Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia

Department of Psychiatry, Columbia University, New York, New York, United States
Neuropsychopharmacology (Impact Factor: 7.05). 01/2007; 31(12):2767-75. DOI: 10.1038/sj.npp.1301207
Source: PubMed


The purpose of this study was to determine whether schizophrenia was associated with alterations in alcohol response that might explain the elevated risk for AUDs in this population. In a randomized, double-blind, placebo-controlled, counter-balanced 3 test day laboratory study, the effects of alcohol were compared in 23 subjects with schizophrenia (without any previous alcohol use disorder (AUD) but with some alcohol exposure) and in 14 healthy subjects matched for age, gender, education, and lifetime exposure to alcohol. Standard alcohol drinks in a scheduled design were administered to produce blood alcohol levels of 0, 0.02-0.04 mg%, or 0.06-0.08 mg%. Schizophrenia symptoms, perceptual alterations, stimulant and depressant subjective effects of alcohol, and 'high' were measured before alcohol administration and at several post-drug time points. Verbal learning and recall, vigilance and distractibility, and motor function were assessed once per test day. Relative to healthy subjects, subjects with schizophrenia reported greater euphoria and stimulatory effects in response to alcohol. Alcohol produced small transient increases in positive psychotic symptoms and perceptual alterations without affecting negative symptoms. Alcohol also impaired several aspects of immediate and delayed recall, and vigilance, and distractibility. Schizophrenia patients showed increased euphoric and stimulatory responses to alcohol. These exaggerated positive responses to alcohol doses may contribute to the increased risk for AUDs associated with schizophrenia. The absence of 'beneficial' effects of alcohol does not support a self-medication hypothesis of alcohol use in schizophrenia.

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Available from: Tahir Tellioglu, Apr 15, 2014
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    • "Neurodevelopmental abnormalities involving these systems in NVHLs may be particularly sensitive to the reinforcing effects of ethanol when sucrose is present, as suggested by our findings. While the euphoric effects of ethanol may be a subjective correlate of the positive reinforcing effects of ethanol [21], the euphoric effects of ethanol have been shown to be enhanced in schizophrenia when patients are given a carbohydrate/ethanol solution [22]. "
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    ABSTRACT: Alcohol abuse in schizophrenia exceeds rates in the general population and worsens illness outcomes. Neonatal ventral hippocampal lesion (NVHL) rats model multiple schizophrenia dimensions including addiction vulnerability. This study compared NVHL vs. SHAM-controls in operant alcohol seeking and consumption. NVHLs enhanced consumption of combined ethanol/sucrose solution but neither ethanol or sucrose only solutions, consistent with increased vulnerability specific to carbohydrate-laden alcohol beverages typically consumed in early stages of human alcoholism.
    Behavioural brain research 04/2011; 218(2):346-9. DOI:10.1016/j.bbr.2010.12.017 · 3.03 Impact Factor
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    • "Both dopaminergic and serotonergic systems play a crucial role in the development of ethanol dependence (Kuriyama and Ohkuma, 1990; Uzbay, 2008), and recent reports indicate that there is a relationship between schizophrenia and ethanol dependence (D'Souza et al., 2006; Seeman et al., 2006; Conroy et al., 2007). There may be potential beneficial effects of new atypical antipsychotic drugs in the treatment of the signs of ethanol withdrawal as well as blocking the craving effects of ethanol (Drake et al., 2000; Hutchison et al., 2003). "
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    ABSTRACT: Comorbid substance use in schizophrenic patients is common, and substance dependence is a predictive factor for psychosis. The present study was designed to investigate the effects of risperidone, quetiapine and ziprasidone, atypical antipsychotic drugs, on ethanol withdrawal syndrome (EWS) in rats. Adult male Wistar rats were used in the study. Ethanol (7.2%, v/v) was given to rats via a liquid diet for 21 days. An isocaloric liquid diet without ethanol was given to control rats. Risperidone (1 and 2 mg/kg), quetiapine (8 and 16 mg/kg), ziprasidone (0.5 and 1 mg/kg) and vehicle were injected into rats intraperitoneally at 1.5 and 5.5 h of ethanol withdrawal. At the 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, stereotyped behaviors, abnormal gait and posture, tail stiffness and agitation were recorded or rated. Following the observations at the 6th hour, the rats were tested for audiogenic seizures. All three drugs had some significant inhibitory effects on EWS-induced behavioral signs beginning at the 2nd hour of withdrawal. The drugs also significantly reduced the incidence of audiogenic seizures. Overall, risperidone and quetiapine seemed to be more effective than ziprasidone in ameliorating the withdrawal signs. Doses of the drugs used in the present study did not produce any significant changes in locomotor activities of naïve rats. Our results suggest that risperidone, quetiapine and ziprasidone had beneficial effects on EWS in rats. Thus, these drugs may be helpful for controlling withdrawal signs in ethanol-dependent patients.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 12/2010; 35(2):528-36. DOI:10.1016/j.pnpbp.2010.12.009 · 3.69 Impact Factor
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    • "The high prevalence of alcohol use disorders (AUD, i.e. alcohol abuse or dependence) among patients with schizophrenia is now well established: in the Koskinen et al.’ meta-analysis of 60 studies, the median current rate of AUD was 9.4% and median of lifetime AUD prevalence 20.6% (Koskinen et al., 2009). The high comorbidity of AUD and schizophrenia may be related to male gender, younger persons (Cantor-Graae et al., 2001), availability of drugs (Dixon, 1999), increased vulnerability to the effects of alcohol in patients with schizophrenia (D'Souza et al., 2006; Krystal et al., 2006), or neurobiological factors (Chambers et al., 2001). The high prevalence of substance abuse in patients with schizophrenia has sometimes been interpreted as self-medication for negative symptoms, anhedonia, depression or neuroleptic side effects, but no convincing evidence supports this idea (Mueser et al., 1998; D'Souza et al., 2006). "
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    ABSTRACT: Objective: Some studies have found that high levels of impulsivity and sensation seeking, particularly disinhibition are associated with substance abuse in patients with schizophrenia, as in the general population. However, no study has assessed impulsivity and sensation seeking specifically in schizophrenia patients with alcohol abuse or dependence. Materials and methods: We compared impulsivity and sensation seeking in a group of schizophrenia patients (DSM-III-R criteria) with lifetime alcohol abuse or dependence (n = 34) and in a group without lifetime substance abuse or dependence (n = 66). The patients were assessed using the composite international diagnostic interview (CIDI) for DSM-III-R disorders, the positive and negative syndrome scale (PANSS), the Barratt impulsivity scale (BIS), the Zuckerman seeking sensation scale (SSS), and the physical anhedonia scale (PAS). Results: The mean scores for impulsivity and sensation seeking were higher in the group with lifetime alcohol abuse or dependence than in the group without substance abuse or dependence (BIS: 63.4 ± 18.7 vs 51.3 ± 14.2 respectively, ANOVA: F = 11.12, p = 0.001; SSS: 17.6 ± 5.9 vs 13.5 ± 6.7 respectively, ANOVA: F = 7.45, p = 0.008). There was no significant difference between the two groups on PAS score. Conclusion: Increased impulsivity or sensation seeking may be a link between schizophrenia and alcohol abuse or dependence.
    Frontiers in Psychiatry 09/2010; 1:135. DOI:10.3389/fpsyt.2010.00135
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