Study Report

Reference	Hess, C.,2009 PMID: 18982239
Citation	Hess, C., A. Reif, et al. (2009). A functional dopamine-beta-hydroxylase gene promoter polymorphism is associated with impulsive personality styles, but not with affective disorders. J Neural Transm 116(2): 121-130.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	182 patients with affective disorders(58 with unipolar depression and 124 with bipolar disorder),407 adult ADHD patients,637 patients with personality disorders(12 in the Cluster A subsample,372 in the Cluster B subsample,118 in the Cluster C subsample) and 387 control subjects
SNP/Region/Marker Size	1 SNP
Predominant Ethnicity	Caucasian
Population	German
Gender	Patients with affective disorders:35% male (41% male in unipolar depression patients and 31% male in bipolar disorder patients), Adult ADHD patients:54% male;Patients with personality disorders:44% male (42% male in the Cluster A subsample,44% male in the Cluster B subsample,43% male in the Cluster C subsample);Control subjects:48% male
Age Group	Adults : mean age(year):55(SD=14)in patients with affective disorders,34(SD=10) in adult ADHD patients,35(SD=12)in patients with personality disorders(37(SD=12) in the Cluster A subsample,34(SD=13) in the Cluster B subsample,38(SD=13) in the Cluster C subsample) and 33(SD=11)in control subjects

Sample Diagnosis	NEO-PI-R
Sample Status	Patients with affective disorders:All subjects were of Caucasian descent and ascertained at the Department of Psychiatry and Psychotherapy in Wurzburg. All patients were inpatients at the Department of Psychiatry at least once. None of the subjects showed significant neurological comorbidity, epilepsy,mental retardation, a history of substance abuse or other somatic disorders suggesting organic affective disorder. While 75% subjects with bipolar disorder had a positive family history for bipolar disorder or depression in first or second degree relatives, only 32% patients suffering from unipolar depression had a positive family history, in almost all cases for depression. Adult ADHD patients:All subjects were of Caucasian origin. Details on the sample can be obtained from Jacob et al. (2007). Patients with personality disorders: All subjects were of Caucasian origin. The sample has been described earlier in further detail (Jacob et al. 2004,2005). Control subjects: The control group was recruited in the Lower Franconia area in Germany and of Caucasian origin.
Technique	genotyping
Statistical Method	chi-square tests; eta-square tests
Result Summary	No differences in DBH C-1021T genotype distribution were observed between patients with affective disorders and healthy control subjects. Also when the patient sample was divided into uni- and bipolar patients versus controls, no significant differences emerged. Furthermore, no clear-cut association was detected between the TT genotype and personality disorder clusters while there was a significant association with adult ADHD. However, personality disorder patients carrying the DBH TT genotype exhibited higher neuroticism and novelty seeking scores as compared to individuals with the CC or CT genotype. Analyses on the level of the neuroticism and novelty seeking subscales revealed that the DBH TT genotype was primarily associated with personality features related to impulsiveness and aggressive hostility. Also adult ADHD patients carrying the homozygous TT genotypes displayed by significantly increased neuroticism scores; when both personality disorder and adult ADHD patient were analyzed together, TT carriers also displayed by significantly lower conscientiousness levels. Our results thus do not implicate the DBH C-1021T polymorphism in the pathophysiology of depressive disorders or personality disorders, yet homozygosity at this locus appears to increase the risk towards personality traits related to impulsiveness, aggression and related disease states, namely adult ADHD. These data argue for a dimensional rather than categorical effect of genetic variance in DBH activity; accordingly, the inconsistency of previous findings concerning DbetaH levels in affective disorders might be caused by the underlying association of the TT genotype at DBH-1021 with impulsive personality traits.