Psychiatry Research 219 (2014) 693–695
Contents lists available at ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Brief report
Association between dopa decarboxylase gene variants and borderline personality disorder Arian Mobascher a,n, Martin Bohus b, Norbert Dahmen a, Lydie Dietl c, Ina Giegling d,e, Martin Jungkunz b, Nikolaus Kleindienst b, Matthias Limberger b, Eva Meisenzahl d, Marcella Rietschel f, Stefan Roepke c, Christian Schmahl b, Björn Schott c,g, Cornelia E. Schwarze a, André Tadić a, Jens Treutlein f, Friederike Vogel a, Stephanie H. Witt f, Thomas Zetzsche d, Dan Rujescu d,e, Klaus Lieb a a
Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany Department of Psychosomatic Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany c Department of Psychiatry, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany d Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany e Department of Psychiatry and Psychotherapy, Martin-Luther University Halle-Wittenberg, Germany f Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany g Leibniz Institute for Neurobiology, Magdeburg, Germany b
art ic l e i nf o
a b s t r a c t
Article history: Received 8 April 2014 Received in revised form 5 June 2014 Accepted 20 June 2014 Available online 28 June 2014
Despite heritability estimates of 37–69%, research has identified few genetic risk variants for borderline personality disorder (BPD). The present collaborative candidate gene study of 987 BPD cases and 1110 healthy controls found an association between BPD and single nucleotide polymorphism rs12718541 in the dopa decarboxylase gene. & 2014 Published by Elsevier Ireland Ltd.
Keywords: Dopa decarboxylase Borderline personality disorder Single nucleotide polymorphism
1. Introduction Although estimates of the heritability of borderline personality disorder (BPD) range from 37% to 69% (Torgersen et al., 2000; Distel et al., 2008; Kendler et al., 2008), the variants that mediate the genetic risk for BPD remain largely unknown, and only a few small-scale studies on this issue have been published (Calati et al., 2013; Amad et al., 2014). Obvious candidates include genes that regulate the neurotransmitters serotonin, dopamine, and norepinephrine, since these amines play important roles in mood regulation, suicidality, aggression, and impulsivity, i.e. the important subdomains of BPD symptomatology (Friedel, 2009; Lieb et al., 2004; Leichsenring et al., 2011). The final step in the synthesis of serotonin and dopamine is catalyzed by dopa decarboxylase (DDC), also known as aromatic L-amino acid decarboxylase. To date, however, no study has investigated DDC variants within the
n
Corresponding author. Tel.: þ 49 6131 17 2140; fax: þ 49 6161 17 3459. E-mail address: [email protected] (A. Mobascher).
http://dx.doi.org/10.1016/j.psychres.2014.06.031 0165-1781/& 2014 Published by Elsevier Ireland Ltd.
context of BPD. In an earlier unpublished pilot study at the Mainz site 89 genetic variants in 12 candidate genes were tested – including nine variants in the DDC gene – in a sample of N ¼165 BPD cases and N ¼ 153 age- and sex-matched healthy controls. A nominally significant association was found between BPD and the G allele of rs12718541 in DDC (binary logistic regression corrected for age and sex): p¼ 0.013, odds ratio (OR) ¼1.511 (CI¼1.093–2.09). The purpose of the present collaborative study was to replicate this initial finding in the largest BPD sample collected for the purposes of genetic studies to date.
2. Subjects, materials and methods Four German academic institutions contributed study participants to the replication sample (cases/healthy controls): Mannheim (275/0), Mainz (83/112), Berlin (383/0), and Munich (81/845). The total sample (pilot and replication sample combined) comprised: 987 BPD cases (mean age: 29.8 years (S.D. 8.6); N ¼90.5% females); and 1110 healthy controls (mean age: 40.7 years (S.D. 14.2); 78.2% females). A lifetime diagnosis of BPD was assigned on the basis of either the German version of the International Personality Disorder Examination (Loranger
694
A. Mobascher et al. / Psychiatry Research 219 (2014) 693–695
Table 1 Single marker frequencies and association with borderline personality disorder. Case, control ratio counts
Case, control frequencies
p valuea
OR (CI)a
1324:272, 1461:315 1074:518, 1188:620 1103:515, 999:519 943:681, 838:686 701:875, 662:844 517:1069, 563:1237 949:637, 1015:733 401:1213, 370:1142 421:1167, 458:1338
0.830, 0.823 0.675, 0.657 0.682, 0.658 0.581, 0.550 0.445, 0.440 0.326, 0.313 0.598, 0.581 0.248, 0.245 0.265, 0.255
0.982 0.238 0.063 0.035 0.612 0.378 0.309 0.750 0.513
1.002 1.105 1.175 1.189 1.043 1.078 1.087 1.030 1.062
(0.818–1.229) (0.936–1.304) (0.991–1.393) (1.012–1.396) (0.887–1.226) (0.912–1.275) (0.926–1.275) (0.858–1.238) (0.887–1.270)
(b) Pilot study and replication sample combined rs2060762 G 1593:323, 1702:370 rs4947535 A 1296:608, 1382:724 rs3757472 C 1326:610, 1195:617 rs12718541 G 1145:797, 995:823 rs1451371 C 849:1039, 784:1012 rs4947584 T 616:1284, 664:1434 rs1470750 C 1130:772, 1197:849 rs3735273 C 1462:470, 1363:443 rs12666409 A 494:1412, 533:1559
0.831, 0.821 0.681, 0.656 0.685, 0.659 0.590, 0.547 0.450, 0.437 0.324, 0.316 0.594, 0.585 0.757, 0.755 0.259, 0.255
0.743 0.110 0.065 0.007 0.437 0.648 0.458 0.739 0.466
1.030 1.126 1.151 1.214 1.058 1.035 1.055 1.028 1.061
(0.861–1.232) (0.973–1.303) (0.991–1.337) (1.054–1.399) (0.917–1.221) (0.893–1.199) (0.916–1.216) (0.874–1.209) (0.905–1.242)
SNP
Assoc allele
(a) Replication sample rs2060762 G rs4947535 A rs3757472 C rs12718541 G rs1451371 C rs4947584 T rs1470750 C rs3735273 C rs12666409 A
SNP¼ single nucleotide polymorphism, OR ¼ odds ratio, and CI ¼ confidence interval. a
Binary logistic regression controlled for age and sex. Numbers are provided for the associated allele.
et al., 1994) (Mannheim site), or the German version of the Structured Clinical Interview for DSM-IV axis-II (Wittchen et al., 2007) (all other centers). Interviews were conducted by trained and experienced raters. Exclusion criteria were dementia or other organic brain syndromes with cognitive impairment, a lifetime diagnosis of a psychotic disorder, and non-Caucasian descent. All subjects provided written informed consent prior to inclusion. The study was approved by the respective local ethical committees, and was conducted in accordance with the Declaration of Helsinki. Rs12718541 and the eight other previously tested non-coding DDC single nucleotide polymorphisms (SNPs) were investigated in the larger replication sample using the iPLEX assay and a MassARRAY MALDI-TOF mass spectrometer (SEQUENOM, Hamburg, Germany). Call rates were between 96% and 98%. Allele frequencies were similar to HapMap CEU (Utah residents with ancestry from northern and western Europe) sample frequencies (www.hapmap.org). Deviations from Hardy–Weinberg equilibrium (HWE) were calculated using Haploview (Version 4.1). Single marker associations were investigated by applying logistic regression analyses (additive model) corrected for age and sex using SPSS 21. No SNP showed deviation from HWE.
3. Results In the replication sample, the G allele of rs12718541 was again associated with a diagnosis of BPD: p ¼0.035; OR ¼1.189 (CI¼ 1.012–1.396), thus replicating the initial finding (though only with nominal statistical significance). Analogous analyses in the combined sample provided the following results: p ¼0.007; OR¼ 1.214 (CI ¼1.054–1.399). See Table 1 for further details. In subsequent analyses, no association was found with any individual BPD DSM-IV item or the number of items in patients (p 40.1).
4. Discussion The present results support the hypothesis that genetic variation in the monoaminergic neurotransmitter systems contributes to BPD susceptibility (Ni et al., 2009; Perez-Rodriguez et al., 2010; Wagner et al., 2010). Whether it is rs12718541 per se, or a variant in linkage disequilibrium with it, that contributes to BPD remains unclear. Although no DDC variant has been implicated in a frequent amino acid change (queried via UCSC/dbSNP http:// genome.ucsc.edu/) or as a cis-expression quantitative trait locus
(eQTLs) (queried via the PheGenI database; http://www.ncbi.nlm. nih.gov/gap/phegeni), previous authors have postulated that rs12718541 may constitute an intronic splicing enhancer (Yu et al., 2006). Interestingly, association between this variant and another psychiatric phenotype has already been reported: in the study by Yu et al. (2006) of association between DDC variants and smoking-related phenotypes, rs12718541 showed the strongest association with the Fagerstrom Test of Nicotine Dependence (FTND) score, (p ¼0.0002). Research has also shown an association between BPD and both smoking and nicotine dependence (Becoña et al., 2013). However, since Yu et al. (2006) found the association between the A allele and smoking, doubt exists as to whether rs12718541 contributes to this co-morbidity. Furthermore, as smoking behavior/nicotine dependence was not systematically assessed in our patients, it was impossible to test whether the present finding of association between the G allele and BPD would have become stronger by excluding smokers from the analysis. Thus the relationship among DDC variants, BPD, and smoking behavior requires clarification in future studies. The present study had several limitations. Firstly, only nine genetic variants were tested and thus tagging of the DDC gene was incomplete. In consequence, additional association findings within the DDC gene if they were present could not be determined. Secondly, although our sample is the largest to date for genetic studies in BPD patients, it is still very small compared to others in the field of psychiatric genetics, and therefore does not have the power to identify genome-wide associations in a systematic manner. However, candidate studies remain of value and may generate interesting findings. Furthermore, the fact that the direction of the association finding was not driven by a single sample but by the joint effect of the pilot and the different replication samples increases the likelihood that it represents a true association.
Acknowledgments We thank all our study participants.
A. Mobascher et al. / Psychiatry Research 219 (2014) 693–695
References Amad, A., Ramoz, N., Thomas, P., Jardri, R., Gorwood, P., 2014. Genetics of borderline personality disorder: systematic review and proposal of an integrative model. Neuroscience and Biobehavioral Reviews 40, 6–19. Becoña, E., Fernández del Río, E., López-Durán, A., Piñeiro, B., Martínez, Ú., 2013. Axis II disorders and cigarette smoking among adults from the general population. Journal of Personality Disorders 27, 411–424. Calati, R., Gressier, F., Balestri, M., Serretti, A, 2013. Genetic modulation of borderline personality disorder: systematic review and meta-analysis. Journal of Psychiatric Research 47, 1275–1287. Distel, M.A., Trull, T.J., Derom, C.A., Thiery, E.W., Grimmer, M.A., Martin, N.G., Willemsen, G., Boomsma, D.I., 2008. Heritability of borderline personality disorder features is similar across three countries. Psychological Medicine 38, 1219–1229. Friedel, R.O., 2009. Dopamine dysfunction in borderline personality disorder: a hypothesis. Neuropsychopharmacology 29, 1029–1039. Kendler, K.S., Aggen, S.H., Czajkowski, N., Røysamb, E., Tambs, K., Torgersen, S., Neale, M.C., Reichborn-Kjennerud, T., 2008. The structure of genetic and environmental risk factors for DSM-IV personality disorders: a multivariate twin study. Archives of General Psychiatry 65, 1438–1446. Leichsenring, F., Leibing, E., Kruse, J., New, A.S., Leweke, F., 2011. Borderline personality disorder. Lancet 377, 74–84. Lieb, K., Zanarini, M.C., Schmahl, C., Linehan, M.M., Bohus, M., 2004. Borderline personality disorder. Lancet 364, 453–461. Loranger, A.W., Sartorius, N., Andreoli, A., Berger, P., Buchheim, P., Channabasavanna, S.M., Coid, B., Dahl, A., Diekstra, R.F.W., Ferguson, B., Jacobsberg, L.B.,
695
Mombour, D.A., Pull, C., Ono, Y., Regier, D.A., 1994. The International Personality Disorder Examination. The World Health Organization/Alcohol, Drug Abuse, and Mental Health Administration international pilot study of personality disorders. Archives of General Psychiatry 51, 215–224. Ni, X., Chan, D., Chan, K., McMain, S., Kennedy, J.L., 2009. Serotonin genes and gene– gene interactions in borderline personality disorder in a matched case-control study. Progress in Neuropsychopharmacology & Biological Psychiatry 33, 128–133. Perez-Rodriguez, M.M., Weinstein, S., New, A.S., Bevilacqua, L., Yuan, Q., Zhou, Z., Hodgkinson, C., Goodman, M., Koenigsberg, H.W., Goldman, D., Siever, L.J., 2010. Tryptophan-hydroxylase 2 haplotype association with borderline personality disorder and aggression in a sample of patients with personality disorders and healthy controls. Journal of Psychiatric Research 44, 1075–1081. Torgersen, S., Lygren, S., Oien, P.A., Skre, I., Onstad, S., Edvardsen, J., Tambs, K., Kringlen, E., 2000. A twin study of personality disorders. Comprehensive Psychiatry 41, 416–425. Wagner, S., Baskaya, O., Anicker, N.J., Dahmen, N., Lieb, K., Tadić, A., 2010. The catechol o-methyltransferase (COMT) val(158)met polymorphism modulates the association of serious life events (SLE) and impulsive aggression in female patients with borderline personality disorder (BPD). Acta Psychiatrica Scandinavica 122, 110–117. Wittchen, H.U., Zaudig, M., Fydrich, T., 2007. Structured Clinical Interview for DSMIV [in German]. Hogrefe, Gottingen. Yu, Y., Panhuysen, C., Kranzler, H.R., Hesselbrock, V., Rounsaville, B., Weiss, R., Brady, K., Farrer, L.A., Gelernter, J., 2006. Intronic variants in the dopa decarboxylase (DDC) gene are associated with smoking behavior in European-Americans and African-Americans. Human Molecular Genetics 15, 2192–2199.
Contents lists available at ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Brief report
Association between dopa decarboxylase gene variants and borderline personality disorder Arian Mobascher a,n, Martin Bohus b, Norbert Dahmen a, Lydie Dietl c, Ina Giegling d,e, Martin Jungkunz b, Nikolaus Kleindienst b, Matthias Limberger b, Eva Meisenzahl d, Marcella Rietschel f, Stefan Roepke c, Christian Schmahl b, Björn Schott c,g, Cornelia E. Schwarze a, André Tadić a, Jens Treutlein f, Friederike Vogel a, Stephanie H. Witt f, Thomas Zetzsche d, Dan Rujescu d,e, Klaus Lieb a a
Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany Department of Psychosomatic Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany c Department of Psychiatry, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany d Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany e Department of Psychiatry and Psychotherapy, Martin-Luther University Halle-Wittenberg, Germany f Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany g Leibniz Institute for Neurobiology, Magdeburg, Germany b
art ic l e i nf o
a b s t r a c t
Article history: Received 8 April 2014 Received in revised form 5 June 2014 Accepted 20 June 2014 Available online 28 June 2014
Despite heritability estimates of 37–69%, research has identified few genetic risk variants for borderline personality disorder (BPD). The present collaborative candidate gene study of 987 BPD cases and 1110 healthy controls found an association between BPD and single nucleotide polymorphism rs12718541 in the dopa decarboxylase gene. & 2014 Published by Elsevier Ireland Ltd.
Keywords: Dopa decarboxylase Borderline personality disorder Single nucleotide polymorphism
1. Introduction Although estimates of the heritability of borderline personality disorder (BPD) range from 37% to 69% (Torgersen et al., 2000; Distel et al., 2008; Kendler et al., 2008), the variants that mediate the genetic risk for BPD remain largely unknown, and only a few small-scale studies on this issue have been published (Calati et al., 2013; Amad et al., 2014). Obvious candidates include genes that regulate the neurotransmitters serotonin, dopamine, and norepinephrine, since these amines play important roles in mood regulation, suicidality, aggression, and impulsivity, i.e. the important subdomains of BPD symptomatology (Friedel, 2009; Lieb et al., 2004; Leichsenring et al., 2011). The final step in the synthesis of serotonin and dopamine is catalyzed by dopa decarboxylase (DDC), also known as aromatic L-amino acid decarboxylase. To date, however, no study has investigated DDC variants within the
n
Corresponding author. Tel.: þ 49 6131 17 2140; fax: þ 49 6161 17 3459. E-mail address: [email protected] (A. Mobascher).
http://dx.doi.org/10.1016/j.psychres.2014.06.031 0165-1781/& 2014 Published by Elsevier Ireland Ltd.
context of BPD. In an earlier unpublished pilot study at the Mainz site 89 genetic variants in 12 candidate genes were tested – including nine variants in the DDC gene – in a sample of N ¼165 BPD cases and N ¼ 153 age- and sex-matched healthy controls. A nominally significant association was found between BPD and the G allele of rs12718541 in DDC (binary logistic regression corrected for age and sex): p¼ 0.013, odds ratio (OR) ¼1.511 (CI¼1.093–2.09). The purpose of the present collaborative study was to replicate this initial finding in the largest BPD sample collected for the purposes of genetic studies to date.
2. Subjects, materials and methods Four German academic institutions contributed study participants to the replication sample (cases/healthy controls): Mannheim (275/0), Mainz (83/112), Berlin (383/0), and Munich (81/845). The total sample (pilot and replication sample combined) comprised: 987 BPD cases (mean age: 29.8 years (S.D. 8.6); N ¼90.5% females); and 1110 healthy controls (mean age: 40.7 years (S.D. 14.2); 78.2% females). A lifetime diagnosis of BPD was assigned on the basis of either the German version of the International Personality Disorder Examination (Loranger
694
A. Mobascher et al. / Psychiatry Research 219 (2014) 693–695
Table 1 Single marker frequencies and association with borderline personality disorder. Case, control ratio counts
Case, control frequencies
p valuea
OR (CI)a
1324:272, 1461:315 1074:518, 1188:620 1103:515, 999:519 943:681, 838:686 701:875, 662:844 517:1069, 563:1237 949:637, 1015:733 401:1213, 370:1142 421:1167, 458:1338
0.830, 0.823 0.675, 0.657 0.682, 0.658 0.581, 0.550 0.445, 0.440 0.326, 0.313 0.598, 0.581 0.248, 0.245 0.265, 0.255
0.982 0.238 0.063 0.035 0.612 0.378 0.309 0.750 0.513
1.002 1.105 1.175 1.189 1.043 1.078 1.087 1.030 1.062
(0.818–1.229) (0.936–1.304) (0.991–1.393) (1.012–1.396) (0.887–1.226) (0.912–1.275) (0.926–1.275) (0.858–1.238) (0.887–1.270)
(b) Pilot study and replication sample combined rs2060762 G 1593:323, 1702:370 rs4947535 A 1296:608, 1382:724 rs3757472 C 1326:610, 1195:617 rs12718541 G 1145:797, 995:823 rs1451371 C 849:1039, 784:1012 rs4947584 T 616:1284, 664:1434 rs1470750 C 1130:772, 1197:849 rs3735273 C 1462:470, 1363:443 rs12666409 A 494:1412, 533:1559
0.831, 0.821 0.681, 0.656 0.685, 0.659 0.590, 0.547 0.450, 0.437 0.324, 0.316 0.594, 0.585 0.757, 0.755 0.259, 0.255
0.743 0.110 0.065 0.007 0.437 0.648 0.458 0.739 0.466
1.030 1.126 1.151 1.214 1.058 1.035 1.055 1.028 1.061
(0.861–1.232) (0.973–1.303) (0.991–1.337) (1.054–1.399) (0.917–1.221) (0.893–1.199) (0.916–1.216) (0.874–1.209) (0.905–1.242)
SNP
Assoc allele
(a) Replication sample rs2060762 G rs4947535 A rs3757472 C rs12718541 G rs1451371 C rs4947584 T rs1470750 C rs3735273 C rs12666409 A
SNP¼ single nucleotide polymorphism, OR ¼ odds ratio, and CI ¼ confidence interval. a
Binary logistic regression controlled for age and sex. Numbers are provided for the associated allele.
et al., 1994) (Mannheim site), or the German version of the Structured Clinical Interview for DSM-IV axis-II (Wittchen et al., 2007) (all other centers). Interviews were conducted by trained and experienced raters. Exclusion criteria were dementia or other organic brain syndromes with cognitive impairment, a lifetime diagnosis of a psychotic disorder, and non-Caucasian descent. All subjects provided written informed consent prior to inclusion. The study was approved by the respective local ethical committees, and was conducted in accordance with the Declaration of Helsinki. Rs12718541 and the eight other previously tested non-coding DDC single nucleotide polymorphisms (SNPs) were investigated in the larger replication sample using the iPLEX assay and a MassARRAY MALDI-TOF mass spectrometer (SEQUENOM, Hamburg, Germany). Call rates were between 96% and 98%. Allele frequencies were similar to HapMap CEU (Utah residents with ancestry from northern and western Europe) sample frequencies (www.hapmap.org). Deviations from Hardy–Weinberg equilibrium (HWE) were calculated using Haploview (Version 4.1). Single marker associations were investigated by applying logistic regression analyses (additive model) corrected for age and sex using SPSS 21. No SNP showed deviation from HWE.
3. Results In the replication sample, the G allele of rs12718541 was again associated with a diagnosis of BPD: p ¼0.035; OR ¼1.189 (CI¼ 1.012–1.396), thus replicating the initial finding (though only with nominal statistical significance). Analogous analyses in the combined sample provided the following results: p ¼0.007; OR¼ 1.214 (CI ¼1.054–1.399). See Table 1 for further details. In subsequent analyses, no association was found with any individual BPD DSM-IV item or the number of items in patients (p 40.1).
4. Discussion The present results support the hypothesis that genetic variation in the monoaminergic neurotransmitter systems contributes to BPD susceptibility (Ni et al., 2009; Perez-Rodriguez et al., 2010; Wagner et al., 2010). Whether it is rs12718541 per se, or a variant in linkage disequilibrium with it, that contributes to BPD remains unclear. Although no DDC variant has been implicated in a frequent amino acid change (queried via UCSC/dbSNP http:// genome.ucsc.edu/) or as a cis-expression quantitative trait locus
(eQTLs) (queried via the PheGenI database; http://www.ncbi.nlm. nih.gov/gap/phegeni), previous authors have postulated that rs12718541 may constitute an intronic splicing enhancer (Yu et al., 2006). Interestingly, association between this variant and another psychiatric phenotype has already been reported: in the study by Yu et al. (2006) of association between DDC variants and smoking-related phenotypes, rs12718541 showed the strongest association with the Fagerstrom Test of Nicotine Dependence (FTND) score, (p ¼0.0002). Research has also shown an association between BPD and both smoking and nicotine dependence (Becoña et al., 2013). However, since Yu et al. (2006) found the association between the A allele and smoking, doubt exists as to whether rs12718541 contributes to this co-morbidity. Furthermore, as smoking behavior/nicotine dependence was not systematically assessed in our patients, it was impossible to test whether the present finding of association between the G allele and BPD would have become stronger by excluding smokers from the analysis. Thus the relationship among DDC variants, BPD, and smoking behavior requires clarification in future studies. The present study had several limitations. Firstly, only nine genetic variants were tested and thus tagging of the DDC gene was incomplete. In consequence, additional association findings within the DDC gene if they were present could not be determined. Secondly, although our sample is the largest to date for genetic studies in BPD patients, it is still very small compared to others in the field of psychiatric genetics, and therefore does not have the power to identify genome-wide associations in a systematic manner. However, candidate studies remain of value and may generate interesting findings. Furthermore, the fact that the direction of the association finding was not driven by a single sample but by the joint effect of the pilot and the different replication samples increases the likelihood that it represents a true association.
Acknowledgments We thank all our study participants.
A. Mobascher et al. / Psychiatry Research 219 (2014) 693–695
References Amad, A., Ramoz, N., Thomas, P., Jardri, R., Gorwood, P., 2014. Genetics of borderline personality disorder: systematic review and proposal of an integrative model. Neuroscience and Biobehavioral Reviews 40, 6–19. Becoña, E., Fernández del Río, E., López-Durán, A., Piñeiro, B., Martínez, Ú., 2013. Axis II disorders and cigarette smoking among adults from the general population. Journal of Personality Disorders 27, 411–424. Calati, R., Gressier, F., Balestri, M., Serretti, A, 2013. Genetic modulation of borderline personality disorder: systematic review and meta-analysis. Journal of Psychiatric Research 47, 1275–1287. Distel, M.A., Trull, T.J., Derom, C.A., Thiery, E.W., Grimmer, M.A., Martin, N.G., Willemsen, G., Boomsma, D.I., 2008. Heritability of borderline personality disorder features is similar across three countries. Psychological Medicine 38, 1219–1229. Friedel, R.O., 2009. Dopamine dysfunction in borderline personality disorder: a hypothesis. Neuropsychopharmacology 29, 1029–1039. Kendler, K.S., Aggen, S.H., Czajkowski, N., Røysamb, E., Tambs, K., Torgersen, S., Neale, M.C., Reichborn-Kjennerud, T., 2008. The structure of genetic and environmental risk factors for DSM-IV personality disorders: a multivariate twin study. Archives of General Psychiatry 65, 1438–1446. Leichsenring, F., Leibing, E., Kruse, J., New, A.S., Leweke, F., 2011. Borderline personality disorder. Lancet 377, 74–84. Lieb, K., Zanarini, M.C., Schmahl, C., Linehan, M.M., Bohus, M., 2004. Borderline personality disorder. Lancet 364, 453–461. Loranger, A.W., Sartorius, N., Andreoli, A., Berger, P., Buchheim, P., Channabasavanna, S.M., Coid, B., Dahl, A., Diekstra, R.F.W., Ferguson, B., Jacobsberg, L.B.,
695
Mombour, D.A., Pull, C., Ono, Y., Regier, D.A., 1994. The International Personality Disorder Examination. The World Health Organization/Alcohol, Drug Abuse, and Mental Health Administration international pilot study of personality disorders. Archives of General Psychiatry 51, 215–224. Ni, X., Chan, D., Chan, K., McMain, S., Kennedy, J.L., 2009. Serotonin genes and gene– gene interactions in borderline personality disorder in a matched case-control study. Progress in Neuropsychopharmacology & Biological Psychiatry 33, 128–133. Perez-Rodriguez, M.M., Weinstein, S., New, A.S., Bevilacqua, L., Yuan, Q., Zhou, Z., Hodgkinson, C., Goodman, M., Koenigsberg, H.W., Goldman, D., Siever, L.J., 2010. Tryptophan-hydroxylase 2 haplotype association with borderline personality disorder and aggression in a sample of patients with personality disorders and healthy controls. Journal of Psychiatric Research 44, 1075–1081. Torgersen, S., Lygren, S., Oien, P.A., Skre, I., Onstad, S., Edvardsen, J., Tambs, K., Kringlen, E., 2000. A twin study of personality disorders. Comprehensive Psychiatry 41, 416–425. Wagner, S., Baskaya, O., Anicker, N.J., Dahmen, N., Lieb, K., Tadić, A., 2010. The catechol o-methyltransferase (COMT) val(158)met polymorphism modulates the association of serious life events (SLE) and impulsive aggression in female patients with borderline personality disorder (BPD). Acta Psychiatrica Scandinavica 122, 110–117. Wittchen, H.U., Zaudig, M., Fydrich, T., 2007. Structured Clinical Interview for DSMIV [in German]. Hogrefe, Gottingen. Yu, Y., Panhuysen, C., Kranzler, H.R., Hesselbrock, V., Rounsaville, B., Weiss, R., Brady, K., Farrer, L.A., Gelernter, J., 2006. Intronic variants in the dopa decarboxylase (DDC) gene are associated with smoking behavior in European-Americans and African-Americans. Human Molecular Genetics 15, 2192–2199.
