Brain stimulation and other biological non-pharmacological interventions in mental disorders: An umbrella review

Non-Invasive Brain Stimulation Effects on Biomarkers of Tryptophan Metabolism: A Scoping Review and Meta-Analysis

“…More recently, a meta-analysis sought to identify which biomarkers of kynurenine pathway activity differentiate psychiatric disorders, finding KA/QA being significantly lower in MDD and bipolar disorder patients compared to healthy controls [ 9 ]. However, despite ECT having significant antidepressant effects (in uni- and bipolar patients) [ 17 ], two included studies reported null effects of ECT on QA/KA, an inversed form [ 33 , 52 ], but a third reported significant reductions of the QA/KA ratio [ 54 ]—suggesting less neurotoxic QA and more neuroprotective KA, and no studies investigating these ratios after tDCS nor rTMS ( Figure 4 ). Consistent with these effects, our meta-analysis indicated no effects on plasma KA levels and KA/KYN ratio following ECT [ 35 , 52 ].…”

“…Likewise for NIBS, not all techniques were considered, such as transcranial electric stimulation, though several more exist beyond those reviewed here [ 22 ]. We sought studies using ECT, rTMS, and tDCS as these are frequently discussed in reviews on the therapeutic efficacy of NIBS and mechanisms of action, e.g., [ 17 , 139 ]. Lastly, our univariate focus on biomarker levels may not be sufficient to elucidate the mechanisms of action by NIBS and the relation between TRP metabolism and health condition—this aim will require future studies to utilize cross-domain expertise, including biomarker effects.…”

“…Search terms for NIBS were initially based on techniques in a recent expert review [ 22 ], however we focused our search here to ECT, rTMS, and tDCS because preliminary searches to test the feasibility of this review could not identify relevant studies for other NIBS techniques and these techniques are frequently discussed in reviews on the therapeutic efficacy of NIBS and mechanisms of action, e.g, [ 17 ]. The subset of TRP metabolites, and corresponding terms for the products of the serotonin and kynurenine pathways that we reviewed were based on recent expert reviews [ 5 , 7 ].…”

“…Noninvasive brain stimulation (NIBS) techniques have demonstrated therapeutic utility across neuropsychiatric disorders, with varied levels of efficacy and quality of evidence [ 17 ]. Those techniques under review here are repetitive transcranial magnetic stimulation (rTMS) [ 17 , 18 , 19 , 20 ], transcranial direct current stimulation (tDCS) [ 17 , 18 ], and electroconvulsive therapy (ECT) [ 17 ]—each considered non-invasive as no breaching or implantation occurs during treatment [ 21 ]. Current efforts are aimed at developing precise protocols for these techniques [ 22 ].…”

Interventional psychiatry: the elephants in the room

“…Though originally proposed for brain stimulation techniques such as electroconvulsive therapy, 1 interventional psychiatry also extends to surgical procedures (e.g., circuit-based neurosurgery for intractable obsessive-compulsive disorder 2 ), novel pharmacological interventions (e.g., ketamine or esketamine), enhanced psychotherapy approaches (e.g., psychedelic-assisted psychotherapy), or complex digital interventions (e.g., cognitive control training combined with non-invasive brain stimulation). Whereas the field of brain stimulation with its substantial array of techniques, including recent developments such as temporal interference stimulation 3 and focused ultrasound, 4 has been systematically established over decades, 5 the inclusion of many other novel interventions is making it a very rapidly growing field of innovation.…”