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Transcranial Photobiomodulation to Augment Lithium in Bipolar-I Disorder

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... 36,37 One pilot with 4 patients diagnosed with BD I showed that PBM could successfully augment lithium therapy. 38 Lastly, PBM using TILS has also shown beneficial effects in individuals with cognitive complaints, such as improved reaction time and accuracy. 25 One PBM study in individuals with mild cognitive impairment (MCI) found improved cognitive scores, sleep, anxiety, affect, and quality of life measures, 39 while another study on individuals with MCI showed improved executive functioning, clock drawing, immediate recall, praxis memory, visual attention, and task switching, as well as a trend of improved EEG amplitude and connectivity measures. ...
... 3,10,75-79 These modalities have been standardized and validated as proper instruments to understand differences in cerebral energy metabolism and hemodynamics between adults with BD and healthy age-matched controls. Given that PBM has been shown to augment lithium therapy in patients with BD I, 38 future studies should explore the use of PBM as an adjunct therapy for BD together with pharmacological intervention. ...
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This is the first study to examine if transcranial infrared laser stimulation (TILS) improves cognition in older euthymic bipolar patients, who exhibit greater cognitive decline than is expected for age-matched controls. TILS is a non-invasive novel form of photobiomodulation that augments prefrontal oxygenation and improves cognition in young adults by upregulating the mitochondrial respiratory enzyme cytochrome-c-oxidase. We used a crossover sham-controlled design to examine if TILS to bilateral prefrontal cortex produces beneficial effects on cognition in 5 euthymic bipolar patients (ages 60-85). We measured cognitive flexibility, verbal fluency, working memory, sustained attention and impulsivity with tasks that have been shown to differentiate between healthy older adults and older bipolar adults. We found TILS-induced improvements in cognitive performance on the tasks that measure cognitive flexibility and impulsivity, after 5 weekly sessions of TILS. We concluded that TILS appeared both safe and effective in helping alleviate the accelerated cognitive decline present in older bipolar patients.
... Another pilot case series study from our MGH lab [88] showed a promising beneficial effect of transcranial NIR PBM therapy on sexual function in four patients with type-I bipolar disorder. All patients were white non-Hispanic, and two were female; their average age was 38.5 ± 13 years. ...
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Sexual dysfunction (SD) is frequently encountered in patients suffering from depression. There is a bidirectional relationship between various types of SD and depression, so the presence or treatment of one condition may exacerbate or improve the other condition. The most frequent sexual problem in untreated depressed patients is declining sexual desire, while in treated depressed patients it is difficulties with erection/ejaculation and with orgasm. Numerous classes of neuropsychiatric medications, commonly used in depressed patients—such as antidepressant, antipsychotic, alpha sympathetic, and opioid drugs—may cause SD. Photobiomodulation (PBM) therapy, also called low-level light/laser therapy, is a novel neuromodulation technique for neuropsychiatric conditions, such as depression. Transcranial PBM (tPBM) targets the cellular metabolism—through the mitochondrial respiratory enzyme, cytochrome c oxidase—and has numerous cellular and physiological beneficial effects on the central nervous system. This paper represents a comprehensive review of the application of tPBM to SD, coexisting with depression or induced by antidepressant medications.
... Recently, Maiello et al. (2019) carried out a pilot study to evaluate the anxiolytic effects of PBMT, and their results showed anxiety reduction and sleep improvement. At the same time, Mannu et al. (2019) applied this therapy in patients diagnosed with bipolar disorder and found anhedonia reductions along with increases in libido and improvements in sleep, anxiety, impulsivity, and irritability. Chao (2019) used LEDs to treat two patients diagnosed with Gulf War Syndrome, characterized by the presence of multiple concurrent symptoms, including headaches, joint pain, gastrointestinal problems, fatigue, and even cognitive problems. ...
Article
Photobiomodulation is a brain modulation technique that has become a promising treatment for multiple pathologies. This systematic review collects studies up to 2019 about the beneficial effects of photobiomodulation as a therapy for treating psychological disorders and a tool for modulating cognitive processes. This technique is mostly used for the treatment of depression and stress, as well as to study its effects on psychological variables in healthy subjects. Despite the lack of parameters used, photobiomodulation seems to achieve enough brain penetration to produce beneficial effects in healthy subjects and patients with multiple pathologies. The best parameters are the wavelengths of 810 nm for the treatment of depression and 1064 nm for cognitive enhancement, along with a scalp irradiance of 250 mW/cm² and a scalp yield of 60 J/cm². It weekly application on the bilateral prefrontal area and the default mode network seems to be ideal for the maintenance of the effects. Photobiomodulation could be used as an effective and safe therapy for the treatment of multiple psychological pathologies.
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Transcranial near-infrared radiation (NIR) is an innovative treatment for major depressive disorder (MDD), but clinical evidence for its efficacy is limited. Our objective was to investigate the tolerability and efficacy of NIR in patients with MDD. We conducted a proof of concept, prospective, double-blind, randomized study of 6 sessions of NIR versus sham treatment for patients with MDD, using a crossover design. Four patients with MDD with mean age 47 ± 14 (SD) years (1 woman and 3 men) were exposed to irradiance of 700 mW/cm(2) and a fluence of 84 J/cm(2) for a total NIR energy of 2.40 kJ delivered per session for 6 sessions. Baseline mean HAM-D17 scores decreased from 19.8 ± 4.4 (SD) to 13 ± 5.35 (SD) after treatment (t = 7.905; df = 3; P = 0.004). Patients tolerated the treatment well without any serious adverse events. These findings confirm and extend the preliminary data on NIR as a novel intervention for patients with MDD, but further clinical trials are needed to better understand the efficacy of this new treatment. This trial is registered with ClinicalTrials.gov NCT01538199.
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Near-infrared low-level laser (NIR-LLL) irradiation penetrates scalp and skull and can reach superficial layers of the cerebral cortex. It was shown to improve the outcome of acute stroke in both animal and human studies. In this study we evaluated whether transcranial laser stimulation (TLS) with NIR-LLL can modulate the excitability of the motor cortex (M1) as measured by transcranial magnetic stimulation (TMS). TLS was applied for 5 minutes over the representation of the right first dorsal interosseal muscle (FDI) in left primary motor cortex (M1), in 14 healthy subjects. Motor evoked potentials (MEPs) from the FDI, elicited by single-pulse TMS, were measured at baseline and up to 30 minutes after the TLS. The average MEP size was significantly reduced during the first 20 minutes following the TLS. The pattern was present in 10 (71.5%) of the participants. The MEP size reduction correlated negatively with the motor threshold at rest. TLS with NIR-LLL induced transitory reduction of the excitability of the stimulated cortex. These findings give further insights into the mechanisms of TLS effects in the human cerebral cortex, paving the way for potential applications of TLS in treatment of stroke and in other clinical settings. Lasers Surg. Med. © 2013 Wiley Periodicals, Inc.
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Many studies have reported beneficial effects from the application of near-infrared (NIR) light photobiomodulation (PBM) to the body, and one group has reported beneficial effects applying it to the brain in stroke patients. We have reported that the measurement of a patient's left and right hemispheric emotional valence (HEV) may clarify data and guide lateralized treatments. We sought to test whether a NIR treatment could 1. improve the psychological status of patients, 2. show a relationship between immediate psychological improvements when HEV was taken into account, and 3. show an increase in frontal pole regional cerebral blood flow (rCBF), and 4. be applied without side effects. We gave 10 patients, (5 M/5 F) with major depression, including 9 with anxiety, 7 with a past history of substance abuse (6 with an opiate abuse and 1 with an alcohol abuse history), and 3 with post traumatic stress disorder, a baseline standard diagnostic interview, a Hamilton Depression Rating Scale (HAM-D), a Hamilton Anxiety Rating Scale (HAM-A), and a Positive and Negative Affect Scale (PANAS). We then gave four 4-minute treatments in a random order: NIR to left forehead at F3, to right forehead at F4, and placebo treatments (light off) at the same sites. Immediately following each treatment we repeated the PANAS, and at 2-weeks and at 4-weeks post treatment we repeated all 3 rating scales. During all treatments we recorded total hemoglobin (cHb), as a measure of rCBF with a commercial NIR spectroscopy device over the left and the right frontal poles of the brain. At 2-weeks post treatment 6 of 10 patients had a remission (a score </= 10) on the HAM-D and 7 of 10 achieved this on the HAM-A. Patients experienced highly significant reductions in both HAM-D and HAM-A scores following treatment, with the greatest reductions occurring at 2 weeks. Mean rCBF across hemispheres increased from 0.011 units in the off condition to 0.043 units in the on condition, for a difference of 0.032 (95% CI: -0.016, 0.080) units, though this result did not reach statistical significance. Immediately after treatment the PANAS improved to a significantly greater extent with NIR "on" relative to NIR "off" when a hemisphere with more positive HEV was treated than when one with more negative HEV was treated. We observed no side effects. This small feasibility study suggests that NIR-PBM may have utility for the treatment of depression and other psychiatric disorders and that double blind randomized placebo-controlled trials are indicated. ClinicalTrials.gov Identifier: NCT00961454.
Article
Objective: 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). Background: t-PBM with NIR light is a new treatment for MDD. NIR light is absorbed by mitochondria; it boosts cerebral metabolism, promotes neuroplasticity, and modulates endogenous opioids, while decreasing inflammation and oxidative stress. Materials and methods: We conducted a double-blind, sham-controlled study on the safety and efficacy (change in Hamilton Depression Rating Scale [HAM-D17] total score at end-point) of adjunct t-PBM NIR [823 nm; continuous wave (CW); 28.7 × 2 cm2; 36.2 mW/cm2; up to 65.2 J/cm2; 20-30 min/session], delivered to dorsolateral prefrontal cortex, bilaterally and simultaneously, twice a week, for 8 weeks, in subjects with MDD. Baseline observation carried forward (BOCF), last observation carried forward (LOCF), and completers analyses were performed. Results: The effect size for the antidepressant effect of t-PBM, based on change in HAM-D17 total score at end-point, was 0.90, 0.75, and 1.5 (Cohen's d), respectively for BOCF (n = 21), LOCF (n = 19), and completers (n = 13). Further, t-PBM was fairly well tolerated, with no serious adverse events. Conclusions: t-PBM with NIR light demonstrated antidepressant properties with a medium to large effect size in patients with MDD. Replication is warranted, especially in consideration of the small sample size.
Article
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.
Article
Major depressive disorder is a common debilitating mood disorder that affects quality of life. Prefrontal cortex abnormalities, an imbalance in neurotransmitters, neuroinflammation, and mitochondrial dysfunction are the major factors in the etiology of major depressive disorder. Despite the efficacy of pharmacotherapy in the treatment of major depressive disorder, 30%–40% of patients do not respond to antidepressants. Given this, exploring the alternative therapies for treatment or prevention of major depressive disorder has aroused interest among scientists. Transcranial photobiomodulation therapy is the use of low-power lasers and light-emitting diodes in the far-red to near-infrared optical region for stimulation of neuronal activities. This non-invasive modality improves the metabolic capacity of neurons due to more oxygen consumption and ATP production. Beneficial effects of transcranial photobiomodulation therapy in the wide range of neurological and psychological disorders have been already shown. In this review, we focus on some issues relating to the application of photobiomodulation therapy for major depressive disorder. There is some evidence that transcranial photobiomodulation therapy using near-infrared light on 10-Hz pulsed mode appears to be a hopeful technique for treatment of major depressive disorder. However, further studies are necessary to find the safety of this method and to determine its effective treatment protocol.
Article
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.
Article
Background and objective: Photobiomodulation (PBM) also known as low-level light therapy has been used successfully for the treatment of injury and disease of the nervous system. The use of PBM to treat injury and diseases of the brain requires an in-depth understanding of light propagation through tissues including scalp, skull, meninges, and brain. This study investigated the light penetration gradients in the human cadaver brain using a Transcranial Laser System with a 30 mm diameter beam of 808 nm wavelength light. In addition, the wavelength-dependence of light scatter and absorbance in intraparenchymal brain tissue using 660, 808, and 940 nm wavelengths was investigated. Study design/material and methods: Intact human cadaver heads (n = 8) were obtained for measurement of light propagation through the scalp/skull/meninges and into brain tissue. The cadaver heads were sectioned in either the transverse or mid-sagittal. The sectioned head was mounted into a cranial fixture with an 808 nm wavelength laser system illuminating the head from beneath with either pulsed-wave (PW) or continuous-wave (CW) laser light. A linear array of nine isotropic optical fibers on a 5 mm pitch was inserted into the brain tissue along the optical axis of the beam. Light collected from each fiber was delivered to a multichannel power meter. As the array was lowered into the tissue, the power from each probe was recorded at 5 mm increments until the inner aspect of the dura mater was reached. Intraparenchymal light penetration measurements were made by delivering a series of wavelengths (660, 808, and 940 nm) through a separate optical fiber within the array, which was offset from the array line by 5 mm. Local light penetration was determined and compared across the selected wavelengths. Results: Unfixed cadaver brains provide good anatomical localization and reliable measurements of light scatter and penetration in the CNS tissues. Transcranial application of 808 nm wavelength light penetrated the scalp, skull, meninges, and brain to a depth of approximately 40 mm with an effective attenuation coefficient for the system of 2.22 cm(-1) . No differences were observed in the results between the PW and CW laser light. The intraparenchymal studies demonstrated less absorption and scattering for the 808 nm wavelength light compared to the 660 or 940 nm wavelengths. Conclusions: Transcranial light measurements of unfixed human cadaver brains allowed for determinations of light penetration variables. While unfixed human cadaver studies do not reflect all the conditions seen in the living condition, comparisons of light scatter and penetration and estimates of fluence levels can be used to establish further clinical dosing. The 808 nm wavelength light demonstrated superior CNS tissue penetration.
Article
The hypothesis is proposed that pre-biotic bacterial cell(s) and the first cells capable of growth/division did not require a cytoplasmic membrane. A gel-like microscopic structure less than a cubic micrometer may have had a dual role as both an ancient pre-cytoplasm and a boundary layer to the higher-entropy external environment. The gel pre-cytoplasm exposed to radiant energy, especially in the infrared (IR) region of the EM spectrum resulted in the production of an exclusion zone (EZ) with a charge differential (-100 to -200 mV) and boundary that may have been a possible location for the latter organization of the first cytoplasmic membrane. Pre-biotic cells and then-living cells may have used hydrogen as the universal energy source, and thermosynthesis in their bioenergetic processes. These components will be discussed as to how they are interconnected, and their hypothesized roles in the origin of life.
Article
Low-power, near-infra-red laser irradiation has been used to relieve patients from various kinds of pain, though the precise mechanisms of such biological actions of the laser have not yet been resolved. To investigate the cellular mechanisms by near-infra-red laser on the nervous system, we examined the effect of 830-nm laser irradiation on the energy metabolism of the rat brain. The diode laser was applied for 15 min with an irradiance of 4.8 W/cm(2). Tissue adenosine triphosphate (ATP) content of the irradiated area in the cerebral cortex was 19% higher than that of the non-treated area, whereas the adenosine diphosphate (ADP) content showed no significant difference. Laser irradiation at another wavelength (652 nm) had no effect on either ATP or ADP contents. The temperature of the tissue was increased by 4.4-4.7 degrees C during the irradiation of both wavelengths. These results suggest that the increase in tissue ATP content did not result from the thermal effect, but from a specific effect of the laser operated at the 830-nm wavelength.