Abstinent Alcoholic Patients Research Articles

Chronic alcohol exposure disrupts CB1 regulation of GABAergic transmission in the rat basolateral amygdala.

The basolateral nucleus of the amygdala (BLA) is critical to the pathophysiology of anxiety-driven alcohol drinking and relapse. The endogenous cannabinoid/type 1 cannabinoid receptor (eCB/CB1 ) system curbs BLA-driven anxiety and stress responses via a retrograde negative feedback system that inhibits neurotransmitter release, and BLA CB1 activation reduces GABA release and drives anxiogenesis. Additionally, decreased amygdala CB1 is observed in abstinent alcoholic patients and ethanol withdrawn rats. Here, we investigated the potential disruption of eCB/CB1 signaling on GABAergic transmission in BLA pyramidal neurons of rats exposed to 2-3 weeks intermittent ethanol. In the naïve rat BLA, the CB1 agonist WIN 55,212-2 (WIN) decreased GABA release, and this effect was prevented by the CB1 antagonist AM251. AM251 alone increased GABA release via a mechanism requiring postsynaptic calcium-dependent activity. This retrograde tonic eCB/CB1 signaling was diminished in chronic ethanol exposed rats, suggesting a functional impairment of the eCB/CB1 system. In contrast, acute ethanol increased GABAergic transmission similarly in naïve and chronic ethanol exposed rats, via both presynaptic and postsynaptic mechanisms. Notably, CB1 activation impaired ethanol's facilitation of GABAergic transmission across both groups, but the AM251-induced and ethanol-induced facilitation of GABA release was additive, suggesting independent presynaptic sites of action. Collectively, the present findings highlight a critical CB1 influence on BLA GABAergic transmission that is dysregulated by chronic ethanol exposure and, thus, may contribute to the alcohol-dependent state.

Startle-response based tasks and laboratory measures of impulsivity in abstinent alcoholic patients.

It is well known that impulsivity is a risk factor for the development of Addictive Disorders, and more specifically Alcohol Use Disorders (AUD). Recently, the Startle-Response Based Tasks (SRBT) and its different forms of plasticity have been found to be impaired in the alcoholic population. This is the first study to explore the correlation between impulsivity laboratory tasks and the SRBT test, in order to determine whether impulsivity and startle response (SR) could be related and in turn, explain their association with Alcohol Dependence (AD). 40 men, who met DSM-IV criteria for AD and had been abstinent for at least one month. Impulsivity was assessed using three laboratory tests: Continuous Performance Test (CPT), Stop-Signal Task (SST) and Differential Reinforcement for Low-Rate Responding (DRL6). Patients also underwent the SR test. They were compared to 40 matched controls. Impulsivity laboratory measures tasks (SST and commissions of the CPT) correlated positively with the magnitude of SR (P < 0.05) and with habituation (P < 0.05). Scores on DRL6 correlated negatively with the magnitude of SR (P < 0.05). This was not found in the control group. The fact that impulsivity laboratory measures and the SR are correlated in patients but not in controls, could imply the existence of a common link for these two measures in alcoholic patients. Our findings support the hypothesis of the existence of two different vulnerability pathways for the development of AUD: anxiety and disinhibitory behaviour.

Cytotoxic T lymphocytes and natural killer cells display impaired cytotoxic functions and reduced activation in patients with alcoholic hepatitis.

The dynamics and role of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, and NKT cells in the life-threatening inflammatory disease alcoholic hepatitis is largely unknown. These cells directly kill infected and damaged cells through, e.g., degranulation and interferon-γ (IFNγ) production, but cause tissue damage if overactivated. They also assist tissue repair via IL-22 production. We, therefore, aimed to investigate the frequency, functionality, and activation state of such cells in alcoholic hepatitis. We analyzed blood samples from 24 severe alcoholic hepatitis patients followed for 30 days after diagnosis. Ten healthy abstinent volunteers and 10 stable abstinent alcoholic cirrhosis patients were controls. Using flow cytometry we assessed cell frequencies, NK cell degranulation capacity following K562 cell stimulation, activation by natural killer group 2 D (NKG2D) expression, and IL-22 and IFNγ production. In alcoholic hepatitis we found a decreased frequency of CTLs compared with healthy controls (P < 0.001) and a similar trend for NK cells (P = 0.089). The NK cell degranulation capacity was reduced by 25% compared with healthy controls (P = 0.02) and by 50% compared with cirrhosis patients (P = 0.04). Accordingly, the NKG2D receptor expression was markedly decreased on NK cells, CTLs, and NKT cells (P < 0.05, all). The frequencies of IL-22-producing CTLs and NK cells were doubled compared with healthy controls (P < 0.05, all) but not different from cirrhosis patients. This exploratory study for the first time showed impaired cellular cytotoxicity and activation in alcoholic hepatitis. This is unlikely to cause hepatocyte death but may contribute toward the severe immune incompetence. The results warrant detailed and mechanistic studies.

Fatores de risco cardiovascular em alcoolistas em tratamento

OBJETIVO: Avaliar a presença de fatores de risco cardiovascular, com ênfase na hipertensão e na adiposidade corporal, em alcoolistas abstinentes ou não abstinentes em tratamento. MÉTODO: Trata-se de um estudo transversal com 65 pacientes alcoolistas em tratamento no CAP-Sad. O grau de dependência do álcool foi avaliado pelo SADD (Short Alcohol Dependence Data) e o uso de outras drogas, pelo ASSIST (Alcohol Smoking and Substance Involvement Screening Test). Foram avaliados o perfil bioquímico e o antropométrico dos usuários. RESULTADOS: Participaram do estudo 42 homens e 23 mulheres. A maioria dos participantes (67,74%) apresentou dependência alcoólica grave, com uso de álcool associado principalmente a cigarro (66,15%). A média da circunferência da cintura (CC) foi significativamente maior entre os abstinentes, em comparação aos não abstinentes (AB: 88,15 ± 15,95 x NA: 81,04 ± 9,86; p = 0,03). Pacientes abstinentes há mais tempo tiveram maior sobrepeso/obesidade e adiposidade abdominal (CC) do que os não abstinentes e abstinentes recentes, com razão de chances de 5,25. Os abstinentes apresentaram razão de chances de 3,38 para %GC acima da média, independente do tempo de abstinência. CONCLUSÃO: Pacientes alcoolistas abstinentes apresentam mais sobrepeso/ obesidade, adiposidade corporal (%GC) e abdominal (CC) do que os não abstinentes. É importante o acompanhamento multiprofissional no tratamento de alcoolistas com abordagem para fatores de risco cardiovasculares, principalmente evitando o ganho de peso.

Neural Evidence for Emotional Involvement in Pathological Alcohol Craving

Reducing craving is a key to success in the treatment of alcohol dependence. The emotion circuit may be involved in pathological craving for alcohol. In this study, we investigated neural correlates of emotional involvement in craving in alcohol dependence. The study included 17 detoxified alcoholic patients and 25 social drinkers. We used functional magnetic resonance imaging to examine brain activation (blood oxygen level-dependent signals) while participants reported craving and emotion in response to visually presented, alcohol-related stimuli and emotional stimuli. In the craving-rating paradigm, negative emotional stimuli as well as alcohol cues activated craving-related brain regions in alcoholic patients. Activations of the inferior parietal lobule and dorsolateral prefrontal cortex by negative emotional stimuli were negatively correlated with craving; meanwhile limbic activation was positively correlated with craving. For the emotion paradigm, greater limbic activation was evident by alcohol-related stimuli in the alcohol-dependent group. Our findings constitute neural evidence for emotional involvement in pathological craving for alcohol, underscoring the importance of emotion management in abstinent alcoholic patients for relapse prevention.

Markers of Bone Resorption and Formation During Abstinence in Male Alcoholic Patients

Reduced bone mineral density (BMD) is commonly found in alcohol-dependent patients. Many risk factors have been reported, yet the course of markers of bone formation and resorption in abstinent alcoholic patients have not received much attention. In a prospective longitudinal study, we investigated BMD in male abstinent inpatients of an alcohol rehabilitation clinic aged 21 to 50years at baseline and after 8weeks of treatment. At baseline and at week 8, all patients had blood drawn for the analysis of liver function tests, calcium, phosphate, parathormone, 25-hydroxyvitamin D, osteocalcin (OC), serum crosslaps, sex hormones, and prolactin. BMD was determined by dual X-ray absorptiometry in the lumbar spine and the proximal right femur. We also determined the amount of physical activity prior to inpatient treatment by using the International Physical Activity Questionnaire (IPAQ). Low BMD was found in 15.1% of the patients for the lumbar spine, in 5.7% for the femoral neck, and in 1.9% for the total hip. BMD differed significantly from normal values, in the lumbar spine and in the femoral neck. At baseline, crosslaps were elevated in 34% of the patients, while OC levels were lowered in 17%. Over the course of the 8weeks, we found a significant increase in OC plasma levels, indicating a higher rate of bone formation during continuous abstinence. There were also positive correlations between IPAQ scores and BMD as reflected by Z-scores in all regions, pointing to a protective effect of physical activity. In summary, this report confirms earlier cross-sectional studies of lowered BMD in alcoholic noncirrhotic men. We could also demonstrate that the initial imbalance between bone formation and resorption seems to adjust toward a balance between the two during abstinence.

Impairments of Prepulse Inhibition of the Startle Response in Abstinent Alcoholic Male Patients

Prepulse inhibition (PPI) of the startle reflex, which refers to the ability of innocuous sensory events to reduce the startle reflex, has been described as an operational measure of sensorimotor gating that is reduced in several neuropsychiatric disorders, such as schizophrenia, but experience is lacking in addictions and alcoholism. The aim of this study was to examine the existence of impairments in the startle response and PPI in abstinent alcoholic men. Testing for PPI was conducted on 60 abstinent alcoholic men aged 18-65 years (mean 46.37) who met DSM-IV criteria for alcohol dependence and had been abstinent for more than a month at the time of testing. The comparison group were compared with 37 sex- age- and education-matched controls without alcohol dependence. Magnitudes of the startle reflex were lower in patients than in controls. The differences were statistically significant (P < 0.05) in trials with prepulses presented 30 and 120 ms before the onset of the startle stimulus. There was also a statistically significant (P < 0.05) reduced percentage of PPI when the prepulse was presented 30 ms before the startle stimulus. These data suggest that sensory information processing mechanisms could be damaged in abstinent alcoholic patients. The fact that these findings are common to other psychiatric disorders could indicate the existence of a common vulnerability marker and explain the high degree of comorbidity between alcoholism and other mental illnesses.

Patients with functional psychoses show similar visual backward masking deficits

Recent genetic, behavioral, and clinical studies suggest that functional psychoses (schizophrenia, bipolar disorder, schizoaffective disorder), previously thought to be distinct from each other, may belong to one continuum. The shine-through masking paradigm is a potential endophenotype of schizophrenia with high sensitivity and specificity for discriminating between patients, their clinically unaffected relatives, and healthy controls. Hence, if schizophrenia, bipolar disorder and schizoaffective disorder belong to one common disease, strong masking deficits are expected to occur in all three diseases whereas no masking deficits are expected for abstinent alcoholic or depressive patients. Indeed, we found masking to be much stronger in psychotic patients compared to controls and to depressive patients and abstinent alcoholics, who performed on similar levels.

Reduced Fronto‐Cerebellar Functional Connectivity in Chronic Alcoholic Patients

Alcohol dependence is associated with neurocognitive deficits related to neuropathological changes in structure, metabolism, and function of the brain. Impairments of motor functioning in alcoholics have been attributed to well-characterized neuropathological brain abnormalities in cerebellum. Using functional magnetic resonance imaging (fMRI), we studied in vivo the functional connectivity between cerebellar and cortical brain regions. Participants were 10 uncomplicated chronic alcoholic patients studied after 5 to 7 days of abstinence when signs of withdrawal had abated and 10 matched healthy controls. We focused on regions of prefrontal, frontal, temporal, and parietal cortex that exhibited an fMRI response associated with nondominant hand finger tapping in the patients but not in the controls. We predicted that fronto-cerebellar functional connectivity would be diminished in alcoholics compared with controls. Functional connectivity in a circuit involving premotor areas (Brodmann Area 6) and Lobule VI of the superior cerebellum was reduced in the patients compared with the controls. Functional connectivity was also reduced in a circuit involving prefrontal cortex (Brodmann Area 9) and Lobule VIII of the inferior cerebellum. Reductions in connectivity were specific to fronto-cerebellar circuits and were not found in other regions examined. Our findings show a pattern in recently abstinent alcoholic patients of specific deficits in functional connectivity and recruitment of additional brain regions for the performance of a simple finger-tapping task. A small sample, differences in smoking, and a brief abstinence period preclude definitive conclusions, but this pattern of diminished fronto-cerebellar functional connectivity is highly compatible with the characteristic neuropathological lesions documented in alcoholics and may reflect brain dysfunction associated with alcoholism.

Platelet activity and genetics of MAO B: How do they relate to impulsivity and aggression?

Low platelet MAO B activity has been shown to be associated with alcoholism as well as impulsivity.So far it is not clear, if polymorphisms of the MAO B gene are related to MAO B levels in platelets and to aspects of alcoholism and impulsivity. So this study investigated, if the intron 13 A/G polymorphism of the MAO B gene is related to MAO B plasma levels and if both biomarkers relate to aspects of alcoholism and impulsivity. Methods: A sample of 60 male abstinent alcoholic patients participated in an experimental Go/NoGo discrimination task as a behavioral measure of impulsivity, filled in questionnaires on aggression and impulsivity, and gave blood samples for genetic analyses and MAO B activity in platelets. Results: Although platelet MAO activity and the genotype were neither associated to each other nor to aspects of alcohol history, both the G allele of the genotype and lower MAO B activity were related to faster reaction times in the behavioral impulsivity paradigm. On questionnaires G allele carriers scored higher on aggression, while A allele carriers were higher on experience seeking. MAO B activity, on the other hand, was associated with impulsivity. So the two biomarkers evidently differentially affect impulsivity and antisocial behavior but may both relate to the component of speed. Conclusions: The MAO B intron 13 A/G polymorphism may not be the most crucial of several genetic polymorphisms for MAO B activity, but does indicate relevance as a behavioral marker.

Clinical effectiveness of attentional bias modification training in abstinent alcoholic patients

A new training to decrease attentional bias (attentional bias modification training, ABM) was tested in a randomized controlled experimental study with alcohol-dependent patients as an addition to cognitive behavioral therapy. In alcohol dependence, attentional bias has been associated with severity of alcoholism, craving, treatment outcome, and relapse. Forty-three patients with DSM-IV diagnosis of alcohol dependence were randomly assigned to an ABM intervention or control training. The procedure consisted of five sessions in which patients were trained to disengage attention from alcohol-related stimuli (ABM condition) or in which they were trained on an irrelevant reaction-time test (control condition). We measured the effects of ABM on the visual-probe task, with stimuli that were presented in the ABM and with new stimuli. Craving was measured with the Desires for Alcohol Questionnaire. Follow-up data were gathered for overall treatment success, and relapse up to 3 months after the intervention. ABM was effective in increasing the ability to disengage from alcohol-related cues. This effect generalized to untrained, new stimuli. There were no significant effects on subjective craving. For other outcome measures there were indications of clinically relevant effects. Results indicate that ABM among alcohol-dependent patients was effective and that it may affect treatment progression. Large-scale trials are warranted to further investigate this new field.

PW01-235 - Impairments on the startle reflex and the prepulse inhibition in abstinent alcoholic males

ObjectivesStartle reflex (SR) is a defensive response to sudden, intense stimuli. Prepulse inhibition (PPI) refers to the ability of innocuous sensory events to reduce SR. PPI has been described as an operational measure of sensorimotor gating that is reduced in several neuropsychiatric disorders, such as schizophrenia, but there is no extensive experience in addictions and alcoholism. The objective of this study was to examine the existence of impairments on SR and PPI in abstinent alcoholic males.MethodsSubjects were 40 abstinent alcoholic males, aged 18 to 65 years (mean age 44.73), who had met DSM-IV criteria for Alcohol Dependence, being abstinent for more than a month at the moment they were tested. Participants underwent testing for PPI. Subjects were then compared with 35 equal controls.ResultsMagnitudes of the SR were lower in abstinent alcoholic males when compared with controls. This differences were significant (p&lt; 0,05) in trials with prepulse presented 30, 60 or 120 msec before the onset of startle stimulus. There was a significant less percentage of PPI when prepulse was presented 30 msec before the startle stimulus (p&lt; 0,05).ConclusionsAbstinent alcoholic males exhibit a decrease in the startle response magnitude and in the PPI of the SR. These data suggest that sensory information processing mechanisms could be damaged in abstinent alcoholic patients. The fact that these findings are common to other psychiatric disorders, could indicate the existence of a common vulnerability marker, and could explain the important comorbidity between alcoholism and other mental illness.

Decreased neural activity in reward circuitry during personal reference in abstinent alcoholics—A fMRI study

Two of the most striking features in alcoholism are the irresistible craving for alcohol and the proceeding neglect of other activities and pleasures that were formerly relevant. Craving has been investigated extensively and is commonly due to a dysfunctional reward system. The neural basis of the neglect of self-relevant interests, which can be described as altered personal reference, and its association to the reward system, however, remains unclear. Using fMRI, we investigated neural activity during a paradigm that tested for both reward and personal reference with regard to the same stimuli, i.e., alcoholic and nonalcoholic pictures, in healthy subjects and abstinent alcoholic patients. Alcoholic patients showed slightly reduced signal changes in the brain stem adjacent to ventral tegmental area (VTA) and in the ventromedial prefrontal cortex (VMPFC) during the reward task, while we found no alterations in the right and left ventral striatum (VS). The same regions (VS, VTA, and VMPFC), however, showed reduced signal changes during personal reference with lack of neural differentiation between high and low referenced stimuli in alcoholic patients. In summary, we demonstrate for the first time neurophysiological alterations in reward circuitry during personal reference in alcoholic patients. Our results underline the important role of the reward circuitry during personal reference in the pathophysiology of alcohol addiction.

Estimated risk of hepatotoxicity after an acute acetaminophen overdose in alcoholics

A published logistic regression model based on the Canadian Acetaminophen Overdose Study registry was used to calculate the risk of hepatotoxicity after an acute acetaminophen overdose and to estimate a treatment threshold line for alcoholic patients who did not co-ingest alcohol (i.e., abstinent alcoholics) on the Rumack–Matthew nomogram. The risk of hepatotoxicity in nonalcoholic and abstinent alcoholic patients was calculated at the acetaminophen concentration of 150 μg/ml at 4 h (37.5 μg/ml at 12 h) treatment threshold line. This corresponds to the “possible risk” line on the Rumack–Matthew nomogram and represents a 1.6% risk of hepatotoxicity for nonalcoholic patients at or below this line. At or below this same 150 μg/ml at 4-h line, abstinent alcoholic patients have a hepatotoxicity risk of 10.7%. The risk of hepatotoxicity in abstinent alcoholics' equivalent to that of nonalcoholics (i.e., 1.6%) occurs at a lower acetaminophen concentrations treatment threshold line, that is, 104 μg/ml at 4 h (26 μg/ml at 12 h). Because of difficulties plotting this new line on the familiar Rumack–Matthew semilogarithmic scale, a line connecting 100 μg/ml at 4 h (25 μg/ml at 12 h) is proposed. This line equates to a 1.1% risk of hepatotoxicity in abstinent alcoholic patients. The analysis supports the observation that based on the published model abstinent alcoholics might have a greater risk of hepatotoxicity after an acute acetaminophen overdose. This proposed new risk line can be used in hypothesis generation for future clinical studies in this alcohol related problem.

Granulocyte‐colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis

Liver failure is the major cause of death in alcoholic steatohepatitis (ASH). In experimental hepatitis, granulocyte-colony stimulating factor (G-CSF) mobilizes hematopoietic stem cells, induces liver regeneration, and improves survival. We studied the short-term effects of G-CSF on CD34+ stem cell mobilization, liver cell proliferation, and liver function in patients with ASH. Twenty-four patients (mean age 54 years) with alcoholic cirrhosis [Child-Turcotte-Pugh score 10 (7-12)] and concomitant biopsy-proven ASH [Maddrey score 36 (21-60)] were randomized to standard care associated with 5 days of G-CSF (10 microg/kg/day, group A, n = 13) or standard care alone (group B, n = 11). Serial measurement of CD34+ cells, liver tests, cytokines [hepatocyte growth factor (HGF); tumor necrosis factor alpha; tumor necrosis factor-R1; interleukin-6; alfa-fetoprotein], and (13)C-aminopyrine breath tests were performed. Proliferating hepatic progenitor cells [HPC; double immunostaining (Ki67/cytokeratin 7)], histology, and neutrophils were assessed on baseline and day 7 biopsies. Abstinent alcoholic patients with cirrhosis served as controls for immunohistochemistry. G-CSF was well tolerated. At day 7, both CD34+ cells (+747% versus -6%, P < 0.003), and HGF (+212% versus -7%, P < 0.03) increased in group A but not in group B. Cytokines and aminopyrine breath test changes were similar between groups. On repeat biopsy, a >50% increase in proliferating HPC was more frequent in group A than in group B (11 versus 2, P < 0.003). Changes in Ki67+/cytokeratin 7+ cells correlated with changes in CD34+ cells (r = 0.65, P < 0.03). Neutrophils and histological changes were similar in both groups. G-CSF mobilizes CD34+ cells, increases HGF, and induces HPC to proliferate within 7 days of administration. Larger trials would be required to determine whether these changes translate into improved liver function.

Chronic Smoking Is Associated With Differential Neurocognitive Recovery in Abstinent Alcoholic Patients: A Preliminary Investigation

Approximately 50 to 90% of individuals in North America seeking treatment for alcoholism are chronic smokers. A growing body of evidence suggests that chronic cigarette smokers show a pattern of neurocognitive dysfunction similar to that observed in alcoholic patients. However, previous studies investigating neurocognitive recovery in abstinent alcoholic patients did not specifically consider the potential effects of chronic cigarette smoking. This study comprehensively compared longitudinal neurocognitive changes over 6 to 9 months of abstinence among 13 nonsmoking recovering alcoholic patients (ALC) and 12 actively smoking ALC. The neurocognitive performance of the alcoholic groups was compared with nonsmoking light-drinking controls (nonsmoking LD). Nonsmoking ALC exhibited a significantly greater magnitude of longitudinal improvement than smoking ALC on measures of cognitive efficiency, executive skills, visuospatial skills, and working memory. Both nonsmoking ALC and smoking ALC demonstrated equivalent improvement on auditory-verbal learning, auditory-verbal memory, and processing speed. Nonsmoking LD showed no significant changes in neurocognition over time. In cross-sectional comparisons at 6 to 9 months of abstinence, nonsmoking ALC were superior to smoking ALC on measures of auditory-verbal learning, auditory-verbal memory, cognitive efficiency, executive skills, processing speed, and working memory. The longitudinal and cross-sectional neurocognitive differences observed between nonsmoking and smoking ALC remained significant after covarying for group differences in education, estimated premorbid intelligence alcohol consumption, and other potentially confounding variables. In smoking ALC, greater smoking severity was inversely related to longitudinal improvement on multiple neurocognitive measures. These preliminary results suggest that chronic smoking may modulate neurocognitive recovery in abstinent alcoholic patients. More generally, chronic smoking may impact neurocognition in other conditions where is it a prevalent behavior.

Adrenocorticotropic Hormone/Cortisol Response to Physical Exercise in Abstinent Alcoholic Patients

Alterations in the hypothalamic-pituitary-adrenal (HPA) axis in alcoholic patients have been reported in various experimental conditions. To establish whether alcoholism affects the HPA axis activation during physical exercise, 10 recent abstinent alcoholic patients (age range: 33-45 years; duration of alcohol dependence: range 4-6 years) were tested by exercising on a bicycle ergometer. Ten age-matched healthy nonalcoholic men participated as controls. The workload was gradually increased at 3-minute intervals until exhaustion and lasted about 15 minutes for all subjects. Alcoholic patients were tested at 3 time points, at 4, 6, and 8 weeks after alcohol withdrawal, whereas controls were tested only once. Main outcome measurements were circulating levels of adrenocorticotropic hormone (ACTH) and cortisol and physiological variables during physical exercise [heart rate, blood pressure, ventilation, frequency of breathing, tidal volume, oxygen consumption (VO2), carbon oxide production (VCO2), and respiratory exchange ratio (R)]. Similar basal and exercise-induced changes in physiological variables were observed in controls and alcoholic patients in all tests. Basal levels of ACTH and cortisol were similar in all tests performed on alcoholic patients and on normal controls. In normal subjects, exercise induced a significant increase in plasma ACTH and serum cortisol levels, with peak levels at 20 minutes for ACTH (84% higher than baseline) and at 30 minutes for cortisol (70% higher than baseline). After 4 weeks of abstinence, slight but not significant ACTH/cortisol responses to physical exercise were observed in alcoholic patients (mean peaks were 10 and 18% higher than baseline, respectively, for ACTH and cortisol). By contrast, when the exercise test was repeated after 6 weeks abstinence, ACTH/cortisol levels rose significantly versus baseline (mean peak levels of ACTH and cortisol were 48 and 38% higher than baseline, respectively, for ACTH and cortisol). However, the hormonal responses were significantly lower than in the normal controls. At 8 weeks of abstinence, ACTH/cortisol responses were significantly higher than 2 weeks previously, and were not distinguishable from the increments observed in the normal controls (76 and 68% higher than baseline, respectively, for ACTH and cortisol). In concurrence with previous reports showing alterations of the HPA axis in the central nervous system in alcohol-dependent subjects, these data show a defect of the neuroendocrine mechanism(s) underlying the ACTH/cortisol response to physical exercise for at least a month after alcohol withdrawal, with reconstitution of a normal hormonal response at 8 weeks.

An open trial of cognitive-behavioral treatment for insomnia comorbid with alcohol dependence

Objective: We evaluated the efficacy of cognitive-behavioral treatment for insomnia in recovering alcoholic patients in an open pilot study. Methods: Seven abstinent alcoholic patients (3 women, mean age 38.6 ± 10.8 years) recruited from outpatient and residential treatment facilities met the Diagnostic and Statistic Manual of Mental Disorders – Fourth edition (DSM-IV) criteria for insomnia comorbid with alcohol dependence and participated in eight individual treatment sessions. Participants were free of other medical, psychiatric, and sleep disorders. Daily sleep diaries were completed beginning two weeks before treatment until two weeks after treatment. Measures of sleep, daytime functioning, and drinking were collected. Results: Diary-rated sleep latency [ F (2, 10) = 14.4, p < .001], wake after sleep onset [ F (2, 10) = 7.7, p = .009], and sleep efficiency [ F (2, 10) = 28.3, p < .001] improved as did patient-rated and clinician-rated Insomnia Severity Index (ISI) and the Dysfunctional Beliefs and Attitudes about Sleep – Short Form (DBAS-SF). Compared to pre-treatment, significant post-treatment improvements were found on scales measuring depression and anxiety symptoms, fatigue, and quality of life. No one relapsed to alcohol during treatment. Conclusions: Cognitive-behavioral insomnia therapy may benefit recovering alcoholics with mild to moderate insomnia by improving sleep and daytime functioning. Effects on relapse remain to be determined. Findings need to be interpreted cautiously due to the uncontrolled design and lack of follow-up assessments.

Time Course of Attention for Alcohol Cues in Abstinent Alcoholic Patients: The Role of Initial Orienting

Addicted people are characterized by enhanced attention for drug cues leading to drug use. However, there is little research on the component processes of attention in individuals with alcoholism. Here, we examine 2 distinct components of attention in abstinent alcohol-dependent individuals and social drinkers of alcohol, that is to say, the initial orienting to alcohol-related cues, and the maintenance of attention to them. The present study used an "alcohol" version of the visual probe detection task with alcohol-related or neutral pictures being presented briefly (i.e., 50 ms), to assess initial orienting, or longer (i.e., 500 and 1,250 ms), to assess the maintenance of attention. Only alcoholic patients were faster in detecting a probe displayed immediately after pictures related to alcohol presented for 50 ms than in detecting the same probe replacing non-alcohol-related pictures. However, when pictures were presented for 500 ms, only social alcohol drinkers were faster in detecting the probe replacing alcohol scenes. At a stimulus of 1,250 ms duration, no group showed attentional bias toward alcohol cues. In addition, the severity of alcoholism measured by the total number of prior detoxification treatments was positively correlated with the attentional bias (or "attraction") for alcohol pictures presented for 50 ms. These results show that, subsequent to initial visual orienting to alcohol-related cues, abstinent patients' attention was disengaged from these stimuli, thus suggesting a visual approach-disengagement attentional pattern. The influence of these findings on relapse was discussed.

Correlation of Alcohol Craving With Striatal Dopamine Synthesis Capacity and D2/3 Receptor Availability: A Combined [18F]DOPA and [18F]DMFP PET Study in Detoxified Alcoholic Patients

In abstinent alcoholic patients, a low availability of dopamine D2/3 receptors in the ventral striatum and adjacent putamen was associated with a high level of craving for alcohol. Alcohol craving may also depend on presynaptic dysfunction of striatal dopamine production, which may contribute to the risk of relapse. In this study, positron emission tomography (PET) was used to compare dopamine synthesis capacity in the striatum in alcoholic patients and healthy comparison subjects. Positron emission tomography (PET) was used to map the net blood-brain clearance of the dopa decarboxylase substrate 6-[18F]fluoro-l-dopa, an index of dopamine synthesis capacity, in the striatum of 12 detoxified male alcoholic patients and 13 age-matched healthy men. The parametric maps were correlated with results of an earlier [18F]desmethoxyfallypride PET study of dopamine D2/3 receptor availability in the same 12 alcoholic patients and in 12 of the healthy volunteers. Alcohol craving was measured with the Alcohol Craving Questionnaire. Patients were followed for 6 months, and alcohol intake was recorded. The magnitude of net blood-brain clearance in the striatum did not differ significantly between detoxified alcoholic patients and the comparison subjects. However, a voxel-wise correlation analysis of net blood-brain clearance in the alcoholic patients linked low levels of dopamine synthesis capacity in the bilateral putamen with high levels of alcohol craving. After normalization of net blood-brain clearance maps to the voxel-wise estimates of dopamine D2/3 receptor availability, there was still a negative correlation with alcohol craving. Alcohol craving at the time of scanning was associated with high level of alcohol intake in the 6-month follow-up period. Simultaneous assay by PET of pre- and postsynaptic markers of dopamine neurotransmission indicated that a striatal dopamine deficit correlated with alcohol craving, which was associated with a high relapse risk.