Jobst Böning

Personality Traits Predict Treatment Outcome in Alcohol-Dependent Patients

Personality traits are important individual characteristics modifying responses to therapy in various diseases. The aim of this study was to identify personality traits that may predict treatment outcome in alcohol-dependent patients. The present analysis was based on a total of 146 alcohol-dependent patients (109 male, 37 female) after detoxification. The variable of interest was treatment outcome (abstinence/relapse) after a 1-year follow-up. To identify personality traits as predictors of treatment outcome, 5 personality questionnaires (NEO 5-Factor Inventory, Temperament and Character Inventory, Eysenck Personality Questionnaire, Eysenck Impulsiveness-Venturesomeness-Empathy Scale and Sensation-Seeking Scale) were applied. Data analysis was performed by using a classification and regression tree analysis (CART; a nonparametric technique for data with a complex structure) in order to find a decision rule to predict treatment outcome from personality traits. The CART model identified psychoticism and persistence as the 2 most relevant discriminatory parameters, of which psychoticism was used as the first node in the model, classifying 64% of the patients correctly as relapsed and 12% correctly as abstinent. In addition, the risk of relapse was even higher in patients with a substantial score in psychoticism and a low score in persistence. When comparing relapsed and abstinent patients, further variables, such as scores for novelty seeking (20.9 ± 5.5 vs. 18.5 ± 5.9) and impulsiveness (8.4 ± 3 vs. 7.2 ± 3.5), showed significance. In addition, relapsed patients lived alone more often than abstinent patients (52 vs. 25%, p = 0.004). In conclusion, this analysis demonstrated that specific personality characteristics, namely psychoticism and persistence, are usable predictors for the risk of relapse in alcohol-dependent patients.

Increased levels of calcium-sensitive adenylyl cyclase subtypes in the limbic system of alcoholics: evidence for a specific role of cAMP signaling in the human addictive brain.

We examined the amounts of several adenylyl cyclase (AC) isoforms and of cAMP-response element binding protein (CREB) in alcoholic and control brains. Immunoreactivity of type I AC was significantly increased in alcoholic nucleus accumbens and corpus amygdaloideum. Immunoreactivity of type VIII AC was also increased in alcoholic corpus amygdaloideum and hippocampus. CREB immunoreactivities were unchanged. These findings indicate that the brain-region specific increase of Ca(2+)-sensitive AC may contribute to the pathophysiology of alcoholism.

Quantitative reduction of type I adenylyl cyclase in human alcoholics

The amounts of adenylyl cyclase type I (AC I) were examined in various parts of the postmortem brains from alcoholics who prior to death had been abstinent from alcohol for at least 6 months and compared with controls using immunoblot analysis with anti-AC I specific antibody. It was revealed that a significant reduction of AC I was observed in both frontal and temporal cortices. On the other hand, in other areas (occipital cortex, caudate nucleus, putamen, and hippocampus) the amounts were comparable between alcoholics and controls. In the next step, we examined two subtypes of human AC mRNA levels (AC I and AC VIII) in blood cells by quantitative RT-PCR using [alpha-32P]dCTP with two sets of the synthetic oligonucleotide primers based on the DNA sequences reported elsewhere (Villacres, E.C. et al., Genomics 16 (1993) 473-478; J. Parma et al., Biochem. Biophys. Res. Commun. 179 (1991) 455-462). The amounts of amplified DNAs of both AC I and AC VIII were significantly smaller in alcoholics than in controls. On the other hand, the amounts of amplified DNA of beta-actin DNA were almost equal between alcoholics and controls. It appears from these results that a reduction in the amount of AC subtypes may be a biological marker for alcoholics.

No association of dopamine receptor sensitivity in vivo with genetic predisposition for alcoholism and DRD2/ DRD3 gene polymorphisms in alcohol dependence

This study sought to examine dopamine receptor sensitivity among alcoholics in vivo and to explore whether this sensitivity might be associated with functional variations of dopamine D2 (DRD2) and D3 (DRD3) receptor genes along with a genetic predisposition for alcoholism as reflected by an alcohol‐dependent first‐degree relative. We analyzed the −141C Ins/Del polymorphism in the promoter region of the DRD2 gene and the Ser9Gly (BalI) polymorphism in exon 1 of the DRD3 gene in 74 alcohol‐dependent Caucasian men with or without genetic predisposition for alcoholism. In vivo dopamine receptor sensitivity was assessed by measuring apomorphine‐induced growth hormone release. A three‐way analysis of variance revealed no significant effects of DRD2, DRD3 genotypes and genetic predisposition on dopamine receptor sensitivity. Given the explorative and preliminary character of this investigation, we cannot provide evidence that in alcohol‐dependent Caucasian men a genetic predisposition for alcoholism along with functional variants of the DRD2 and DRD3 genes are associated with differences in dopamine receptor sensitivity.

Reflection-impulsivity, personality and performance : a psychometric and validity study of the Matching Familiar Figures Test in detoxified alcoholics

Abstract Impulsiveness is frequently discussed in the context of alcoholism and self-rating questionnaires are widely used to measure it. While probes of behavior are utilized very rarely in alcoholics they may be especially suitable for measuring impulsivity within a clinical context. In this study we used the Matching Familiar Figures Test (MFFT), a behavioral test to investigate the reflection–impulsivity dimension. Examined were 161 detoxified patients who were suffering from alcohol dependence but who otherwise had no other comorbid psychiatric disorders. The patients were assigned numerous performance tests and personality questionnaires to investigate the relationship between the reflection–impulsivity-classification in the MFFT, clinical data as related to alcoholism, and self-rated personality and performance measures. We found no evidence for a relationship between clinical data as related to alcoholism and reflection–impulsivity. MFFT-reflective alcoholics were more intelligent, their concentration ability was higher, and they reacted faster in reaction time tasks than MFFT-impulsives. These results support authors who consider the MFFT to be primarily an ability test. However, the traditional classification depends more strongly on individual variability in performance than the item-based classification proposed here. The most interesting personality difference between MFFT-reflectives and MFFT-impulsives was the difference in Novelty Seeking (NS). NS scores were significantly higher among MFFT-impulsives compared to MFFT-reflectives. Additionally, a logistic regression analysis identified the NS-subscore “Impulsiveness vs. Reflection” as a significant predictor of the MFFT-classification. These results confirm the hypothesis that the MFFT is useful as an objective behavioral measurement tool for a certain cognitive aspect of impulsivity (quick, intuitive decision vs. carefully considered decision). However, our analysis also affirms that this aspect of impulsivity is closely linked to intelligence.

Dopamine D2 (DAD2) and dopamine D3 (DAD3) receptor gene polymorphisms and treatment outcome in alcohol dependence

Summary.The dopaminergic system is critically involved in reward mechanisms mediating the reinforcing effects of alcohol. The intention of this study was to investigate the genotypic frequencies of the −141C Ins/Del polymorphism of the DAD2 receptor gene as well as the Bal I polymorphism of the DAD3 receptor and their potential association with treatment outcome in alcoholism. Therefore, individuals suffering from primary alcohol dependence were clinically and genetically characterized and followed prospectively over a period of one year after inpatient treatment.No association was found between DAD2 or DAD3 receptor gene variants and treatment outcome as reflected by abstinence/relapse after one year. Taking into account potential stratification effects, such as family history, gender, age of onset, or severity of the disease an association with DAD2 or DAD3 gene variants could neither be found. In conclusion, we found no evidence that the DAD2 or DAD3 gene variants investigated have a major influence on treatment outcome in primary alcohol dependence.

Gender and personality in alcoholism

Summary¶The topic gender and personality in alcoholism is discussed on the background of a research project on clinical aspects of alcoholism at the University of Würzburg, Germany. The data of this study are presented in the context of two questions: Which personality differences are there between women and men dependent on alcohol, and is there a connection between these personality differences and features of the alcohol dependence? Additionally, we take a look at gender-related differences in the development of alcoholism. In a first step, gender differences in the development and the course of alcoholism are investigated. The data revealed only weak differences between female and male alcoholics when important confounding variables like age and education are taken into consideration. Secondly, the female and male alcoholics are matched according to age and education and their personality structures are compared by using several well-established and standardized self-report questionnaires. No serious gender differences concerning the main characteristics of alcohol dependence could be discovered. However, some remarkable personality differences between female and male alcoholics are found: women scored significantly higher on Neuroticism and Harm-Avoidance while men reached significantly higher scores on Venturesomeness and Sensation-Seeking. In order to detect a possible connection between alcoholism and gender-related personality differences, both males and females are subdivided into two groups using the scores of Neuroticism, Harm-Avoidance, Venturesomeness and Sensation-Seeking, respectively. We have found no indication for a gender-specific relevance of personality differences between female and male alcoholics with regard to Harm-Avoidance, Venturesomeness or Sensation-Seeking. However, differences in Neuroticism have revealed a greater relevance in alcohol-dependent women than in men.

Neuroendocrine responses to fenfluramine and its relationship to personality in alcoholism.

Summary. This study investigates the relationship between personality and serotonergic reactivity in alcohol dependence. Personality characteristics were assessed according to the Temperament and Character model of Cloninger, the five-factor model of McCrae and Costa, Zuckermans Sensation Seeking as well as Eysencks impulsiveness/venturesomeness. Placebo-controlled prolactin response to the serotonin (5-HT) reuptake inhibitor/releaser fenfluramine served as an indicator for the reactivity of serotonergic neurotransmission. Forty abstinent alcohol-dependent men were subdivided into high and low prolactin responders according to their level of neuroendocrine response. High responders were characterized by decreased harm avoidance while their extraversion and venturesomeness scores were increased in comparison to low responders. The data demonstrates that harm avoidance on the one hand and extraversion/venturesomeness on the other are inversely correlated to serotonergic neurotransmission. These results support a specific relationship between personality traits and the serotonergic system.

Reduced immunoreactivity of type I adenylyl cyclase in the postmortem brains of alcoholics

Reduced adenylyl cyclase activity after chronic ethanol exposure has been reported. In this study, we investigated by immunoblotting whether quantitative changes of adenylyl cyclase isoforms (type I, type II, and type V/VI adenylyl cyclases) exist in membrane preparations of the temporal cortex obtained from six alcoholics and six age-matched controls. The immunoreactivity of type I adenylyl cyclase decreased significantly in the temporal cortex of alcoholics when compared with controls (p < 0.05), whereas those of type II and type V/VI adenylyl cyclases showed no changes between the groups. These findings suggest that these isoform-specific afterations in the adenylyl cyclase system may be involved in the pathophysiology of alcoholism.

Immunologische Blut-Liquor-Schrankendiagnostik im Verlauf des Delirium tremens

SummaryFifty chronic alcoholics with acute withdrawal (in the state of delirium tremens) were examined initially and in the following weeks by quantitatively testing immunoglobulins in the serum and in the cerebrospinal fluid to study the dynamics of the blood-CSF barrier. Compared to other persons of the same age, acutely delirious patients show a pathologic IgG-IgA constellation in the CSF which does not depend on the serum. That points to an infrastructural barrier function disorder. After 2–4 weeks, delirium tremens, normally in the process of recovering, shows distinct sanitation of the immunologic spectrum of the CSF. With regard to their dynamic proceedings, the results confirm other findings on brain metabolism, biochemistry, neurophysiology, and pathologic anatomy during delirium tremens.The totally and progressively disturbed blood-CSF barrier system of complicated cases of delirium tremens (e.g., Korsakovs and Wernickes syndromes) seems to provide the possibility of deterioration of the clinical syndrome. The method, simple to implement in the laboratory, permits not only an overall evaluation of the dynamic blood-CSF barrier function in acute and postdelirious state, but also provides both the possibility to diagnose a persistent infrastructural residual syndrome and to indicate a pathophysiologic complication of the clinical course.ZusammenfassungBei 50 chronischen Alkoholkranken mit akutem Entzugsdelir wurde initial und in den folgenden Wochen mittels quantitativer Immun globulinbestimmung im Serum und Liquor cerebrospinalis die Schrankendynamik der Blut-Liquor-Barriere untersucht. Akute Delirante weisen im Vergleich zu altersrepräsentativen Referenzpersonen eine nichtserumspiegelabhängige pathologische IgG-IgA-Konstellation im Liquor auf, die als Hinweis für eine infrastrukturelle Schrankenfunktionsstörung zu deuten ist. Nach 2 bis 4 Wochen zeichnet sich beim sich klinisch regelhaft restituierenden Delir eine deutliche Sanierungstendenz des immunologischen Liquorspektrums ab. Die Befunde korrespondieren mit verlaufsdynamisch orientierten Untersuchungen anderer Autoren über Hirnstoffwechsel, Biochemie, Neurophysiologie und mit pathologisch-anatomischen Befunden.Bei verlaufskomplizierten Delirien (z. B. Korsakow-, Wernicke-Syndrom) scheinen ein ausnahmslos und eher progredient gestörtes Blut-Liquor-Funktionssystem auch Beurteilungsmöglichkeiten für eine klinische Syndromverschlechterung abgeben zu können. Die labortechnisch einfach zu realisierende Routinemethodik erlaubt nicht nur ein globales Beurteilungskriterium für die dynamische Blut-Liquor-Schrankenfunktion im akuten und postdeliranten Zustand. Sie vermag neben dem Aufdecken eines persistierenden infrastrukturellen Residualsyndroms auch eine Indikatorfunktion für eine pathophysiologisch bedingte klinische Verlaufskomplikation abzugeben.