A 2008 paper by Thoeringer et. al., published in the Journal of Neural Transmission [1] described a study of 238 adult Caucasian patients recruited from an Anxiety Disorders Outpatient Clinic in Europe presenting various anxiety disorders, including panic disorder, agoraphobia, social phobia and generalized anxiety disorder. As there are many genetic studies linking the GABA system to anxiety disorders and related personality traits, the patients were genotyped for various polymorphisms in the SLC6A1 (GABA transporter 1), along with 267 controls without anxiety disorder.
Five polymorphisms in SLC6A1 or in the promoter region were found to be nominally associated with anxiety disorders. Although none were statistically significant alone, the authors found a significant combined effect of all investigated polymorphisms, which strongly suggested a major role of SLC6A1 in the genetic susceptibility of pathological anxiety. Looking at patients with panic disorder, those with the most severe panic disorder were significantly more likely than controls to have two related polymorphisms in the SLC6A1.
GABA (gamma-aminobutyric acid) is a neurotransmitter that decreases activity in the neurons of the brain and inhibits the excitability of nerve cells. Drugs that block the GABA transporter molecule inhibit the removal of GABA from the nerve synapses, thereby prolonging the action of GABA. Tiagabine, a selective GABA transporter 1 blocker, is used as an antiepileptic, but has off-label use for anxiety disorder. This is thought to be due to the augmentation of GABA function as a neurotransmitter in the brain. This drug has side-effects, however, and other methods of reducing panic disorder have been investigated.
Kava-kava (Piper methysticum) is a traditional plant-based medicine found in the Western Pacific region which has been shown to reduce anxiety. Kava-kava is legal in most countries, and is generally safe when the root from a ‘noble’ cultivar is used. A study of kava-kava for anxiety reduction using the Hamilton Anxiety Rating Scale (HAMA) as the primary outcome found that patients with generalized anxiety disorder who had polymorphisms in SLC6A1 and in the 5′ flanking region potentially responded to kava-kava supplementation with a more significant reduction in HAMA rating than in patients without the polymorphisms. [2] Treatment consisted of tablets standardized to contain 60 mg of kavalactones per tablet for a total daily dose of 120 mg of kavalactones for the first 3-week controlled phase, being titrated to 240 mg of kavalactones in nonresponse at the 3-week mark for the second 3-week controlled phase, or placebo.
An algorithm in the Lumen app in Opus 23 determines how many relevant SNPs a client has in SLC6A1 that are reported in their 23andMe raw data, and which may make treatment with kava-kava more effective in reducing anxiety disorder and panic symptoms.
References:
- Thoeringer, C.K., Ripke, S., Unschuld, P.G. et al. The GABA transporter 1 (SLC6A1): a novel candidate gene for anxiety disorders. J Neural Transm (2009) 116: 649. doi:10.1007/s00702-008-0075-y. PMCID: PMC2694916
- Sarris J, Stough C, Bousman CA, et.al. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. 2013 Oct;33(5):643-8. doi: 10.1097/JCP.0b013e318291be67. PMID: 23635869
