A preliminary examination of cortical neurotransmitter levels associated with heavy drinking in posttraumatic stress disorder

Abstract

Posttraumatic stress disorder (PTSD) patients have low cortical concentrations of γ-aminobutyric acid (GABA) and elevated glutamate (Glu) as measured by proton magnetic resonance spectroscopy (1H MRS). Alcohol use disorder (AUD) is highly comorbid with PTSD, but the neurobiological underpinnings are largely unknown. We wanted to determine if PTSD patients with AUD have normalized cortical GABA and Glu levels in addition to metabolite alterations common to AUD. We compared brain metabolite concentrations in 10 PTSD patients with comorbid AUD (PAUD) with concentrtations in 28 PTSD patients without AUD and in 20 trauma-exposed controls (CON) without PTSD symptoms. We measured concentrations of GABA, Glu, N-acetylaspartate (NAA), creatine- (Cr) and choline-containing metabolites (Cho), and myo-Inositol (mI) in three cortical brain regions using 1H MRS and correlated them with measures of neurocognition, insomnia, PTSD symptoms, and drinking severity. In contrast to PTSD, PAUD exhibited normal GABA and Glu concentrations in the parieto-occipital and temporal cortices, respectively, but lower Glu and trends toward higher GABA levels in the anterior cingulate cortex (ACC). Temporal NAA and Cho as well as mI in the ACC were lower in PAUD than in both PTSD and CON. Within PAUD, more cortical GABA and Glu correlated with better neurocognition. Heavy drinking in PTSD is associated with partially neutralized neurotransmitter imbalance, but also with neuronal injury commonly observed in AUD.

Hyperarousal and Beyond: New Insights to the Pathophysiology of Insomnia Disorder through Functional Neuroimaging Studies

“…Higher glutamate in the parieto-occipital cortex has been linked to insomnia symptoms in patients with post-traumatic stress disorder [30,31] but has not been linked to PI per se [32,33,34]. …”

“…Conversely, positive allosteric modulators of the GABA A receptor (e.g., benzodiazepines, “z drugs”, and barbiturates) have sedating effects and are efficacious short-term treatments for insomnia [41,42]. With one exception that found that individuals with PI had higher GABA concentrations than GS in the occipital cortex [32], the majority of 1H MRS studies suggest insomnia is associated with lower GABA levels in the parieto-occipital cortex [30,31,33,34] or anterior cingulate [33]. Because MRS reflects presynaptic concentrations of GABA, these findings may suggest that insomnia involves impaired inhibitory control.…”

PTSD: from neurobiology to pharmacological treatments

“…Perturbations in the glutamatergic system have also been replicated in human population. In a recent magnetic resonance spectroscopy (MRS) study, patients with PTSD compared with trauma-exposed controls were shown to have elevated glutamate levels in the lateral temporal cortex and lower levels in ACC in PTSD with alcohol use disorder (Pennington, Abe, Batki, & Meyerhoff, 2014). Elevated serum glutamate levels were recently reported in patients with PTSD 3 months after a traumatic accident compared with healthy controls (Nishi et al, 2015).…”

Multimodal and Site-Specific Plasticity of Amygdala Parvalbumin Interneurons after Fear Learning

“…However, many studies posit that co-regulation of excitation and inhibition may be important for network stability and that excitation:inhibition (E:I) imbalance may be a factor in some psychiatric conditions (Dorrn et al, 2010; Gouty-Colomer et al, 2015; House et al, 2011; Katagiri et al, 2007; Vogels et al, 2011). Notably, decreased GABA levels as well as GABA receptor binding and polymorphisms have been associated with PTSD (Bremner et al, 2000; Feusner et al, 2001; Geuze et al, 2008; Meyerhoff et al, 2014; Pennington et al, 2014; Rossi et al, 2009; Rosso et al, 2014), and reduced GABA levels are predictive of disease progression (Vaiva et al, 2006; Vaiva et al, 2004). Changes in inhibitory synaptic markers suggest that plasticity of GABAergic transmission in the basolateral amygdala may also be a feature of aversive memory formation under normal conditions (Chhatwal et al, 2005; Heldt and Ressler, 2007; Lin et al, 2011).…”