Glutamate and GABA contributions to medial prefrontal cortical activity to emotion: Implications for mood disorders

Stan, Ana D.; Schirda, Claudiu; Bertocci, Michele; Bebko, Genna; Kronhaus, Dina M.; Aslam, Haris; LaBarbara, Eduard J.; Tanase, Costin; Lockovich, Jeanette; Pollock, Myrna; Stiffler, Richelle; Phillips, Mary L.

doi:10.1016/j.pscychresns.2014.05.016

Cited by 37 publications

(29 citation statements)

References 62 publications

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“…Of note, a MRS study by Hasler et al (2010) has observed a prefrontal GABA decrease in 10 healthy volunteers during a threat-of-shock condition vs a nonthreatening control condition. Recently, it has been demonstrated that the amygdala activity and the connectivity between vmPFC and amygdala are altered in anxious subjects (Stan et al, 2014). Particularly, Bishop et al (2004) have reported that individuals with both low and high anxiety levels showed an increased amygdala response to attended threat-related stimuli, but only highly anxious subjects showed an augmented amygdala response to unattended threat-related stimuli.…”

Section: Discussionmentioning

confidence: 99%

GABA content within the ventromedial prefrontal cortex is related to trait anxiety

Pizzi

Padulo

Brancucci

et al. 2015

Soc Cogn Affect Neurosci

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The ventromedial prefrontal cortex (vmPFC) plays a key role in emotion processing and regulation. vmPFC dysfunction may lead to disinhibition of amygdala causing high anxiety levels. c-Aminobutyric acid (GABA) inter-neurons within vmPFC shape the information flow to amygdala. Thus, we hypothesize that GABA content within vmPFC could be relevant to trait anxiety. Forty-three healthy volunteers aged between 20 and 88 years were assessed for trait anxiety with the Subscale-2 of the State-Trait-Anxiety Inventory (STAI-Y2) and were studied with proton magnetic resonance spectroscopy to investigate GABA and Glx (glutamateþglutamine) contents within vmPFC. Total creatine (tCr) was used as internal reference. Partial correlations assessed the association between metabolite levels and STAI-Y2 scores, removing the effect of possible nuisance factors including age, educational level, volumes of gray matter and white matter within magnetic resonance spectroscopy voxel. We observed a positive relationship between GABA/tCr and STAI-Y2 scores. No significant relationships were found between Glx/tCr and STAI-Y2 and between tCr/water and STAI-Y2. No differences were found between males and females as regards to age, STAI-Y2, GABA/tCr, Glx/tCr, tCr/water, gray matter and white matter volumes. We suggest a close relationship between GABA content within vmPFC and trait anxiety providing new insights in the physiology of emotional brain.

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Section: Discussionmentioning

confidence: 99%

GABA content within the ventromedial prefrontal cortex is related to trait anxiety

Pizzi

Padulo

Brancucci

et al. 2015

Soc Cogn Affect Neurosci

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“…GABA has a target signal and PTSD patients in a pMRS study of insulae metabolites were found to have a significantly lower metabolic GABA signal interpreted as a deficiency in inhibitory GABA neurochemical state; this may explain the clinically permissive activation of PTSD memories and recurrence of invasive recall symptoms [65]. Deficiencies in GABA have been reported in schizophrenia and other disorders [66]. …”

Section: Molecular Imagingmentioning

confidence: 99%

Corticotropin releasing hormone and imaging, rethinking the stress axis

Contoreggi

2015

Nuclear Medicine and Biology

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The stress system provides integration of both neurochemical and somatic physiologic functions within organisms as an adaptive mechanism to changing environmental conditions throughout evolution. In mammals and primates the complexity and sophistication of these systems has surpassed other species in triaging neurochemical and physiologic signaling to maximize chances of survival. Corticotropin releasing hormone (CRH) and its related peptides and receptors have been identified over the last three decades and are fundamental molecular initiators of the stress response. They are crucial in the top down regulatory cascade over a myriad of neurochemical, neuroendocrine and sympathetic nervous system events. From neuroscience, we’ve seen that stress activation impacts behavior, endocrine and somatic physiology and influences neurochemical events that one can capture in real time with current imaging technologies. To delineate these effects one can demonstrate how the CRH neuronal networks infiltrate critical cognitive, emotive and autonomic regions of the central nervous system (CNS) with somatic effects. Abundant preclinical and clinical studies show inter-regulatory actions of CRH with multiple neurotransmitters/peptides. Stress, both acute and chronic has epigenetic effects which magnify genetic susceptibilities to alter neurochemistry; stress system activation can add critical variables in design and interpretation of basic and clinical neuroscience and related research. This review will attempt to provide an overview of the spectrum of known functions and speculative actions of CRH and stress responses in light of imaging technology and its interpretation. Metabolic and neuroreceptor positron emission/single photon tomography (PET/SPECT), functional magnetic resonance imaging (fMRI), anatomic MRI, diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (pMRS) are technologies that can delineate basic mechanisms of neurophysiology and pharmacology. Stress modulates the myriad of neurochemical and networks within and controlled through the central and peripheral nervous system and the effects of stress activation on imaging will be highlighted.

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“…Importantly, guilty rumination figured more prominently in women than in men with depression (Nolen-Hoeksema, 2012; Shors et al, 2017). A study combining fMRI and magnetic resonance spectroscopy revealed a significant negative correlation between GABA concentration in the dmPFC and BOLD signals in sgACC during exposure to sad face in contrast to control images (Stan et al, 2014). In individuals with treatment-refractory depression undergoing a 4-week course of repetitive transcranial magnetic stimulation of the dmPFC, higher baseline sgACC to dmPFC connectivity was associated with better treatment outcomes (Salomons et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Depression in chronic ketamine users: Sex differences and neural bases

Zhang

Hung³

et al. 2017

Psychiatry Research: Neuroimaging

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Chronic ketamine use leads to cognitive and affective deficits including depression. Here, we examined sex differences and neural bases of depression in chronic ketamine users. Compared to non-drug using healthy controls (HC), ketamine-using females but not males showed increased depression score as assessed by the Center of Epidemiological Studies Depression Scale (CES-D). We evaluated resting state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC), a prefrontal structure consistently implicated in the pathogenesis of depression. Compared to HC, ketamine users (KU) did not demonstrate significant changes in sgACC connectivities at a corrected threshold. However, in KU, a linear regression against CES-D score showed less sgACC connectivity to the orbitofrontal cortex (OFC) with increasing depression severity. Examined separately, male and female KU showed higher sgACC connectivity to bilateral superior temporal gyrus and dorsomedial prefrontal cortex (dmPFC), respectively, in correlation with depression. The linear correlation of sgACC-OFC and sgACC-dmPFC connectivity with depression was significantly different in slope between KU and HC. These findings highlighted changes in rsFC of the sgACC as associated with depression and sex differences in these changes in chronic ketamine users.

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Glutamate and GABA contributions to medial prefrontal cortical activity to emotion: Implications for mood disorders

Cited by 37 publications

References 62 publications

GABA content within the ventromedial prefrontal cortex is related to trait anxiety

GABA content within the ventromedial prefrontal cortex is related to trait anxiety

Corticotropin releasing hormone and imaging, rethinking the stress axis

Depression in chronic ketamine users: Sex differences and neural bases

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