Paul Verbanck

Alcohol and withdrawal: From animal research to clinical issues

The withdrawal syndrome in alcohol-dependent patients appears to be a major stressful event whose intensity increases with repetition of detoxifications according to a kindling process. Disturbances in the balance between excitatory and inhibitory neural processes are reflected in a perturbed physical state while disturbances in the balance between positive and negative reinforcements are reflected in a perturbed mood state. Our purpose is to link the different behavioral outcomes occurring during withdrawal with specific biological brain mechanisms from the animal to the human being. Better understanding of the various biological mechanisms underlying withdrawal from alcohol will be the key to design and to apply appropriate pharmaceutical management, together with appropriate therapy aimed at inducing protracted abstinence.

Galanin decreases the activity of locus coeruleus neurons in vitro

A brain slice preparation was used to examine the effects of galanin on the spontaneous firing rate of locus coeruleus noradrenergic neurons. Galanin (10(-9)-10(-7) M), added to the bath, inhibited the firing of 14 out of 19 neurons in a concentration-dependent manner. The observed effect was quite variable, ranging from 20 to 100% at 10(-7) M. Experiments performed in low-Ca2+, high-Mg2+ medium also showed a significant inhibition by galanin (10(-7) M) in three out of five neurons, which suggests that the peptide acts directly.

Alcohol cues increase cognitive impulsivity in individuals with alcoholism

BackgroundIndividuals with alcoholism are characterized by both attentional bias for alcohol cues and prepotent response inhibition deficit. We tested the hypothesis that alcoholics exhibit greater cognitive disinhibition when the response to be suppressed is associated with alcohol-related information.MethodsForty recently detoxified individuals with alcoholism were compared with 40 healthy non-substance abusers on the “Alcohol-Shifting Task”, a variant of the go/no-go paradigm requiring a motor response to targets and no response to distracters. The aim was to test the ability of alcoholics to discriminate between alcohol-related and neutral words. Sometimes, the alcohol-related words were the targets for the “go” response, with neutral words as distracters, sometimes the reverse. Several shifts in target type occurred during the task.ResultsAlcoholics made significantly more commission errors (i.e., press a key when a distracter displayed) and more omission errors (i.e., not press a key when a target displayed) than controls. Moreover, the number of commission errors was greater in alcoholics when alcohol-related stimuli had to be detected.ConclusionsThese results demonstrate that alcoholics exhibit a basic prepotent response inhibition deficit, which is enhanced when the response to be suppressed is related to alcohol. We discuss clinical and theoretical implications of these findings.

Response inhibition deficit is involved in poor decision making under risk in nonamnesic individuals with alcoholism.

Individuals with alcoholism exhibit poor decision making as reflected by their continued alcohol use despite encountering problems and by low performance in laboratory tasks of decision making. Here, the authors investigated the relative contribution of several distinct processes of executive functions in performance on the Iowa Gambling Task (IGT; A. Bechara, A. R. Damasio, H. Damasio, & S. W. Anderson, 1994) in recently detoxified individuals with alcoholism. Compared to matched healthy participants, individuals with alcoholism showed below-normal scores in the last 20 trials of the IGT as well as on other tasks of executive functions, specifically those assessing the capacity to manipulate information stored in working memory, detect abstract rules, or inhibit prepotent responses. Prepotent response inhibition best predicted performance in the late trials of the IGT, that is, when participants have likely acquired knowledge about the reward/punishment contingencies of the task. These results underline the important role that response inhibition plays in decision making, especially in risky situations, when knowledge of the probability of a given outcome becomes available (i.e. decisions under risk).

Impaired emotional facial expression recognition in alcoholics, opiate dependence subjects, methadone maintained subjects and mixed alcohol-opiate antecedents subjects compared with normal controls.

The present study aims to explore whether an impairment in emotional facial expressions (EFE) decoding is specific to alcoholism compared with opiate dependence. An EFE decoding test consisting of 16 photographs of EFE portraying happiness, anger, sadness and disgust was administered to five different groups of 30 subjects each: recently detoxified alcoholics (RA); opiate addicts under methadone maintenance treatment (OM); detoxified opiate addicts (OA); detoxified subjects with both alcohol and opiate dependence antecedents (DAO); and normal controls (NC). Repeated measures analysis of variance using a multivariate approach was conducted on EFE decoding accuracy scores with group as the between-subjects factor. Accuracy scores were significantly lower in RA and DAO than in OM and OA, which had significantly lower scores than NC. Low accuracy scores in RA and DAO confirm previous results indicating that alcoholism is associated with impaired EFE recognition. Results in OM and OA indicate that opiate dependence is also associated with an impaired EFE decoding but less than in alcoholism. Alcohol and opiate chronic consumption could both exercise a deleterious effect on EFE-decoding brain function, alcohol having the most severe impact. Alternatively, EFE-decoding problems could be present before the development of alcohol and opiate dependence, with an additional effect of chronic alcohol consumption on EFE decoding. In this context, EFE-decoding impairment could reflect a more general emotional intelligence deficit in addicted populations.

Evidence for the presence of N-methyl-D-aspartate receptors in the ventral tegmental area of the rat : an electrophysiological in vitro study

Extracellular recordings were obtained from spontaneously active, presumed dopaminergic neurons of the ventral tegmental area (VTA) of the rat in a slice preparation. Bath-applied N-methyl-D-aspartate (NMDA) (1-20 microM) activated all neurons tested (n = 36). This effect was clearly concentration-dependent (n = 14), quickly reversible and reproducible. No bursting type of discharge was observed during NMDA infusion. The NMDA receptor blocker DL-2-amino-5-phosphonovaleric acid (50 microM) reversibly antagonized the increase in cell firing produced with 10 microM NMDA by 83.5 +/- 3% (mean +/- S.E.M.) (n = 8, P less than 0.05). Lowering the Mg2+ concentration of the perfusion fluid to one-third of its normal value significantly enhanced the excitatory effect of 5 microM NMDA (n = 7, P less than 0.05), but not of 500 nM carbachol (n = 6). Finally, NMDA did not modify the sensitivity of dopaminergic autoreceptors of VTA neurons (n = 8), when compared to controls (n = 10). These observations strongly support the presence of specific NMDA receptors in the VTA.

Impaired emotional facial expression recognition in alcoholism compared with obsessive-compulsive disorder and normal controls.

Emotional facial expression (EFE) decoding skills have been shown to be impaired in recovering alcoholics (RA). The aim of the present study is to replicate these results and to explore whether these abnormalities are specific to alcoholism using two control groups: non-patient controls (NC) and patients with obsessive-compulsive disorder (OC). Twenty-two alcoholic patients at the end of their detoxification process (RA) were compared to 22 OC and 22 NC matched for age, sex and education level. They were presented with 12 photographs of facial expressions portraying different emotions: happiness; anger; and fear. Each emotion was displayed with mild (30%) and moderate (70%) intensity levels. Each EFE was judged on 8 scales labeled happiness, sadness, fear, anger, disgust, surprise, shame and contempt. For each scale, subjects rated the estimated intensity level. RA were less accurate in EFE decoding than OC and NC, particularly for anger and happiness expressions. RA overestimated the emotional intensity for mild intensity level expressions compared with both OC and NC while no significant differences emerged for moderate intensity level expressions. Deficits in EFE decoding skills seem to be specific to RA when compared with OC. Comparison with other psychopathological groups is still needed. Possible consequences of EFE decoding deficits in RA include distorted interpersonal relationships.

Is the P300 deficit in alcoholism associated with early visual impairments (P100, N170)? An oddball paradigm

OBJECTIVE Studies exploring chronic alcoholism with event-related potentials (ERPs) have shown delayed latency and reduced amplitude of the P300, a long-lasting positive potential reflecting decisional processing. This P300 deficit in alcoholism is generally interpreted as a disturbance in central nervous system inhibition or in memory/attention. The present study aimed at identifying if this electrophysiological deficit is already present on earlier components, and advances a new hypothesis concerning the interpretation of the P300 alteration. METHODS Patients suffering from alcoholism and matched healthy controls had to detect, in an oddball paradigm, emotional faces among a succession of neutral faces. Behavioral performance and ERP data (recorded from 32 electrodes) were analyzed. RESULTS In line with previous studies, data showed that alcoholism led to a P300 deficit. Moreover, we observed for the first time that this deficit begins at earlier visual (P100) and face-processing (N170) stages, and we found high positive correlations between P100, N170 and P300 for amplitude and latency values, suggesting cumulative deficits on the cognitive continuum. CONCLUSIONS We suggest that the P300 deficit observed in chronic alcoholism could be linked to earlier visuo-spatial deficits rather than being an impairment of the specific processes linked to the P300. SIGNIFICANCE These results call for reconsidering the interpretation of P300 impairments at a fundamental and clinical level, and shows that earlier ERP components must be taken into account in future studies.

Major depression is associated with impaired processing of emotion in music as well as in facial and vocal stimuli

BACKGROUND The processing of emotional stimuli is thought to be negatively biased in major depression. This study investigates this issue using musical, vocal and facial affective stimuli. METHODS 23 depressed in-patients and 23 matched healthy controls were recruited. Affective information processing was assessed through musical, vocal and facial emotion recognition tasks. Depression, anxiety level and attention capacity were controlled. RESULTS The depressed participants demonstrated less accurate identification of emotions than the control group in all three sorts of emotion-recognition tasks. The depressed group also gave higher intensity ratings than the controls when scoring negative emotions, and they were more likely to attribute negative emotions to neutral voices and faces. LIMITATIONS Our in-patient group might differ from the more general population of depressed adults. They were all taking anti-depressant medication, which may have had an influence on their emotional information processing. CONCLUSIONS Major depression is associated with a general negative bias in the processing of emotional stimuli. Emotional processing impairment in depression is not confined to interpersonal stimuli (faces and voices), being also present in the ability to feel music accurately.

Reduced cholecystokinin immunoreactivity in the cerebrospinal fluid of patients with psychiatric disorders.

The close relationship of cholecystokinin peptides with some of the dopamine pathways and the limbic system suggests a putative role for these peptides in the pathophysiology of neuropsychiatric disorders such as Parkinsons disease, manic-depression and schizophrenia. By use of radioimmunoassay, we report a significant decrease in cholecystokinin-immunoreactivity in the cerebrospinal fluid of patients with bipolar manic-depression and untreated schizophrenia in comparison to control subjects.