M. Marin

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

AIMS 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Correlation Between Clinical and Drinking Variables, and Psychophysiological Processes Involved in Alcohol Dependence

Background Alcoholics show attentional bias when viewing alcohol-related pictures, a low magnitude of the startle response when viewing alcohol-related cues, and a poor inhibitory control. However, it has not been studied which clinical and drinking variables modulate these paradigms. Objectives To explore which clinical and drinking variables modulate attentional bias, affective modulation of the startle reflex and behavioural inhibition in alcoholics. Methods 127 alcoholics were tested with 3 psychophysiological tasks: the dot probe task (attentional bias), the startle response when viewing alcohol cues (affective modulation of the startle reflex) and the Stop Signal Task-Modified (behavioural inhibition). Clinical variables were evaluated using the Barrat Scale (BS), the Hamilton Anxiety Scale (HAS) and the Hamilton depression Scale (HDS). Drinking variables were assessed with the Timeline follow back (TLF). Results Attentional bias correlated with the number of drinking days, mean intake of alcohol and score of the HDS. Affective modulation of the startle reflex correlated with mean intake of alcohol, scores of the HDS and the BS. Behavioural inhibition correlated with scores of the HDS, the HAS and the BS. Conclusions Psychophysiological tasks correlated with drinking variables (mean intake of alcohol and the number of drinking days) and clinical variables (impulsivity, anxiety and depression). Clinicians should take these variables into account when treating alcoholics because they can be controlled with appropriate pharmacological treatment and it is well known that attentional bias, affective modulation of the startle reflex and behavioural inhibition are implicated in maintaining alcohol consumption and increasing the risk of relapse.

Startle-Response Based Tasks and Laboratory Measures of Impulsivity in Abstinent Alcoholic Patients

AIMS 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). METHODS SUBJECTS 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. RESULTS 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. CONCLUSIONS 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.

EPA-0843 - Relationship between psychophysiological processes involved in alcohol dependence

Background Current data suggest that at least three psychophysiological paradigms are involved in Alcohol Dependence: attentional bias; affective modulation of the startle reflex and behavioural inhibition. These three paradigms have not been studied together in a sample of alcohol dependent subjects. Objectives To show that the performance on these three psychophysiological processes allows discriminating alcohol dependent subjects (with different severity) from healthy controls. Methods 59 alcohol dependent subjects were assessed with the following three psychophysiological tasks: The dot probe task (which assesses attentional bias), the startle response when viewing alcohol cues (which evaluates affective modulation of the startle reflex), and the Modified- Stop Signal-Task (which measures behavioral inhibition). The Severity of Alcohol Dependence Scale (SAD) was used for grouping patients based on their dependence severity. 52 healthy subjects were assessed as the control group. Results All three paradigms correctly discriminated between patients and controls. Patients were divided into three subgroups according to their scores on the SAD (mild, moderate and severe dependence). The performance of the three groups in the three paradigms studied was also different. Patients with more severe dependence had more attentional bias for alcohol cues, exhibited lower magnitudes of startle response when viewing alcohol cues, and showed lower capacity to inhibit their behaviour when words related to alcohol were being seen. Conclusions Subjects with alcohol dependence showed different psychophysiological response patterns compared to controls in the three paradigms studied. These response patterns seem to be associated with the severity of dependence, and they could be used to determine the outcome of the treatment in patients with alcohol dependence.

1999 – Continuation (C-ECT) and maintenance (M-ECT) electroconvulsive therapy as an alternative treatment to pharmacotherapy: a review

Introduction ECT has demonstrated to be an effective and safe biological treatment that can be considered as an alternative to pharmacotherapy, especially for treating severe, resistant and recurrent, affective, psychotic and catatonic symptoms. CECT refers to the one that is started after acute treatment and lasts for a maximum period of 6 months with the objective of preventing relapse. M-ECT is the one that is started once C-ECT has ended with the aim of preventing recurrences. The aim of this study was to explore the evidence for using C-ECT and M-ECT as an alternative to pharmacotherapy. Methods We performed a search in MEDLINE, PubMed and Cochrane, from 1950 until the present to identify articles in which C-ECT and M-ECT were used as alternative treatments to pharmacotherapy. Results C-ECT and M-ECT have demonstrated to be an effective and safe alternative to pharmacotherapy in Unipolar Depression, Bipolar Disorder and Schizophrenia, especially in the prevention of relapse and recurrences. It reduces number and days of hospitalization. In combination with pharmacotherapy, it increases effectiveness of pharmacological treatment. It does not affect cognitive functioning. Conclusions C-ECT and M-ECT should be considered as an alternative to pharmacotherapy in the treatment of affective and psychotic, severe, resistant and recurrent symptoms. It is an effective and safe treatment, which prevents relapse and recurrences in severe mental illness, reducing hospitalization rates and health costs.

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

Objectives Startle 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. Methods Subjects 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. Results Magnitudes of the SR were lower in abstinent alcoholic males when compared with controls. This differences were significant (p Conclusions Abstinent 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.

P03-219 - New agents for the benzodiazepine withdrawal syndrome

Objectives Benzodiazepines are widely used drugs. However, their chronic use has revealed that they can lead to dependence. The objective of this study is to review the different pharmacological strategies used in the management of benzodiazepine dependence and new trends in pharmacological interventions. Method We searched in MEDLINE and in the Cochrane Database System Review, selecting studies from 1980 until the present, in which a pharmacological intervention was made for benzodiazepine detoxification in mono-dependence cases. Results There is a consensus about gradual rather than abrupt tapering benzodiazepines in benzodiazepine discontinuation. Other extended traditional strategy has been switching from short half-life to long half-life benzodiazepines before gradual taper. A great variety of agents have been used as adjuvant medication in Benzodiazepine Withdrawal Syndrome (BWS) with varying degrees of success. In the last years research has focus in the use of anticonvulsant drugs. Both carbamzepine and valproate, have demonstrated to be beneficial in benzodiazepine discontinuation. Also, preliminary data suggest that new anticonvulsant agents (gabapentin, pregabalin, oxcarbazepine and topiramate) could be helpful. Discussion Although multiple drugs have been investigated for pharmacological management of BWS, only few have demonstrated significant efficacy. Anticonvulsant drugs are one of them. Both, carbamazepine and valproate, have shown benefits in reducing withdrawal severity. The available data currently support the use of new anticonvulsant (gabapentin, pregabalin, oxacarbazepine and topiramate), in the treatment of different drug-dependences such as alcohol, cocaine and opiate dependence. Moreover, there is a growing trend in the literature toward the use of these agents in benzodiazepine mono-dependence.

PW01-236 - Impulsivity and startle habituation as vulnerability markers for alcoholism

Background Impulsivity has been considered as a risk factor for alcohol dependence. Recent research is focusing on paradigms of the startle response (SR), specifically prepulse inhibition (PPI) and startle habituation (SH), as vulnerability markers for alcoholism. It has been demonstrated impairments in the PPI and the SH in offspring of alcoholics. It has also been shown, using personality questionnaires, that faster habituation may be associated with tendency toward impulsivity and behavioral disinhibition. Our goal is to study the correlation between impulsivity laboratory measures and the SR paradigms, in order to see if they could share a common base as endophenotypes for alcoholism. Method The subjects were 40 abstinent alcoholic males, aged 18 to 65 years (mean age 44.73) and 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 and habituation of the acoustic startle response. Impulsivity was assessed with three different laboratory measures: Continuous Performance Test (CPT), Stop-Signal Task and Differential Reinforcement for Low-Rate Responding (DRL6). Analyses were performed using SPSS v.10.0. Results We found a significant positive correlation between CPT-tasks and SH (p Conclusions Our findings suggest the existence of a common base between impulsivity and SH as vulnerability markers for alcohol dependence. Further studies are needed to assess if both could share a common genetic origin.