Article2005

Association study of 90 candidate gene polymorphisms in panic disorder

Eduard Maron · Tiit Nikopensius · Sulev Kõks · Signe Altmäe · Evelin Heinaste · Kristel Vabrit +8 more

89 citations0/0 files storedPsychiatric Genetics

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Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes Genetic Associations and Epidemiology Neurotransmitter Receptor Influence on Behavior

Abstract

OBJECTIVE: In the present investigation we screened a large number of single nucleotide polymorphisms in the genes relevant to the neurobiology of anxiety for their association with panic disorder (PD). METHODS: The study sample included 127 patients with PD and 146 healthy control subjects. Using Arrayed Primer Extension technology we genotyped 90 polymorphisms in 21 candidate genes of serotonin, cholecystokinin, dopamine and opioid neurotransmitter systems. The association and haplotype analyses were performed in the whole group (PD-all) and in the subgroups of PD comorbid with major depression (PD-comorbid, n = 60) and without any comorbidity (PD-pure, n = 42). RESULTS: From the set of 90 polymorphisms, eight single nucleotide polymorphism markers in eight genes displayed at least a nominal association with any of the studied PD phenotype subgroups. Several polymorphisms of cholecystokinin, serotonin and dopamine systems were associated with PD-all and/or PD-comorbid phenotypes, while pure PD was associated only with HTR2A receptor 102T-C (P = 0.01) and DRD1 receptor -94G-A (P = 0.02) polymorphisms. Haplotype analysis supported an association of the cholecystokinin gene TG haplotype with the PD-all group (P = 0.04), whereas DRD1 receptor CAA and HTR2A receptor AT haplotypes were associated with a lower risk for PD-pure phenotype (P = 0.03 and P = 0.04, respectively). CONCLUSIONS: The study results suggest that genetic variants of several candidate genes of neurotransmitter systems, each of a minor individual effect, may contribute to the susceptibility to PD. Our data also indicate that genetic variability may have a distinctive influence on pure and comorbid phenotypes of PD.

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References

1998The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10 1998The mini international neuropsychiatric interview 2000Neuroanatomical Hypothesis of Panic Disorder, Revised 1994Panic and panic disorder in the United States 1998Lifetime Panic-Depression Comorbidity in the National Comorbidity Survey 1986Relationship Between Panic Disorder and Agoraphobia 1993Panic disorder in women: a population-based twin study 1998Neurobiology of panic disorder

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2009Genetics of anxiety and trauma-related disorders 2008The genetic basis of panic and phobic anxiety disorders 2014Etiology, triggers and neurochemical circuits associated with unexpected, expected, and laboratory-induced panic attacks

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