Panic disorders: The role of genetics and epigenetics

Summary & key facts

Panic disorder involves sudden episodes of intense fear and physical symptoms. Research shows many factors may play a role, but no single gene or epigenetic change explains the disorder. Family and twin studies point to a strong inherited component. Genetic studies have identified some candidate genes and regions, and some epigenetic differences have been reported, but results are not definitive and larger studies are needed.

Key facts:

• Twin, family, and adoption studies suggest panic disorder runs in families and has a strong familial component.
• Linkage studies indicate panic disorder is not caused by a single gene but likely involves multiple genes.
• Early candidate-gene studies reported associations with genes such as NPY, ADORA2A, COMT, and IKBKE.
• Genome-wide association studies (GWAS) did not find any genome-wide significant single genes, but implicated regions/genes including NPY5R (on 4q31.3-32) and BDKRB2 (on 14q32).
• Epigenetic studies reported MAOA hypomethylation that, together with negative life events, was related to panic disorder.
• GAD1 (glutamate decarboxylase 1) hypomethylation was reported specifically in panic disorder patients in some studies.
• Studies have examined methylation changes in the noradrenaline transporter gene (SLC6a2) promoter in relation to panic disorder, but findings are not conclusive.
• The authors conclude that no single gene or epigenetic pattern fully explains panic disorder and that larger studies are needed to confirm current findings and clarify causes.

Abstract

Panic disorder is characterized by symptoms with abrupt surges of fear with palpitations, sweating, trembling, heat sensations. Considering its disease burden on each individual and on society, understanding its etiology is important. Though no one specific etiology has been known, like other psychiatric disorders, multiple factors such as genetic, environmental, neurobiological, psychopathological factors have been suggested. In this article, we reviewed currently known etiologies and related study results, regarding especially genetic and epigenetic aspects of the panic disorder. Early studies, including twin studies, family studies, adoption studies suggested highly familial trait of panic disorder. Linkage studies, either, found panic disorder is not a single gene disorder but confirmed existence of multiple related genes. Chromosome and candidate gene studies found few related genes, NPY, ADORA2A, COMT, IKBKE. Newer method, genome-wide association studies (GWAS) have been searching for newer genes. No genome-wide significant genes, however, were detected, confirming previously known candidate genes, NPY5R on 4q31.3-32, BDKRB2 on 14q32, instead. Epigenetic modification has also been studied on many different psychiatric disorders. Monoamine oxidase A (MAOA) hypomethylation, taken together with negative life events, showed relation with panic disorder. Glutamate decarbodylases 1 (GAD1) hypomethylation was also specific on panic disorder patients. Relation with noradrenaline transporter (NET) gene SLC6a2 promoter methylation has also been studied. In conclusion, no specific gene or epigenetic pattern can fully explain etiology of panic disorder. Few genes and epigenetic patterns, however, showed strong association with panic disorder compared to healthy controls. Considering its multivariable background, further studies with larger populations can confirm current results and clarify etiologies of panic disorder.

Topics

Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes Child and Adolescent Psychosocial and Emotional Development Schizophrenia research and treatment

Categories

Clinical Psychology Psychology Social Sciences

Tags

Anxiety Bioinformatics Biology Candidate gene Epigenetics Gene Genetic association Genetics Genome-wide association study Genotype Medicine Panic Panic disorder Psychiatry Single-nucleotide polymorphism

Conditions & symptoms

Anxiety Panic disorder and phobias Panic