Unpredictable neonatal stress enhances adult anxiety and alters amygdala gene expression related to serotonin and GABA.
Anxiety-related disorders are among the most common psychiatric illnesses, thought to have both genetic and environmental causes. Early-life trauma, such as abuse from a caregiver, can be predictable or unpredictable, each resulting in increased prevalence and severity of a unique set of disorders. In this study, we examined the influence of early unpredictable trauma on both the behavioral expression of adult anxiety and gene expression within the amygdala. Neonatal rats were exposed to unpaired odor-shock conditioning for 5 days, which produces deficits in adult behavior and amygdala dysfunction. In adulthood, we used the Light/Dark box test to measure anxiety-related behaviors, measuring the latency to enter the lit area and quantified urination and defecation. The amygdala was then dissected and a microarray analysis was performed to examine changes in gene expression. Animals that had received early unpredictable trauma displayed significantly longer latencies to enter the lit area and more defecation and urination. The microarray analysis revealed over-represented genes related to learning and memory, synaptic transmission and trans-membrane transport. Gene ontology and pathway analysis identified highly represented disease states related to anxiety phenotypes, including social anxiety, obsessive-compulsive disorders, post-traumatic stress disorder and bipolar disorder. Addiction-related genes were also overrepresented in this analysis. Unpredictable shock during early development increased anxiety-like behaviors in adulthood with concomitant changes in genes related to neurotransmission, resulting in gene expression patterns similar to anxiety-related psychiatric disorders.
Child Study Center, Center for Early Childhood Health & Development, Child & Adolescent Psychiatry, New York University School of Medicine, New York, NY 10010, United States; Emotional Brain Institute, Nathan Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962, United States. Electronic address: emma.sarro@nyumc.org.
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Sarro
Child Study Center, Center for Early Childhood Health & Development, Child & Adolescent Psychiatry, New York University School of Medicine, New York, NY 10010, United States; Emotional Brain Institute, Nathan Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962, United States.
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Sullivan
The Children's Hospital of Philadelphia, Department of Anesthesiology and Critical Care Medicine, Perelman School of Medicine at the University of Pennsylvania, United States.
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Barr
D000679:Amygdala / Q000254:growth & development / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety; D001008:Anxiety Disorders / Q000378:metabolism*; D003214:Conditioning, Classical; D004597:Electroshock; D005786:Gene Expression Regulation; D063990:Gene Ontology; D008297:Male; D009483:Neuropsychological Tests; D009812:Odorants; D055696:Olfactory Perception; D051381:Rats; D020318:Rats, Long-Evans; D012701:Serotonin / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism*; D013315:Stress, Psychological; D035501:Uncertainty; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D012701:Serotonin; D005680:gamma-Aminobutyric Acid
IPA; Ingenuity Pathways Analysis; PN; PTST; anxiety; early life; microarray; percentage of false predictions; pfp; post-traumatic stress disorder; postnatal; rodent; stress; unpredictable