Association of the trace amine associated receptor 6 (TAAR6) gene with schizophrenia and bipolar disorder in a Korean case control sample

Trace amines and their receptors may be implicated in the pathogenesis of psychiatric disorders. Previous studies have reported association of the trace amine associated receptor 6 (TAAR6) gene with susceptibility to schizophrenia and bipolar disorder but results have not been consistent. The purpose of this study was to examine these associations in Korean patients and also to test for association of TAAR6 with susceptibility to major depressive disorder (MDD). A case control sample consisting of 281 patients with schizophrenia, 190 patients with bipolar disorder, 187 patients with MDD and 288 psychiatrically healthy control subjects, was examined. Patients with schizoaffective disorder were not included in any of the psychiatric samples. Five single nucleotide polymorphisms (SNPs: rs4305745; rs8192625; rs7452939; rs6903874 and rs6937506) were genotyped in the TAAR6 gene and in the 3' regulatory region, using pyrosequencing. SNP rs6903874 was significantly associated with schizophrenia (p = 0.012) and bipolar disorder (p = 0.004). A three SNP haplotype consisting of alleles GCT from SNPs rs7452939, rs6903874 and rs6937506, respectively, was significantly over-represented in patients with schizophrenia (p = 0.0003) and bipolar disorder (p = 0.00002). A second three SNP haplotype (GTT) derived from the same SNPs was significantly under-represented in patients with bipolar disorder (p = 0.001). The GTT haplotype associations withstand the most rigorous corrections for multiple testing. These findings strongly support association of the TAAR6 gene with susceptibility to both schizophrenia and bipolar disorder in Korean patients. Further studies are needed to confirm these findings in this and other populations and to identify functional variants in TAAR6 that may be implicated in pathogenesis.     

Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression.

BACKGROUND: Previous genetic studies investigating a possible involvement of variations at the brain derived neurotrophic factor (BDNF) gene locus in major depressive disorder (MDD), bipolar affective disorder (BPAD), and schizophrenia have provided inconsistent results. METHODS: We performed single-marker and haplotype analyses using three BDNF polymorphisms in 2,376 individuals (465 MDD, 281 BPAD, 533 schizophrenia, and 1,097 control subjects). RESULTS: Single-marker analysis did not provide strong evidence for association. Haplotype analysis of marker combination rs988748-(GT)n-rs6265 produced nominally significant associations for all investigated phenotypes (global p values: MDD p = .00006, BPAD p = .0057, schizophrenia p = .016). Association with MDD was the most robust finding and could be replicated in a second German sample of MDD patients and control subjects (p = .0092, uncorrected). Stratification of our schizophrenia sample according to the presence or absence of a lifetime history of depressive symptoms showed that our finding in schizophrenia might be attributable mainly to the presence of depressive symptoms. CONCLUSIONS: Association studies of genetic variants of the BDNF gene with various psychiatric disorders have been published with reports of associations and nonreplications. Our findings suggest that BDNF may be a susceptibility gene for MDD and schizophrenia-in particular, in a subgroup of patients with schizophrenia with a lifetime history of depressive symptoms.     

Sex-specific association between bipolar affective disorder in women and GPR50, an X-linked orphan G protein-coupled receptor

GPR50 is an orphan G protein-coupled receptor (GPCR) located on Xq28, a region previously implicated in multiple genetic studies of bipolar affective disorder (BPAD). Allele frequencies of three polymorphisms in GPR50 were compared in case-control studies between subjects with BPAD (264), major depressive disorder (MDD) (226), or schizophrenia (SCZ) (263) and ethnically matched controls (562). Significant associations were found between an insertion/deletion polymorphism in exon 2 and both BPAD (P=0.0070), and MDD (P=0.011) with increased risk associated with the deletion variant (GPR50(Delta502-505)). When the analysis was restricted to female subjects, the associations with BPAD and MDD increased in significance (P=0.00023 and P=0.0064, respectively). Two other single-nucleotide polymorphisms (SNPs) tested within this gene showed associations between: the female MDD group and an SNP in exon 2 (P=0.0096); and female SCZ and an intronic SNP (P=0.0014). No association was detected in males with either MDD, BPAD or SCZ. These results suggest that GPR50(Delta502-505), or a variant in tight linkage disequilibrium with this polymorphism, is a sex-specific risk factor for susceptibility to bipolar disorder, and that other variants in the gene may be sex-specific risk factors in the development of schizophrenia.     

No association of the brain-derived neurotrophic factor (BDNF) gene polymorphisms with panic disorder

Several lines of evidence suggest that genetic factors might contribute to susceptibility to panic disorder. Our previous studies show that the brain-derived neurotrophic factor (BDNF) may play a role in the pathophysiology of major depressive disorders and eating disorders. Assuming that BDNF may be implicated in the putative common pathophysiology of depression and anxiety, we analyzed the association of two BDNF gene single nucleotide polymorphisms (SNPs), 132C > T (formerly named C270T) in the noncoding region of exon V and 196G > A (val66met) in the coding region of exon XIIIA, with panic disorder. In this study, 109 patients with panic disorder diagnosed according to the DSM-IV criteria, and 178 control subjects were recruited. There were no significant differences in the frequency of the genotype or allele in these two SNPs between patients and controls [132C > T in exon V: genotype, p = 1.0, allele, p = 0.59; 196G > A (val66met) in exon XIIIA: genotype, p = 0.77, allele, p = 0.78]. Furthermore, no significant associations of agoraphobia with the two SNPs were detected. This study suggests that the BDNF gene polymorphisms are not associated with panic disorder in our Japanese population.     

A possible association between missense polymorphism of the breakpoint cluster region gene and lithium prophylaxis in bipolar disorder

Lithium is one of the most commonly used drugs for the treatment of bipolar disorder. To prescribe lithium appropriately to patients, predictors of response to this drug were explored, and several genetic markers are considered to be good candidates. We previously reported a significant association between genetic variations in the breakpoint cluster region (BCR) gene and bipolar disorder. In this study, we examined a possible relationship between response to maintenance treatment of lithium and Asn796Ser single-nucleotide polymorphism in the BCR gene. Genotyping was performed in 161 bipolar patients who had been taking lithium for at least 1 year, and they were classified into responders for lithium mono-therapy and non-responders. We found that the allele frequency of Ser796 was significantly higher in non-responders than in responders. Further investigation is warranted to confirm our findings.     

Prevalence, correlates, and comorbidity of bipolar I disorder and axis I and II disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions

OBJECTIVE: To present nationally representative data on 12-month and lifetime prevalence, correlates, and comorbidity of bipolar I disorder. METHOD: The data were derived from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Prevalences and associations of bipolar I disorder with sociodemographic correlates and Axis I and II disorders were determined. RESULTS: Prevalences of 12-month and lifetime DSM-IV bipolar I disorder were 2.0% (95% CI = 1.82 to 2.18) and 3.3% (95% CI = 2.76 to 3.84), respectively, and no sex differences were observed. The odds of bipolar I disorder were significantly greater among Native Americans, younger adults, and respondents who were widowed/separated/divorced and of lower socioeconomic status and significantly lower among Asians and Hispanics (p < .05). Men were significantly (p < .05) more likely to have unipolar mania and earlier onset and longer duration of manic episodes, while women were more likely to have mixed and major depressive episodes and to be treated for manic, mixed, and major depressive episodes. Bipolar I disorder was found to be highly and significantly related (p < .05) to substance use, anxiety, and personality disorders, but not to alcohol abuse. CONCLUSION: Bipolar I disorder is more prevalent in the U.S. population than previously estimated, highlighting the underestimation of the economic costs associated with this illness. Associations between bipolar I disorder and Axis I and II disorders were all significant, underscoring the need for systematic assessment of comorbidity among bipolar I patients.     

CDH13 and HCRTR2 May Be Associated with Hypersomnia Symptom of Bipolar Depression: A Genome-Wide Functional Enrichment Pathway Analysis

Although bipolar disorder is highly heritable, the identification of specific genetic variations is limited because of the complex traits underlying the disorder. We performed a genome-wide association study of bipolar disorder using a subphenotype that shows hypersomnia symptom during a major depressive episode. We investigated a total of 2,191 cases, 1,434 controls, and 703,012 single nucleotide polymorphisms (SNPs) in the merged samples obtained from the Translational Genomics Institute and the Genetic Association Information Network. The gene emerging as the most significant by statistical analysis was rs1553441 (odds ratio=0.4093; p=1.20×10^-5; Permuted p=6.0×10^-6). However, the 5×0^-8 threshold for statistical significance required in a genome-wide association study was not achieved. The functional enrichment pathway analysis showed significant enrichments in the adhesion, development-related, synaptic transmission-related, and cell recognition-related pathways. For further evaluation, each gene of the enriched pathways was reviewed and matched with genes that were suggested to be associated with psychiatric disorders by previous genetic studies. We found that the cadherin 13 and hypocretin (orexin) receptor 2 genes may be involved in the hypersomnia symptom during a major depressive episode of bipolar disorder.     

Association study of the frizzled-3 (FZD3) gene with schizophrenia and mood disorders

Summary. Two research groups have recently reported a significant association between schizophrenia and genetic variants of Frizzled-3 (FZD3) gene. We examined a possible association in a Japanese sample of schizophrenia, bipolar disorder, unipolar depression and controls with four single nucleotide polymorphisms (SNPs), tested in previous reports. We failed to find significant association in the four SNPs or haplotype analysis. The FZD3 gene might not play a role in conferring susceptibility to major psychosis in our sample.     

Association between polymorphisms in the vesicle-associated membrane protein-associated protein A (<Emphasis Type="Italic">VAPA</Emphasis>) gene on chromosome 18p and bipolar disorder

Linkage studies in bipolar disorder (BPD) suggest that a susceptibility locus exists on chromosome 18p11. The vesicle-associated membrane protein-associated protein A (VAPA) gene maps to this region. VAPA interacts with presynaptic proteins and is necessary for vesicular neurotransmission. Dysregulation of synaptic neurotransmission might contribute to the pathophysiology of BPD. In this study, we hypothesize that genetic variations in the VAPA gene contribute to BPD. We tested this hypothesis by genotyping 6 SNPs (rs494015; rs29193; rs29162; rs29145; rs29067; rs29066) in BPD patients (n = 570) and healthy controls (n = 730). Genotype and allele frequencies were compared between groups using Chi square contingency analysis. Linkage disequilibrium (LD) between markers was calculated and estimated haplotype frequencies were compared between groups. Single marker analysis revealed an association of rs29067 and rs29066 with BPD; however, after permutation correction, only rs29066 showed a trend towards an allelic association (P = 0.066). Haplotype analysis did not show any significant association with disease after permutation correction. Our results provide suggestive evidence of an association between SNPs in the 3'UTR of the VAPA gene and BPD. Interestingly, these SNPs are in close proximity to the microsatellite marker D18S464, which showed significant signals in previous linkage studies of BPD. Additional studies are necessary to confirm and elucidate the role of VAPA as a susceptibility gene for BPD on chromosome 18p.     

Quinone oxidoreductase (NQO1) gene polymorphism may not confer a susceptibility to mood disorders

Quinone oxidoreductase (NQO1) plays a key role in the cellular antioxidant defense by detoxifying quinine derivatives. Case-control association study of the possible relationship between the NQO1 gene polymorphism and mood disorders (patients with major depressive disorder, n=61; patients with bipolar I disorder, n=80; control, n=106) was carried out using PCR-based techniques. These preliminary results showed that the NQO1 gene polymorphism was not related to a susceptibility to mood disorders.     

Dopamine receptor D1 gene -48A/G polymorphism is associated with bipolar illness but not with schizophrenia in a Polish population

Dysregulation of dopaminergic neurotransmission has been implicated in the etiology of major psychoses. The dopamine D(1) receptor (DRD1) plays a role in some brain functions and mechanisms of psychotropic drugs. Therefore, the DRD1 gene makes a good candidate gene for molecular genetic studies in schizophrenia and bipolar affective disorder. In the present study, the -48A/G polymorphism of the DRD1 gene was estimated in patients with schizophrenia (n=407) or bipolar affective disorder (n=380), and in healthy controls (n=399). No association was found between the polymorphism studied and schizophrenia, either in the whole group of patients or in subgroups divided by gender, age at onset or predominance of positive or negative symptoms. A statistical trend was obtained for an association between this polymorphism and bipolar affective disorder (p=0.059 for genotypes, p=0.073 for alleles). The G/G genotype and G allele were significantly more frequent in patients with bipolar disorder, type II (p=0.016 for genotypes, p=0.008 for alleles), especially in the women subgroup (p=0.054 for genotypes, p=0.024 for alleles). An association between the G/G genotype and bipolar affective disorder with disease onset after 18 years of age was also found (p=0.022). These data suggest that the -48A/G polymorphism of the DRD1 gene may be involved in the etiology of bipolar disorder in a Polish population.     

Dopamine receptor D2 Ser/Cys 311 variant is associated with delusion and disorganization symptomatology in major psychoses

The D2 receptor (DRD2) is a binding site of many psychoactive drugs and it has been proposed as a genetic risk factor for psychiatric disorders. The aim of this investigation was to study the DRD2 S311C variant in major psychoses. We studied 1182 inpatients with diagnoses of bipolar disorder (n = 480), major depressive disorder (n = 269), schizophrenia (n = 366), delusional disorder (n = 44), psychotic disorder not otherwise specified (n = 23) and 267 healthy controls. Eight hundred and eighty-seven subjects were also scored for their lifetime symptomatology using the the Operational Criteria checklist for psychotic illness (OPCRIT). DRD2 variants were not associated with affected subjects even when possible confounders like gender and onset were considered. When we considered the 887 subjects with the symptomatologic analysis, we observed a significant association of the DRD2 S311C variant with both delusion and disorganization features. The association was present independently from diagnoses. Our results do not show that coding variants of the DRD2 S311C play a major role in conferring susceptibility to major psychoses, but they may be connected with disorganized and delusional symptomatology independently from diagnoses.     

Familial aggregation of postpartum mood symptoms in bipolar disorder pedigrees

OBJECTIVES: We sought to determine if postpartum mood symptoms and depressive episodes exhibit familial aggregation in bipolar I pedigrees. METHODS: A total of 1,130 women were interviewed with the Diagnostic Interview for Genetic Studies as part of the National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative Study and were asked whether they had ever experienced mood symptoms within four weeks postpartum. Women were also asked whether either of two major depressive episodes described in detail occurred postpartum. We examined the odds of postpartum mood symptoms in female siblings, who had previously been pregnant and had a diagnosis of bipolar I, bipolar II, or schizoaffective (bipolar type) disorders (n = 303), given one or more relatives with postpartum mood symptoms. RESULTS: The odds ratio for familial aggregation of postpartum mood symptoms was 2.31 (p = 0.011) in an Any Mood Symptoms analysis (n = 304) and increased to 2.71 (p = 0.005) when manic symptoms were excluded, though this was not significantly different from the Any Mood Symptoms analysis. We also examined familial aggregation of postpartum major depressive episodes; however, the number of subjects was small. CONCLUSIONS: Limitations of the study include the retrospective interview, the fact that the data were collected for other purposes and the inability to control for such factors as medication use. Taken together with previous studies, these data provide support for the hypothesis that there may be a genetic basis for the trait of postpartum mood symptoms generally and postpartum depressive symptoms in particular in women with bipolar disorder. Genetic linkage and association studies incorporating this trait are warranted.     

Family-based association of FKBP5 in bipolar disorder

The FKBP5 gene product forms part of a complex with the glucocorticoid receptor and can modulate cortisol-binding affinity. Variations in the gene have been associated with increased recurrence of depression and with rapid response to antidepressant treatment. We sought to determine whether common FKBP5 variants confer risk for bipolar disorder. We genotyped seven tag single-nucleotide polymorphisms (SNPs) in FKBP5, plus two SNPs previously associated with illness, in 317 families with 554 bipolar offspring, derived primarily from two studies. Single marker and haplotypic analyses were carried out with FBAT and EATDT employing the standard bipolar phenotype. Association analyses were also conducted using 11 disease-related variables as covariates. Under an additive genetic model, rs4713902 showed significant overtransmission of the major allele (P=0.0001), which was consistent across the two sample sets (P=0.004 and 0.006). rs7757037 showed evidence of association that was strongest under the dominant model (P=0.001). This result was consistent across the two datasets (P=0.017 and 0.019). The dominant model yielded modest evidence for association (P<0.05) for three additional markers. Covariate-based analyses suggested that genetic variation within FKBP5 may influence attempted suicide and number of depressive episodes in bipolar subjects. Our results are consistent with the well-established relationship between the hypothalamic-pituitary-adrenal (HPA) axis, which mediates the stress response through regulation of cortisol, and mood disorders. Ongoing whole-genome association studies in bipolar disorder and major depression should further clarify the role of FKBP5 and other HPA genes in these illnesses.     

A case-control association study and family-based expression analysis of the bipolar disorder candidate gene PI4K2B

Bipolar disorder, schizophrenia and recurrent major depression are complex psychiatric illnesses with a substantial, yet unknown genetic component. Linkage of bipolar disorder and recurrent major depression with markers on chromosome 4p15–p16 has been identified in a large Scottish family and three smaller families. Analysis of haplotypes in the four chromosome 4p-linked families, identified two regions, each shared by three of the four families, which are also supported by a case-control association study. The candidate gene phosphatidylinositol 4-kinase type-II beta (PI4K2B) lies within one of these regions. PI4K2B is a strong functional candidate as it is a member of the phosphatidylinositol pathway, which is targeted by lithium for therapeutic effect in bipolar disorder. Two approaches were undertaken to test the PI4K2B candidate gene as a susceptibility factor for psychiatric illness. First, a case-control association study, using tagging SNPs from the PI4K2B genomic region, in bipolar disorder (n = 368), schizophrenia (n = 386) and controls (n = 458) showed association with a two-marker haplotype in schizophrenia but not bipolar disorder (rs10939038 and rs17408391, global P = 0.005, permuted global P = 0.039). Second, expression studies at the allele-specific mRNA and protein level using lymphoblastoid cell lines from members of the large Scottish family, which showed linkage to 4p15–p16 in bipolar disorder and recurrent major depression, showed no difference in expression differences between affected and non-affected family members. There is no evidence to suggest that PI4K2B is contributing to bipolar disorder in this family but a role for this gene in schizophrenia has not been excluded.     

A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder

The genetic basis of bipolar disorder has long been thought to be complex, with the potential involvement of multiple genes, but methods to analyze populations with respect to this complexity have only recently become available. We have carried out a genome-wide association study of bipolar disorder by genotyping over 550,000 single-nucleotide polymorphisms (SNPs) in two independent case-control samples of European origin. The initial association screen was performed using pooled DNA, and selected SNPs were confirmed by individual genotyping. While DNA pooling reduces power to detect genetic associations, there is a substantial cost saving and gain in efficiency. A total of 88 SNPs, representing 80 different genes, met the prior criteria for replication in both samples. Effect sizes were modest: no single SNP of large effect was detected. Of 37 SNPs selected for individual genotyping, the strongest association signal was detected at a marker within the first intron of diacylglycerol kinase eta (DGKH; P=1.5 x 10(-8), experiment-wide P<0.01, OR=1.59). This gene encodes DGKH, a key protein in the lithium-sensitive phosphatidyl inositol pathway. This first genome-wide association study of bipolar disorder shows that several genes, each of modest effect, reproducibly influence disease risk. Bipolar disorder may be a polygenic disease.     

Bipolar II disorder: personality and outcome in two clinical samples

OBJECTIVE: To compare the personality traits and disorders of patients with bipolar II disorder and major depression and to examine the impact on treatment outcome of a bipolar II diagnosis. METHOD: Patients from two clinical trials, a depressive sample (n = 195, 10% bipolar II) and a bulimic sample (n = 135, 16% bipolar II), were assessed for personality traits using DSM-IV criteria. Patients were randomised to treatments (fluoxetine or nortriptyline for depressive sample; cognitive behaviour therapy for bulimic sample) and followed for 3 years (depressive sample) or 5 years (bulimic sample) to assess the impact on outcome of a bipolar II diagnosis. RESULTS: Bipolar II patients were assessed as having more borderline, histrionic and schizotypal personality traits than patients with major depression. A baseline bipolar II diagnosis did not impact negatively on treatment outcome, and less than 5% of bipolar II patients developed bipolar I disorder during follow up. CONCLUSIONS: The low rate of conversion of bipolar II to bipolar I disorder and the lack of adverse impact of the diagnosis on outcome, questions the need for antimanic or mood stabiliser medication in most bipolar II patients.     

Association analysis of FEZ1 variants with schizophrenia in Japanese cohorts.

BACKGROUND: DISC1 has been suggested as a causative gene for psychoses in a large Scottish family. We recently identified FEZ1 as an interacting partner for DISC1. To investigate the role of FEZ1 in schizophrenia and bipolar disorder, case-control association analyses were conducted in Japanese cohorts. METHODS: We performed a mutation screen of the FEZ1 gene and detected 15 polymorphisms. Additional data on informative polymorphisms were obtained from public databases. Eight single nucleotide polymorphisms (SNPs) were analyzed in 119 bipolar disorder and 360 schizophrenic patients and age- and gender-matched control subjects. All genotypes were determined with the TaqMan assay, and selected samples were confirmed by sequencing. RESULTS: The two adjacent polymorphisms displayed a nominally significant association with schizophrenia (IVS2+ 1587G>A, p = .014; 396T   

Variation at the DAOA/G30 locus influences susceptibility to major mood episodes but not psychosis in schizophrenia and bipolar disorder

CONTEXT: Variation at the DAOA/G30 locus has been described to be associated with both schizophrenia and bipolar disorder, but there is little consistency between studies of the tested polymorphisms or variants showing association. OBJECTIVES: To obtain a stringent replication of association in large samples of both disorders using consistent clinical and laboratory methods, and to test the hypothesis that association at DAOA/G30 identifies an underlying domain of psychopathological abnormalities that cuts across traditional diagnostic categories. DESIGN: A systematic study of polymorphisms at DAOA/G30 using genetic case-control association analysis. SETTING: Subjects were unrelated and ascertained from general psychiatric inpatient and outpatient services. PARTICIPANTS: White persons from the United Kingdom meeting criteria for DSM-IV schizophrenia (n = 709) or bipolar I disorder (n = 706) and 1416 ethnically matched controls. METHODS: Nine polymorphisms that tag common genetic variations at DAOA/G30 were genotyped in all of the individuals, and comparisons were made between affected and unaffected individuals. RESULTS: We identified significant association (P = .01-.047) between 3 single-nucleotide polymorphisms and bipolar disorder but failed to find association with schizophrenia. Analyses across the traditional diagnostic categories revealed significant evidence (P = .002-.02) for association with 4 single-nucleotide polymorphisms in the subset of cases (n = 818) in which episodes of major mood disorder had occurred (gene-wide P = .009). We found a similar pattern of association in bipolar cases and in schizophrenia cases in which individuals had experienced major mood disorder. In contrast, we found no evidence for association in the subset of cases (n = 1153) in which psychotic features occurred (all P>.08). CONCLUSIONS: Despite being originally described as a schizophrenia susceptibility locus, our data suggest that variation at the DAOA/G30 locus does not primarily increase susceptibility for prototypical schizophrenia or psychosis. Instead, our results imply that variation at the DAOA/G30 locus influences susceptibility to episodes of mood disorder across the traditional bipolar and schizophrenia categories.     

Psychotic features in bipolar and unipolar depression

BACKGROUND: While some prior studies have found higher rates of psychotic depression in those with bipolar disorder or a bipolar relative, others have failed to confirm these observations. We examined the relationship of psychotic depression to polarity in several large familial samples of mood disorder. METHODS: A total of 4,724 subjects with major mood disorder in three family studies on the genetics of bipolar I disorder (BPI) or recurrent major depressive disorder (MDDR) were administered semi-structured interviews by clinicians. Determination of psychotic features was based on a report of hallucinations and/or delusions during the most severe depressive episode in the Schedule for Affective Disorders and Schizophrenia-Lifetime Version or the Diagnostic Interview for Genetic Studies interview. Rates of psychotic depression were calculated by diagnostic category and comparisons were made between diagnoses within and across studies using the generalized estimating equation. RESULTS: A diagnosis of BPI disorder was strongly predictive of psychotic features during depression compared to MDDR [odds ratio (OR) = 4.61, p < 0.0005]. Having bipolar II compared to MDDR was not predictive of psychosis (OR = 1.05, p = 0.260), nor was having a family history of BPI in MDDR subjects (OR = 1.20, p = 0.840). CONCLUSIONS: Psychotic features during a depressive episode increased the likelihood of a BPI diagnosis. Prospective studies are needed to confirm these findings. The potential genetic underpinnings of psychotic depression warrant further study.