Cortical inhibition, facilitation and plasticity in late-life depression: effects of venlafaxine pharmacotherapy

Abstract

Background: Late-life depression is often associated with non-response or relapse following conventional antidepressant treatment. The pathophysiology of late-life depression likely involves a complex interplay between aging and depression, and may include abnormalities in cortical inhibition and plasticity. However, the extent to which these cortical processes are modifiable by antidepressant pharmacotherapy is unknown. Methods: Sixty-eight patients with late-life depression received 12 weeks of treatment with open-label venlafaxine, a serotonin-norepinephrine reuptake inhibitor (≤ 300 mg/d). We combined transcranial magnetic stimulation of the left motor cortex with electromyography recordings from the right hand to measure cortical inhibition using contralateral cortical silent period and paired-pulse short-interval intracortical inhibition paradigms; cortical facilitation using a paired-pulse intracortical facilitation paradigm; and short-term cortical plasticity using a paired associative stimulation paradigm. All measures were collected at baseline, 1 week into treatment (n = 23) and after approximately 12 weeks of treatment. Results: Venlafaxine did not significantly alter cortical inhibition, facilitation or plasticity after 1 or 12 weeks of treatment. Improvements in depressive symptoms during treatment were not associated with changes in cortical physiology. Limitations: The results presented here are specific to the motor cortex. Future work should investigate whether these findings extend to cortical areas more closely associated with depression, such as the dorsolateral prefrontal cortex. Conclusion: These findings suggest that antidepressant treatment with venlafaxine does not exert meaningful changes in motor cortical inhibition or plasticity in late-life depression. The absence of changes in motor cortical physiology, alongside improvements in depressive symptoms, suggests that age-related changes may play a role in previously identified abnormalities in motor cortical processes in late-life depression, and that venlafaxine treatment does not target these abnormalities.

Low-Dose Augmentation With Buprenorphine for Treatment-Resistant Depression: A Multisite Randomized Controlled Trial With Multimodal Assessment of Target Engagement

“…Despite prior evidence of interactions between opioid, GABA, and glutamate systems ( 40 ), we did not observe any significant changes in TMS measures of cortical inhibition, facilitation, or plasticity after either BPN or PBO augmentation. Similarly, our previous study of open-label venlafaxine in older adults with MDD did not show an effect of venlafaxine on these cortical measures ( 41 ). Our findings suggest that low-dose augmentation of venlafaxine with BPN does not further engage GABAergic and glutamatergic mechanisms in the cortex.…”

Characteristic changes of prefrontal and motor areas in patients with type 2 diabetes and major depressive disorder during a motor task of tai chi chuan: A functional near-infrared spectroscopy study

“…The excitability in prefrontal and motor areas reduced in patients with T2DM and MDD Previous studies have shown that brain excitability of the prefrontal and motor areas in MDD patients reduced compared to healthy subjects, which was related to symptoms like interest drops and reduced activity [31][32][33][34]. similarly, in the present study, we found that patients with T2DM and MDD exhibited lower activation in FPA in comparison with T2DM patients and healthy individuals.…”

Depresssion, anxiety and other cognitive consequences of social isolation: Drug and non‐drug treatments

“…76 Twelve weeks of treatment with venlafaxine (≤300 mg/day) does not exert meaningful changes in motor cortical inhibition or plasticity in late-life depression. 78 Venlafaxine improves social phobia and avoidant personality disorder symptomatology in SSRI non-responders. 79 While SI could cause cognitive dysfunction and decrease synaptic protein (synaptophysin or PSD93) expression in different brain regions associated with cognition in middle-aged rats, the SSRI antidepressant citalopram (10 mg/kg, ip) could significantly improve learning and memory and partially restore synaptophysin or PSD93 expression in the prefrontal cortex, hippocampus, and amygdala in SI rats.…”

“…This drug (5 mg/kg/day) is been shown to alleviate the loss of myelin and oligodendrocytes (OLs), mitigate depression‐like behaviours, and improve cognitive function in cuprizone‐fed animals 76 . Twelve weeks of treatment with venlafaxine (≤300 mg/day) does not exert meaningful changes in motor cortical inhibition or plasticity in late‐life depression 78 . Venlafaxine improves social phobia and avoidant personality disorder symptomatology in SSRI non‐responders 79 …”