a-protocol-for-transcranial-photobiomodulation-therapy-in-mice

A Protocol for Transcranial Photobiomodulation Therapy in Mice

Transcranial photobiomodulation is a potential innovative noninvasive therapeutic approach for improving brain bioenergetics, brain function in a wide ...

Harvard Medical School

Massachusetts General Hospital

The objective of this study was to examine the efficacy and tolerability of intermittent dosing of venlafaxine for the treatment of premenstrual dysphoric disorder. One hundred and twenty-four women aged 18 to 45 years, with regular menstrual cycles and who reported significant premenstrual symptoms, were assessed prospectively to confirm their diagnosis of premenstrual dysphoric disorder. Twenty subjects with confirmed premenstrual dysphoric disorder entered a single-blind, placebo phase (1 cycle). Placebo nonresponders (n = 12) received 2 cycles of intermittent (premenstrual) treatment with venlafaxine (75 to 112.5 mg/d). Subjects initiated treatment 14 days before the anticipated onset of menses and discontinued it on the second day of bleeding. Doses could be adjusted after cycle 1 based on subjects' response and tolerability. Response to treatment was assessed based on changes in the Daily Rating Severity of Problems and Premenstrual Tension Syndrome Questionnaire scores from baseline (before the placebo cycle), as well as Clinical Global Impression-Severity scores. Discontinuation symptoms were assessed between treatment cycles, using the Discontinuation-Emergent Signs and Symptoms questionnaire. Eleven subjects concluded 2 cycles of intermittent dosing with venlafaxine. Nine subjects (81.8%) showed satisfactory response based on Clinical Global Impression of < or = 2. Changes in Daily Rating Severity of Problems scores and subscores (depression, physical symptoms, and anger) and in Premenstrual Tension Syndrome Questionnaire scores were significant (P < 0.05 for all comparisons, Wilcoxon tests). Intermittent treatment was well tolerated. This preliminary report suggests that premenstrual use of venlafaxine is an efficacious and well-tolerated treatment for premenstrual dysphoric disorder.

Efficacy and tolerability of premenstrual use of venlafaxine (flexible dose) in the treatment of premenstrual dysphoric disorder.

Previous reports of increased rates of cardiovascular risk factors in major depressive disorder (MDD) with anger attacks led the authors to hypothesize that MDD with anger attacks may be associated with brain vascular changes (magnetic resonance imaging white matter hyperintensities [WMHs]). Sixty-five subjects meeting DSM-III-R criteria for major depressive disorder were administered brain magnetic resonance imaging scans at 1.5T to detect T2 WMH. The severity of brain WMH was classified with the Fazekas scale. We used standardized scales to assess melancholic MDD, atypical MDD, and MDD with anger attacks. In logistic regression analyses, MDD with anger attacks was associated with higher severity of subcortical WMH and of total WMH, but not with periventricular WMH. Atypical and melancholic MDD subtypes were not significantly associated with brain WMH. In conclusion, subcortical brain vascular lesions may be more prevalent or severe in MDD with anger attacks.

Major depressive disorder with anger attacks and subcortical MRI white matter hyperintensities.

Traumatic brain injury (TBI) is a growing health concern affecting civilians and military personnel. In this review, treatments for the chronic TBI patient are discussed, including pharmaceuticals, nutraceuticals, cognitive therapy, and hyperbaric oxygen therapy. All available literature suggests a marginal benefit with prolonged treatment courses. An emerging modality of treatment is near-infrared (NIR) light, which has benefit in animal models of stroke, spinal cord injury, optic nerve injury, and TBI, and in human trials for stroke and TBI. The extant literature is confounded by variable degrees of efficacy and a bewildering array of treatment parameters. Some data indicate that diodes emitting low-level NIR energy often have failed to demonstrate therapeutic efficacy, perhaps due to failing to deliver sufficient radiant energy to the necessary depth. As part of this review, we present a retrospective case series using high-power NIR laser phototherapy with a Class IV laser to treat TBI. We demonstrate greater clinical efficacy with higher fluence, in contrast to the bimodal model of efficacy previously proposed. In ten patients with chronic TBI (average time since injury 9.3 years) given ten treatments over the course of 2 months using a high-power NIR laser (13.2 W/0.89 cm(2) at 810 nm or 9 W/0.89 cm(2) at 810 nm and 980 nm), symptoms of headache, sleep disturbance, cognition, mood dysregulation, anxiety, and irritability improved. Symptoms were monitored by depression scales and a novel patient diary system specifically designed for this study. NIR light in the power range of 10-15 W at 810 nm and 980 nm can safely and effectively treat chronic symptoms of TBI. The clinical benefit and effects of infrared phototherapy on mitochondrial function and secondary molecular events are discussed in the context of adequate radiant energy penetration. 

Treatments for traumatic brain injury with emphasis on transcranial near-infrared laser phototherapy.

We compared treatment response (≥50 decrease in Nine-Item Patient Health Questionnaire total score) among 24 Latinos with major depressive disorder, presenting with and without specific psychosislike symptoms: A, hearing noises or house sounds, B, hearing voices calling one's name, C, seeing fleeting visions such as shadows, and D, symptoms more likely to be truly psychotic (e.g., poorly defined and short-lasting voices [other than B], fleeting paranoid ideation, or fleeting ideas of reference). 18 subjects (75%) endorsed symptoms of cluster A, 12 (50%) of cluster B, 10 (31%) of cluster C, and 12 (50%) of cluster D. Only subjects who reported symptoms from the D cluster exhibited significantly unfavorable depressive outcomes (compared to those with absence of D symptoms). The authors propose a phenomenological differentiation between benign psychosislike symptoms (clusters A-C) and the expression of the psychotic continuum (cluster D) in depressed Latinos. 

Treatment Outcome in Depressed Latinos Predicted by Concomitant Psychosislike Symptoms.

We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: "near-infrared radiation," "NIR," "low-level light therapy," "low-level laser therapy," or "LLLT" plus "depression." We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD.

Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis.

Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown.

Rapid and Sustained Reductions in Current Suicidal Ideation Following Repeated Doses of Intravenous Ketamine: Secondary Analysis of an Open-Label Study.

Long-Term Near-Infrared Photobiomodulation for Anxious Depression Complicated by Takotsubo Cardiomyopathy.

This study examined whether a culturally focused psychiatric consultation program (CFP) for Latino Americans was equally effective in reducing depressive symptoms in English-speaking and Spanish-speaking patients.

Patient primary language in a culturally focused intervention for Latino Americans with depression.

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.

Sex Differences in the Association between Heavy Drinking and Behavioral Distress Tolerance and Emotional Reactivity Among Non-Depressed College Students.

Our objective was to test the antidepressant effect of transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light in subjects suffering from major depressive disorder (MDD).

Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial.

This study was aimed to evaluate the effects of near-infrared (NIR) photobiomodulation (PBM) combined with coenzyme Q (CoQ) on depressive-like behavior, cerebral oxidative stress, inflammation, and apoptosis markers in mice. To induce a depressive-like model, mice were subjected to sub-chronic restraint stress for 5 consecutive days. NIR PBM (810 nm laser, 33.3 J/cm) and/or CoQ (500 mg/kg/day, gavage) were administered for five days concomitantly with immobilization. Behavior was evaluated by the forced swim test (FST), tail suspension test (TST), and open field test (OFT). Mitochondrial membrane potential as well as oxidative stress, neuroinflammatory, and markers of apoptosis were evaluated in the prefrontal cortex (PFC) and hippocampus (HIP). The serum levels of pro-inflammatory cytokines, cortisol, and corticosterone were also measured. PBM or CoQ, or the combination, ameliorated depressive-like behaviors induced by restraint stress as indicated by decreased immobility time in both the FST and TST. PBM and/or CoQ treatments decreased lipid peroxidation and enhanced total antioxidant capacity (TAC), GSH levels, GPx and SOD activities in both brain areas. The neuroinflammatory response in the HIP and PFC was suppressed, as indicated by decreased NF-kB, p38, and JNK levels in PBM and/or CoQ groups. Intrinsic apoptosis biomarkers, BAX, Bcl-2, cytochrome c release, and caspase-3 and -9, were also significantly down-regulated by both treatments. Furthermore, both treatments decreased the elevated serum levels of cortisol, corticosterone, TNF-, and IL-6 induced by restraint stress. Transcranial NIR PBM and CoQ therapies may be effective antidepressant strategies for the prevention of psychopathological and behavioral symptoms induced by stress.

Near-Infrared Photobiomodulation Combined with Coenzyme Q for Depression in a Mouse Model of Restraint Stress: Reduction in Oxidative Stress, Neuroinflammation, and Apoptosis.

Article	Year
Efficacy and tolerability of premenstrual use of venlafaxine (flexible dose) in the treatment of premenstrual dysphoric disorder. Journal of clinical psychopharmacology\| PubMed ID: 15349012	2004
Major depressive disorder with anger attacks and subcortical MRI white matter hyperintensities. The Journal of nervous and mental disease\| PubMed ID: 17299307	2007
Treatments for traumatic brain injury with emphasis on transcranial near-infrared laser phototherapy. Neuropsychiatric disease and treatment\| PubMed ID: 26347062	2015
Treatment Outcome in Depressed Latinos Predicted by Concomitant Psychosislike Symptoms. The Journal of nervous and mental disease\| PubMed ID: 26356091	2015
Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis. Neurophotonics\| PubMed ID: 26989758	2016
Rapid and Sustained Reductions in Current Suicidal Ideation Following Repeated Doses of Intravenous Ketamine: Secondary Analysis of an Open-Label Study. The Journal of clinical psychiatry\| PubMed ID: 27232360	2016
Long-Term Near-Infrared Photobiomodulation for Anxious Depression Complicated by Takotsubo Cardiomyopathy. Journal of clinical psychopharmacology\| PubMed ID: 29601319	2018
Patient primary language in a culturally focused intervention for Latino Americans with depression. Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists\| PubMed ID: 29697708	2018
Sex Differences in the Association between Heavy Drinking and Behavioral Distress Tolerance and Emotional Reactivity Among Non-Depressed College Students. Alcohol and alcoholism (Oxford, Oxfordshire)\| PubMed ID: 29947730	2018
Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial. Photomedicine and laser surgery\| PubMed ID: 30346890	2018
Near-Infrared Photobiomodulation Combined with Coenzyme Q for Depression in a Mouse Model of Restraint Stress: Reduction in Oxidative Stress, Neuroinflammation, and Apoptosis. Brain research bulletin\| PubMed ID: 30385146	2018

Paolo Cassano

Biography

JoVE Journal Publications

Other Publications