Photobiomodulation for Major Depressive Disorder: Linking Transcranial Infrared Light, Biophotons and Oxidative Stress

Abstract

Incompletely treated major depressive disorder (MDD) poses an enormous global health burden. Conventional treatment for MDD consists of pharmacotherapy and psychotherapy, though a significant number of patients do not achieve remission with such treatments. Transcranial photobiomodulation (t-PBM) is a promising novel therapy that uses extracranial light, especially in the near-infrared (NIR) and red spectra, for biological and therapeutic effects. The aims of this Review are to evaluate the current clinical and preclinical literature on t-PBM in MDD and to discuss candidate mechanisms for effects of t-PBM in MDD, with specific attention to biophotons and oxidative stress. A search on PubMed and ClinicalTrials.gov identified clinical and preclinical studies using t-PBM for the treatment of MDD as a primary focus. After a systematic screening, only 19 studies containing original data were included in this review (9 clinical and 10 preclinical trials). Study results demonstrate consensus that t-PBM is a safe and potentially effective treatment; however, varying treatment parameters among studies complicate definitive conclusions about efficacy. Among other mechanisms of action, t-PBM stimulates the complex IV of the mitochondrial respiratory chain and induces an increase in cellular energy metabolism. We suggest that future trials include biological measures to better understand the mechanisms of action of t-PBM and to optimize treatment efficiency. Of particular interest going forward will be studying potential effects of t-PBM—an external light source on the NIR spectra—on neural circuitry implicated in depression.

Inflammation in obsessive–compulsive disorder: A literature review and hypothesis‐based potential of transcranial photobiomodulation

“…t‐PBM can modulate cortical excitability (Chaieb et al., 2015; Konstantinović et al., 2013), improve cerebral perfusion (Henderson & Morries, 2015; Nawashiro et al., 2012; Salgado et al., 2015) and oxygenation (Tian et al., 2016). t‐PBM is a safe (Cassano et al., 2022) and effective treatment for neuropsychiatric disorders, including major depressive (Caldieraro & Cassano, 2019; Cassano et al., 2015, 2018; Vieira, Gersten, et al., 2023; Vieira, Iosifescu, et al., 2023) and bipolar disorder (Mannu et al., 2019; O'Donnell et al., 2022), Alzheimer's (Dos Santos Cardoso et al., 2020; Yang et al., 2022) and Parkinson's disease (Ahrabi et al., 2022; Liebert et al., 2021), and traumatic brain injury (Naeser et al., 2014; Poiani et al., 2018).…”

“…However, the potential of t‐PBM in treating OCD might extend beyond its anti‐inflammatory effects, as there could be a direct influence on neural activity and circuitry implicated in OCD pathology. The modulation of cellular mechanisms such as cAMP, NO, Ca 2+ , and CREB by t‐PBM points to a potential direct impact on neurons, astrocytes, and microglia, not solely through inflammatory pathways but also via photophysical and photochemical processes in mitochondria‐rich cells (de Freitas & Hamblin, 2016; Dompe et al., 2020; Vieira, Gersten, et al., 2023).…”

“…This exploration should not be limited to its potential anti‐inflammatory effects in OCD but should also encompass its potential direct impact on neural cells (De Marchi et al., 2021; Esteves et al., 2022; Lima et al., 2014; Lu et al., 2017; Shaikh‐Kader et al., 2021; Zheng et al., 2021). t‐PBM's ability to influence neurons, astrocytes, and microglia through photophysical and photochemical processes in mitochondria‐rich cells offers another avenue of potential therapeutic benefits in OCD (de Freitas & Hamblin, 2016; Dompe et al., 2020; Vieira, Gersten, et al., 2023).…”

“…When applied to the scalp, near‐infrared (NIR) light, the main light source for t‐PBM, increases cerebral blood flow, oxygenation, and metabolism, which enhances neuronal plasticity and promotes neuroprotection (Henderson & Morries, 2015; Nawashiro et al., 2012; Salgado et al., 2015; Tian et al., 2016). In this regard, t‐PBM has proven therapeutic potential in a wide range of neuropsychiatric disorders, including MDD (Cassano et al., 2015, 2018; Vieira, Gersten, et al., 2023; Vieira, Iosifescu, et al., 2023), bipolar disorder (Mannu et al., 2019), Alzheimer's disease (Dos Santos Cardoso et al., 2020), Parkinson's disease (Liebert et al., 2021), and traumatic brain injury (Naeser et al., 2014).…”

Introduction

“…Applied over the scalp, transcranial PBM with near-infrared light has shown effectiveness in clinical applications, including treating MDD and generalized anxiety, and improving cognitive function in dementia. Vieira and colleagues 23 review the evidence supporting current models that explain the mechanisms of action of transcranial PBM and the clinical trials exploring indications of PBM in psychiatric illness.…”