A deletion in tropomyosin-related kinase B and the development of human anxiety.
BACKGROUND
The tropomyosin-related kinase B (TrkB)/brain-derived neurotrophic factor system has been associated with psychiatric disorders, and animal models of defects in this system suggest that it might have a particular role in anxiety.


METHODS
DNA sequencing and cloning were used to identify a mutation in TrkB, and four different cell lines were used to assess functionality. Clinical samples were from a 22-year longitudinal cohort representative of the Quebec general population (n = 640 subjects), randomly selected when they were in kindergarten. Anxiety-related traits were measured with the Social Behaviour Questionnaire, the Diagnostic Assessment of Personality Pathology-Brief Questionnaire, and the Diagnostic Interview Schedule for DSM-IIIR.


RESULTS
An 11 base pair deletion in TrkB is significantly associated with increases in anxiety traits during childhood and the development of anxiety disorders in adulthood. We found that this deletion impaired transcription in some human cell lines.


CONCLUSIONS
The identification of this deletion provides additional support for the role of TrkB in modulating anxiety-related traits in human.
McGill Group for Suicide Studies, McGill University, Montreal, QC, Canada.
Carl
C
Ernst
Brigitte
B
Wanner
Jelena
J
Brezo
Frank
F
Vitaro
Richard
R
Tremblay
Gustavo
G
Turecki
D001007:Anxiety / Q000235:genetics* / Q000523:psychology; D002170:Canada; D002648:Child; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010552:Personality Assessment; D011494:Protein Kinases / Q000235:genetics*; D012044:Regression Analysis; D017384:Sequence Deletion / Q000235:genetics*; D012919:Social Behavior; D011795:Surveys and Questionnaires; D055815:Young Adult
D011494:Protein Kinases; C041311:tropomyosin kinase