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Major depressive disorder (MDD) is a leading cause of disability worldwide with current FDA approved treatments often not providing sustained relief to patients. Transcranial photobiomodulation (tPBM) with near-infrared light (NIR) is a neuromodulation technique that affects mitochondrial metabolism and has shown beneficial clinical outcomes in neurological and psychiatric disorders. At the cellular level tPBM causes various effects including increased oxygen consumption, increased adenosinetriphosphate (ATP) production, and short bursts of reactive oxygen species (ROS). Decreasing oxidative stress through lowering the secondary production of ROS, and increasing neural connectivity, through boosting of neurogenesis and synaptogenesis, as well as increasing energy metabolism are putative mechanisms for tPBM antidepressant effect. Preliminary clinical trials have shown that NIR tPBM is effective at decreasing symptoms of depression compared to sham, however optimal dosimetry is still uncertain. In some reports, the antidepressant effects of tPBM were sustained after treatment discontinuation. Choice of adequate treatment parameters is likely critical to the efficacy and tolerability of tPBM for MDD. General conclusions can be drawn to guide clinicians to the off-label use of tPBM for MDD in clinical practice. [ Psychiatr Ann . 2022;52(11):466–471.]

The 21st century has brought forth major advancements in device-based treatments for psychiatric disorders such as major depressive disorder (MDD). One of the most exciting technologies on the rise in this field is transcranial alternating current stimulation (tACS). The small but rapidly growing body of knowledge on tACS suggests that this wearable, low-cost, noninvasive neuromodulation method could provide a safe and effective alternative, or augmentation, to pharmacological interventions for MDD. While device parameters for treatment of MDD need refinement before this method is ready for standardized clinical use, we expect that tACS will make a significant impact on psychiatric treatment in the coming years. [ Psychiatr Ann . 2022;52(11):456–460.]

Cranial electrotherapy stimulation (CES) is a noninvasive neuromodulation technique that has potential for treating several psychiatric diseases. This method consists of delivering bilateral low-intensity electrical current, via a pair of electrodes, to different anatomical targets around the head. This kind of stimulation is believed to interact with brain oscillation patterns, resulting in changes in connectivity of brain networks. CES has been observed to be a safe intervention with no serious side effects reported in randomized controlled trials. Unequivocal efficiency of CES has not been demonstrated for the treatment of major depressive disorder (MDD); however, some data suggest that CES could be an effective therapy for MDD, either as a standalone or in combination with pharmacological treatment and psychological therapy. CES devices are portable devices that do not required trained personnel to administer the treatment and therefore allow the patients to self-administer the treatment at home. [ Psychiatr Ann . 2022;52(11):461–465.]

Of all home-based and wearable neuromodulation techniques currently in use for treatment of major depressive disorder (MDD), transcranial direct current stimulation (tDCS) has the greatest evidence and efficacy for antidepressant response. The potential of tDCS, given that it is safe, low-cost, portable, and easy to use, is promising. We review clinical trials and meta-analyses on the efficacy of tDCS for MDD, and discuss standard protocols, safety, and side effects. The use of tDCS in bipolar disorder is also explored. Clinicians should fully understand their patient's profile before recommending tDCS, as certain medications, depression subtypes, and age can influence treatment planning and response. [ Psychiatr Ann . 2022;52(11):451–455.]

Background: Major depressive disorder (MDD) is prevalent and has significant impact on individuals and society. Cognitive symptoms are frequent in MDD and insufficiently treated by antidepressant medications. Transcranial photobiomodulation (t-PBM) is a novel device therapy which shows promise as an antidepressant and pro-cognitive treatment. To date, despite the encouraging results, the optimal stimulation parameters of t-PBM to treat MDD are not established, and clinical studies are very heterogeneous in terms of these parameters. While the literature provides guidance on the appropriate fluence to achieve therapeutic results, little is known on the other parameters. Objective: To evaluate the relationship between different parameters and the antidepressant effect of t-PBM. Methods: We reviewed clinical studies on MDD and on depressive symptoms comorbid with other diseases. We calculated the standardized effect size of the change in symptoms severity before and after t-PBM and we performed a descriptive analysis of the reviewed papers. Results: The greatest effect sizes for the antidepressant effect were found in studies using pulse-wave t-PBM with high peak irradiance (but low average irradiance) over large skin surface. One well-designed and sufficiently powered, double-blind, sham-controlled trial indicated that t-PBM with low irradiance over a small skin surface is ineffective to treat depression. Conclusion: The use of t-PBM for Alzheimer’s disease and for dementia is still at its inception; these dosimetry lessons from the use of t-PBM for depression might serve as guidance.

Background: Transcranial photobiomodulation (tPBM) has recently emerged as a potential cognitive enhancement technique and clinical treatment for various neuropsychiatric and neurodegenerative disorders by delivering invisible near-infrared light to the scalp and increasing energy metabolism in the brain. Objective: We assessed whether transcranial photobiomodulation with near-infrared light modulates cerebral electrical activity through electroencephalogram (EEG) and cerebral blood flow (CBF). Methods: We conducted a single-blind, sham-controlled pilot study to test the effect of continuous (c-tPBM), pulse (p-tPBM), and sham (s-tPBM) transcranial photobiomodulation on EEG oscillations and CBF using diffuse correlation spectroscopy (DCS) in a sample of ten healthy subjects [6F/4 M; mean age 28.6±12.9 years]. c-tPBM near-infrared radiation (NIR) (830 nm; 54.8 mW/cm2; 65.8 J/cm2; 2.3 kJ) and p-tPBM (830 nm; 10 Hz; 54.8 mW/cm2; 33%; 21.7 J/cm2; 0.8 kJ) were delivered concurrently to the frontal areas by four LED clusters. EEG and DCS recordings were performed weekly before, during, and after each tPBM session. Results: c-tPBM significantly boosted gamma (t = 3.02, df = 7, p

Low-dose testosterone has been shown to improve depression symptom severity, fatigue, and sexual function in small studies in women not formally diagnosed with major depressive disorder. The authors sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function in women with antidepressant-resistant major depression. A functional MRI (fMRI) substudy examined effects on activity in the anterior cingulate cortex (ACC), a brain region important in mood regulation.The authors conducted an 8-week randomized double-blind placebo-controlled trial of adjunctive testosterone cream in 101 women, ages 21-70, with antidepressant-resistant major depression. The primary outcome measure was depression symptom severity as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. The primary outcome of the fMRI substudy (N=20) was change in ACC activity.The participants' mean age was 47 years (SD=14) and their mean baseline MADRS score was 26.6 (SD=5.9). Eighty-seven (86%) participants completed 8 weeks of treatment. MADRS scores decreased in both study arms from baseline to week 8 (testosterone arm: from 26.8 [SD=6.3] to 15.3 [SD=9.6]; placebo arm: from 26.3 [SD=5.4] to 14.4 [SD=9.3]), with no significant difference between groups. Improvement in fatigue and sexual function did not differ between groups, nor did side effects. fMRI results showed a relationship between ACC activation and androgen levels before treatment but no difference in ACC activation with testosterone compared with placebo.Adjunctive transdermal testosterone, although well tolerated, was not more effective than placebo in improving symptoms of depression, fatigue, or sexual dysfunction. Imaging in a subset of participants demonstrated that testosterone did not result in greater activation of the ACC.

The application of photobiomodulation therapy (PBMT) for neuronal stimulation is studied in different animal models and in humans, and has shown to improve cerebral metabolic activity and blood flow, and provide neuroprotection via anti-inflammatory and antioxidant pathways. Recently, intranasal PBMT (i-PBMT) has become an attractive and potential method for the treatment of brain conditions. Herein, we provide a summary of different intranasal light delivery approaches including a nostril-based portable method and implanted deep-nasal methods for the effective systemic or direct irradiation of the brain. Nostril-based i-PBMT devices are available, using either lasers or light emitting diodes (LEDs), and can be applied either alone or in combination to transcranial devices (the latter applied directly to the scalp) to treat a wide range of brain conditions such as mild cognitive impairment, Alzheimer's disease, Parkinson's disease, cerebrovascular diseases, depression and anxiety as well as insomnia. Evidence shows that nostril-based i-PBMT improves blood rheology and cerebral blood flow, so that, without needing to puncture blood vessels, i-PBMT may have equivalent results to a peripheral intravenous laser irradiation procedure. Up to now, no studies were conducted to implant PBMT light sources deep within the nose in a clinical setting, but simulation studies suggest that deep-nasal PBMT via cribriform plate and sphenoid sinus might be an effective method to deliver light to the ventromedial part of the prefrontal and orbitofrontal cortex. Home-based i-PBMT, using inexpensive LED applicators, has potential as a novel approach for neurorehabilitation; comparative studies also testing sham, and transcranial PBMT are warranted. FS is on the Scientific Advisory Board and consultant of Niraxx Light Therapeutics Inc., and a consultant of ProNeuroLIGHT LLC. TW was supported by the European Union’s Horizon 2020 Research and Innovation Programme, under the Marie Skłodowska-Curie Grant Agreement No 713690, and by the Science Foundation Ireland (SFI) and the European Regional Development Fund (Grant Number 13/RC/2073). PC’s salary was supported by the Harvard Psychiatry Department (Dupont-Warren Fellowship and Livingston Award), by the Brain and Behavior Research Foundation (NARSAD Young Investigator Award) and by the Photothera Inc. unrestricted grant. Drug donation from TEVA. Travel reimbursement from Pharmacia-Upjohn. PC has received consultation fees from Janssen Research and Development. PC has filed a provisional patent related to the use of nearinfrared light in psychiatry. PhotoMedex, Inc. supplied four devices for a clinical study. PC is/has 1. Received unrestricted funding from Litecure Inc. to conduct a study on transcranial photobiomodulation for the treatment of major depressive disorder; 2. Received unrestricted funding from Cerebral Sciences to conduct a study on transcranial photobiomodulation for the treatment of generalized anxiety disorder; 3. Co-founded, member of the board of directors and consultant of Niraxx Light Therapeutics Inc., a company focused on the development of new modalities of treatment based on near-infrared light. MRH was supported by US NIH Grants R01AI050875 and R21AI121700. MRH is on the following Scientific Advisory Boards: Transdermal Cap Inc., Cleveland, - 25 - OH, United States; Photothera Inc., Carlsbad, CA, United States; BeWell Global Inc., Wan Chai, Hong Kong; Hologenix Inc. Santa Monica, CA, United States; LumiThera, Inc., Poulsbo, WA, United States; Vielight, Toronto, ON, Canada; Bright Photomedicine, São Paulo, Brazil; Quantum Dynamics LLC, Cambridge, MA, United States; Global Photon Inc, Bee Cave, TX, United States; Medical Coherence, Boston MA, United States; NeuroThera, Newark, DE, United States; JOOVV Inc., Minneapolis–Saint Paul, MN, United States; AIRx Medical, Inc., Pleasanton, CA, United States; FIR Industries, Inc., Ramsey, NJ, United States; UVLRx Therapeutics, Oldsmar, FL, United States; Ultralux UV Inc, Lansing, MI, United States; Illumiheal & Petthera, Shoreline, WA, United States; MB Laser Therapy, Houston, TX, United States. MRH has been a Consultant for: Lexington int., Boca Raton, FL, United States; USHIO Corp., Japan; Merck KGaA, Darmstadt, Germany; Philips Electronics Nederland B.V.; Johnson & Johnson Inc., Philadelphia, PA; Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany. MRH is a Stockholder in Global Photon Inc., Bee Cave, TX, United States and Mitonix, Newark, DE, United States. JOD was a paid business consultant for ProNeuroLIGHT LLC, Kerrville, TX, USA. The other authors have no conflicts of interest to disclose. peer-reviewed

Kleine-Levin syndrome (KLS) is a rare neuropsychiatric disorder, characterized by recurrent episodes of idiopathic hypersomnia, and cognitive and behavioral abnormalities, such as memory loss and child-like language. There is no definitive etiology for KLS; however, there are hypotheses of genetic predisposition, autoimmune mechanisms, and abnormal thalamic and hypothalamic functioning. Similarly, there is no definitive treatment for KLS as one method may be beneficial for one patient and not for another. We present a case of KLS in a patient who has no clinical improvement in symptoms with a variety of treatments. The parents of the patient agreed to attempt a trial of intranasal photobiomodulation (i-PBM) with red light, in combination with methylene blue (MB). The patient showed remission of the KLS episode following treatment with no further KLS episodes reported after treatment.

Background and objective: Photobiomodulation (PBM) therapy is a promising and noninvasive approach to stimulate neuronal function and improve brain repair. The optimization of PBM paramete...

Background: Transcranial photobiomodulation (t-PBM) is a noninvasive modality that may improve cognitive function in both healthy and diseased subjects. Objective: This systematic review and meta-analysis addresses the question of whether t-PBM improves cognitive function in healthy adults. Methods: We searched MEDLINE using PubMed, EMBASE, SCOPUS, Web of Science, and Cochrane Library up to March 2019. We also searched ProQuest and Google Scholar databases for unpublished material. The search was limited to articles on the procognitive effects of t-PBM in healthy adults. The initial search resulted in 871 studies, of which nine publications met our criteria for inclusion and exclusion. Seven studies were performed on young, healthy subjects (17–35 years), and two studies were conducted on older (≥49 years), normal subjects. A meta-analysis was performed on six full-text publications whose subjects were young adults. Results: t-PBM administration improved cognition-related outcomes by an 0.833 standardized mean difference (SMD; 95% confidence interval (CI): 0.458–1.209, 14 comparisons) in young, healthy participants. Funnel plotting revealed asymmetry, which was validated using Egger's (p = 0.030) and Begg's regression (p = 0.006) tests. However after reanalysis, this asymmetry disappeared in the attention subgroup, but not in the memory subgroup. The trim-and-fill analysis indicated two studies were lacking required data. Thus, the effect size was adjusted from an SMD of 0.761 (95% CI: 0.573–0.949) to 0.949 (0.779–1.120). The overall quality score of the studies was modest. Conclusions: We demonstrated a significant, beneficial effect of t-PBM on cognitive performance of young, healthy individuals; however, the heterogeneity of the data was high. This could be due to the modest quality or to the low number of included studies, or to the differences between the various subdomains assessed. These shortcomings should be meticulously addressed before concluding that t-PBM is a cognitive-enhancing intervention in healthy individuals.

Background Photobiomodulation (PBM) with red and near-infrared light (NIR) –also known as Low-Level Light Therapy–is a low risk, inexpensive treatment–based on non-retinal exposure–under study for several neuropsychiatric conditions. The aim of this paper is to discuss the proposed mechanism of action and to perform a systematic review of pre-clinical and clinical studies on PBM for major depressive disorder (MDD). Methods A search on MEDLINE and EMBASE databases was performed in July 2017. No time or language restrictions were used. Studies with a primary focus on MDD and presenting original data were included (n = 17). References on the mechanisms of action of PBM also included review articles and studies not focused on MDD. Results Red and NIR light penetrate the skull and modulate brain cortex; an indirect effect of red and NIR light, when delivered non-transcranially, is also postulated. The main proposed mechanism for PBM is the enhancement of mitochondrial metabolism after absorption of NIR energy by the cytochrome C oxidase; however, actions on other pathways relevant to MDD are also reported. Studies on animal models indicate a benefit from PBM that is comparable to antidepressant medications. Clinical studies also indicate a significant antidepressant effect and good tolerability. Limitations Clinical studies are heterogeneous for population and treatment parameters, and most lack an appropriate control. Conclusions Preliminary evidence supports the potential of non-retinal PBM as a novel treatment for MDD. Future studies should clarify the ideal stimulation parameters as well as the overall efficacy, effectiveness and safety profile of this treatment.

BACKGROUND Telehealth has provided many researchers, especially those conducting psychosocial research, with the tools necessary to transition from in-person to remote clinical trials during the COVID-19 pandemic. A growing body of research supports the effectiveness of telemental health for a variety of psychiatric conditions, but few studies have examined telemental health for individuals with comorbid medical diagnoses. Furthermore, little is known about the remote implementation of clinical trials examining telemental health interventions. OBJECTIVE This paper outlines the procedural modifications used to facilitate conversion of an in-person randomized controlled trial of cognitive behavioral therapy (CBT) for depression in individuals with traumatic brain injury (TBI; CBT-TBI) to a telemental health study administered remotely. METHODS Given the nature of remote implementation and specific challenges experienced by individuals with TBI, considerations related to treatment delivery, remote consent, data management, neuropsychological assessment, safety monitoring, and delivery of supportive material have been discussed. Feasibility, acceptability, and safety were evaluated by examining attendance and participant responses on self-report measures of treatment satisfaction and suicidal behavior. RESULTS High rates of treatment attendance, assessment completion, study retention, and satisfaction with the intervention and modality were reported by participants who completed at least one telemental health CBT-TBI session. CONCLUSIONS Study modifications are necessary when conducting a study remotely, and special attention should be paid to comorbidities and population-specific challenges (eg, cognitive impairment). Preliminary data support the feasibility, acceptability, and safety of remotely conducting a randomized controlled trial of CBT-TBI. CLINICALTRIAL ClinicalTrials.gov NCT03307070; https://clinicaltrials.gov/ct2/show/NCT03307070

Background Evidence-based pharmacological treatments for posttraumatic stress disorder (PTSD) are few and of limited efficacy. Previous work suggests that angiotensin type 1 receptor inhibition facilitates fear inhibition and extinction, important for recovery from PTSD. This study tests the efficacy of the angiotensin type 1 receptor antagonist losartan, an antihypertensive drug, repurposed for the treatment of PTSD. Methods A randomized controlled trial was conducted for 10 weeks in 149 men and women meeting DSM-5 PTSD criteria. Losartan (vs. placebo) was flexibly titrated from 25 to 100 mg/day by week 6 and held at highest tolerated dose until week 10. Primary outcome was the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) change score at 10 weeks from baseline. A key secondary outcome was change in CAPS-5 associated with a single nucleotide polymorphism of the ACE gene. Additional secondary outcomes included changes in the PTSD Checklist for DSM-5 and the Patient Health Questionnaire-9, and proportion of responders with a Clinical Global Impressions–Improvement scale of “much improved” or “very much improved.” Results Both groups had robust improvement in PTSD symptoms, but there was no significant difference on the primary end point, CAPS-5 measured as week 10 change from baseline, between losartan and placebo (mean change difference, 0.9, 95% confidence interval, −3.2 to 5.0). There was no significant difference in the proportion of Clinical Global Impressions–Improvement scale responders for losartan (58.6%) versus placebo (57.9%), no significant differences in changes in PTSD Checklist for DSM-5 or Patient Health Questionnaire-9, and no association between ACE genotype and CAPS-5 improvement on losartan. Conclusions At these doses and durations, there was no significant benefit of losartan compared with placebo for the treatment of PTSD. We discuss implications for failure to determine the benefit of a repurposed drug with strong a priori expectations of success based on preclinical and epidemiological data.

Major depressive disorder (MDD) is associated with prefrontal hypometabolism and mitochondrial dysfunction. Photobiomodulation (PBM) is a novel treatment under development for MDD. PBM uses near-infrared (NIR) or red light to modulate metabolism and functioning of different tissues and organs, including the brain. NIR and red light are nonionizing electromagnetic irradiations and can be delivered by noninvasive procedures. Most PBM studies evaluated the direct effect of light on the brain when it is delivered transcranially (t-PBM). However, an indirect effect has also been proposed when light is delivered to other parts of the body (other than the head). The suggested primary mechanism of action of PBM for MDD is the absorption of light energy by a mitochondrial enzyme, the cytochrome C oxidase, resulting in the increase of adenosine triphosphate production. Initial evidence on PBM for MDD indicates it is a safe and effective treatment option.

Objective: Nonresponse to selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor treatment is common in patients with major depressive disorder (MDD), particularly in women, occurring in about 70% of patients despite adequate dosing. Well-tolerated augmentation strategies are needed, particularly ones that do not cause or exacerbate symptoms such as fatigue and sexual dysfunction. Low-dose testosterone has been shown to improve depression symptom severity, fatigue and sexual function in small studies of women not formally diagnosed with MDD. We sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function in women with treatment-resistant MDD. A functional MRI (fMRI) substudy examined effects of testosterone on activity in the anterior cingulate cortex (ACC), a brain region important in mood regulation. Methods: Randomized, double-blind, placebo-controlled, 8-week trial of adjunctive testosterone cream (AndroFeme® 1, Lawley Pharmaceuticals, Australia) in 101 women, ages 21–70, with treatment-resistant MDD. Testosterone was titrated to achieve blood levels near the upper normal reference limit. Primary outcome measure was depression severity by Montgomery-Asberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. fMRI substudy (n=20) primary outcome was change in ACC activity. Results: Mean age was 47±14 (SD) years and mean baseline MADRS score was 26.6±5.9. Eighty-seven (86%) participants completed 8 weeks of treatment. MADRS depression scores decreased in both arms [testosterone: 26.8±6.3 to 15.3±9.6; placebo: 26.3±5.4 to 14.4±9.3 (baseline to 8 weeks, respectively)], with no difference between groups (p=0.91). Fatigue and sexual function improved without differences between groups. There were no group differences in side effects. fMRI results demonstrated a relationship between ACC activation and androgen levels pretreatment but no difference in ACC activation with treatment. Conclusions: This rigorously designed, double-blinded clinical trial did not find significant group differences between adjunctive low dose transdermal testosterone and placebo for antidepressant augmentation in women with treatment-resistant MDD and had a high placebo response rate. Low-dose testosterone was well tolerated but failed to differentially impact overall depressive symptom severity, fatigue, or sexual dysfunction. Testosterone did not result in greater activity in a brain region (ACC) implicated in MDD etiopathology compared to placebo. Thus, the addition of low-dose testosterone to ineffective antidepressant treatment should not be recommended for women with MDD. Further studies using strategies designed to reduce placebo effects may be warranted.

SignificanceMajor depressive disorder (MDD) affects over 40 million US adults in their lifetimes. Transcranial photobiomodulation (t-PBM) has been shown to be effective in treating MDD, but the current treatment dosage does not account for anatomical head and brain changes due to aging.AimWe study effective t-PBM dosage and its variations across age groups using state-of-the-art Monte Caxrlo (MC) simulations and age-dependent brain atlases ranging between 5 to 85 years of age.ApproachAge-dependent brain models are derived from 18 MRI brain atlases. Two extracranial source positions, F3-F4 and Fp1-Fpz-Fp2 in the EEG 10-20 system, are simulated at five selected wavelengths and energy depositions at two MDD-relevant cortical regions – dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) – are quantified.ResultsAn overall decrease of energy deposition was found with increasing age. A strong negative correlation between the thickness of extra-cerebral tissues (ECT) and energy deposition, suggesting that increasing ECT thickness over age is primarily responsible for reduced energy delivery. The F3-F4 position appears to be more efficient in reaching dlPFC compared to treating vmPFC via the Fp1-Fpz-Fp2 position.ConclusionQuantitative simulations revealed age-dependent light delivery across the lifespan of human brains, suggesting the needs for personalized and age-adaptive t-PBM treatment planning.

We performed 3-D Monte Carlo simulations to investigate the light dosage of transcranial photobiomodulation (t-PBM) across lifespan. An overall decrease in energy deposition was found as a result of increasing thicknesses of the extra-cerebral tissues.

Photobiomodulation also called “low-level light therapy” or “low-level laser therapy” is a novel device-based treatment used in a variety of conditions including muscle pain, wounds, neuropathic pain, headache, periorbital wrinkles, and alopecia and is currently under investigation for different psychiatric conditions, including anxiety disorders.

ObjectiveOur objective was to assess whether transcranial photobiomodulation (tPBM) with near-infrared light (NIR) shows modulatory effects on cerebral electrical activity through electroencephalogram (EEG) and cerebral blood flow (CBF).BackgroundtPBM has emerged as a novel intervention for several neuropsychiatric conditions due to its neuroprotective and neuroenhancement effects.MethodsWe conducted a single-blind, sham-controlled pilot study to test the effect of continuous (c-tPBM), pulse (p-tPBM) and sham (s-tPBM) transcranial photobiomodulation on EEG oscillations and CBT using diffuse correlation spectroscopy (DCS) in a sample of ten healthy subjects [6 F/ 4 M; mean age 28.6 ± 12.9 (SD) years]. c-tPBM NIR (830 nm; 54.8 mW/cm²; 65.8 J/cm²; 2.3 kJ) and p-tPBM (830 nm; 10Hz; 54.8 mW/cm²; 33%; 21.7 J/cm²; 0.8 kJ) were delivered concurrently to the frontal areas (F4, Fp2, Fp1, F3 - total surface 35.8 cm²) by four LED clusters (TPBM-1000 Litecure). EEG and DCS recordings were performed weekly before, during, and after each tPBM session (in sequence: c-tPBM, s-tPBM and p-tPBM).ResultsOnly c-tPBM significantly boosted gamma (t = 3.02, df = 7, p < .02) and beta (t = 2.91, df = 7, p < .03) EEG spectral powers in eyes-open recordings and gamma power (t = 3.61, df = 6, p < .015) in eyes-closed recordings, with the largest effects in the posterior regions. There was no significant effect of NIR-tPBM on CBF compared to sham.ConclusionsOur data suggest a dose-dependent effect of tPBM with NIR (c-tPBM) on cerebral gamma and beta neuronal activity. Altogether, our findings support the neuromodulatory effect of transcranial NIR.

Background Heavy episodic drinking (HED) is a common behavior among college students that is associated with severe negative consequences. Negative reinforcement processes have been applied to elucidate mechanisms underlying relationships between consumption of alcohol and the desire to alleviate negative feelings. Distress tolerance (DT) and emotional reactivity are two mechanisms that are consistent with the self-medication model that may contribute to HED. The current study investigated relationships between DT, emotional reactivity, defined as frustration reactivity and irritability reactivity, and HED in a non-depressed college population. Given differential patterns of consumption and motivation for drinking between males and females, sex differences were also examined. Short summary The study examined two constructs consistent with negative reinforcement processes, behavioral distress tolerance (DT) and emotional reactivity (frustration reactivity and irritability reactivity), to explain heavy episodic drinking (HED) among non-depressed college students. Behavioral DT and frustration reactivity independently predicted HED. Higher HED was associated with higher frustration reactivity and lower behavioral DT in women, but nor in men. Methods One-hundred-ten college students without depressive symptoms completed alcohol use measures and the Paced Auditory Serial Attention Task (PASAT-C) to assess behavioral DT and emotional reactivity. Results DT and frustration reactivity independently predicted HED. The association between DT and HED was moderated by sex such that higher levels of DT predicted higher HED among females, but not among males. Higher frustration reactivity scores were associated with a greater number of HED. Conclusions Results provide supporting evidence that DT and emotional reactivity are distinct factors, and that they predict HED independently. Results underscore the importance of examining sex differences when evaluating the association between HED and negative reinforcement processes in this population.

Background and aims To present incidental findings in patients with low back pain (LBP) who received photobiomodulation (PBM) administered to the back and thighs as an adjunct to physical therapy (PT) and then experienced improvement in concurrent depression. Materials and methods Five outpatients with LBP and concurrent self-reported depression were treated for LBP over five weeks with PT (5-sessions) and concurrent PBM (final 3-sessions), and retrospectively matched to five control patients treated with PT alone (5-sessions). The PBM device emitted light at 850nm and 660 nm with an irradiance of 100 mW/cm2 and fluence of 3 J/cm2 on 12 symmetrical posterior sites (thoracic, lumbar and thighs) for 30 sec/site. Results Both groups had non-significant differences in all baseline scores, except for higher functional status (ARGS) in the PBM-group (33.6 ± 12.2 vs.18.6 ± 3.6, t(8) = 2.638, p = 0.030). After treatment, the mean decrease in depression scores (OMSQ-12 item #6) was significantly larger in the PBM-group (43.0 ± 22.0 vs. 8.0 ± 5.7, t(8) = 3.449, p = 0.009). Improvement in functional status (ARGS) in the PBM-group was similar to that in the controls (42.0 ± 13.5 vs. 43.4 ± 11.1, t(8) = 0.179, p = 0.862), suggesting group differences in antidepressant effect were independent of functional status improvement. Conclusions This preliminary investigation suggests that an antidepressant effect may result from PBM to the back and thighs in patients with LBP and concurrent depression.

Background Telehealth has provided many researchers, especially those conducting psychosocial research, with the tools necessary to transition from in-person to remote clinical trials during the COVID-19 pandemic. A growing body of research supports the effectiveness of telemental health for a variety of psychiatric conditions, but few studies have examined telemental health for individuals with comorbid medical diagnoses. Furthermore, little is known about the remote implementation of clinical trials examining telemental health interventions. Objective This paper outlines the procedural modifications used to facilitate conversion of an in-person randomized controlled trial of cognitive behavioral therapy (CBT) for depression in individuals with traumatic brain injury (TBI; CBT-TBI) to a telemental health study administered remotely. Methods Given the nature of remote implementation and specific challenges experienced by individuals with TBI, considerations related to treatment delivery, remote consent, data management, neuropsychological assessment, safety monitoring, and delivery of supportive material have been discussed. Feasibility, acceptability, and safety were evaluated by examining attendance and participant responses on self-report measures of treatment satisfaction and suicidal behavior. Results High rates of treatment attendance, assessment completion, study retention, and satisfaction with the intervention and modality were reported by participants who completed at least one telemental health CBT-TBI session. Conclusions Study modifications are necessary when conducting a study remotely, and special attention should be paid to comorbidities and population-specific challenges (eg, cognitive impairment). Preliminary data support the feasibility, acceptability, and safety of remotely conducting a randomized controlled trial of CBT-TBI. Trial Registration ClinicalTrials.gov NCT03307070; https://clinicaltrials.gov/ct2/show/NCT03307070

Background: Transcranial photobiomodulation (t-PBM) consists in the delivery of near-infrared light (NIR) to the scalp, directed to cortical areas of the brain. NIR t-PBM recently emerged ...

Objective: Our aim was to test the anxiolytic effect of transcranial photobiomodulation (t-PBM) with near-infrared light (NIR) in subjects suffering from generalized anxiety disorder (GAD). Background: t-PBM with NIR is an experimental, noninvasive treatment for mood and anxiety disorders. Preliminary evidence indicates a potential anxiolytic effect of transcranial NIR. Methods: Fifteen subjects suffering from GAD were recruited in an open-label 8-week study. Each participant self-administered t-PBM daily, for 20 min (continuous wave; 830 nm peak wavelength; average irradiance 30 mW/cm(2); average fluence 36 J/cm(2); total energy delivered per session 2.9 kJ: total output power 2.4 W) broadly on the forehead (total area 80 cm(2)) with an LED-cluster headband (Cerebral Sciences). Outcome measures were the reduction in total scores of the Hamilton Anxiety Scale (SIGH-A), the Clinical Global Impressions-Severity (CGI-S) subscale and the Pittsburgh Sleep Quality Index (PSQI) subscales from baseline to last observation carried forward. Results: Of the 15 recruited subjects (mean age 30 ± 14 years; 67% women), 12 (80%) completed the open trial. Results show a significant reduction in the total scores of SIGH-A (from 17.27 ± 4.89 to 8.47 ± 4.87; p

Transcranial photobiomodulation (t-PBM) with red and near-infrared light (NIR)—also known as low-level light therapy—is a low risk, inexpensive treatment—based on nonretinal exposure—under study for several neuropsychiatric conditions. Red and NIR light penetrate the skull and modulate brain cortex. The main proposed mechanism for PBM is the enhancement of mitochondrial metabolism after absorption of NIR energy by the cytochrome C oxidase. Actions on other pathways relevant to major depressive disorder (MDD), to anxiety disorders and to posttraumatic stress disorder (PTSD) are also reported. Clinical studies indicate a significant antidepressant and anxiolytic effect and good tolerability. However, clinical studies are heterogeneous for population and treatment parameters, and most lack an appropriate control. Future studies should clarify the ideal stimulation parameters as well as the overall efficacy, effectiveness, and safety profile of this treatment for MDD, anxiety disorders, and PTSD.