Treating neuropathic pain and comorbid affective disorders: Preclinical and clinical evidence.

INTRODUCTION: Neuropathic pain (NP) significantly impacts quality of life and often coexists with affective disorders such as anxiety and depression. Addressing both NP and its psychiatric manifestations requires a comprehensive understanding of therapeutic options. This study aimed to review the main pharmacological and non-pharmacological treatments for NP and comorbid affective disorders to describe their mechanisms of action and how they are commonly used in clinical practice. METHODS: A review was conducted across five electronic databases, focusing on pharmacological and non-pharmacological treatments for NP and its associated affective disorders. The following combination of MeSH and title/abstract keywords were used: "neuropathic pain," "affective disorders," "depression," "anxiety," "treatment," and "therapy." Both animal and human studies were included to discuss the underlying therapeutic mechanisms of these interventions. RESULTS: Pharmacological interventions, including antidepressants, anticonvulsants, and opioids, modulate neural synaptic transmission to alleviate NP. Topical agents, such as capsaicin, lidocaine patches, and botulinum toxin A, offer localized relief by desensitizing pain pathways. Some of these drugs, especially antidepressants, also treat comorbid affective disorders. Non-pharmacological techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and photobiomodulation therapy, modulate cortical activity and have shown promise for NP and mood disorders. CONCLUSIONS: The interconnection between NP and comorbid affective disorders necessitates holistic therapeutic strategies. Some pharmacological treatments can be used for both conditions, and non-pharmacological interventions have emerged as promising complementary approaches. Future research should explore novel molecular pathways to enhance treatment options for these interrelated conditions.

Use of Tobacco Products and Suicide Attempts Among Elementary School-Aged Children.

Importance: The use of tobacco products, including e-cigarettes and vaping, has rapidly increased among children. However, despite consistent associations found between smoking cigarettes and suicidal behaviors among adolescents and adults, there are limited data on associations between emerging tobacco products and suicidal behaviors, especially among preadolescent children. Objective: To examine whether the use of tobacco products is associated with nonsuicidal self-injury (NSSI), suicidal ideation (SI), and suicide attempts (SAs) among preadolescent children. Design, Setting, and Participants: This cohort study, conducted from September 1, 2022, to September 5, 2023, included participants in the Adolescent Brain Cognitive Development study, a population-based cohort of 11 868 US children enrolled at 9 and 10 years of age. The cross-sectional investigation focused on 3-year periods starting from the baseline to year 2 of follow-up. Statistical analysis was performed from October 1, 2022, to June 30, 2023. Main Outcomes and Measures: Children's use of tobacco products was assessed based on youth reports, including lifetime experiences of various nicotine-related products, supplemented with hair toxicologic tests. Main outcomes were children's lifetime experiences of NSSI, SI, and SAs, assessed using the K-SADS-5 (Kiddie Schedule for Affective Disorders and Schizophrenia for the DSM-5). Multivariate logistic regression was conducted to examine the associations of the use of tobacco products with NSSI, SI, and SAs among the study participants. Sociodemographic, familial, and children's behavioral, temperamental, and clinical outcomes were adjusted in the analyses. Results: Of 8988 unrelated study participants (median age, 9.8 years [range, 8.9-11.0 years]; 4301 girls [47.9%]), 101 children (1.1%) and 151 children (1.7%) acknowledged lifetime use of tobacco products at baseline and at 18-month follow-up, respectively. After accounting for various suicide risk factors and potential confounders, children reporting use of tobacco products were at a 3 to 5 times increased risk of SAs (baseline: n = 153 [adjusted odds ratio (OR), 4.67; 95% CI, 2.35-9.28; false discovery rate (FDR)-corrected P < .001]; year 1: n = 227 [adjusted OR, 4.25; 95% CI, 2.33-7.74; FDR-corrected P < .001]; and year 2: n = 321 [adjusted OR, 2.85; 95% CI, 1.58-5.13; FDR-corrected P = .001]). Of all facets of impulsivity measures that were significant correlates of use of tobacco products, negative urgency was the only independent risk factor for SAs (adjusted OR, 1.52 [95% CI, 1.31-1.78]; FDR-corrected P < .001). In contrast, children's alcohol, cannabis, and prescription drug use were not associated with SAs. Conclusions and Relevance: This study of US children suggests that the increased risk of SAs, consistently reported for adolescents and adults who smoke cigarettes, extends to a range of emerging tobacco products and manifests among elementary school-aged children. Further investigations are imperative to clarify the underlying mechanisms and to implement effective preventive policies for children.

Protocol Report on the Transcranial Photobiomodulation for Alzheimer's Disease (TRAP-AD) Study.

BACKGROUND: Alzheimer's disease's (AD) prevalence is projected to increase as the population ages and current treatments are minimally effective. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates into the cerebral cortex, stimulates the mitochondrial respiratory chain, and increases cerebral blood flow. Preliminary data suggests t-PBM may be efficacious in improving cognition in people with early AD and amnestic mild cognitive impairment (aMCI). METHODS: In this randomized, double-blind, placebo-controlled study with aMCI and early AD participants, we will test the efficacy, safety, and impact on cognition of 24 sessions of t-PBM delivered over 8 weeks. Brain mechanisms of t-PBM in this population will be explored by testing whether the baseline tau burden (measured with 18F-MK6240), or changes in mitochondrial function over 8 weeks (assessed with 31P-MRSI), moderates the changes observed in cognitive functions after t-PBM therapy. We will also use changes in the fMRI Blood-Oxygenation-Level-Dependent (BOLD) signal after a single treatment to demonstrate t-PBM-dependent increases in prefrontal cortex blood flow. CONCLUSION: This study will test whether t-PBM, a low-cost, accessible, and user-friendly intervention, has the potential to improve cognition and function in an aMCI and early AD population.

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.

Photobiomodulation: An Emerging Treatment Modality for Depression.

Major depressive disorder (MDD) is considered a global crisis. Conventional treatments for MDD consist of pharmacotherapy and psychotherapy, although a significant number of patients with depression respond poorly to conventional treatments and are diagnosed with treatment-resistant depression (TRD). Transcranial photobiomodulation (t-PBM) therapy uses near-infrared light, delivered transcranially, to modulate the brain cortex. The aim of this review was to revisit the antidepressant effects of t-PBM, with a special emphasis on individuals with TRD. A search on PubMed and ClinicalTrials.gov tracked clinical studies using t-PBM for the treatment of patients diagnosed with MDD and TRD.