Transcranial Direct Current Stimulation: Evaluating Clinical Implications for Depression and Anxiety

Frontal transcranial direct current stimulation (tDCS) acutely enhances executive function–related neural and behavioral performance in individuals with major depressive disorder and comorbid anxiety, but does not reduce—and may increase—physiological and neural markers of threat sensitivity.

In a double-blind, randomized experiment, 101 participants with major depressive disorder and elevated anxiety received a single 30-minute session of active or sham tDCS targeting the bilateral dorsolateral prefrontal cortex during fMRI. Following stimulation, participants completed a task-based attentional load paradigm with emotional face distractors and a None–Predictable–Unpredictable (NPU) threat task measuring eyeblink startle responses. Primary outcomes focused on objective behavioral performance, neural activation patterns, and psychophysiological indices of threat sensitivity rather than clinical symptom change.

Active tDCS significantly improved task accuracy and reaction times and increased activation in executive control regions, including the bilateral inferior frontal gyrus, mid-cingulate cortex, and parietal cortex, particularly under high attentional load. These findings indicate enhanced task engagement and executive functioning following stimulation. Contrary to the study’s hypotheses, however, tDCS did not attenuate threat sensitivity. Instead, active stimulation was associated with increased amygdala activation under low attentional load and heightened anxiety-potentiated startle responses and self-reported anxiety during unpredictable threat conditions.

Together, the results suggest that a single session of prefrontal tDCS can enhance cognitive control and performance in anxious depression but does not produce anxiolytic effects at the neural or physiological level. The coexistence of improved executive function with heightened threat reactivity highlights the complexity of tDCS effects on frontoparietal–amygdala circuitry and suggests that stimulation context and task engagement may be critical determinants of outcome.

The authors emphasize that these findings reflect acute, mechanistic effects rather than clinical efficacy and underscore the need for future studies exploring task-engaged stimulation, repeated dosing, and combined therapeutic approaches. Optimizing stimulation parameters and pairing tDCS with interventions that actively engage target circuits may help clarify its role as a potential adjunctive treatment for depression with comorbid anxiety.