5.2. Future Research Directions
depressive disorder, panic disorder, phobias, anxiety
DISORDERS
The findings in this study between Kava treatment, anxiety symptoms, and GABA levels warrant further examination. Given the role the dACC may play in hallmark anxiety cognition symptoms in GAD, as well as evidence of kava efficacy in the literature, it would be of value to examine whether kava-based modulations were observed on selected HAM-A items (such as cognitive over somatic symptoms), which might clarify the pattern observed in the ROI. Similarly, a division of higher anxiety and low anxiety may reveal different Kava responses. Secondly, beyond the modulation of GABA by Kava, given the likely mechanisms in the GABA metabolic shunt of Kava in preclinical studies on NMDA receptors, an examination of glutamate levels may also reveal Kava mechanisms beyond GABA, supporting recent preclinical research and offering potential avenues for future therapeutic approaches.This current study was valuable for understanding the mechanisms of Kava in GAD, and future research should extend Kava dosing in other anxiety cohorts and healthy controls and assess patterns of GABA levels in comparison with GAD. This could include major depressive disorder or state-based anxiety disorders, such as phobias and panic disorder, to delineate differences in ROI GABA levels and determine the relationship to anxiety symptoms.There remains a shortfall in brain biomarker research in anxiety disorders, especially GAD. Emerging approaches now exist to guide the identified need, such as the Research Domain Criteria (RDoC) framework [This current study showed that GABA metabolic data were successful in producing differences that could be utilised as GAD biomarkers, with some considerations. The assessment of the neurobiological effects of Kava is novel in GAD samples and shows how our methodology could be applied to other anxiolytic phytomedicines. Data from MRS GABA can contribute to an integrative efficacy model of imaging modalities and psychological measures for future efficacy studies of biological substrates. More work is needed in the establishing of biomarkers for clinical benefit, but there is a strong translational rationale for the investigation of novel anxiolytics like Kava as GAD treatment, as demonstrated in this current study.