The symptomatic profile of panic disorder is shaped by the 5-HTTLPR polymorphism

TY - JOUR

T1 - The symptomatic profile of panic disorder is shaped by the 5-HTTLPR polymorphism

AU - Lonsdorf, Tina B

AU - Rück, Christian

AU - Bergström, Jan

AU - Andersson, Gerhard

AU - Ohman, Arne

AU - Schalling, Martin

AU - Lindefors, Nils

PY - 2009/11/13

Y1 - 2009/11/13

N2 - The short allele of a functional polymorphism (5-HTTLPR) in the serotonin transporter (5-HTT) promoter is associated with reduced serotonin transporter expression, lower in vivo 5-HTT binding, higher neuroticism and amygdala reactivity as well as facilitated fear conditioning and is a candidate variant for panic disorder. However, case-control studies have consistently failed to show an association between 5-HTTLPR and panic disorder. As psychiatric disorders are broadly defined phenotypes merging different symptoms to syndromes, they may not be very well suited for genetic association studies. An alternative approach is to measure symptoms along continuous symptom dimensions which may more appropriately reflect their biological underpinnings and may reveal subpopulations within clinical diagnostic groups. We recorded the symptomatic profile in 73 in panic disorder patients using observer-rated instruments (Panic Disorder Severity Scale, PDSS; Montgomery-Asberg Depression Rating Scale, MADRS) and hypothesized more severe symptoms in patients carrying the 5-HTTLPR s-allele. We observed a strong association between bi- and triallelic 5-HTTLPR polymorphisms and the symptomatic profile. Carriers of the 5-HTTLPR s-allele suffered from most severe panic and depressive symptoms. Our data highlight the importance of defining appropriate phenotypes for psychiatric genetic studies and demonstrate that the 5-HTTLPR genotype may be related to the symptomatic profiles rather than to the vulnerability to develop panic disorder.

AB - The short allele of a functional polymorphism (5-HTTLPR) in the serotonin transporter (5-HTT) promoter is associated with reduced serotonin transporter expression, lower in vivo 5-HTT binding, higher neuroticism and amygdala reactivity as well as facilitated fear conditioning and is a candidate variant for panic disorder. However, case-control studies have consistently failed to show an association between 5-HTTLPR and panic disorder. As psychiatric disorders are broadly defined phenotypes merging different symptoms to syndromes, they may not be very well suited for genetic association studies. An alternative approach is to measure symptoms along continuous symptom dimensions which may more appropriately reflect their biological underpinnings and may reveal subpopulations within clinical diagnostic groups. We recorded the symptomatic profile in 73 in panic disorder patients using observer-rated instruments (Panic Disorder Severity Scale, PDSS; Montgomery-Asberg Depression Rating Scale, MADRS) and hypothesized more severe symptoms in patients carrying the 5-HTTLPR s-allele. We observed a strong association between bi- and triallelic 5-HTTLPR polymorphisms and the symptomatic profile. Carriers of the 5-HTTLPR s-allele suffered from most severe panic and depressive symptoms. Our data highlight the importance of defining appropriate phenotypes for psychiatric genetic studies and demonstrate that the 5-HTTLPR genotype may be related to the symptomatic profiles rather than to the vulnerability to develop panic disorder.

KW - Adult

KW - Analysis of Variance

KW - Chi-Square Distribution

KW - Female

KW - Gene Frequency

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Panic Disorder

KW - Polymorphism, Genetic

KW - Psychiatric Status Rating Scales

KW - Serotonin Plasma Membrane Transport Proteins

KW - Young Adult

U2 - 10.1016/j.pnpbp.2009.08.004

DO - 10.1016/j.pnpbp.2009.08.004

M3 - SCORING: Journal article

C2 - 19683026

VL - 33

SP - 1479

EP - 1483

JO - PROG NEURO-PSYCHOPH

JF - PROG NEURO-PSYCHOPH

SN - 0278-5846

IS - 8

ER -