Affective temperaments (TEMPS-A) in panic disorder and healthy probands: Genetic modulation by 5-HTT variation

Abstract

Objectives

Temperamental traits as ascertained by the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Auto-Questionnaire (TEMPS-A) have been suggested as promising intermediate phenotypes of mental disorders. In anxiety disorders, however, TEMPS scales and their genetic underpinnings are still understudied.

Methods

TEMPS-A scores in 109 patients with panic disorder (PD) were compared to a sample of 536 healthy probands. All participants were genotyped for serotonin transporter gene variation (5-HTTLPR/rs25531).

Results

PD patients displayed significantly increased scores on the dysthymic, cyclothymic, irritable and anxious subscales, and lower scores on the hyperthymic subscale, respectively (all ps < 0.001) compared to healthy probands. In the total sample, the less active 5-HTTLPR/rs25531 S/L_G alleles were associated with higher scores on the dysthymic, cyclothymic, irritable and anxious temperaments (all ps < 0.01), but not the hyperthymic subscale. Mediation analyses revealed anxious temperament in particular to mediate the relationship between 5-HTT genotype and PD.

Conclusions

Dysthymic, cyclothymic, irritable and notably anxious temperament could serve as valuable intermediate phenotypes in efforts to unravel neurobiological, particularly serotonin system related genetic pathomechanisms associated with PD and potentially contribute to a panel of vulnerability markers guiding early targeted preventive interventions.

Keywords:

• Temperament
• TEMPS-A
• anxious
• anxiety disorders
• serotonin transporter

Acknowledgements

The authors acknowledge the recruiting efforts by Dr. Tina Lonsdorf, Institute for Systems Neuroscience, University Medical Centre Hamburg-Eppendorf, and the skilful technical support by Dr. Maximilian Geiger, Sandra Bolay-Gehrig and Carola Gagel. KD, MAS and PZ are members of the Anxiety Disorders Research Network (ADRN), European College of Neuropsychopharmacology (ECNP).

Statement of interest

All authors report no potential conflicts of interest.

Additional information

Funding

This project was supported by the German Research Foundation (DFG) – project no. 44541416 TRR 58 ‘Fear, Anxiety, Anxiety Disorders’, projects C02 (KD) and Z02 (KD, JD, UD, UL, PP).