Opioid system genes in alcoholism: A case–control study in Croatian population

Due to their involvement in dependence pathways, opioid system genes represent strong candidates for association studies investigating alcoholism. In this study, single nucleotide polymorphisms within the genes for mu (OPRM1) and kappa (OPRK1) opioid receptors and precursors of their ligands – proopiomelanocortin (POMC), coding for beta-endorphin and prodynorphin (PDYN) coding for dynorphins, were analyzed in a case–control study that included 354 male alcohol-dependent and 357 male control subjects from Croatian population. Analysis of allele and genotype frequencies of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN revealed no differences between the tested groups. The same was true when alcohol-dependent persons were subdivided according to the Cloninger’s criteria into type-1 and type-2 groups, known to differ in the extent of genetic control. Thus, the data obtained suggest no association of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN with alcoholism in Croatian population.     

Le modèle du tempérament et du caractère de Cloninger appliqué dans le trouble bipolaire de l’adulte : recension de la littérature d’une approche tempéramentale

Context

Although psychiatric research uses clear diagnostic criteria to describe bipolar disorders, therapists in clinical practice are often confronted with patients presenting a number of symptoms with different degrees of intensity and belonging to more than one diagnostic category. With respect to this actual clinical complexity, there is an increasing interest in a dimensional approach of psychopathological traits to gain better understanding of mental disorders. In the 1980s, Robert Cloninger elaborated on a psychobiological model to explain personality in clinical groups as well as in general population. His model was then operationalised with a questionnaire evaluating temperament (harm avoidance, novelty seeking, reward dependence and persistence) and character (self-directeness, cooperativeness, self-transcendence): the Temperament and Character Inventory (TCI).

Objective

To review all studies conducted in adult bipolar samples on temperament and character according to Cloninger's psychobiological model.

Materials and methods

A search was conducted on MedLine and PsycInfo for all articles written in English or French, between 1986 and September 2008, on temperament and character in bipolar disorder. The words bipolar disorder or mania had to be associated with the following keywords temperament, TCI, Cloninger, TPQ, harm avoidance, novelty seeking, reward dependence.

Results

Across studies, compared to the general population, bipolar subjects have significantly higher harm avoidance, higher novelty seeking and lower self-directness. Some studies have investigated differences between bipolar disorders and other psychopathologies like depression, and borderline personality disorder. Among studies on depression and bipolar disorder, there is no consensus on the findings. Compared to borderline personality disorder patients, bipolar disorder subjects have lower harm avoidance and higher self-directness and cooperativeness. This finding is consistent with Cloninger's hypothesis that all personality disorders have lower self-directness than any axis I disorder. With respect to other temperament and character traits, studies yielded results either contradictory or non-significant. No difference was found when the bipolar group was subdivided according to the clinical presentation (type I vs II) and the suicidal risk, apart from harm avoidance. Bipolar subjects with substance related disorders displayed higher novelty seeking and lower persistence, which might be explained by a low dopaminergic activity that had to be compensated with drug intake. Low persistence causes greater difficulties to overcome substance dependence. However, it is not possible to determine whether these temperament characteristics are specifically linked to bipolar disorder, substance related disorders, or both. Similar limitations apply to bipolar patients with comorbid anxiety disorders, who presented higher harm avoidance and lower self-directness.

Conclusions

Across studies, there are limitations which impede the generalization of the findings to other clinical populations. Age, gender, cultural characteristics, mood status during evaluation, group size, versions of the TCI questionnaire, suicidal risk, clinical type (BP I vs II) and comorbidity differ from one study to another. These methodological variables should be controlled in future studies. Nevertheless, adult bipolar patients appear to present a different temperamental profile than other clinical groups and general population. Therefore, Cloninger's psychobiological model of temperament remains an interesting avenue for future researches in bipolar disorder.     

Comorbidity of alcohol dependence with attention-deficit hyperactivity disorder: differences in phenotype with increased severity of the substance disorder, but not in genotype (serotonin transporter and 5-hydroxytryptamine-2c receptor)

BACKGROUND: Nearly 50% of subjects with continuing symptoms of attention-deficit hyperactivity disorder (ADHD) in adulthood have been reported to show a comorbid substance use disorder. Both ADHD and alcohol dependence have a high genetic load and might even share overlapping sources of genetic liability. Recently, the functional relevant polymorphism within the promoter region of the serotonin transporter gene (5-HTT) and the 5-hydroxytryptamine-2c (5-HT2c) receptor Cys23Ser have been proposed as candidate genes for both entities. METHODS: We investigated phenotype and 5-HTT/5-HT2c genotype characteristics in 314 alcoholics of German descent. RESULTS: There was no significant difference in 5-HTT genotype or 5-HT2c allele distribution between alcoholics and matched controls. Sixty-seven alcoholics fulfilled DSM-IV criteria of ADHD with ongoing symptoms in adulthood and had a Wender Utah Rating Scale score greater than 90. Thirty had ADHD plus antisocial personality disorder. The subgroup of alcoholics with ADHD (ADHD+) showed a significantly higher daily and record ethanol intake per month, an earlier age at onset of alcohol dependence, and a higher frequency of suicidal ideation, court proceedings, and antisocial personality disorder. In our sample, more than 50% of type 2 alcoholics according to Cloninger consist of the ADHD+ and/or antisocial personality disorder-positive subjects. There were no differences in 5-HTT genotype or 5-HT2c allele distribution between the ADHD+ subgroups and alcoholics without comorbidity and matched controls, respectively. CONCLUSIONS: Comorbidity of alcoholism and ADHD forms a distinct phenotype that shows an increased severity of the substance disorder. This phenotype contributes substantially to the so-called type 2 alcoholics according to Cloninger. In our sample, the functional relevant 5-HTT promoter and the 5-HT2c receptor Cys23Ser polymorphism do not contribute to the supposed common genetic predisposition of ADHD and alcohol dependence.