CONCLUSIONS: We suggest that leptin may modulate withdrawal-induced craving in alcoholic subjects.     

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.     

Hypothalamic-pituitary-adrenal axis activity, dehydroepiandrosterone sulphate and their relationships with aggression in early and late alcohol withdrawal

The study aims at investigating the relationship between hypothalamic-pituitary-adrenal (HPA) axis alterations and aggression level in alcoholic patients during early and late alcohol withdrawal. Serum levels of basal cortisol and dehydroepiandrosterone sulphate (DHEAS) were measured three times, and cortisol and DHEAS response to dexamethasone twice during the early and late withdrawal periods in alcohol dependent males (n=30) and once in healthy control males (n=20). Abnormal cortisol non-suppression response to dexamethasone in dexamethasone suppression test (DST) was observed in some proportion of the patients in early withdrawal, which normalized in late withdrawal. The study revealed reduced basal DHEAS levels and reduced DHEAS response to dexamethasone in late withdrawal. When the patients were assessed in two separate groups as high- and low-aggressives, in the high-aggression group abnormality in DST was observed during both early and late withdrawal periods, in the low-aggression group it was observed only in early withdrawal. While basal DHEAS levels were low in the high-aggression group only in early withdrawal, it was reduced in the low-aggression group during late withdrawal period. Some alterations of the HPA axis during alcohol withdrawal might be associated not only with alcohol use per se but also with aggressivity tendency of alcoholic patients.     

男性酒依赖患者食欲素A与急性期戒断反应的相关性

目的探讨男性酒依赖患者血浆食欲素A(orexin-A,OXA)浓度与急性期酒精戒断反应、心理渴求之间的关系。方法纳入60例男性酒依赖患者和60名健康成年男性。收集一般人口学资料,检测血浆OXA浓度,以及总胆固醇、肌酸激酶、谷丙转氨酶、谷草转氨酶、血糖及血钾水平,使用修订版临床酒精戒断症状评估量表中文版(clinic institute alcohol withdrawal syndrome scale,CIWA-Ar)及视觉模拟量表(visual analogues scale,VAS)评估患者酒精戒断反应严重程度和心理渴求程度;患者组接受戒酒治疗14 d后,再次检测OXA及血生化指标,以及评估CIWA-Ar及VAS。结果入组时患者组血浆OXA、总胆固醇、肌酸激酶、谷丙转氨酶、谷草转氨酶及血糖水平高于对照组(均P<0.05),血钾浓度低于对照组(P<0.05)。在入组时患者组中轻度戒断反应者血浆OXA水平低于中度或重度戒断反应者(均P<0.05)。患者组治疗前后血浆OXA浓度、CIWA-Ar评分、VAS得分存在统计学差异(均P<0.05)。患者入组时血浆OXA的水平与CIWA-Ar评分(r=0.34,P<0.01)和VAS评分(r=0.47,P<0.01)均具有统计学相关性。结论在急性酒精戒断期男性酒依赖患者血浆OXA水平可能与戒断反应、渴求有关。     

Prolactin shifts after neuroleptic withdrawal

Neuroleptic-induced alterations in serum prolactin levels may have important clinical implications. Twenty-two stable schizophrenic patients, taken off medication over a 3-week period, were followed for 40 weeks or until the neuroleptic was reinstituted. Serum prolactin levels were measured during neuroleptic treatment and during the neuroleptic-free period. When serum prolactin levels were plotted over time, 55% of the subjects showed shifting prolactin levels in the shape of a "V" (i.e., a fall in prolactin level preceding an increase in the level) in the early weeks following withdrawal. Subjects with the "V" shape had significantly lower prolactin levels during neuroleptic treatment than those without the "V" shape. The pathophysiological significance of the prolactin "V" pattern is uncertain. It is consistent, however, with transient dopaminergic hyperactivity following neuroleptic withdrawal.     

Apolipoprotein E gene polymorphism and previous alcohol withdrawal seizures

Aim of this study was to investigate the possible association of apolipoprotein E (ApoE) gene polymorphism with a history of alcohol withdrawal seizures. We included 194 patients with alcohol dependence who were divided into patients with (SZ+) and without (SZ-) previous alcohol withdrawal seizures. ApoE genotypes were determined using PCR. For statistical analysis we examined the number of ApoE alleles (ApoE2: n=36; ApoE3: n=311; ApoE4: n=41). A significant positive association with a positive history of withdrawal seizures (SZ+) was found in the ApoE3 allele group (Fisher's exact test: p=0.006) while a significant negative association was observed in the ApoE2 allele group (Fisher's exact test: p=0.029). For the ApoE4 allele group no significant differences were found regarding a history of withdrawal seizures. Our findings suggest an association between the apolipoprotein E3 gene variant and an elevated risk of alcohol withdrawal seizures. These preliminary results must be validated in further studies.     

Elevated alpha synuclein mRNA levels are associated with craving in patients with alcoholism.

BACKGROUND: Alpha synuclein has been found elevated in dopamine neurons of cocaine abusers and in rats whose alcohol preference is inbred. METHODS: The alpha synuclein mRNA expression level was measured by quantitative polymerase chain reaction in the blood of 75 male alcoholics and 69 nondrinking healthy control subjects. Alcohol craving was assessed by the Obsessive-Compulsive Drinking Scale total score, including subscales for obsessive and compulsive craving. RESULTS: The alpha synuclein expression in patients with alcoholism (2.79 DeltaCT; SD = 1.69; p = .021) was significantly higher when compared with healthy control subjects (2.20 DeltaCT; SD = 1.59). Increased alpha synuclein levels significantly predict Obsessive-Compulsive Drinking Scale total score (odds ratio = 1.44, 95% confidence interval: 1.01-2.06, p = .042) and especially Obsessive-Compulsive Drinking Scale obsessive subscale (odds ratio = 1.74, 95% confidence interval: 1.18-2.58, p = .005) but not Obsessive-Compulsive Drinking Scale compulsive subscale alcohol craving. CONCLUSIONS: Higher levels of alpha synuclein are associated with an increase in alcohol craving. The present results provide a novel pathophysiological approach to the explanation of craving mechanisms.     

Concomitant endocrine and immune alterations during alcohol intoxication and acute withdrawal in alcohol-dependent subjects

Although both alcohol intoxication and withdrawal have been demonstrated to produce significant endocrine alterations, no data exist on the effects of acute withdrawal on immune functions. Therefore, the current study investigated the effect of alcohol intoxication and acute withdrawal on plasma cortisol, prolactin and catecholamines, and blood leukocyte subset distribution in alcohol-dependent subjects. Nine male alcoholics admitted to the university clinic for alcohol dependence and 9 age-matched controls participated in the study. Blood was drawn from the alcohol-dependent subjects at 10:30 a.m. on day 0 (chronic alcohol intoxication), at the same time during acute alcohol withdrawal (day 1) and following the resolution of acute withdrawal (day 7). Blood was drawn from age- and gender-matched healthy control subjects at the corresponding time points. Plasma was then analyzed for hormone concentrations and blood examined for leukocyte subsets by flow cytometry. Alcohol-dependent patients displayed significantly elevated plasma cortisol during intoxication and withdrawal, which decreased to control levels following resolution of acute withdrawal. Small elevations of plasma prolactin and catecholamines were also observed during intoxication. Furthermore, alcohol-dependent subjects showed reduced absolute numbers of CD4(+) and CD8(+) T cells and natural killer cells compared with healthy controls across all time points. In contrast, although monocyte numbers were lower in alcohol-dependent patients during intoxication, acute alcohol withdrawal increased the number of monocytes in patients. Thus, alcohol dependence produces a general suppression of leukocyte subset populations in blood. However, resolution of acute alcohol withdrawal is associated with a return of plasma cortisol to control levels, and a concomitant increase in peripheral blood monocyte numbers.     

Differential diagnostic value of postictal serum prolactin determination

Determination of serum prolactin concentration was carried out under standardized conditions on 70 hospitalised patients after different types of epileptic, syncopal and psychogenic seizures. In cases of unconsciousness of unknown cause and of unobserved seizures there is evidence that the determination of postictal prolactin may help to clarify the diagnosis. Excluding patients with epileptic seizures due to alcohol withdrawal only in 70% of the patients was there a significant elevation of serum prolactin. The clinical procedure thus appears to be of importance also in the differential diagnosis of psychogenic seizures. Patients with epileptic seizures due to alcohol withdrawal showed an elevated prolactin concentration in only 45% of cases. Whereas an elevated serum prolactin level indicates the occurrence of a grand mal seizure, a normal prolactin level does not positively exclude epileptic seizures.     

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.     

Cerebrospinal fluid monoamine metabolites during alcohol withdrawal syndrome and recovered state

The aim of the study was to examine changes in cerebrospinal fluid (CSF) monoamine concentrations related to alcohol withdrawal. Lumbar puncture was performed in 8 healthy volunteers (control group) and 36 chronic alcoholic patients following alcohol withdrawal. A second lumbar puncture was performed in 20 of these patients after recovery from the withdrawal. CSF 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured. Alcohol withdrawal phenomena in all patients were classified in the following three groups: (i) major withdrawal syndrome: alcohol-withdrawal delirium, (ii) minor withdrawal syndrome: evident autonomic nervous hyperactivity without hallucination or clouding of consciousness, and (iii) asymptomatic type: a withdrawal period without overt symptoms. MHPG concentration was significantly increased in the major withdrawal syndrome, as compared with other groups, including the controls. No change in MHPG was found in the patients without overt autonomic nervous syndrome. A positive correlation between CSF-MHPG and intensity of withdrawal symptoms (r = 0.60, p less than 0.02) was found. A higher correlation between CSF-MHPG and intensity of autonomic nervous disturbances was also found (r = 0.86, p less than 0.001). CSF-HVA was significantly low during the alcohol delirium. It is suggested that a close relationship may exist between autonomic nervous disturbances and increase in central noradrenergic activity, as well as between the alcohol delirium and decrease in central dopaminergic activity.     

Kinetics of Serum Neuron-Specific Enolase and Prolactin in Patients After Single Epileptic Seizures

PURPOSE: To investigate and compare the temporal profile of serial levels of neuron-specific enolase (NSE) and prolactin in serum from patients after single epileptic seizures. METHODS: Measurement of NSE and prolactin by sensitive immunoassays in 21 patients with complex partial seizure (CPSs: n = 11) and secondarily generalized tonic-clonic seizures (SGTCSs; n = 10) during continuous video-EEG monitoring at four different time points (1, 3, 6, and 24 h after ictal event). Statistical analysis was performed by using a repeated-measures analysis of variance (ANOVA) model. RESULTS: Mean+/-SD values for NSE levels (ng/ml) were 12.5 +/-4.4 (1 h), 10.8+/-3.8 (3 h), 11.1+/-4.9 (6 h), and 8.2+/-1.9 (24 h). The corresponding prolactin levels (mU/L) were 1,311+/-1,034, 232+/-158, 237+/-175, and 251+/-98. There was a significant decrease of NSE and prolactin levels over time (p < 0.001). The pair-wise comparison of NSE levels showed significant differences between the time points 1 vs. 24 h (p < 0.001), 3 vs. 24 h (p = 0.007), and 6 vs. 24 h (p = 0.009). In contrast, serum prolactin levels showed a significant difference between 1 vs. 3 h (p < 0.001) only. Most of the NSE levels remained normal after CPSs and SGTCSs. At 1 h after the seizure, only 33% of the subjects had increased NSE, whereas abnormal prolactin levels occurred with a sensitivity of 80%. CONCLUSIONS: In contrast to prolactin, serum NSE is not a sensitive marker of individual seizures. Only some individuals showed an increase of NSE beyond the prolactin-sensitive time frame after a single seizure, and mean NSE levels were not significantly increased compared with those of normal controls.     

Biological markers to predict previous alcohol withdrawal seizures: a risk assessment

Summary. Recent studies have shown that both, elevated homocysteine and prolactin plasma levels are associated with a higher risk of alcohol withdrawal seizures. The aim of this study was to evaluate the predictive qualities of a combined assessment of homocysteine and prolactin for previous alcohol withdrawal seizures. Therefore, 117 male patients suffering from alcohol dependency were included into the study. Homocysteine was measured directly at admission, prolactin the morning following admission for detoxification treatment. Pearson’s χ²-test showed significant results for the combined assessment of both parameters (χ² = 14.71, p = 0.001). Multivariate logistic regression also revealed significant predictive qualities (p = 0.001, OR = 9.23, 95%CI = 2.36–36.05). A combination of both, homocysteine and prolactin, may help to assess the individual risk of alcohol withdrawal seizures in clinical practice.