No association of clock gene T3111C polymorphism and affective disorders.

CLOCK was hypothesised to be related to susceptibility of affective disorders. To test subsamples of affectively disordered patients, we examined age of onset (AoO), numbers of episodes and melancholic type of clinical manifestation. Using PCR and RFLP, we investigated in patients with unipolar depression and bipolar disorder (BP) whether the CLOCK T3111C SNP is associated with affective disorders (n=102) compared to healthy controls (n=103). No differences were found either in genotype or allele frequency distributions of T3111C polymorphism between patients compared to healthy controls (p>0.2). No deviations from Hardy-Weinberg Equilibrium (HWE) were detected either in patients, or healthy controls. Results suggest that there is no association between the T3111C SNP and affective disorders in general. Data of our sample replicate prior findings of Desan et al. [Am. J. Med. Genet. 12 (2000) 418]. Subsamples of patients with high numbers of affective episodes did show some deviations in genotypes (p=0.0585).

No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism.

BACKGROUND: A polymorphism in the serotonin transporter promoter gene region (5-HTTLPR) has been shown to influence the quantity of serotonin transporter expressed in human cell lines: the 5-HTTLPR short allele (s) has been associated with reduced 5-HTT expression when compared to cells carrying the 5-HTTLPR long allele (l). We performed a single photon emission computed tomography (SPECT) study using the ligand [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT) to measure 5-HTT availability in 16 healthy subjects genotyped for 5-HTTLPR. METHODS: SPECT scans were performed 24 hours after tracer injection, regions of interest anatomically corresponding to the thalamus-hypothalamus and mesencephalon-pons areas were compared to the binding in the cerebellum, representing the nondisplaceable [(123)I]-beta-CIT-binding (results expressed as target activity minus cerebellum activity/cerebellum activity). DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods. RESULTS: Specific binding ratios in the thalamus-hypothalamus were 2.65 +/- 0.4 in subjects with the l/l genotype (n = 3), 2.76 +/- 0.5 in subjects with the l/s genotype (n = 9), and 2.77 +/- 0.4 in subjects with the s/s genotype (n = 4). Binding ratios in the mesencephalon-pons were 1.43 +/- 0.3 (l/l; n = 3), 1.37 +/- 0.3 (l/s; n = 9), and 1.28 +/- 0.3 (s/s; n = 4). None of these differences was statistically significant. CONCLUSIONS: Our data provide no evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects.

No evidence for a schizophrenia susceptibility gene in the vicinity of IL2RB on chromosome 22.

Pulver et al. [1994a] reported modest linkage evidence for a dominantly (D) inherited "schizophrenia gene" in the vicinity of IL2RB on chromosome 22q12, and Coon et al. [1994] adduced moderate evidence under a recessive (R) model. We report here a replication study to test the hypothesis that one of these two models (or a third, intermediate (I) model) adequately describes the co-segregation of schizophrenia and chromosome 22q12 markers in an independent sample of 23 multiplex families. Altogether nine transmission models were evaluated. The models differed depending on whether the 15 family members with a diagnosis of schizophrenia spectrum disorders were considered unaffected (a "narrow" (N) definition), affected (a "wide" (W) definition), or declared "unknown" (U). The entire region between D22S268 and D22S307 is excluded (i.e., lod <-2) for models RN, RW, RU, and IW. Lod scores for the remaining models are uniformly negative; albeit, equivocal with respect to the dominant hypothesis over a small region between D22S268 and IL2RB. Nonparametric analysis under both diagnostic criteria also failed to yield any evidence for a susceptibility locus in this region of chromosome 22.

European Multicentre Association Study of Schizophrenia: a study of the DRD2 Ser311Cys and DRD3 Ser9Gly polymorphisms.

As part of the European Multicentre Association Study of Schizophrenia (EMASS), we studied polymorphisms in the dopamine DRD2 and DRD3 receptor genes. The EMASS collaboration was established to create a large, statistically powerful sample of schizophrenic patients and controls from different European centres. Previous studies have suggested associations between schizophrenia and the Ser311Cys polymorphism in exon 7 of the dopamine DRD2 receptor gene [Arinami et al., (1994): Lancet 343:703-704] and a polymorphism Ser9gly in exon 1 of the dopamine DRD3 receptor gene [Crocq et al. (1992): J Med Genet 29:858-860]. We tested for these associations in samples of 373 and 413, and 311 and 306 patients and controls, respectively. We found no evidence for allelic association between schizophrenia and the Cys311 variant of the DRD2 receptor gene and no homozygotes for this variant were observed by any group. However, an excess of homozygotes for both alleles of the DRD3 polymorphism was observed in schizophrenic patients (chi2 = 8.54, P = 0.003, odds ratio = 1.64, 95% CI = 1.18-2.29). We also observed a significant excess of the 1-1 (Ser9Ser) genotype (chi2 = 8.13, P = 0.004, odds ratio = 1.7, 95% CI = 1.18-2.4). No evidence of heterogeneity between samples was detected and there was no evidence of an allelic association. These findings suggest that the rare Cys311 variant in exon 7 of the DRD2 receptor gene does not play a role in the pathogenesis of schizophrenia in European populations. Currently, our results do support the previous findings of an association between increased homozygosity of the Ser/Gly variant of the Dopamine D3 receptor gene and schizophrenia.

Anticipation in schizophrenia.

In various genetic disorders it has been observed that the severity of illness increases and the age at onset decreases in successive generations. This phenomenon is termed anticipation. We sampled 15 families, totalling 123 individuals with at least one person affected by a disease of the schizophrenia spectrum in the index generation in each family (IG; n = 33 affected out of a total of 67 individuals) and in the parental generation (PG; n = 16 affected out of a total of 56 individuals). The pedigrees had originally been identified for linkage studies in schizophrenia. We found a significant difference between IG and PG regarding severity of illness as defined by Kendler et al's hierarchical model of categories of the schizophrenia spectrum (p = 0.001). Age at onset was significantly earlier in the IG (21.6 +/- 6.6 years) than in the PG (40.2 +/- 9.2 years) (p = 0.0001). We excluded a potential birth cohort effect by investigating a control sample consisting of two non-overlapping birth cohorts of patients with schizophrenia. Age at onset between the two groups of the control sample did not differ. Anticipation is an important aspect in the investigation of a possible genetic basis, at least for the familial form of schizophrenia. Active research on a molecular level with special emphasis on trinucleotide repeats might be able to shed further light on this phenomenon.

Genetic polymorphisms for drug metabolism (CYP2D6) and tardive dyskinesia in schizophrenia.

In the present study, the occurrence of tardive dyskinesia (TD) in chronic schizophrenia patients was investigated in relation to pharmacogenetic polymorphisms. It is known that the metabolism of important neuroleptic drugs is influenced by polymorphisms of the CYP2D6 gene, which encodes the cytochrome P450 enzyme debrisoquine/spartein hydroxylase. Forty-five patients meeting the DSM IV criteria for schizophrenia, chronic course, were recruited. The patients were examined for the mutations CYP2D6*3, CYP2D6*4 and CYP2D6*5. The CYP2D6 genotype distribution in the patient group did not differ from that in healthy Caucasian populations. Tardive dyskinesia was found in 26 patients (57.8%). When comparing patients without CYP2D6 mutations with patients heterozygous for one mutation, we found a higher incidence of TD in the latter (81.3% vs. 46.4%, p = 0.031, multiple regression analysis), which demonstrates a significant influence of the CYP2D6 genotype of the manifestation of TD. As slight differences in the metabolism of drugs in patients heterozygous for CYP2D6 mutations and patients without such mutations are known, we conclude that heterozygous carriers of 2D6 mutated alleles may show an increased susceptibility to developing TD.

Normal CAG repeats in the Huntington gene in a family with benign familial chorea.

Benign familial chorea (BFC) is a rare neurological disease with an autosomal dominant transmission. The disorder is characterized by its early onset in childhood, a non-progressive course of choreatic movements and the absence of intellectual impairment. There is one study describing an expanded (CAG)n repeat in the gene IT15 (Huntington) on chromosome 4p (causative for Huntington's chorea) in a family reported to have BFC that was diagnosed on the basis of onset and non-progressive course. We failed to find an expansion of the (CAG)n repeats in an Austrian family having BFC. The three affected individuals of the family had 18-25 CAG repeats. These results indicate that the diagnostic criteria for BFC should include a normal result in the analysis of the (CAG)n repeat region of the Huntington gene.

Non-association of dopamine D4 and D2 receptor genes with personality in healthy individuals.

Recently, different research groups reported conflicting results with regard to an association of dopamine 4 receptor (DRD4) genotypes and the personality dimension of novelty seeking (NS). High scores for NS seemed to be associated with long alleles of a DRD4 polymorphism. Furthermore, an association between personality traits and the dopamine 2 (DRD2) receptor gene was reported. NS and persistence (PS) high scores seemed to be associated with alleles of DRD2. We examined 109 (78 female and 31 male) normal healthy individuals using Cloninger's Temperament and Character Inventory (TCI) in order to replicate these findings. We genotyped a 48 base pair variable number of tandem repeats (from two to eight repeats) polymorphism in the third exon of DRD4 and a Cys311Ser polymorphism in exon 7 of DRD2. We tested alleles and genotypes of DRD4 (allele 7 absent or present; genotype 4,4 versus 4,7), and Ser/Cys and Cys/Cys genotypes of DRD2 for associations with TCI values. NS and the alleles and genotypes of DRD4 did not show any association. In associating the genotypes of DRD2 with TCI scales (NS, harm avoidance, reward dependence and PS), we also found no association. Recent findings associating NS with DRD4 could not be replicated. With regard to DRD2, we tested a different polymorphism as published recently and could not find an association of TCI scales with the gene. The present results therefore do not provide evidence that the DRD2 and DRD4 receptor genes contribute a common and relevant effect to personality traits.

Schizophrenia and the dopamine-beta-hydroxylase gene: results of a linkage and association study.

Alterations in dopamine neurotransmission and disturbed norepinephrine activity have been implicated in the pathogenesis of schizophrenia. We considered the dopamine-beta-hydroxylase (DBH) gene located on the long arm of chromosome 9 (9q34.3) as a candidate gene for schizophrenia. DBH catalyzes the synthesis of norepinephrine from dopamine in noradrenergic neurons. In addition to DBH we used in the linkage study DNA markers ABL (centromeric) and D9S114 (telomeric). The aim of this study was to test linkage and association between PCR-based genotyped markers and schizophrenia. A simulation was done to investigate the power of our sample. In 34 Austrian families we could not detect linkage between schizophrenia and schizophrenia spectrum disorders and the three genetic markers. We could not find any significant deviation in allelic or genotypic distribution from expectations. Based on our results we conclude that the DBH gene seems to have no strong contribution in the etiology of schizophrenia.

Dopamine D3 receptor gene polymorphism and response to clozapine in schizophrenic Pakastani patients.

The dopamine D3 receptor (DRD3) appears to play an important role in the mediation of antipsychotic drug action. Genetic association of treatment response to the atypical antipsychotic drug clozapine with the DRD3 polymorphism Ser9Gly was investigated in a sample of 32 schizophrenic patients. We found association of treatment response with allele Gly-9 (P=0.0058) and with genotypes consisting of Gly-9 (P=0.033) by this pharmacogenetic approach. A combined analysis with two previous studies (Shaikh et al., Hum. Genet. 97 (1996) 714-719; Malhotra et al., Mol. Psychiatry 3 (1998) 72-75) further substantiates these results (P=0.0041).

No change in striatal dopamine re-uptake site density in psychotropic drug naive and in currently treated Tourette's disorder patients: a [(123)I]-beta-CIT SPECt-study.

BACKGROUND: There is evidence that Tourette's disorder (TD) is associated with abnormalities in the dopaminergic system involving the dopamine transporter (DAT). Data from [(123)I]-beta-CIT single photon emission computed tomography (SPECT) studies and postmortem findings concerning DAT densities in TD patients are not conclusive. The objective of our study was to measure DAT densities with [(123)I]-beta-CIT binding in TD patients who were either psychotropic drug naive or currently treated with antipsychotics (AP) and healthy controls. METHOD: Altogether 20 TD patients were investigated. A total of 15 patients were psychotropic drug naive and five were currently treated with AP. Ten psychotropic drug naive patients were compared with ten age and sex matched healthy subjects. Five currently treated patients were compared with five age and sex matched psychotropic drug naive TD patients. The investigation was carried out using [(123)I]-beta-CIT (2-beta-carbomethoxy-3-beta(4-iodophenyl)-tropane and SPECT. Regions of interest (ROI) were drawn over the striatum and the cerebellum. RESULTS: The DAT densities measured by the striatal/cerebellar (S/C) binding ratio did not differ between drug naive TD patients and the controls. The difference between currently AP treated and psychotropic drug naive TD patients did not reach the level of significance. There was no correlation between the ratio and severity of tics and illness. CONCLUSION: Our study with psychotropic drug naive TD patients contributed to clarify the inconsistent results concerning the DAT.

Comparison of methadone and slow-release morphine maintenance in pregnant addicts.

AIMS: To investigate whether the neonatal abstinence syndrome (NAS) is different in children born to women maintained on slow-release morphine, compared with those maintained on methadone, and to compare additional drug consumption in these groups of women. DESIGN, SETTING AND PARTICIPANTS: An open, randomized trial was conducted in an established clinic. Forty-eight pregnant women who presented to the clinic as opiate or polysubstance abusers were enrolled and maintained on either methadone (24 women) or slow-release morphine (24 women) up to and following delivery. The programme included psychosocial therapy and support for their opiate-addicted partners. MEASUREMENTS: Standard urinalysis methods were used to measure consumption of cocaine and benzodiazepines during pregnancy. Injection sites were monitored to indicate additional opiate use. NAS was measured according to Finnegan score and the amount of phenobarbiturates prescribed to alleviate the symptoms. FINDINGS: No difference was found in the number of days that NAS was experienced by neonates born to methadone or morphine maintained mothers (mean = 16 and 21 days, respectively). All children were born healthy and no serious complications arose. Fewer benzodiazepines (p < 0.05) and fewer additional opiates (p < 0.05) were consumed by the morphine-maintained women compared with those who took methadone, but no difference was seen in cocaine consumption. Nicotine consumption was reduced significantly in both groups during pregnancy (p < 0.02). CONCLUSIONS: Both methadone and morphine are suitable maintenance agents for pregnant opiate addicts. Maintenance agents that result in a less prolonged NAS should be studied in further trials.

Buprenorphine versus methadone maintenance for the treatment of opioid dependence.

AIMS: To evaluate the effectiveness of buprenorphine compared with methadone maintenance therapy in opiate addicts over a treatment period of 24 weeks. DESIGN: Subjects were randomized to receive either buprenorphine or methadone in an open, comparative study. SETTING: Subjects were recruited and treated at the drug addiction outpatient clinic at the University of Vienna. PARTICIPANTS: Sixty subjects (19 females and 41 males) who met DSM-IV criteria for opioid dependence and were seeking treatment. INTERVENTION: Subjects received either sublingual buprenorphine (2-mg or 8-mg tablets; maximum daily dose 8 mg) or oral methadone (racemic D -/+ L-methadone; maximum daily dose 80 mg). A stable dose was maintained following the 6-day induction phase. MEASUREMENT: Assessment of treatment retention and illicit substance use (opiates, cocaine and benzodiazepines) was made by urinalysis. FINDINGS: The retention rate was significantly better in the methadone maintained group (p < 0.05) but subjects completing the study in the buprenorphine group had significantly lower rates of illicit opiate consumption (p = 0.04). CONCLUSION: The results support the superiority of methadone with respect to retention rate. However, they also confirm previous reports of buprenorphine use as an alternative in maintenance therapy for opiate addiction, suggesting that a specific subgroup may be benefiting from buprenorphine. This is the first comparative trial to use sublingual buprenorphine tablets: previously published comparison studies refer to 30% solutions of buprenorphine in alcohol.

Treatment of opioid-dependent pregnant women with buprenorphine.

AIMS: To assess the maternal and fetal acceptability of buprenorphine and neonatal abstinence syndrome (NAS) in children born to buprenorphine-maintained mothers. DESIGN AND SETTING: Open-label, flexible dosing, inpatient induction with outpatient maintenance, conducted at the University of Vienna within the existing pregnancy and drug addiction program. PARTICIPANTS: Fifteen opioid-dependent pregnant women. INTERVENTION: Sublingual buprenorphine tablets (1-10 mg/day). MEASUREMENTS: Mothers: withdrawal symptoms (Wang Scale), nicotine dependence (Fagerström Scale: FTQ) and urinalysis. Neonates: birth outcome and NAS (Finnegan Scale). FINDINGS: All subjects were opioid-, nicotine- and cannabis-dependent. Buprenorphine was well tolerated during induction (Wang Score < or = 4) and illicit opioid use was negligible (91% opioid-negative). All maternal, fetal and neonatal safety laboratory measures were within normal limits or not of clinical significance. Mean birth outcome measures including gestational age at delivery (39.6 +/- 1.5 weeks), Apgar scores (1 min = 8.9; 5 min = 9.9; and 10 min = 10), birth weight (3049 +/- 346 g), length (49.8 +/- 1.9 cm) and head circumference (34.1 +/- 1.8 cm) were within normal limits. The NAS was absent, mild (without treatment) and moderate (with treatment) in eight, four and three neonates, respectively. The mean duration of NAS was 1.1 days. CONCLUSIONS: Buprenorphine appears to be well accepted by mother and fetus, and associated with a low incidence of NAS. Further investigation of buprenorphine as a maintenance agent for opioid-dependent pregnant women is needed.

Linkage of mood disorders with D2, D3 and TH genes: a multicenter study.

BACKGROUND: It has been suggested that the dopaminergic system is involved in the pathophysiology of mood disorders. We conducted a multicenter study of families with mood disorders, to investigate a possible linkage with genes coding for dopamine receptor D2, dopamine receptor D3 and tyrosine hydroxylase (TH). METHODS: Twenty three mood disorder pedigrees collected within the framework of the European Collaborative Project on Affective Disorders were analyzed with parametric and non-parametric linkage methods. Various potential phenotypes were considered, from a narrow (only bipolar as affected) to a broad (bipolar+major depressive+schizoaffective disorders) definition of affection status. RESULTS: Parametric analyses excluded linkage for all the candidate genes, even though small positive LOD (Limit of Detection) scores were observed for TH in three families. Non-parametric analyses yielded negative results for all markers. CONCLUSION: The D2 and D3 dopamine receptors were, therefore, not a major liability factor for mood disorders in our sample, whereas TH may play a role in a subgroup of patients.

Mirtazapine in recurrent brief depression.

Recurrent brief depression (RBD) has a high prevalence in the general population (approximately 10%). At present, data on the treatment of RBD are sparse. Results of treatment studies with selective serotonin reuptake inhibitors (fluoxetine, paroxetine) did not demonstrate superiority of the active drug over placebo in RBD. We report about two patients with RBD treated with mirtazapine over a period of 4 months. Mirtazapine is a noradrenergic with specific selective serotoninergic antidepressant. Patients had to keep a diary in order to document psychopathological symptoms of major depression according to DSM-IV. We showed a marked reduction of severity, duration and frequency of brief depressive episodes in two patients with RBD treated with 30 mg mirtazapine over a period of 4 months. Mirtazapine enhances serotonergic as well as noradrenergic neurotransmission. This dual mechanism of action may be necessary to improve RBD. Consequently, mirtazapine might be a treatment option for patients with RBD. However, our preliminary observations need to be substantiated in controlled studies.

Fluoxetine treatment in patients with recurrent brief depression.

Recurrent brief depression (RBD) fulfills DSM-IV criteria for major depression except duration. Depressive episodes last at least 2 days but less than 2 weeks occurring at least once a month for 12 consecutive months without association to the menstrual cycle. RBD has a high prevalence in the general population (approximately 10%). At present, there are few double-blind controlled studies indicating that selective serotonine reuptake inhibitors (SSRIs) might not be effective in treatment of RBD. However, most of those studies include patients with a history of frequent suicide attempts and depressive episodes lasting shorter 2 weeks. It has previously been shown that fluoxetine was effective in patients with RBD in an open-label study. The objective of our study was to reinvestigate these contradictory results concerning the effectiveness of fluoxetine in patients with RBD. Seventeen patients with RBD according to DSM-IV and ICD-10 diagnostic criteria, who had no history of major depression were treated with a dosage of 20-40 mg fluoxetine daily. Patients had to keep a diary in order to document psychopathological symptoms according to DSM-IV. We also used the 21-item Hamilton Depression Rating Scale (HAM-D), the Beck Depression Inventory (BDI) and the Clinical Global Impressions (CGI). Duration of the study was 8 weeks. The diaries of nine patients were observed for a clinical observation period of 20 weeks after the end of the study with continued fluoxetine treatment. Two patients who initially fulfilled diagnostic criteria for RBD suffered from depressive episodes that lasted longer than 2 weeks. Therefore, their data had to be excluded from primary analysis. In the remaining 15 patients, we showed statistically significant improvement of depressive episodes measured by patient's diary, HIAM-D, BDI and CGI that persisted over the clinical observation period. Frequency of depressive episodes showed a significant decrease during fluoxetine treatment. Duration and severity of the single depressive episodes also decreased but did not reach statistical significance. In accordance with previous studies, fluoxetine could be a treatment option for patients with RBD. Treatment of RBD with SSRIs has been discussed controversially in the literature. Our study shows the effectiveness of fluoxetine in this depressive disorder. To confirm these preliminary results, a double-blind controlled study is necessary.

Effective open-label treatment of tourette's disorder with olanzapine.

Olanzapine is an atypical antipsychotic drug which shows a high antagonistic affinity to the D1, D2 and D4 and the 5-HT2A and 5-HT2c receptors. The goal of our investigation was to assess the efficacy of olanzapine in patients with Tourette's disorder who were either antipsychotic naive or who did not tolerate and/or did not respond to previous antipsychotic treatments in an open-label pilot study. Fourteen patients with a mean (SD 12.4) age of 32.6 years were treated for a period of 6 weeks. Seven patients did not respond to, or did not tolerate, previous neuroleptic treatments and seven patients were antipsychotic naive. All patients received olanzapine in ascending dosage, following a washout period of 1 week. Initial dosage was 10 mg/day with a maximum dosage of 20 mg/day. The Yale Global Tic Severity Scale (YGTSS), Fischer Symptom Check List-Neuroleptika and the Clinical Global Impression Severity Scale (CGI) were used. Two of the 14 patients did not complete the investigation. The mean dosage of olanzapine was 15 mg/day (SD 3.3) at day 42 (end of the study). The YGTSS scores and the CGI significantly decreased over the treatment period. The only side-effect observed was mild sedation which decreased during the course of the investigation and two patients had weight gain of 3-5 kg with increased appetite. In our study, we found that olanzapine was a safe and effective treatment alternative to other antipsychotics. In order to confirm these preliminary results, double-blind placebo controlled trials are warranted.

Behavioral effects of tryptophan depletion in seasonal affective disorder associated with the serotonin transporter gene?

There is some evidence that the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) may be involved in the pathogenesis of seasonal affective disorder (SAD). Short-term tryptophan (TRP) depletion was carried out in 18 drug-free remitted patients who met DSM-IV criteria for SAD. Behavioral effects were measured with the Hamilton Depression Rating Scale (HDRS) both 24 h before and 24 h after TRP depletion. Some of the patients showed behavioral responses such as lowered mood, feelings of guilt, loss of interest, agitation, loss of energy, fatigue, social withdrawal, increased appetite, and carbohydrate craving. It was the aim of our study to investigate whether the genotypes of the serotonin transporter gene were associated with symptoms of transient depressive relapse after TRP depletion. In addition, we matched the SAD patients with healthy control subjects to see if alleles and genotypes of the serotonin transporter gene were associated with SAD. High molecular weight DNA was isolated from peripheral blood leukocytes using standard methods. For the 5-HTT receptor gene, a 17-bp repetitive element of intron 2 was genotyped (variable number tandem repeat, VNTR). Alterations in HDRS scores after TRP depletion showed no significant association with alleles or genotypes of the 5-HTT gene, although heterozygotes showed a trend toward increased HDRS scores. The serotonin transporter is known to play a critical role in the termination of serotonergic neurotransmission by sodium-dependent uptake of 5-HT into the presynaptic neuron. The present study in a small group of SAD patients was unable to demonstrate that the 5-HTT gene plays a role in the pathogenesis of SAD or in short-term depressive relapse after TRP depletion.

Association study of schizophrenia spectrum disorders and dopamine D3 receptor gene: is schizoaffective disorder special?

Alterations in dopamine neurotransmission have been hypothesized to play a role in the etiology of schizophrenia. We considered the dopamine D3 receptor gene on chromosome 3 as a candidate gene for an association analysis. We compared PCR-based genotype markers for healthy controls (n=120) and patients (n=95) with schizophrenia and schizophrenia spectrum disorders as diagnosed by consensus according to DSM-III-R. Our results possibly indicate an association of schizoaffective disorder with DRD3 homozygosity (P=0.056).