Cortical and subcortical gamma amino acid butyric acid deficits in anxiety and stress disorders: Clinical implications

Table 2 Gamma amino acid system butyric acid effects of psychotropics with anxiolytic activity

Drug	Effect on GABA system	Test paradigm	Comments	Ref.
Benzodiazepines	Agonists at GABAA receptor complex	Alprazolam blocked ACC activation induced by CCK4 in controls.	fMRI study in 16 healthy male subjects	Leicht et al[71]
		Preclinical study of BZD effects on conditioned and unconditioned fear in mice	α2 subunit-containing GABAA receptors sufficient for BZD anxiolysis of unconditioned fear. α1 and α2 subunits needed to suppress conditioned fear	Smith et al[72]
SSRIs	Increased cortical GABA levels	Clinical MRS-GABA in MDD patients		Sanacora et al[73]
	Increased neuroactive steroid levels in the CNS	CSF ALLO increases in SSRI treated MDD patients (n = 15)		Uzunova et al[74]
TCAs	Increased release of GABA	Preclinical; desipramine effects studied		Korf et al[75]
MAOIs	Increase total brain GABA	Preclinical study of phenelzine effects		Paslawski et al[76]
Gabapentin	Increased cortical GABA	MRS-GABA in seizure patients	Chronic medication admin	Petroff et al[77]
PGB	Increased release of GABA	PGB decreases activation of left insula and amygdala in response to emotional images	fMRI activation study in 16 healthy humans	Aupperle et al[78]
Tiagabine	Blocks GAT-1 and inhibits synaptic GABA reuptake	FDG-PET study pre and post a 6-week tiagabine trial for social phobia	15 social anxiety disorder patients and 10 controls. vmPFC metabolism increased with treatment	Evans K et al[79]
Vigabatrin	Blocks GABA transaminase	Blocks CCK4 panic in healthy humans	Not clinically available due to ocular AEs	Zwanger et al[80]

GABA: Gamma amino acid butyric acid; mPFC: Medial prefrontal cortex; PET: Positron emission tomography; FDG: Fluorodeoxyglucose; PGB: Pregabalin; ACC: Anterior cingulate cortex; BZD: Benzodiazepine full agonist; MRS: Magnetic resonance spectroscopy; CNS: China national standards.