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Greater imbalance between neurochemical systems indicates worse PTSD symptoms

Overlapping expression of serotonin transporter and substance P/neurokinin-1 receptors differed among individuals with PTSD vs. healthy controls, and lower overlap was associated with worse PTSD symptoms, according to recent findings.

“Emerging research is beginning to elucidate neurochemical alterations in PTSD. Given the defined onset by pairing of previously neutral cues with intense negative affect, fear conditioning has been suggested to be an important etiological mechanism,” Andreas Frick, PhD, of Uppsala University, Uppsala, Sweden, and colleagues wrote. “Accordingly, several lines of evidence suggest similar neurochemical underpinnings of PTSD and fear conditioning, including serotonergic modulation. Patients with PTSD, and individuals prone to fear-conditioning processes, display exaggerated serotonin-modulated amygdala activity and reduced serotonin transporter availability.”

Researchers assessed serotonin and substance P/neurokinin-1 (SP/NK1) systems individually and their overlapping expression in 16 individuals with PTSD and 16 healthy controls. Study participants were imaged with the highly selective radiotracers [¹¹C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [¹¹C]GR205171 that assessed serotonin transporter and NK1 receptor availability.

Voxel-wise analyses in the amygdala indicated an increased number of NK1 receptors, but not serotonin transporters, among participants with PTSD.

Symptom severity was negatively related to serotonin transporter availability in the amygdala and NK1 receptors moderated this relationship, according to researchers.

Serotonin transporter availability was increased in the precentral gyrus and posterior cingulate cortex of participants with PTSD, according to exploratory, voxel-wise whole-brain analyses.

Participants with PTSD exhibited a lower degree of overlapping expression between serotonin transporter and NK1 receptors in the putamen, thalamus, insula and lateral orbitofrontal gyrus, compared with controls. Lower overlap was associated with higher PTSD symptom severity.

Symptomatology was explained more by expression overlap than either individual system, highlighting the significance of accounting for interactions between neurochemical systems.

“The current results indicate that overlapping expression of [serotonin transporter] and NK1 receptors is altered in PTSD and that lower overlap is related to worse symptoms. In the amygdala, a negative relationship between [serotonin transporter] availability and PTSD symptom severity was moderated by NK1 receptor levels, such that lower degree of overlap in expression was related to more severe PTSD symptoms,” Frick and colleagues wrote. “Overlapping expression of [serotonin transporter] and NK1 receptors explained more of the symptomatology than either system individually. Studying interactions between several neurotransmitter systems in a multimodal imaging framework represents a new path in neurobiological anxiety research and may potentially serve to guide future therapeutics.” – by Amanda Oldt

Disclosure: The researchers report no relevant financial disclosures.