Cognitive-behavioral therapy (CBT) for posttraumatic stress disorder (PTSD) not only reduces symptoms but also alters the underlying biology of this disorder, new research suggests.

The study shows "a definitive link between clinical improvement during psychotherapy, structural changes of the brain, and peripheral expression of genes responsible for stress response," Szabolcs Kéri, MD, PhD, of the National Institute of Psychiatry and Addictions and University of Szeged in Hungary, and colleagues write.

"The results highlight the potential relevance of these joined mechanisms, together with the importance of early intervention in PTSD when neuroplastic capacities may be more viable," they add.

The study is published in the December issue of Biological Psychiatry.

Increased Hippocampal Volume

The researchers studied 39 individuals with PTSD who underwent CBT and a control group of 31 trauma-exposed individuals without PTSD who did not have CBT.

They assessed the association between clinical response, hippocampal volume, and expression of the FKBP5 gene, which has been implicated in risk of developing PTSD and which plays a role in regulating stress hormones.

Compared with control individuals, at baseline, patients with PTSD had lower FKBP5 gene expression and smaller volume in the hippocampus and medial orbitofrontal cortex, brain regions involved in learning, memory, and emotion regulation.

Twelve weeks after CBT, patients with PTSD had significantly increased FKBP5 expression and hippocampal volume. At this point, patients did not differ from control participants in hippocampal volume, the researchers say.

"The most noteworthy finding of this study was that clinical improvement during CBT in PTSD was associated with increased hippocampal size and elevated FKBP5 gene expression," the authors write.

"Increased hippocampal volume and elevated FKBP5 expression were significantly correlated, and the primary predictor of clinical improvement was increased FKBP5 expression," they add.

Dr. Szabolcs Kéri

"The results show that structural changes in the brain, such as the shrinkage of the hippocampus, are reversible in trauma victims," Dr. Kéri said in a statement. "Talk therapy may help normalize these alterations and improve symptoms. Furthermore, the regeneration of hippocampus correlated with the expression of a gene that balances the activity of the stress hormone cortisol at the level of cells," he added.

"To put it into a simplified physiological nutshell, the most likely scenario is that the normalization of hippocampal structure and function balanced its regulatory effect on the hypothalamic-pituitary-adrenal gland axis and brainstem centers affecting the functions of the sympathetic and parasympathetic nervous system," Dr. Kéri told Medscape Medical News.

Dr. Kéri said that it is "not surprising" that the structure of the hippocampus changed during CBT.

"Evidence suggests, even from animal models, that social and psychological effects, such as environmental enrichment in animals, enhance neurogenesis and synaptic plasticity in the hippocampus. We speculate that similar changes may occur in individuals receiving psychotherapy," he said.

Psychotherapy Affects Biology

"This study helps to link the alleviation of PTSD symptoms to improvement in stress-related alterations in the body and brain," John Krystal, MD, editor of Biological Psychiatry and chair of the Department of Psychiatry at the Yale University School of Medicine in New Haven, Connecticut, said in a statement.

"This research is a nice demonstration of how psychological interventions have effects on the underlying biology of psychological disorders," Matthew W. Johnson, PhD, associate professor, Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine in Baltimore, Maryland, told Medscape Medical News.

"Often it is assumed by the public that only a medical intervention, such as medication or surgery, can affect biology. But scientifically, we know that environmental experiences, such as psychotherapy, can affect biology," added Dr. Johnson, who was not involved in the study.

The study was supported by the Hungarian Research Fund. The authors and Dr. Johnson have disclosed no relevant financial relationships.

Biol Psychiatry. 2013;74:793-800. Full article