Serotonin transporter genotype impacts amygdala habituation in youth with autism spectrum disorders

Jillian Lee Wiggins; Johnna R Swartz; Donna M Martin; Catherine Lord; Christopher S Monk

doi:10.1093/scan/nst039

Serotonin transporter genotype impacts amygdala habituation in youth with autism spectrum disorders

Soc Cogn Affect Neurosci. 2014 Jun;9(6):832-8. doi: 10.1093/scan/nst039. Epub 2013 Mar 22.

Authors

Jillian Lee Wiggins¹, Johnna R Swartz², Donna M Martin³, Catherine Lord², Christopher S Monk⁴

Affiliations

¹ Department of Psychology, Department of Pediatrics, Neuroscience Program, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA, Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA, and Department of Psychiatry and Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USA leejilli@umich.edu.
² Department of Psychology, Department of Pediatrics, Neuroscience Program, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA, Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA, and Department of Psychiatry and Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USA.
³ Department of Psychology, Department of Pediatrics, Neuroscience Program, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA, Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA, and Department of Psychiatry and Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USADepartment of Psychology, Department of Pediatrics, Neuroscience Program, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA, Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA, and Department of Psychiatry and Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USADepartment of Psychology, Department of Pediatrics, Neuroscience Program, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA, Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA, and Department of Psychiatry and Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USA.
⁴ Department of Psychology, Department of Pediatrics, Neuroscience Program, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA, Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA, and Department of Psychiatry and Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USADepartment of Psychology, Department of Pediatrics, Neuroscience Program, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA, Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA, and Department of Psychiatry and Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USADepartment of Psychology, Department of Pediatrics, Neuroscience Program, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA, Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA, and Department of Psychiatry and Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USADepartment of Psychology, Department of Pediatrics, Neuroscience Program, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA, Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA, and Department of Psychiatry and Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USA.

Abstract

Failure of the amygdala to habituate, or decrease response intensity, to repeatedly presented faces may be one mechanism by which individuals with autism spectrum disorders (ASD) develop and maintain social symptoms. However, genetic influences on habituation in ASD have not been examined. We hypothesized that serotonin transporter-linked promoter region (5-HTTLPR) genotype affects change in amygdala response to repeated sad faces differently in individuals with ASD vs healthy controls. Forty-four youth with ASD and 65 controls aged 8-19 years were genotyped and underwent an event-related functional magnetic resonance imaging scan where they identified the gender of emotional faces presented for 250 ms. The first half of the run was compared with the second half to assess habituation. 5-HTTLPR genotype influences amygdala habituation to sad faces differently for individuals with ASD vs controls. The genotype-by-diagnosis-by-run half interaction was driven by individuals with ASD and low expressing genotypes (S/S, S/L(G) and L(G)/L(G)), who trended toward sensitization (increase in amygdala activation) and whose habituation scores significantly differed from individuals with ASD and higher expressing genotypes (L(A)/L(A), S/L(A) and L(A)/L(G)) as well as controls with low expressing genotypes. Our results show that amygdala response to social stimuli in ASD, which may contribute to social symptoms, is genetically influenced.

Keywords: amygdala; autism; face; functional MRI; habituation; serotonin transporter gene.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Amygdala / physiopathology*
Child
Child Development Disorders, Pervasive / genetics
Child Development Disorders, Pervasive / physiopathology*
Face
Facial Expression
Female
Genotype
Genotyping Techniques
Habituation, Psychophysiologic*
Humans
Magnetic Resonance Imaging
Male
Neuropsychological Tests
Pattern Recognition, Visual / physiology*
Photic Stimulation
Serotonin Plasma Membrane Transport Proteins / genetics*
Social Perception*
Young Adult

Substances

SLC6A4 protein, human
Serotonin Plasma Membrane Transport Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding