The relationship between metacognitive beliefs and symptoms in eating disorders.

The present study aimed to explore the role of dysfunctional metacognitive beliefs in Eating Disorders (EDs) and their potential associations with core and comorbid symptoms. The Metacognition Questionnaire-30 (MCQ-30), the Eating Disorder Examination Questionnaire 6.0 (EDE-Q), the Hospital Anxiety and Depression Scale (HADS) and the Maudsley Obsessive- Compulsive Inventory (MOCI) were used to evaluate 44 Anorexia Nervosa (AN), 50 Bulimia Nervosa (BN) patients and 37 controls. Patients featured more dysfunctional metacognitive beliefs which positively correlated with ED and comorbid symptoms. Both AN and BN patients had higher scores than healthy controls on MCQ-30 total score, Positive Beliefs about Worry, Negative Beliefs about Thoughts Uncontrollability and Danger and Need to Control Thoughts. AN patients also featured higher scores than healthy controls on Cognitive Self-Consciousness. No statistically significant difference was found between the two clinical groups in MCQ-30 total and subscale scores. Among metacognitive beliefs, Negative Beliefs about thoughts Uncontrollability and Danger showed the stronger correlations with core EDs symptoms, (coefficients ranging from 0.24 to 0.40), followed by Need to Control Thoughts (coefficients ranging from 0.22 to 0.38). Dysfunctional metacognitive beliefs were also significantly positively correlated with HADS-Anxiety, HADS-Depression and MOCI Total, in a similar manner. Dysfunctional metacognitive beliefs also predicted 19%, 35%, 20%, and 21% of the variance in Global EDE-Q, HADS-Anxiety, HADS-Depression and MOCI Total scores respectively, in regression analyses. Nevertheless, mediation analysis indicated that the relationship between Negative Beliefs about thoughts Uncontrollability and Danger and core EDs symptomatology as measured by EDE-Q, was not mediated by comorbid anxiety, depression and obsessionality. As a result, dysfunctions in metacognitive beliefs may reflect a common, trans-diagnostic path in AN and BN patients, towards a wide range of symptoms, both core and comorbid.

Clinical factors predicting treatment resistant depression: affirmative results from the European multicenter study.

OBJECTIVES: Clinical variables were investigated in the 'treatment resistant depression (TRD)- III' sample to replicate earlier findings by the European research consortium 'Group for the Study of Resistant Depression' (GSRD) and enable cross-sample prediction of treatment outcome in TRD. EXPERIMENTAL PROCEDURES: TRD was defined by a Montgomery and Åsberg Depression Rating Scale (MADRS) score ≥22 after at least two antidepressive trials. Response was defined by a decline in MADRS score by ≥50% and below a threshold of 22. Logistic regression was applied to replicate predictors for TRD among 16 clinical variables in 916 patients. Elastic net regression was applied for prediction of treatment outcome. RESULTS: Symptom severity (odds ratio (OR) = 3.31), psychotic symptoms (OR = 2.52), suicidal risk (OR = 1.74), generalized anxiety disorder (OR = 1.68), inpatient status (OR = 1.65), higher number of antidepressants administered previously (OR = 1.23), and lifetime depressive episodes (OR = 1.15) as well as longer duration of the current episode (OR = 1.022) increased the risk of TRD. Prediction of TRD reached an accuracy of 0.86 in the independent validation set, TRD-I. CONCLUSION: Symptom severity, suicidal risk, higher number of lifetime depressive episodes, and comorbid anxiety disorder were replicated as the most prominent risk factors for TRD. Significant predictors in TRD-III enabled robust prediction of treatment outcome in TRD-I.

Hypothalamus-pituitary-adrenal (HPA) axis parameters and neurocognitive evaluation in patients with bipolar disorder.

Bipolar disorder is associated with neurocognitive impairment but the etiology of such impairment remains largely unknown. The present study aimed at investigating the performance of bipolar patients in various neuropsychological tasks within the framework of HPA axis hyperactivity model and also the impact of disease characteristics on neuropsychological functioning. Cognitive performance of 60 bipolar-I patients and 30 healthy controls was evaluated by using tasks from the CANTAB battery targeting visual memory, executive function and inhibitory control. Current symptoms were evaluated via administration of the Hamilton Depression Rating Scale (HAMD) and Young Mania Rating Scale (YMRS) whereas assessment of functioning was performed with the Global Assessment of Functioning (GAF). Basal cortisol levels were determined and all patients were administered the Dexamethasone Suppression Test (DST). Statistically significant differences between patients and controls were found in visuo-spatial associative learning and memory, planning, attentional set shifting and inhibitory control. Worse performance in visuospatial associative memory correlated with longer duration of illness and higher levels of basal cortisol. Poorer attentional set shifting was related to higher number of manic episodes. We found no relationship of neurocognitive measures with DST suppression status, current symptom severity or history of psychosis. The results of our study confirm the presence of cognitive deficits in bipolar disorder and provide evidence on the relation of cortisol with neuropsychological functioning, especially visuo-spatial associative memory. Moreover, we have found that number of previous manic episodes and duration of illness is associated with worse cognitive performance. It is known that neurocognitive deficits are evident in many patients with bipolar disorder. These deficits are often a cause of considerable distress and can lead to impairment of psychosocial and occupational functioning. The role of HPA axis needs to be further examined in bipolar disorder. Nevertheless, the identification of factors affecting neurocognitive functioning, like basal cortisol and number of manic episodes, may contribute to the implementation of more appropriate prevention strategies.

Predictors and characteristics of anxiety among adolescent students: a Greek sample.

In the Greek society, there is a strong cultural tendency to overestimate the value of University studies. So students are under high emotional pressure during the long lasting period of the preparation for the university entrance exams. The aim of the present study was to evaluate the level of anxiety in a general adolescent population of senior high school students in Athens, Greece. Also to examine the association between the anxiety's severity with various demographic and socio-cultural factors, as well as with academic performance, extracurricular activities, sleep duration and presence of somatic problems. The sample consisted of 696 adolescent students of three Senior High Schools (SHS) (391 girls and 305 boys). Two of the schools were general education institutions (GE1 and GE2, N=450), while the third was a technical one (TE, N=246). The school sample was selected to reflect the proportion between the two different types of SHSs in Athens as well as other major urban areas in Greece. The State-Trait Anxiety Inventory was administered and personal data were also collected. Statistical significance was set at p<0.05 and analyses were conducted using STATA 7.0. 567 adolescents lived with both parents and 121 with one or none of them. Father's educational level was low for 138, middle for 154, high for 195 and mother's was low for 135, middle for 417, high for 140. The average sleep duration was 7.5 hours per day (SD=1.3). The average time per week spent in school related activities was 7.94 hours (SD=7.56) and in extracurricular activities was 9.02 hours (SD=12.44). 107 adolescents reported somatic complaints in the last year The academic achievement was poor for 233, good for 264, excellent for 196 students. Adolescents with extracurricular activities for more than 11 hours per week had lower scores, both on State and Trait scales. More hours in school-related activities were associated with greater levels of Trait anxiety. Adolescents whose father had a high educational level had lower scores on State anxiety compared to those whose father had a low educational level. Adolescents who reported the presence of somatic problems had a higher score in Trait anxiety. A significant negative correlation was found between sleep duration and both State (r=-0.14, p<0.001) and Trait anxiety (r=-0.10, p=0.008) scores. Stepwise linear regression analyses confirmed the association of gender and of father's educational level with both State and Trait subscale scores. The association of somatic problems with Trait anxiety was greater for girls compared to boys. The hypothesis that there is exam-related anxiety in our sample was not confirmed. There were no differences between school years and GE and TE schools. Also there was not an association of anxiety level with academic achievement and the number of parents the adolescent was living with. This study shows that girls, especially those reporting somatic problems, and adolescents coming from families with low parental education, are particularly prone to higher level of anxiety and that extracurricular activities are linked to lower level of anxiety. These findings could contribute to the planning of preventive measures for student's anxiety.

Fatigue in female patients with major depression: the effect of comorbid anxiety disorders.

Several studies have investigated fatigue in the general population, in primary care facilities as well as in patients with fatigue-related physical diseases, but only marginally in patients with Major Depressive Disorder (MDD). Therefore, the investigation of correlates of depression-related fatigue is highly warranted and expected to facilitate the implementation of effective fatigue-specific treatment strategies. Depressed patients often suffer from comorbid anxiety disorders (CADs) or subthreshold anxiety symptoms. This study aimed to investigate the independent correlation of the severity of fatigue in female patients with MDD with the presence, number and type of CADs. We studied 70 consecutive female MDD patients (48.6% inpatients), aged 23-65 years (mean 48.2±10.6 years), currently in a Major Depressive Episode [17-item Hamilton Depression Rating Scale (HDRS) score≥17] and free of other fatigue-associated conditions. Diagnostic assessments were made with the short structured DSM-IV-based MINI version 5.0.0. Reported fatigue was assessed with the 14-item Chalder Fatigue Questionnaire (FQ). Correlations between the FQ score and age, inpatient status, HDRS score, presence and number of CADs were calculated. Then, stepwise multiple regression analyses were performed, with the FQ score as the dependent variable,so as to isolate independent predictors of the severity of fatigue. 92.9% of patients had clinically significant fatigue. 62.9% were suffering from at least one CAD (38.6% met criteria for one CAD,21.4% for two and 2.9% for three). 51.4% were diagnosed with generalized anxiety disorder (GAD),25.7% with panic disorder and/or agoraphobia (PD/AP), 17.1% with social anxiety disorder and 7.1%with obsessive-compulsive disorder. The FQ score was significantly correlated with the HDRS score(r=0.406, p<0.001), the presence of any CAD(s) (rho=0.4, p=0.001), the number of CADs (rho=0.393,p=0.001), the presence of GAD (rho=0.421, p<0.001) and the presence of PD/AP (rho=0.252, p=0.035).In multiple regression analyses, the presence and number of CADs and the presence of comorbid GAD turned out as significant independent predictors of the FQ score along with the HDRS score.The severity of fatigue in female MDD patients is independently correlated with the presence and number of CADs and, in specific, comorbid GAD. Our findings imply that: (1) this effect might in part account for greater impairment/disability and adverse prognosis for MDD with CADs; (2) high levels of fatigue, putatively clustering with anxiety symptoms, may be a marker of severity and anxiety disorders comorbidity for MDD and may define an "anxious-fatigued" subtype/phenotype in this population; (3) medications and psychotherapies for the management of severe depression-related fatigue should also target CADs.

Meta-analysis of 32 genome-wide linkage studies of schizophrenia.

A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.

Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms.

A genomewide linkage scan was carried out in eight clinical samples of informative schizophrenia families. After all quality control checks, the analysis of 707 European-ancestry families included 1615 affected and 1602 unaffected genotyped individuals, and the analysis of all 807 families included 1900 affected and 1839 unaffected individuals. Multipoint linkage analysis with correction for marker-marker linkage disequilibrium was carried out with 5861 single nucleotide polymorphisms (SNPs; Illumina version 4.0 linkage map). Suggestive evidence for linkage (European families) was observed on chromosomes 8p21, 8q24.1, 9q34 and 12q24.1 in nonparametric and/or parametric analyses. In a logistic regression allele-sharing analysis of linkage allowing for intersite heterogeneity, genomewide significant evidence for linkage was observed on chromosome 10p12. Significant heterogeneity was also observed on chromosome 22q11.1. Evidence for linkage across family sets and analyses was most consistent on chromosome 8p21, with a one-LOD support interval that does not include the candidate gene NRG1, suggesting that one or more other susceptibility loci might exist in the region. In this era of genomewide association and deep resequencing studies, consensus linkage regions deserve continued attention, given that linkage signals can be produced by many types of genomic variation, including any combination of multiple common or rare SNPs or copy number variants in a region.

Fatigue and somatic anxiety in patients with major depression.

The objective this study aimed to investigate the independent contribution of somatic anxiety to the severity of depression-related fatigue. Seventy-six patients (85.5% female), aged 23-65 years (mean 48.7±10.6), diagnosed with major depressive disorder and currently in a major depressive episode (ΜΙΝΙ 5.0.0.) with a 17-item Hamilton Depression Rating Scale (HDRS) score ≥17, were studied. Forty-nine patients (64.5%) were concurrently suf fering from anxiety disorder(s). Patients with physical diseases or other fatigue-related conditions were excluded. Reported fatigue was measured with the 14-item Fatigue Questionnaire (FQ). Based on HDRS item 11 (somatic anxiety) scores, patients were divided into those with somatic anxiety (HDRS-11≥2) and those without (HDRS-11≤1). Pearson's (r) and Spearman's (rho) correlations between FQ score, age, gender, inpatient status, HDRS score and somatic anxiety status were calculated. A multiple regression analysis was then performed, with FQ as the dependent variable. Fifty-seven patients (75%) were rated as suffering from somatic anxiety (HDRS-11≥2). Patients with somatic anxiety had significantly higher HDRS and FQ scores. The FQ score significantly correlated with the HDRS score (r=0.36, p=0.001) and somatic anxiety status (rho=0.35, p=0.002). The FQ score was independently predicted by HDRS score and somatic anxiety status, with standardised beta coefficients of 0.259 (p=0.028) and 0.255 (p=0.031), respectively. R2 was 0.185. Both the severity of depression and the presence of somatic anxiety independently correlate with the severity of reported fatigue in patients with major depression. This finding has potential implications for the management of depression-related fatigue.

Sleep position and laterality of benign paroxysmal positional vertigo.

OBJECTIVE: The aim of this study was to investigate the frequency of posterior semicircular canal benign paroxysmal positional vertigo in each ear, and to assess the association between the ear affected by benign paroxysmal positional vertigo and the head-lying side during sleep onset. Based on a previous study which used objective methods to prove the preference of the elderly for the right head-lying side during sleep, we hypothesised that a predominance of the same head-lying side in benign paroxysmal positional vertigo patients may affect the pathophysiology of otoconia displacement. STUDY DESIGN: We conducted a prospective study of out-patients with posterior semicircular canal benign paroxysmal positional vertigo, confirmed by a positive Dix-Hallpike test. METHODS: One hundred and forty-two patients with posterior semicircular canal benign paroxysmal positional vertigo were interviewed about their past medical history, focusing on factors predisposing to benign paroxysmal positional vertigo. All patients included in the study were able to define a predominant, favourite head-lying side, right or left, during sleep onset. RESULTS: The Dix-Hallpike test was found to be positive on the right side in 82 patients and positive on the left side in 54; six patients were found to be positive bilaterally. During sleep onset, 97 patients habitually laid their head on the right side and the remaining 45 laid their head on the left. The association between the affected ear and the head-lying side during sleep onset was statistically significant (p < 0.001). CONCLUSIONS: Our study found a predominance of right-sided benign paroxysmal positional vertigo, a subjective preference amongst patients for a right head-lying position during sleep onset, and an association between the ear affected by benign paroxysmal positional vertigo and the preferred head-lying side during sleep onset. The clinical and therapeutical implications of this observation are discussed.

[Habits and problems of sleep in adolescent students].

The evaluation of sleep habits and sleep related problems in high school adolescent students in the Athens area and the assessment of these problems' relation to demographic and other variables was investigated by the Athens Insomnia Scale - 5 item version (AIS-5), which was administered to 713 adolescent Senior High School students in the Greater Athens Area. Data such as age, sex, school records, and time spent per week in school-related and extracurricular activities were collected. The sample's mean sleep duration was 7,5 hours, mean bedtime 12:20 am and wake-up time 7:15 am. Total sleep time was not affected by gender, but was influenced by time spent in various activities. Sleep complaints were related to delayed sleep, onset latency and insufficient total duration of sleep. Girls complained more than boys, while correlations showed that students with lower academic per formance and those in second grade were more likely to have higher AIS-5 scores. The results show that sleep time of high school students is dependent on practical matters such as school schedule and other activities, while sleep complaints are related to female gender, bad school performance as well as to the second grade. The difference between actual sleep time and sleep complaints should be considered when studying the sleep of adolescents.

Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study.

The available data from preclinical and pharmacological studies on the role of the C-O-methyl transferase (COMT) support the hypothesis that abnormal catecholamine transmission has been implicated in the pathogenesis of mood disorders (MD). We examined the relationship of a common functional polymorphism (Val108/158Met) in the COMT gene, which accounts for four-fold variation in enzyme activity, with 'early-onset' (EO) forms (less than or equal to 25 years) of MD, including patients with major depressive disorder (EO-MDD) and bipolar patients (EO-BPD), in a European multicenter case-control sample. Our sample includes 378 MDD (120 EO-MDD), 506 BPD (222 EO-BPD) and 628 controls. An association was found between the high-activity COMT Val allele, particularly the COMT Val/Val genotype and EO-MDD. These findings suggest that the COMT Val/Val genotype may be involved in EO-MDD or may be in linkage disequilibrium with a different causative polymorphism in the vicinity. The COMT gene may have complex and pleiotropic effects on susceptibility and symptomatology of neuropsychiatric disorders.

Multicenter linkage study of schizophrenia loci on chromosome 22q.

The hypothesis of the existence of one or more schizophrenia susceptibility loci on chromosome 22q is supported by reports of genetic linkage and association, meta-analyses of linkage, and the observation of elevated risk for psychosis in people with velocardiofacial syndrome, caused by 22q11 microdeletions. We tested this hypothesis by evaluating 10 microsatellite markers spanning 22q in a multicenter sample of 779 pedigrees. We also incorporated age at onset and sex into the analysis as covariates. No significant evidence for linkage to schizophrenia or for linkage associated with earlier age at onset, gender, or heterogeneity across sites was observed. We interpret these findings to mean that the population-wide effects of putative 22q schizophrenia susceptibility loci are too weak to detect with linkage analysis even in large samples.

Social adjustment and self-esteem of bipolar patients: a multicentric study.

The aim of the present study was to investigate impairment in social adjustment and self-esteem of bipolar patients (n=144) in remission for at least 3 months. Patients were recruited among four different centres: Sofia, Athens, Jerusalem and Milan, and were individually matched to control subjects in relation to sex, age and geographical origin. Subjects completed the Rosenberg self-esteem scale (SES) and the self-report version of the social adjustment scale (SAS). Bipolar patients reported to experience more difficulties in social adjustment than controls, specifically for leisure and work activities. Further, our results show that bipolar patients have significantly lower self-esteem compared to controls, even after remission.

Self-esteem, social adjustment and suicidality in affective disorders.

Self-esteem (SE) and social adjustment (SA) are often impaired during the course of affective disorders; this impairment is associated with suicidal behaviour. The aim of the present study was to investigate SE and SA in unipolar or bipolar patients in relation to demographic and clinical characteristics, especially the presence of suicidality (ideation and/or attempt). Forty-four patients, 28 bipolar and 16 unipolar, in remission for at least 3 months, and 50 healthy individuals were examined through a structured clinical interview. SE and SA were assessed by the Rosenberg self-esteem scale and the social adjustment scale, respectively. The results have shown that bipolar patients did not differ from controls in terms of SE, while unipolar patients had lower SE than bipolars and controls. No significant differences in the mean SA scores were found between the three groups. Suicidality during depression was associated only in bipolar patients with lower SE at remission; similar but not as pronounced was the association of suicidality with SA. It is concluded that low SE lasting into remission seems to be related to the expression of suicidality during depressive episodes of bipolar patients, while no similar pattern is evident in unipolar patients.

Excess of allele1 for alpha3 subunit GABA receptor gene (GABRA3) in bipolar patients: a multicentric association study.

The available data from preclinical and pharmacological studies on the role of gamma amino butyric acid (GABA) support the hypothesis that a dysfunction in brain GABAergic system activity contributes to the vulnerability to bipolar affective disorders (BPAD). Moreover, the localization of the alpha3 subunit GABA receptor GABRA3 gene on the Xq28, a region of interest in certain forms of bipolar illness, suggests that GABRA3 may be a candidate gene in BPAD. In the present study, we tested the genetic contribution of the GABRA3 dinucleotide polymorphism in a European multicentric case-control sample, matched for sex and ethnogeographical origin. Allele and genotype (in females) frequencies were compared in 185 BPAD patients and 370 controls. A significant increase of genotype 1-1 was observed in BPAD females compared to controls (P=0.0004). Furthermore, when considering recessivity of allele 1 (females with genotype 1-1 and males carrying allele 1), results were even more significant (P= 0.00002). Our findings suggest that the GABRA3 polymorphism may confer susceptibility to or may be in linkage disequilibrium with another gene involved in the genetic etiology of BPAD.

Lack of association between GABRA3 and unipolar affective disorder: a multicentre study.

Available data on gamma amino butyric acid (GABA) support the hypothesis that a dysfunction in the brain GABAergic system activity contributes to vulnerability to affective disorders (AD), including bipolar disorder (BPAD) and unipolar disorder (UPAD). The localization of the alpha3 subunit GABA receptor (GABRA3) gene in Xq28, a region of interest for BPAD suggests that GABRA3 may be a relevant candidate gene. In the present study, we tested the genetic contribution of the GABRA3 dinucleotide polymorphism in a European multicentre UPAD case-control sample [UPAD (n = 106), controls (n = 212)]. Our negative results suggest that GABRA3 does not confer susceptibility nor is it in linkage disequilibrium with another close gene involved in the genetic aetiology of UPAD.

Variability of 5-HT2C receptor cys23ser polymorphism among European populations and vulnerability to affective disorder.

Substantial evidence supports a role for dysfunction of brain serotonergic (5-HT) systems in the pathogenesis of major affective disorder, both unipolar (recurrent major depression) and bipolar.(1) Modification of serotonergic neurotransmission is pivotally implicated in the mechanism of action of antidepressant drugs(2) and also in the action of mood stabilizing agents, particularly lithium carbonate.(3) Accordingly, genes that code for the multiple subtypes of serotonin receptors that have been cloned and are expressed in brain,(4) are strong candidates for a role in the genetic etiology of affective illness. We examined a structural variant of the serotonin 2C (5-HT2C) receptor gene (HTR2C) that gives rise to a cysteine to serine substitution in the N terminal extracellular domain of the receptor protein (cys23ser),(5) in 513 patients with recurrent major depression (MDD-R), 649 patients with bipolar (BP) affective disorder and 901 normal controls. The subjects were drawn from nine European countries participating in the European Collaborative Project on Affective Disorders. There was significant variation in the frequency of the HT2CR ser23 allele among the 10 population groups included in the sample (from 24.6% in Greek control subjects to 9.2% in Scots, chi(2) = 20.9, df 9, P = 0.01). Logistic regression analysis demonstrated that over and above this inter-population variability, there was a significant excess of HT2CR ser23 allele carriers in patients compared to normal controls that was demonstrable for both the MDD (chi(2) = 7.34, df 1, P = 0.006) and BP (chi(2) = 5.45, df 1, P = 0.02) patients. These findings support a possible role for genetically based structural variation in 5-HT2C receptors in the pathogenesis of major affective disorder.

GABA-A receptor beta3 and alpha5 subunit gene cluster on chromosome 15q11-q13 and bipolar disorder: a genetic association study.

There is accumulated evidence that the genes coding for the receptor of gamma aminobutyric acid (GABA), the most important inhibitory neurotransmitter in the CNS, may be involved in the pathogenesis of affective disorders. In a previous study, we have found a genetic association between the GABA-A receptor alpha5 subunit gene locus (GABRA5) on chromosome 15q11-of 13 and bipolar affective disorder. The aim of the present study was to examine the same subjects to see if there exists a genetic association between bipolar affective disorder and the GABA receptor beta3 subunit gene (GABRB3), which is located within 100 kb from GABRA5. The sample consisted of 48 bipolar patients compared to 44 controls (blood donors). All subjects were Greek, unrelated, and personally interviewed. Diagnosis was based on DSM-IV and ICD-10 criteria. The marker used was a dinucleotide (CA) repeat polymorphism with 12 alleles 179 to 201 bp long; genotyping was successful in all patients and 43 controls. The distribution of GABRB3 genotypes among the controls did not deviate significantly from the Hardy-Weinberg equilibrium. No differences in allelic frequencies between bipolar patients and controls were found for GABRB3, while this locus and GABRA5 did not seem to be in significant linkage disequilibrium. In conclusion, the GABRB3 CA-repeat polymorphism we investigated does not present the observed association between bipolar affective illness and GABRA5. This could be due to higher mutation rate in the GABRB3 CA-repeat polymorphism, but it might also signify that GABRA5 is the gene actually associated with the disease.