Association of dopamine transporter genotype with disruptive behavior disorders in an eight-year longitudinal study of children and adolescents.

Associations between dopamine transporter (DAT1) variable number tandem repeats (VNTR), genotypes, and disruptive behavior were examined in an 8-year longitudinal study of children (n = 183). Half of the children met criteria for attention-deficit/hyperactivity disorder (ADHD) at 4-6 years and half were non-referred comparison children. Consistent with several studies, the non-additive association for the 10-repeat allele was significant for hyperactivity-impulsivity (HI) symptoms. However, consistent with other studies, exploratory analyses of the non-additive association of the 9-repeat allele of DAT1 with HI and oppositional defiant disorder (ODD) symptoms also were significant. The inconsistent association between DAT1 and child behavior problems in this and other samples may reflect joint influence of the 10-repeat and 9-repeat alleles.     

A meta-analysis of association studies between the 10-repeat allele of a VNTR polymorphism in the 3'-UTR of dopamine transporter gene and attention deficit hyperactivity disorder.

The association between the 10-repeat allele of the dopamine transporter gene (DAT) and attention deficit hyperactivity disorder (ADHD) is uncertain. This study aimed to conduct a meta-analysis of the association between the 10-repeat allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region (UTR) of the DAT1 gene and ADHD. We pooled up 18 published transmission disequilibrium test (TDT) studies between the 40-base pair VNTR polymorphism in the3'-UTR of the DAT1 gene and ADHD. It included a total of 1,373 informative meioses, 7 haplotype-based haplotype relative risk (HHRR) studies, and 6 case-control-based association studies. There were statistically significant evidences for heterogeneity of the odds ratio in TDT and HHRR studies (P < 0.10), but not in case-control studies. The results of random effects model showed small but significant association between ADHD and the DAT1 gene in TDT studies (OR = 1.17, 95% CI = 1.05-1.30, chi-square = 8.11, df = 1, P = 0.004), but not in HHRR and case-control studies. The 10-repeat allele of a VNTR polymorphism in the 3'-UTR the DAT1 gene has a small but significant role in the genetic susceptibility of ADHD. These meta-analysis findings support the involvement of the dopamine system genes in ADHD liability variation. However, more work is required to further identify the functional allelic variants/mutations that are responsible for this association.     

Association of the DAT1 polymorphism with attention deficit hyperactivity disorder (ADHD): a family-based approach.

The dopamine transporter gene (DAT1) is of particular interest in the genetic study of attention deficit hyperactivity disorder (ADHD), because psychostimulants interact directly with the dopamine transporter protein. Association between ADHD and the 10-repeat allele of a 40 base pair (bp) variable number of tandem repeats (VNTR) polymorphism of DAT1 was first reported in 1995 [Cook et al. (1995); Am J Hum Genet 56:993-998]. Subsequently, several investigators have also confirmed this association, although others reported conflicting results. We analyzed the DAT1 polymorphism in a sample of 33 Korean probands with a Diagnostic and Statistical Manual of Mental Disorders version IV (DSM-IV) diagnosis of ADHD and found evidence of increased transmission of the 10-repeat allele using transmission disequilibrium test (TDT) (P = 0.001; OR = 7.88, CI = 2.20-28.29). These data support the role of DAT1 in ADHD susceptibility among Asian populations.     

Attention-deficit hyperactivity disorder: a study of association with both the dopamine transporter gene and the dopamine D4 receptor gene.

Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. The role of genetic factors in its etiology is strongly supported by family, adoption, and twin studies. Several investigations have reported associations between ADHD and both the 7-repeat allele of the 48 bp VNTR at the DRD4 gene and the 10-repeat allele of the 40 bp VNTR at the DAT1 gene, but the results have been inconsistent. A sample of 81 Brazilian ADHD children and adolescents and their parents were screened for these DRD4 and DAT1 VNTRs. An excess of the DRD4 7-repeat allele was observed when both ADHD probands and their parents were compared with an ethnically matched control sample (chi-square = 11.55, P = 0.03; chi-square = 12.17, P = 0.03, respectively). However, haplotype relative risk (HRR) analysis showed no preferential transmission of the DRD4 7-repeat allele. No evidence of association with the DAT1 polymorphism was detected by both approaches. Nevertheless, an interaction effect of both genes on ADHD hyperactive/impulsive dimension was observed (F = 4.68; P = 0.03). These results add to the group of studies that together suggest a small effect of these genes in the susceptibility to ADHD.     

Dopamine transporter polymorphism associated with externalizing behavior problems in children

Early childhood externalizing behavior is a stable and heritable pattern of aggressive and delinquent behavior that often leads to the development of serious psychiatric disorders such as conduct disorder and attention deficit hyperactivity disorder. We examined the relationship between parent reported externalizing behavior (assessed at ages 4, 7, and 9 years) and the VNTR polymorphism of the 3' untranslated region of SLC6A3 (DAT1) in a community sample of 790 children ascertained as part of our longitudinal twin and adoption studies. We applied the sibling-based methodology developed by Fulker et al. [1999: Am J Hum Genet 64:259-267] for estimating allelic association with quantitative traits, while controlling for population stratification. An extension of these methods allowed for the inclusion of monozygotic twins, dizygotic twins, siblings, and singletons. We have demonstrated that the 9-repeat variant of the DAT1 is a significant risk allele for externalizing behavior at ages 4 (P=0.001) and 7 years (P=0.02). Although the effect size was negligible at age 9 (P=0.92), a formal test of the developmental decrease in effect across the three ages was non-significant (P=0.70).     

Family-based and case-control association studies of DRD4 and DAT1 polymorphisms in Chinese attention deficit hyperactivity disorder patients suggest long repeats contribute to genetic risk for the disorder.

Molecular genetic studies of attention deficit hyperactivity disorder (ADHD) have implicated the variable number of tandem repeat (VNTR) polymorphisms of two candidate genes, the dopamine D4 receptor (DRD4) and the dopamine transporter (DAT1). We sought to determine if these genes were relevant to the etiology of ADHD in China by using both family-based (N = 202 nuclear ADHD families) and case-control (N = 340 ADHD cases, and 226 controls) association study designs. Diagnoses and subtypes were ascertained according to Clinical Diagnostic Interview Scales (CDIS) using DSM-IV criteria. The repeat numbers at the DRD4 VNTR ranged from 2 to 6 repeats in the Han Chinese controls, with the most common being the 4-repeat (77%) and 2-repeat (19.4%) alleles. Neither the 7-repeat allele nor longer repeats were found. For the DAT1 VNTR, the repeat numbers ranged from 6 to 7 repeats and 9 to 11 repeats. The 10-repeat allele was the most frequent (90.7%). The long-repeat alleles of DRD4 (ranging from 4 to 6 repeats) and DAT1 (ranging from 11 to 12 repeats), were present more frequently in ADHD probands than controls (P < 0.05), although there was no significant allelic association when the alleles were analyzed separately from each other and there findings were not supported by within family tests of association. An exploratory stratification by gender suggests that long-repeat alleles of DRD4 and DAT1 may increase the risk for ADHD in Han Chinese children.     

Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD)

Molecular genetic investigations of attention deficit hyperactivity disorder (ADHD) have found associations with a variable number of tandem repeat (VNTR) situated in the 3'-untranslated region of dopamine transporter gene (DAT1), a VNTR in exon 3 of dopamine receptor 4 gene (DRD4) and a microsatellite polymorphism located at 18.5 kb from the 5' end of dopamine receptor 5 gene (DRD5). A number of independent studies have attempted to replicate these findings but the results have been mixed, possibly reflecting inadequate statistical power and the use of different populations and methodologies. In an attempt to clarify this inconsistency, we have combined all the published studies of European and Asian populations up to October 2005 in a meta-analysis to give a comprehensive picture of the role of the three dopamine-related genes using multiple research methods and models. The DRD4 7-repeat (OR=1.34, 95% CI 1.23-1.45, P= 2 x 10(-12)) and 5-repeat (OR=1.68, 95% CI 1.17-2.41, P=0.005) alleles as well as the DRD5 148-bp allele (OR=1.34, 95% CI 1.21-1.49, P= 8 x 10(-8)) confer increased risk of ADHD, whereas the DRD4 4-repeat (OR=0.90, 95% CI 0.84-0.97, P=0.004) and DRD5 136-bp (OR=0.57, 95% CI 0.34-0.96, P=0.022) alleles have protective effects. In contrast, we found no compelling evidence for association with the 480-bp allele of DAT (OR=1.04, 95% CI 0.98-1.11, P=0.20). No significant publication bias was detected in current studies. In conclusion, there is a statistically significant association between ADHD and dopamine system genes, especially DRD4 and DRD5. These findings strongly implicate the involvement of brain dopamine systems in the pathogenesis of ADHD.     

Association of the dopamine receptor D4 (DRD4) gene 7-repeat allele with children with attention-deficit/hyperactivity disorder (ADHD): an update.

Polymorphisms of the dopamine receptor D4 gene DRD4, 11p15.5, have previously been associated with attention-deficit/hyperactivity disorder (ADHD) [Bobb et al., 2005; Am J Med Genet B Neuropsychiatr Genet 132:109-125; Faraone et al., 2005; Biol Psychiatry 57:1313-1323; Thapar et al., 2005; Hum Mol Genet 14 Spec No. 2:R275-R282]. As a follow up to a pilot study [see Castellanos et al., 1998; Mol Psychiatry 3:431-434] consisting of 41 probands and 56 controls which found no significant association between the DRD4 7-repeat allele in exon 3 and ADHD, a greatly expanded study sample (cases n = 166 and controls n = 282) and long term follow-up (n = 107, baseline mean age n = 9, follow-up mean age of n = 15) prompted reexamination of this gene. The DRD4 7-repeat allele was significantly more frequent in ADHD cases than controls (OR = 1.2; P = 0.028). Further, within the ADHD group, the 7-repeat allele was associated with better cognitive performance (measured by the WISC-III) (P = 0.013-0.07) as well as a trend for association with better long-term outcome. This provides further evidence of the role of the DRD4 7-repeat allele in the etiology of ADHD and suggests that this allele may be associated with a more benign form of the disorder.     

Brain perfusion and dopaminergic genes in boys with attention-deficit/hyperactivity disorder.

Neuroimaging studies have suggested the involvement of several brain areas in attention-deficit/hyperactivity disorder (ADHD). Genetic investigations have supported the role of both dopamine D4 receptor gene (DRD4) and dopamine transporter gene (DAT1) in the vulnerability to the disorder. This study evaluates whether the presence of risk alleles at DRD4 and/or DAT1 genes is associated with differences in regional cerebral blood flow (rCBF) in a sample of ADHD boys. The rCBF was compared between ADHD patients with and without risk alleles at DRD4 (7-repeat allele) and/or at DAT1 (homozygosis for the 10-repeat allele) genes by single photon emission computed tomography (SPECT) during continuous performance test. Images were analyzed using statistical parametric mapping (SPM-99). No significant differences in rCBF were found both between ADHD boys with and without the 7-repeat allele at DRD4 locus, as well as between ADHD boys homozygous for the 10-repeat allele and ADHD subjects with other genotypes at the DAT1 locus. However, a significantly higher perfusion in the right middle temporal gyrus was found in the group with risk alleles at both DRD4 and DAT1 loci (n = 6) compared to ADHD boys without risk alleles at both loci (n = 28) (P < 0.05). Our findings suggest that a higher recruitment in middle temporal gyrus, an area associated to working memory and selective attention, should exist to compensate a putative effect of the interaction between these dopaminergic genes.     

Genotypic interaction between DRD4 and DAT1 loci is a high risk factor for attention-deficit/hyperactivity disorder in Chilean families.

Attention-deficit/hyperactivity disorder, ADHD [MIM 126452], is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness, and/or inattentiveness. As part of an ongoing study of ADHD, we carried out a family-based discordant sib-pair analysis to detect possible associations between dopamine receptor D4 (DRD4) and dopamine transporter 1 (DAT1) polymorphisms and ADHD in Chilean families. Both loci individually classified as homozygotes or heterozygotes for the DRD4 7-repeat and DAT1 10-repeat alleles, did not exhibit genotype frequency differences between affected children and their healthy siblings (Fisher's exact test P > 0.25 in both cases). However, the simultaneous presence of both DRD4 7-repeat heterozygosity and DAT1 10 allele homozygosity were significantly higher (34.6%) in cases (26), compared with their unaffected siblings (25) (4%; Fisher's exact test P = 0.0096; odds-ratio, OR = 12.71). Increased density of dopamine transporter in ADHD brains, along with abundance of 7-repeat D4 receptors in prefrontal cortex, which is impaired in ADHD patients, make the observed gene-gene interaction worthy of further incisive studies.     

Confirmation of association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and bipolar I disorder.

Recent studies have indicated that the brain-derived neurotrophic factor (BDNF) gene is involved in the etiology of bipolar disorder (BPD). Two family-based association studies showed that the Val allele of the functional polymorphism Val66Met in the BDNF gene is associated with BPD; however, others could not confirm the results. Here we performed a replication study in an independent sample and tested the hypothesis that the Val66 allele in the BDNF gene confers susceptibility to bipolar I disorder (BPI). Six hundred twenty-one patients with BPI and 998 control subjects were genotyped for the Val66Met polymorphism. All cases and controls were of European descent. All BPI patients had a positive family history of affective disorder. The frequency of the Val allele was significantly increased in BPI patient when compared to controls (chi2 = 4.8; df = 1; P = 0.028; two-sided; OR = 1.22; 95% CI: 1.02-1.47). Results confirm previous findings and suggest that the Val allele increases risk for BPI in patients of European descent. Further studies are necessary to elucidate the involvement of the BDNF gene in the pathophysiology of BPD.     

Meta-analysis of family-based association studies between the dopamine transporter gene and attention deficit hyperactivity disorder

INTRODUCTION: Molecular genetic research has mainly focused on the D4 dopamine receptor (DRD4) and the dopamine transporter (DAT) genes in attention-deficit hyperactivity disorder (ADHD). A recent meta-analysis showed that the DRD4 gene has a significant role in the vulnerability to ADHD. OBJECTIVES: With an equal number of positive and negative association studies between the 10-repeat of the DAT gene and ADHD, a meta-analysis is required for this other candidate gene. METHODS: We re-analysed the 13 published family-based association studies between ADHD and the DAT gene. Following recent recommendations, different biases were specifically assessed, such as the sample-size effect and the time effect. RESULTS: The meta-analysis showed no significant association between ADHD and the DAT gene (P = 0.21), but an important between-samples heterogeneity (P = 0.0009). Odds ratios above 1 are mostly observed in studies with a small number of informative transmissions, and decrease with larger sample size. CONCLUSIONS: Contrary to what was found for the DRD4 gene, the 10-repeat allele of the DAT gene has at most a minor role in the genetic susceptibility of ADHD. The different biases detected herein probably explain the initial impression of a significant impact of the DAT gene on hyperactivity.     

Serotonin 2A receptor gene is associated with personality traits, but not to disorder, in patients with borderline personality disorder

Borderline personality disorder (BPD) is a chronic, disabling, and high-risk mental disorder characterized by a pervasive pattern of instability in regulation of emotion, interpersonal relationships, self-image, and impulse control beginning in early adulthood. BPD affects about 1%-2% of the general population and has a high mortality rate as a result of suicide and impulsive behaviour. The serotonin 2A receptor gene (HTR2A) is considered a candidate gene for BPD because multiple lines of evidence suggest that it plays an important role in suicide, impulsivity and emotional liability. To test for an association between HTR2A and BPD, we genotyped four polymorphisms, rs6313 (T102C), rs4941573, rs2296972 and rs6314 (His452Tyr), in 111 Caucasian patients with BPD and 287 Caucasian healthy controls. The program UNPHASED was used to compare allele and haplotype frequencies between cases and controls. We did not find a significant association between HTR2A and BPD based on allele, genotype or haplotype analyses. However, there were significant associations between HTR2A and personality traits in the BPD patients. The C allele of rs6313 and the A allele of rs4941573 associated with a higher Extraversion score. Our results suggest that the serotonin 2A receptor gene may not play a major role in the aetiology of borderline personality disorder, but may have a role in personality traits.     

No association between VNTR polymorphisms of dopamine transporter gene and attention deficit hyperactivity disorder in Chinese children.

Dopamine transporter (DAT) gene is implicated in the pathogenesis of attention deficit hyperactivity disorder (ADHD). Previously a meta-analysis concluded no association between the variable-number-of-tandem-repeats (VNTR) polymorphisms of the DAT gene and ADHD. However, significant heterogeneity was present among studies and no conclusion can be drawn about the association in any single ethnicity given the small number of studies. There were also conflicting results in Chinese populations. We therefore perform the present study to investigate the association in Chinese children in Hong Kong. In this prospective family-based and case-control study during January to June 2004, we recruited consecutive Chinese children diagnosed with ADHD by DSM-IV criteria, their family members, and sex-matched controls admitted for acute upper respiratory infection, excluding those with perinatal brain insults, mental retardation, or neurological deficits. VNTR polymorphisms of the DAT gene were determined by standard PCR followed by agarose gel electrophoresis. Sixty-four ADHD cases (52 boys, 12 girls), their family members and 64 normal controls were recruited. The 10-repeat allele (92.6%) and the 10/10 repeat genotype (85.2%) were the most prevalent. Both family-based and case-control analyses showed no association between the DAT gene polymorphisms and ADHD (transmission dysequilibrium test: P = 0.99; odds ratio of 10-repeat allele = 0.89 (95%CI 0.35-2.28), P = 0.81; odds ratio of 10/10 repeat genotype = 0.69 (95%CI 0.26-1.84), P = 0.46). We concluded that VNTR polymorphism of the DAT gene is not associated with ADHD in Chinese children, and further studies are needed to clarify the polygenic and environmental influences for pathogenesis of ADHD.     

No support for association between the dopamine transporter (DAT1) gene and ADHD.

Several groups have reported an association between the 10-repeat allele of a dopamine transporter (DAT1) 3'UTR VNTR variant and ADHD but the finding has not been universally observed. An association between DAT1 genotype and stimulant medication response has also been reported although again there are conflicting data. We tested the DAT1 3'VNTR and three SNPs in the putative promoter region of DAT1 for association with ADHD in 263 parent-proband trios. Analyses of genotypes, alleles, and haplotypes were performed using family-based association methods. Case-control analysis of the VNTR in 263 cases and 287 controls was also conducted. In addition, we tested for association between the VNTR marker and stimulant medication response. Comparing allele 10 versus all other alleles combined, no significant association was found with ADHD, using FBAT analysis (chi2 = 0.1 (df 1), P = 0.9, (odds ratio (OR) = 1.0, 95% CI 0.8-1.2), and case-control analysis (chi2 = 0.12 (df 2), P = 0.91). No evidence of association with any of the SNPs in the promoter region was found. Haplotype analysis was also non-significant (chi2 = 3.93, (df 9) global P = 0.85). Finally, no association was found between the DAT 1 VNTR and response to stimulant medication (chi2 = 1.63 (df 3) P = 0.65). We conclude that the 3' VNTR and three additional promoter variants in DAT1 do not appear to be associated with ADHD, or response to stimulant mediation in our sample.     

Case-control and within-family tests for an association between conduct disorder and DAT1

BACKGROUND: Conduct disorder (CD) is characterized by a persistent pattern of violating age-appropriate norms and the rights of others, and is one of the most frequently diagnosed disorders among children. CD is moderately heritable, but we know of no reliable associations with specific genes. Evidence suggests that a variable number tandem repeat polymorphism of the dopamine transporter (DAT1) gene may be associated with externalizing behavior in children. OBJECTIVE: To test for an association between the DAT1 gene and CD. DESIGN: Case-control analyses and a transmission disequilibrium test (TDT) were conducted. SETTING/PARTICIPANTS: Cases were (n=210) adolescents enrolled in a Colorado treatment program for conduct and substance use problems. Controls included adolescents matched to the probands in the treatment program and their siblings (n=162). The TDT was conducted using case families in which DNA from both parents was available (95 trios). RESULTS: The case-control analysis of the full sample did not result in a significant association [chi2 (2,372)=0.13, P=0.94]. Cases with early-onset conduct problems had slightly more 10-repeat alleles than controls, although this difference was not significant [chi2 (2,264)=2.19, P=0.33, 9/10 odds ratio (OR)=1.58, 10/10 OR=2.14]. The TDT also did not result in a significant association [chi2(1)=0.12, P=0.94]. CONCLUSION: Results did not support an association between this polymorphism of the DAT1 gene and CD in adolescents.     

Effect of dopamine transporter genotype on caudate volume in childhood ADHD and controls

Polymorphism of the dopamine transporter genotype (DAT1) confers a small but significant susceptibility to attention deficit hyperactivity disorder (ADHD). We examined whether the volume of the head of caudate, a striatal structure with high DAT expression that is important for inhibitory function, differs by DAT1 in children diagnosed with the disorder relative to age and IQ matched controls. Volume of the head of caudate was delineated in the right and left hemisphere and compared between 7- and 13-year-old children with and without ADHD (combined type) who were carriers of two (10/10) or one (9/10) copy of the 10-repeat DAT1 allele. Caudate volumes were overall smaller in 10/10 than 9/10 children, particularly in the left than right hemisphere. While DAT1 effects did not vary by ADHD diagnosis, overall caudate volumes were smaller in ADHD relative to control children. Altered caudate development associated with 10-repeat homozygosity of DAT1 may contribute susceptibility to ADHD.     

Exon 3 polymorphisms of dopamine D4 receptor (DRD4) gene and attention deficit hyperactivity disorder in Chinese children.

Dopamine D4 receptor (DRD4) gene is implicated in the pathogenesis of attention deficit hyperactivity disorder (ADHD). The 7-repeat allele of the variable-number-of-tandem-repeat (VNTR) polymorphism in exon 3 has been reported to be associated with ADHD. However, studies in Chinese populations have yielded conflicting results. We therefore perform another study to investigate the association between ADHD and DRD4 gene polymorphism in Chinese children in Hong Kong. In this prospective family-based and case-control study during January-June 2004, we recruited consecutive Chinese children diagnosed with ADHD by DSM-IV and sex-matched controls admitted for acute upper respiratory infection, excluding those with perinatal brain insults, mental retardation, or neurological deficits. VNTR polymorphisms of the DRD4 gene were determined by standard PCR followed by agarose gel electrophoresis. Sixty-four ADHD cases (52 boys, 12 girls), their family members, and 64 normal controls were recruited. The 4-repeat allele (84.4%) and the 4/4-repeat genotype (70.3%) were the most prevalent. Both family-based and case-control analyses showed no association between ADHD and DRD4 gene polymorphisms (transmission dysequilibrium test (TDT): P = 0.91 and P = 0.33 for the 7-repeat and 4-repeat alleles, respectively; OR for the 7-repeat allele = 2.01 (95% CI 0.07-60.4, P = 0.66), OR for the 4-repeat allele = 1.51 (95% CI 0.80-2.85, P = 0.2)). However, the longer repeat alleles had a positive trend association with ADHD (P = 0.01) in the case-control analysis. We concluded that ADHD is not associated with a particular VNTR polymorphism of the DRD4 gene. Further studies are needed to clarify the role of repeat length of the VNTR region of the DRD4 gene in the pathogenesis of ADHD.     

DAT1 3'-UTR 9R allele: preferential transmission in Indian children with attention deficit hyperactivity disorder.

Genetic alterations in the dopaminergic system are frequently observed in association with attention deficit hyperactivity disorder (ADHD) and a 40 bp variable number of tandem repeats (VNTR) in the 3'-untranslated region (3'-UTR) of the dopamine transporter gene (DAT1) has been investigated in different populations. Both significant association and lack of association with the10 repeat allele (10R) of DAT1 VNTR have been reported. Objective of the present investigation was to examine association of this polymorphism with ADHD in Indian children. Genotypic data obtained from ADHD probands (n = 79), their parents (n = 148) and control individuals (n = 153) were analyzed for haplotype-based haplotype relative risk analysis (HHRR), transmission disequilibrium test (TDT), and family-based association test (FBAT). HHRR analysis revealed significant (P = 0.009) transmission of shorter alleles (< or =9R). TDT analysis of informative ADHD families (n = 32) also exhibited highly significant transmission of the shorter alleles (P = 0.002). Further analysis by FBAT showed preferential transmission (P = 0.019) of the 9R allele from parents to ADHD probands. It can be inferred from the data obtained that the DAT1 3'-UTR 9R allele may confer risk of ADHD in the Indian population.     

Neuropsychological functioning in patients with borderline personality disorder

Although results have been variable, studies suggest that individuals with borderline personality disorder (BPD) exhibit cognitive deficits suggestive of frontal- and temporal-lobe dysfunction. Patients diagnosed with BPD (n = 18) using two structured interviews, and who were carefully screened for neurological and substance-use disorders, were compared to depressed patients (n = 18) and a nonpsychiatric control group (n = 18) on a series of neuropsychological tasks. The role of emotion on cognitive functioning was assessed by including emotional stimuli and interference on several of the tasks. Little support was found for the neurobehavioral hypothesis of BPD. The BPD group performance did not differ from the normal group on most tasks of executive functioning or memory, and the introduction of emotional stimuli did not impair performance. The depressed group performed less effectively than the other groups. Reasons for variable findings and factors affecting the cognitive functioning of patients with BPD are discussed. There may be considerable heterogeneity in the cognitive functioning of BPD patients, with those exhibiting significant cognitive deficits comprising only a subgroup.