Magnetic Resonance Spectroscopy of Inhibitory Neurotransmission in Post-Traumatic Stress Disorder

Isabella Rosso, Ph.D.

McLean Hospital (Harvard Medical School)

Funded in June, 2010: $200000 for 3 years
LAY SUMMARY .

LAY SUMMARY

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A new form of MRS imaging may aid in assessing PTSD severity and effectiveness of therapies

Investigators will use an advanced method of spectroscopy imaging they developed to directly measure levels of the inhibitory neurotransmitter GABA in patients with post-traumatic stress disorder (PTSD) and determine whether low GABA levels correlate with symptom severity. PTSD is a debilitating anxiety disorder that emerges a month or more following a traumatic event, in which patients re-experience the event through flashbacks and nightmares, and suffer insomnia and hypervigilance as a try to avoid reminders of the trauma. This disorder of “fear conditioning” involves sensitization of neurons in brain regions involved in fear learning, most prominently the hippocampus and dorsal anterior cingulate cortex, a brain area that is also implicated in severe depression.  Evidence indicates that neurons in these regions have heightened excitability, suggesting that not enough GABA is available to inhibit the neurons’ activity. Until now, GABA levels have never been directly measured in PTSD patients. They have developed a new method for using the conventional brain imaging technology proton magnetic resonance spectroscopy (H-MRS), called H-MRS MEAGPRESS.

They will use this new technique to test their hypothesis that PTSD patients have low levels of GABA, and that the lower the levels, the worse the symptoms. Using H-MRS MEGAPRESS imaging in 30 patients with PTSD and 30 people exposed to trauma who did not develop PTSD, the clinical researchers will measure GABA levels in participants’ hippocampus and dorsal anterior cingulate cortex. They also will conduct a psychiatric interview and symptom assessment of all participants.

Significance: If this imaging technique reveals a direct correlation between low GABA levels and PTSD symptom severity, this imaging technique will help to diagnose and predict PTSD outcomes, and also to assess the extent to which dopamine-promoting therapies improve these outcomes.