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Long-Term Near-Infrared Photobiomodulation for Anxious Depression Complicated by Takotsubo Cardiomyopathy
... Little is known about the antidepressant effects of t-PBM in the longterm. One case report on this topic described the outcomes in a patient receiving PBM for 31 months, as an add-on to antidepressant medications to treat MDD with anxious distress (Caldieraro et al., 2018). The treatment was started with intranasal PBM and t-PBM was added in the last 9 months. ...
... The side effects were mild and transient, resolving in less than 24 hrs after treatment (Quah-Smith et al., 2005). A case report combining long-term t-PBM and s-PBM reported the emergence of headaches associated with the procedure (Caldieraro et al., 2018). ...
... However in the same study, an antidepressant effect of just t-PBM -compared to sham-could not be demonstrated for any of the anatomical sites of the light source (Disner et al., 2016). While there is no data comparing transcranial and systemic PBM, a single case study suggested a larger antidepressant effect after t-PBM was added to intranasal stimulation (Caldieraro et al., 2018). ...
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.
... Then, in 2018, this author, using 21 patients diagnosed with depression disorder, achieved a reduction in symptoms in 18 patients after four weeks of LED administration . In addition, in the same year, together with Caldieraro et al. (2018), the author carried out a case study in which this technique was applied intranasally and transcranially to a 78-year-old woman with heart disease who had been diagnosed with anxiety depressive disorder for more than nine months. Results showed that intranasal application improved only the anxiety symptoms, but not the depressive ones, whereas transcranial administration improved both types of symptoms and enhanced quality of life. ...
... Results showed that intranasal application improved only the anxiety symptoms, but not the depressive ones, whereas transcranial administration improved both types of symptoms and enhanced quality of life. During the therapy, the patient reported headaches that increased with the administration of two daily doses of PBMT (Caldieraro et al., 2018). The same results were found by Henderson and Morries (2017), whose study achieved a decrease in depression scores and remission of suicidal ideation after laser administration. ...
... For these reasons, most studies agree that the lengths of 810 and 1064 nm would be versatile and adequate values to achieve effects in the body. Likewise, several authors, such as Caldieraro et al. (2018); Chan et al. (2019); Henderson and Morries (2017), and Salehpour and Rasta (2017), combine different wavelengths to activate different biological mechanisms. ...
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.
... Little is known about the long-term antidepressant effects of PBM. Our group reported the case of a patient receiving PBM for 31 months, as an add-on to antidepressant medication to treat depression with anxious distress [55]. The treatment was started with intranasal PBM, and t-PBM was added in the last 9 months. ...
... As described above, there are studies on t-and s-PBM for MDD, and both modalities have shown potential in the treatment of MDD. In a case reported by our group, improvements on depressive symptoms were more pronounced after t-PBM was added to the systemic delivery [55]. However, there are no other comparisons between the two modalities reported in the literature. ...
... The safety profile of PBM suggests it could be used as maintenance treatment for responders. However, the only evidence for long-term use comes from a case report [55]. Q6. ...
Photobiomodulation (PBM) is a novel device-based treatment for major depressive disorder (MDD). PBM delivers near-infrared (NIR) or red light transcranially or systemically, aiming to modulate mitochondrial bioenergetics metabolism via the delivery of energy to the cytochrome c oxidase (CCO) enzyme. This primary action on mitochondria can lead to secondary effects on other pathways relevant for MDD such as oxidative stress, inflammation, and neurogenesis. Evidence supports that a fraction of the light delivered transcranially can reach the brain and modulate cortical activity and that light delivered in the periphery can exert systemic effects that include the brain. Preclinical studies indicate that PBM can treat depression-like behaviors in animal models of depression and also give some guidance on the optimal stimulation parameters. According to these studies, repeated sessions are more effective than a single session, and pulsed wave is more effective than continuous wave. Clinical studies also support the antidepressant effect of PBM and reinforce the need of repeated sessions. Clinical evidence also indicates that PBM can induce mild adverse effects, but the incidence of serious adverse effects is not different from that observed in sham (i.e., placebo) treatment. At this moment, PBM is an over-the-counter treatment for MDD and can be considered an alternative for patients who do not respond, tolerate, or accept antidepressant medication, evidence-based psychotherapies, or other FDA-approved device-based treatments.
... Transcranial photobiomodulation (t-PBM) with nearinfrared radiation (NIR) has emerged as a potential antidepressant treatment in both animal models [11][12][13][14][15] and human studies. [16][17][18][19] t-PBM consists of delivering NIR-or red light-to the scalp of the patient, which penetrates the skull and modulates function of the adjacent cortical areas of the brain. PBM with red light and/or NIR appears to increase brain metabolism (by activating the cytochrome C oxidase in the mitochondria), to increase neuroplasticity, and to modulate endogenous opioids, while decreasing inflammation and oxidative stress. ...
... [39][40][41] The safety of t-PBM has been studied in a sample of acute 1410 stroke patients, with no significant differences in rates of adverse events between t-PBM and sham exposure. [42][43][44] Uncontrolled studies suggest an antidepressant effect of t-PBM in subjects suffering from MDD. [16][17][18][19] Aims of the study We report here on the first, randomized, double-blind, sham-controlled, pilot trial of the antidepressant effect of t-PBM in MDD patients. ...
... Adult subjects (18-65 years of age) meeting the (Structured Clinical Interview for the DSM-IV-Diagnostic Statistical Manual, Fourth Edition) criteria for MDD, with at least a moderate degree of depression severity [Hamilton Depression Rating Scale (HAM-D 17 ) total score ranging [14][15][16][17][18][19][20][21][22][23][24], were included in the study after providing written informed consent. The MGH IRB required a maximum permitted HAM-D 17 score of 24 to prevent inclusion of patients at greater risk of suicide. ...
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.
... Little is known about the long-term antidepressant effects of PBM. Our group reported the case of a patient receiving PBM for 31 months, as an add-on to antidepressant medication to treat depression with anxious distress (Caldieraro et al., 2018). The treatment was started with intranasal PBM, and t-PBM was added in the last 9 months. ...
... According to the authors, virtually all patients presented a remarkable improvement in their emotional stability and quality of life, as assessed by standardized instruments (Stephan et al., personal communication). As described above, in a case report of a patient receiving PBM for 31 months for MDD with anxious distress, a continuous improvement on the anxiety symptoms was observed during the overall treatment period (Caldieraro et al., 2018). ...
... The study reported by Schiffer et al., reported no adverse events or side effects after a detailed questioning of the patients (Schiffer et al., 2009). In the case report of long-term use of PBM for MDD with anxious distress, the patient presented headaches apparently associated with the treatment (Caldieraro et al., 2018). ...
... i-PBMT is a nose-mediated therapeutic approach that is based on the insertion of one or two small laser/LED equipped portable probes into the nostrils. It is shown that repeated application of nostril-based i-PBMT could potentially improve symptoms associated with neuronal dysfunction caused by cerebral infarction (Xiao et al., 2005), mild traumatic brain injury (TBI) (Bogdanova et al., 2017), mild cognitive impairment (MCI) (Salehpour et al., 2019), Alzheimer's disease (AD) Chao, 2019), PD (Li et al., 1999b), depression and anxiety (Caldieraro et al., 2018), schizophrenia (Liao, 2000), and insomnia (Xu et al., 2001;Saltmarche et al., 2017). Systemic effects of nostril-based intranasal irradiation via the blood cells and components could likely contribute to the observed neurotherapeutic effects (Hennessy and Hamblin, 2016). ...
... Studies have shown associations of hemorheology and cognitive functions (Elwood et al., 2001) and mood states (Gao et al., 2004). It was suggested that the systemic effects of i-PBMT via the blood irradiation mechanisms could also ultimately produce neuroprotective benefits in the brain (Xiao et al., 2005;Hennessy and Hamblin, 2016;Caldieraro et al., 2018). Studies have shown that intranasal blood irradiation has similar neurological outcomes to the intravenous or intravascular laser therapy (Jing, 1999;Dou et al., 2003). ...
... The systemic effects of nostril-based i-PBMT via irradiation of blood cells or blood components were suggested as a possible mechanism of action of this intervention (Xiao et al., 2005;Hamblin, 2016;Hennessy and Hamblin, 2016;Caldieraro et al., 2018). Considering its noninvasive and relatively inexpensive nature, i-PBMT may give the same therapeutic outcome as the intravenous blood irradiation approach (Xiao et al., 2005). ...
The application of photobiomodulation therapy (PBMT) for neuronal stimulation has been studied in different animal models and in humans, and has been 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 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 have been 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.
... 17 The extracranial frontal positions going across the Fp1, Fp2, and FpZ electroencephalography points were also explored based on preliminary results in a case-report of long-term photobiomodulation for MDD. 48 In addition, three of the tested illumination positions were located inside the nasal cavity, as illustrated in Fig. 1, to test an alternative strategy to treat the PFC: one in the nostril (N1, red), the second in the mid-nose (N2, green), and the third near the nose ceiling (cribriform plate, N3, blue). The N1 position is easily accessible and marketed devices already exist to allow clipping a red or NIR light source into the nostril. ...
... The N1 position is easily accessible and marketed devices already exist to allow clipping a red or NIR light source into the nostril. 48 Accessing the N2 position (mid-nose) would require common nonsurgical ear, nose, and throat (ENT) procedures such as rhinoscopy (nasal endoscopy). The N3 position, i.e., near the cribriform plate, is still speculative due to limited accessibility, but has shown promise for light delivery to the deep brain previous modeling. ...
The transcranial photobiomodulation (t-PBM) technique is a promising approach for the treatment of a wide range of neuropsychiatric disorders, including disorders characterized by poor regulation of emotion such as major depressive disorder (MDD). We examine various approaches to deliver red and near-infrared light to the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) in the human brain, both of which have shown strong relevance to the treatment of MDD. We apply our hardware-accelerated Monte Carlo simulations to systematically investigate the light penetration profiles using a standard adult brain atlas. To better deliver light to these regions-of-interest, we study, in particular, intranasal and transcranial illumination approaches. We find that transcranial illumination at the F3-F4 location (based on 10-20 system) provides excellent light delivery to the dlPFC, while a light source located in close proximity to the cribriform plate is well-suited for reaching the vmPFC, despite the fact that accessing the latter location may require a minimally invasive approach. Alternative noninvasive illumination strategies for reaching vmPFC are also studied and both transcranial illumination at the Fp1-FpZ-Fp2 location and intranasal illumination in the mid-nose region are shown to be valid. Different illumination wavelengths, ranging from 670 to 1064 nm, are studied and the amounts of light energy deposited to a wide range of brain regions are quantitatively compared. We find that 810 nm provided the overall highest energy delivery to the targeted regions. Although our simulations carried out on locations and wavelengths are not designed to be exhaustive, the proposed illumination strategies inform the design of t-PBM systems likely to improve brain emotion regulation, both in clinical research and practice.
... In the second case report, a 76-year-old Caucasian female, who carried diagnoses of MDD with "anxious distress", hypertrophic obstructive cardiomyopathy, and Takotsubo cardiomyopathy, underwent NIR t-PBM for a total of 31 months. 86 Over the course of therapy, the patient performed weekly self-report assessments using the Quick Inventory of Depressive Symptomatology Self-Report version (QIDS-SR16) and the Anxiety Symptoms Questionnaire (ASQ). Interestingly, she received both intranasal PBM (i-PBM) and transcranial (t-PBM), alone and in combination at different points. ...
... Headaches were reported in three separate studies. 81,84,86 Other potential side effects related to the active treatment mode were fatigue, localized skin warming, irritability, insomnia, illusions (i.e., "seeing vivid colors" or "tasting from an ashtray"), and abdominal bloating. 81,84 Even larger studies of t-PBM in post-stroke patients, including a pooled sample of 1410 subjects, showed no significant difference in serious adverse effects or mortality between treatment and control groups. ...
Paula Askalsky,1 Dan V Iosifescu1,2 1Department of Psychiatry, NYU Langone School of Medicine, New York, NY, USA; 2Clinical Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USACorrespondence: Dan V IosifescuDepartment of Psychiatry, NYU School of Medicine, One Park Avenue, 8th Floor, New York, NY 10016, USATel +1 646-754-5156Email Dan.Iosifescu@nyumc.orgAbstract: Major depressive disorder (MDD) is a prevalent condition associated with high rates of disability, as well as suicidal ideation and behavior. Current treatments for MDD have significant limitations in efficacy and side effect burden. FDA-approved devices for MDD are burdensome (due to repeated in-office procedures) and are most suitable for severely ill subjects. There is a critical need for device-based treatments in MDD that are efficacious, well-tolerated, and easy to use. In this paper, we review a novel neuromodulation strategy, transcranial photobiomodulation (t-PBM) with near-infrared light (NIR). The scope of our review includes the known biological mechanisms of t-PBM, as well as its efficacy in animal models of depression and in patients with MDD. Theoretically, t-PBM penetrates into the cerebral cortex, stimulating the mitochondrial respiratory chain, and also significantly increases cerebral blood flow. Animal and human studies, using a variety of t-PBM settings and experimental models, suggest that t-PBM may have significant efficacy and good tolerability in MDD. In aggregate, these data support the need for large confirmatory studies for t-PBM as a novel, likely safe, and easy-to-administer antidepressant treatment.Keywords: low-level light therapy, photobiomodulation, near infrared radiation, major depressive disorder, depression
... In addition, after several weeks of laser acupuncture intervention, symptoms improved significantly in depressive patients [275,276]. Furthermore, depressive symptoms evidenced improvement after transcranial (t-PBM) and intranasal (i-PBM) treatment in a case report on a 76-year-old female with major depressive disorder [277]. The beneficial effects of PBM on depression have also been demonstrated in a space restriction-induced depression animal model and in Abelson helper integrationsite-1 (Ahi1) KO mice [208]. ...
... • Increases mitochondrial function, improves blood flow, and reduces swelling [244,247] • Inhibits excessive ROS production and attenuates mitochondrial dysfunction, cytochrome c release, and neuronal apoptosis [243] • Decreases oxidative stress, inhibits inflammation, and attenuates apoptosis [244,247] Stroke • Improves behavioral results after focal cerebral ischemia [16] • Improves neurological rating scores [4,255,256] • Decreases lesion volume, cerebral edema, and gray and white-matter damage [16,18] • Stimulates neurogenesis and improves mitochondrial function [4,262] • Increases cerebral global glucose uptake and blood flow [251,252] • Preserves mitochondrial integrity [263] • Increases mitochondrial function [9,252] • Attenuates mitochondrial fragmentation and restores mitochondrial dynamics [254] • Preserves mitochondrial structure and function [253] • Increases mitophagy and preserves mitochondrial membrane potential [253] • Decreases protein carbonylation, DNA oxidative damage, and lipid peroxidation [254] Depression • Improves the symptoms of patients with severe depression [265] • Improves depressive symptoms [274][275][276][277] • Selectively inhibits nitric oxide synthase (NOS) [264,265,270,271] • Improves ATP production and increases activity and expression of mitochondrial Complex IV [208] PD • Attenuates dopamine loss and reduces the disruption of mitochondrial function and excessive production of ROS [280][281][282][283][284] • Reduces cell loss and inhibits inflammatory amoeboid microglia [287][288][289][290] • Improves Complexes I, II, and III activities, reduces free radical production, and improves behavioral results [252,285] • Improves speech, cognition, gait, and freezing episodes in PD patients [291,292] • Upregulates brain-derived neurotrophic factor (BDNF) expression [286] • Improves mitochondrial function and reduces oxidative stress [293] for neuroprotection for several brain disorders. The mitochondrial dysfunction-related processes that could be targeted and improved upon include impaired ETC function, excessive ROS production, oxidative damage, Ca 2+ overload, aberrant mitophagy, altered mitochondrial dynamics, impaired mitochondrial trafficking, and subsequent neuroinflammation (Fig. 4), of which most are included in the 10 hallmarks of brain aging reported recently [316,317]. ...
Mitochondrial dysfunction plays a central role in the formation of neuroinflammation and oxidative stress, which are important factors contributing to the development of brain disease. Ample evidence suggests mitochondria are a promising target for neuroprotection. Recently, methods targeting mitochondria have been considered as potential approaches for treatment of brain disease through the inhibition of inflammation and oxidative injury. This review will discuss two widely studied approaches for the improvement of brain mitochondrial respiration, methylene blue (MB) and photobiomodulation (PBM). MB is a widely studied drug with potential beneficial effects in animal models of brain disease, as well as limited human studies. Similarly, PBM is a non-invasive treatment that promotes energy production and reduces both oxidative stress and inflammation, and has garnered increasing attention in recent years. MB and PBM have similar beneficial effects on mitochondrial function, oxidative damage, inflammation, and subsequent behavioral symptoms. However, the mechanisms underlying the energy enhancing, antioxidant, and anti-inflammatory effects of MB and PBM differ. This review will focus on mitochondrial dysfunction in several different brain diseases and the pathological improvements following MB and PBM treatment.
... The intranasal PBM technique is also interesting as a nose-mediated therapeutic approach, based on inserting one or two small laser/LEDs, equipped with portable applicators, into the nostrils. This PBM technique could be applied either alone or in combination to transcranial devices [85]. The repeated application of intranasal PBM therapy has been shown to enhance blood rheology and cerebral blood flow (CBF), and it has been suggested to treat a wide range of neurological and neuropsychiatric disorders [83,85]. ...
... This PBM technique could be applied either alone or in combination to transcranial devices [85]. The repeated application of intranasal PBM therapy has been shown to enhance blood rheology and cerebral blood flow (CBF), and it has been suggested to treat a wide range of neurological and neuropsychiatric disorders [83,85]. ...
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.
... 17 The extracranial frontal positions going across the Fp1, Fp2, and FpZ electroencephalography points were also explored based on preliminary results in a case-report of long-term photobiomodulation for MDD. 48 In addition, three of the tested illumination positions were located inside the nasal cavity, as illustrated in Fig. 1, to test an alternative strategy to treat the PFC: one in the nostril (N1, red), the second in the mid-nose (N2, green), and the third near the nose ceiling (cribriform plate, N3, blue). The N1 position is easily accessible and marketed devices already exist to allow clipping a red or NIR light source into the nostril. ...
... The N1 position is easily accessible and marketed devices already exist to allow clipping a red or NIR light source into the nostril. 48 Accessing the N2 position (mid-nose) would require common nonsurgical ear, nose, and throat (ENT) procedures such as rhinoscopy (nasal endoscopy). The N3 position, i.e., near the cribriform plate, is still speculative due to limited accessibility, but has shown promise for light delivery to the deep brain previous modeling. ...
Significance
Major 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.
Aim
We 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.
Approach
Age-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.
Results
An 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.
Conclusion
Quantitative simulations revealed age-dependent light delivery across the lifespan of human brains, suggesting the needs for personalized and age-adaptive t-PBM treatment planning.
... For example, laser therapy combined with attention bias modification can enhance cognitive improvement (Disner et al., 2016). A case report of a 76-year-old white woman diagnosed with MDD with anxious distress showed steady improvement (Caldieraro et al., 2018). ...
Photobiomodulation using light in the red or near-infrared region is an innovative treatment strategy for a wide range of neurological and psychological conditions. Photobiomodulation can promote neurogenesis and elicit anti-apoptotic, anti-inflammatory and antioxidative responses. Its therapeutic effects have been demonstrated in studies on neurological diseases, peripheral nerve injuries, pain relief and wound healing. We conducted a comprehensive literature review of the application of photobiomodulation in patients with central nervous system diseases in February 2019. The NCBI PubMed database, EMBASE database, Cochrane Library and ScienceDirect database were searched. We reviewed 95 papers and analyzed. Photobiomodulation has wide applicability in the treatment of stroke, traumatic brain injury, Parkinson's disease, Alzheimer's disease, major depressive disorder, and other diseases. Our analysis provides preliminary evidence that PBM is an effective therapeutic tool for the treatment of central nervous system diseases. However, additional studies with adequate sample size are needed to optimize treatment parameters.
... Recently, photobiomodulation (PBM) has emerged as a promising treatment for various neurological disorders [9][10][11][12]. Basically, low level red (∼600-700 nm) or near infrared (NIR, 760-1100 nm) light is used in the therapy to preserve, stimulate, and regenerate cells and tissues. ...
The blood-brain barrier (BBB) is a dynamic barrier between the blood microcirculation system and the brain parenchyma, which plays an important role in the pathogenesis of a variety of neurological diseases. Meanwhile, a non-invasive therapeutic approach of photobiomodulation (PBM) has emerged as a promising treatment for neurological disorders through irradiation with near infrared (NIR) light. However, despite multiple encouraging results reported for PBM in vitro and in vivo, the mechanisms of its therapeutic effect on brain, especially on the BBB, remain barely known. Herein, the effect of NIR light irradiation on the in vitro BBB models was studied. 808 nm laser irradiation at the doses of 10 and 30 J/cm2 was found to significantly increase the permeability of this BBB model. The results showed that NIR light affected mitochondria of cells in the in vitro BBB models, leading to an increase in the mitochondrial activity, reactive oxygen species (ROS) level and Ca2+ influx. The activity of matrix metalloproteinases and the expression of the tight junction proteins in the endothelial cells were found to be inhibited by the NIR light, resulting in an increase in the BBB permeability. This study suggested a new strategy for drug transport across the BBB in development of treatments for brain disorders.
... In agreement with other reports Freitas et al., 2014), five days of sub-chronic restraint stress in our study resulted in an increase in the immobility time as compared to the control animals. Recently, transcranial NIR PBM therapy has been suggested as a non-invasive neurostimulation modality in the central nervous system and is emerging as a novel promising treatment to defeat depression (Caldieraro et al., 2018;Cassano et al., 2015;Cassano et al., 2016;. Previous reports from our laboratory and others have shown that repeated delivery of NIR laser therapy produces an antidepressant-like effect in the FST (Mohammed, 2016;Salehpour et al., 2016;Wu et al., 2012;Xu, et al., 2017) and TST (Xu, et al., 2017). ...
This study was aimed to evaluate the effects of near-infrared (NIR) photobiomodulation (PBM) combined with coenzyme Q10 (CoQ10) 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/cm2) and/or CoQ10 (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 CoQ10, 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 CoQ10 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 CoQ10 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-α, and IL-6 induced by restraint stress. Transcranial NIR PBM and CoQ10 therapies may be effective antidepressant strategies for the prevention of psychopathological and behavioral symptoms induced by stress.
... Geçirdiği majör travma ve cerrahi operasyonlar sonrası paraplejik kalması ve mekanik ventilatöre bağımlı hale gelmesi hastanın ağır stres altında kalmasına sebep olmuştur. Çoğu olguda (15,16) olduğu gibi öyküde fiziksel veya emosyonel stres bizim olgumuzda da mevcuttur. ...
... Recently, long-term PBMT showed the overall therapeutic effect in a patient with major depression and anxiety. 35 For the first 22 months, single-modality iN-PBMT (810 nm LED) was applied to both nostrils providing a 10.65 J/cm 2 per nostril. With the progres sive increase of the frequency of iN-PBMT sessions, the anxiety symptoms showed regression with about a 3-fold reduction in Anxiety Symptoms Questionnaire Scores. ...
... Geçirdiği majör travma ve cerrahi operasyonlar sonrası paraplejik kalması ve mekanik ventilatöre bağımlı hale gelmesi hastanın ağır stres altında kalmasına sebep olmuştur. Çoğu olguda (15,16) olduğu gibi öyküde fiziksel veya emosyonel stres bizim olgumuzda da mevcuttur. ...
Takotsubo cardiomyopathy (TC) is a disease mimicking Acute Coronary syndrome with electrocardiographic changes as well as temporary, reversible regional wall motion defect in the apical and middle segments of the left ventricle. It may be associated with emotional and physical stress caused by serious medical discomfort or surgical stress. Although it is more common in postmenopausal women, it is thought that stress-induced catecholamine discharge causes TC. Intensive care patients are at high risk for emotional and physical stress due to various factors such as multisystem diseases and problems due to prolonged hospitalization. In this case report, we aimed to present the characteristics of TC following long-term intensive care follow-up of our patient who was paraplegic due to cervical trauma and conscious, and to discuss the differential diagnosis and evaluate the literature.
... Little is known about the antidepressant effects of t-PBM in the long term. One case report on this topic described the outcomes in a patient receiving PBM for 31 months, as an add-on to antidepressant medications to treat MDD with anxious distress [88]. The treatment was started with intranasal PBM, and t-PBM was added in the last 9 months. ...
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.
... 13 Further, one case report suggested long-term benefits of t-PBM for the treatment of anxiety. 14 The present study was conducted to test the efficacy, safety, and tolerability of repeated t-PBM sessions in a group of anxious subjects with primary GAD. The study also tested the feasibility of using a take-home t-PBM device, in contrast to the more time-consuming and expensive in-office treatment delivery. ...
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/cm2; average fluence 36 J/cm2; total energy delivered per session 2.9 kJ: total output power 2.4 W) broadly on the forehead (total area 80 cm2) 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 < 0.001; Cohen's d effect size = 1.47), in the CGI-S subscale (from 4.53 ± 0.52 to 2.87 ± 0.83; p < 0.001; Cohen's d effect size = 2.04), as well as significant improvements in sleep at the PSQI. t-PBM was well tolerated with no serious adverse events.
Conclusions:
Based on our pilot study, t-PBM with NIR is a promising alternative treatment for GAD. Larger, randomized, double-blind, sham-controlled studies are needed.
... Numerous case series reports and small sham control studies of transcranial PBM's using low powered lasers describe significant symptomatic relief in subjects diagnosed with PD (Santos et al., 2019), PTSD, and vascular and other dementias (Stephan et al., 2017) as well as chronic pain and depression (Gabel et al., 2018). Therapeutic interventions in treating neuropsychiatric disorders including major depression and generalized anxiety using intranasal only and then transcranial stimulation have demonstrated positive response particularly when stimulation utilized EEG-based localization (Caldieraro, Sani, Bui, & Cassano, 2018). Two middle-aged traumatic brain injury survivors receiving daily frontal PBM over several months using transcranial (frontal and midline sagittal) 633 and 870 nm LED-based stimulation showed marked improvement as measured by return to work, sustained attention, and improved executive functioning (Naeser, Saltmarche, Krengel, Hamblin, & Knight, 2011). ...
Aging, as a physiological phenomenon, is complicated with secondary problems that cause enormous health, economic, social, and emotional costs. Neuropsychological problems are among the most important health threats in the aged population. Numerous pharmacological and nonpharmacological approaches have been evaluated to boosting of brain function in healthy elderlies or attenuating of brain malfunctions in the disease conditions. Photobiomodulation (PBM) as a nonpharmacological and noninvasive method has been under investigation for many years in experimental and clinical studies. In this method, the impact of photons at specific wavelengths with photoacceptors within the tissue induces biological responses including improved bioenergetics, increased regional blood flow, stimulation of growth factors, and reduced apoptosis, oxidative stress, and inflammation in the tissue. Besides, the beneficial effects of this intervention on cognitive and behavioral outcomes in a broad spectrum of neuropsychological disorders such as depression, posttraumatic stress disorder, stroke, Alzheimer’s and Parkinson’s disorders have been reported. In this chapter, we will review the current preclinical and clinical evidence regarding the protective effects of PBM in healthy and pathological brain aging conditions. Furthermore, some of the underlying neurobiological mechanisms will be explained.
... This photonic energy is transferred onto subcranial tissues and to an extent, the cortical surface [4]. Intranasal PBM is another therapeutic approach delivering light energy through the nostrils, which has been shown to promote brain function in various CNS diseases such as depression, cerebral infarction, dementia, and Kleine-Levin syndrome [78][79][80][81][82][83]. ...
The glymphatic system is a glial-dependent waste clearance pathway in the central nervous system, devoted to drain away waste metabolic products and soluble proteins such as amyloid-beta. An impaired brain glymphatic system can increase the incidence of neurovascular, neuroinflammatory, and neurodegenerative diseases. Photobiomodulation (PBM) therapy can serve as a non-invasive neuroprotective strategy for maintaining and optimizing effective brain waste clearance. In this review, we discuss the crucial role of the glymphatic drainage system in removing toxins and waste metabolites from the brain. We review recent animal research on the neurotherapeutic benefits of PBM therapy on glymphatic drainage and clearance. We also highlight cellular mechanisms of PBM on the cerebral glymphatic system. Animal research has shed light on the beneficial effects of PBM on the cerebral drainage system through the clearance of amyloid-beta via meningeal lymphatic vessels. Finally, PBM-mediated increase in the blood–brain barrier permeability with a subsequent rise in Aβ clearance from PBM-induced relaxation of lymphatic vessels via a vasodilation process will be discussed. We conclude that PBM promotion of cranial and extracranial lymphatic system function might be a promising strategy for the treatment of brain diseases associated with cerebrospinal fluid outflow abnormality.
... In some studies, an average power density of 1.6 mW/cm 2 can be transmitted through the skin, and skull to reach the cortical surface [89,90]. The best response was found with a laser dose of 8 J/cm 2 in a chronic restraint stress mouse model, which was probably due to increasing 5-HT and decreasing NO levels in the prefrontal cortex and the hippocampal areas [90,91]. Moreover, transcranial PBM therapy can be carried out via an intranasal approach, and might have a larger anti-depressant effect [92][93][94]. ...
Photobiomodulation therapy (PBMT) previously known as low-level laser therapy (LLLT) has been used for over 30 years, to treat neurological diseases. Low-powered lasers are commonly used for clinical applications, although recently LEDs have become popular. Due to the growing application of this type of laser in brain and neural-related diseases, this review focuses on the mechanisms of laser action. The most important points to consider include the photon absorption by intracellular structures; the effect on the oxidative state of cells; and the effect on the expression of proteins involved in oxidative stress, inflammation, pain, and neuronal growth.
... The main limitation of the study is its small number of patients and its short duration. t-PBM is a relatively new field, and many initial studies have had small numbers (9,37,(56)(57)(58), and larger and longer studies are needed. We have completed 31 of 40 patients in a NIDA sponsored double-blind RTC study (Grant #1R43DA050358-01), which has been temporarily interrupted by the pandemic, but to date shows a highly significant treatment * time effect in regard to opioid craving reduction. ...
Background
Opioid use disorders (OUDs) are an epidemic causing catastrophic consequences to individuals, families, and society despite treatments including psychotherapy, substitution therapy or receptor blockers, and psychoeducation. We have developed a novel treatment that combines unilateral transcranial photobiomodulation (t-PBM) to the hemisphere with a more positive valence by Dual Brain Psychology (DBP).Methods
We used a randomized, double blind, placebo-controlled protocol in which 22 patients with significant opioid cravings and a history of recent or current OUD attended three 1-h weekly sessions. After baseline measures of opioid craving and other psychometrics, subjects received two unilateral t-PBM applications (810 nm CW LED, 250 mW/cm2, 60 J/cm2, 4 min) or a sham (foil-covered LED) at F3 or F4. Prior to any treatment we used two tests to determine which hemisphere was more associated with a negative outlook and cravings and treated that side before the more positive hemisphere. Primary outcome measure was an opioid craving scale (OCS). Secondary outcomes were weekly Hamilton Depression (HDRS) and Anxiety (HARS) Rating Scales prior to treatments and at follow-up.ResultsImmediately after treatment the OCS improved significantly for both the sham and active treatments, but one week later the active treatment showed a 51.0% (SD 33.7) decrease in OCS while a week after the sham treatments there was a decrease of only 15.8% (SD 35.0) (by Wilcoxon Sign Rank Test, p = 0.004) and by a mixed model it was p = 0.0071. The effect size for the differences between active and sham was 0.73. For the active treatment from before and after treatment the effect size was 1.51 and for the sham, 0.45. The HDRS improved from a baseline of 15.1 to 8.8 (SD 10.3) a week after the active treatment and to 13.3 (SD 12.9) after the sham (p = 0.0071). HARS improved from 14.7 to 8.0 (SD 13.2) after the active treatments and to 14.3 (SD 16.0) after the sham, p = 0.08. Active treatment of the positive hemisphere after the negative hemisphere significantly improved the OCS, but there was no significant difference after the sham treatment. One patient complained of 2 h of abdominal bloating and dropped out; no other adverse effects were observed.DiscussionUnilateral t-PBM to the hemisphere with a more positive hemispheric emotional valence was an effective and safe treatment for opioid cravings as well as for depression and anxiety. Our results also lend support to the underlying premises of DBP.
The paper evaluates the effectiveness of the use of therapeutic laser exposure (photobiomodulation therapy – PBMT) to minimize acute pain in the early postoperative period in patients after septoplasty. The study included two groups of patients. Patients of the first group (31 patients) underwent septoplasty with standard management in the postoperative period. Patients of the second group (31 patients) also underwent septoplasty, and then added PBMT to the standard measures of the postoperative period at 3, 6 and 24 h after septoplasty (λ = 0.890 μm, P = 10 W, 2 min) and then intranasally 48 h after septoplasty (λ = 0.630 μm, P = 8 W, 2 min). In patients of both groups, heart rate variability and pain were assessed using a visual analog scale within 48 hours after septoplasty. In patients of the second group, after the use of PBMT, the indicators of heart rate variability had a significantly lower total power, compared with patients of the first group. So, after PBMT, the ultra-low-frequency component of the spectral analysis of heart rate variability in the first group was 18580 ± 2067 ms ² , which is significantly higher than in the second group (8086 ± 3003 ms ² ) (p <0.001). The low-frequency component of heart rate variability was also significantly higher in the first group (1871 ± 405 ms ² ) compared to the second (1095 ± 190 ms ² ) (p <0.005), which indicates an increase in the tension of the sympathetic part of the autonomic nervous system in the group without the use of PBMT. In the first 3 hours after surgery, the severity of pain between the groups did not differ significantly (p = 0.07). In the period from 6 to 24 hours after surgery, patients who did not undergo PBMT experienced significantly higher pain than patients with PBMT (p <0.001). Thus, in our study, the group of patients with PBMT showed better results in pain and heart rate variability compared to the classical rehabilitation of patients after septoplasty.
Light modulation plays an important role in understanding the pathology of brain disorders and improving brain function. Optogenetic techniques can activate or silence targeted neurons with high temporal and spatial accuracy and provide precise control, and have recently become a method for quick manipulation of genetically identified types of neurons. Photobiomodulation (PBM) is light therapy that utilizes non-ionizing light sources, including lasers, light emitting diodes, or broadband light. It provides a safe means of modulating brain activity without any irreversible damage and has established optimal treatment parameters in clinical practice. This manuscript reviews 1) how optogenetic approaches have been used to dissect neural circuits in animal models of Alzheimer's disease, Parkinson's disease, and depression, and 2) how low level transcranial lasers and LED stimulation in humans improves brain activity patterns in these diseases. State-of-the-art brain machine interfaces that can record neural activity and stimulate neurons with light have good prospects in the future.
The aim of the study was to evaluate the effectiveness of the use of photobiomodulation therapy (PBMT) to minimize acute pain in the early postoperative period in patients after septoplasty. In total, 62 patients underwent septoplasty under general anesthesia (40 men and 22 women, 18-44 years old) followed by nasal tamponade. Patients of the 1st group did not undergo PBMT, and patients of the 2nd group received PBMT 3, 6, and 24 h after septoplasty (infrared pulsed laser radiation, λ = 0.890 μm, P = 10 W, 2 min in the projection of the wings of the nose). After 48 h, after the removal of tampons, intranasal PBMT with a nozzle in the red range, with λ = 0.63 μm, P = 8 mW, 2 min. ULF, HF, LF, and total power of heart rate variability (HRV), pain syndrome was assessed. ULF, LF, HF, total HRV power were significantly lower in group 2, compared to group 1. In the period from 6 to 24 h after septoplasty, patients of group 1 experienced higher pain than patients with PBMT (p < 0.001). The use of PBMT after septoplasty against the background of nasal tamponade helps to reduce the severity of pain syndrome and the inflammatory response to surgical stress and, consequently, leads to less pronounced changes in the autonomic nervous system in response to surgical stress.
Background:
Anxious-depressive-like behavior has been recognized as an early endophenotype in Alzheimer's disease (AD). Recent studies support early treatment of anxious-depressive-like behavior as a potential target to alleviate memory loss and reduce the risk of developing dementia. We hypothesize that photobiomodulation (PBM) could be an effective method to alleviate depression and anxiety at the early stage of AD pathogenesis.
Objective:
To analyze the effect of PBM treatment on anxious-depressive-like behavior at the early stage of AD.
Methods:
Using a novel transgenic AD rat model, animals were divided into wild-type, AD+sham PBM, and AD+PBM groups. Two-minute daily PBM was applied transcranially to the brain of AD animals from 2 months of age to 10 months of age. After completing PBM treatment at 10 months of age, behavioral tests were performed to measure learning, memory, and anxious-depressive-like behavior. Neuronal apoptosis, neuronal degeneration, neuronal damage, mitochondrial function, neuroinflammation, and oxidative stress were measured to test the effects of PBM on AD animals.
Results:
Behavioral tests showed that: 1) no spatial memory deficits were detected in TgF344 rats at 10 months of age; 2) PBM alleviated anxious-depressive-like behavior in TgF344 rats; 3) PBM attenuated neuronal damage, degeneration, and apoptosis; and 4) PBM suppresses neuroinflammation and oxidative stress.
Conclusion:
Our findings support our hypothesis that PBM could be an effective method to alleviate depression and anxiety during the early stage of AD development. The mechanism underlying these beneficial effects may be due to the improvement of mitochondria function and integrity and the inhibition of neuroinflammation and oxidative stress.
Background
Depression is the most debilitating neuropsychiatric disorder with significant impact on socio-occupational and well being of individual. The exact pathophysiology of depression is still enigmatic though various theories have been put forwarded. There are evidences showing that mitochondrial dysfunction in various brain regions is associated with depression. Recent findings have sparked renewed appreciation for the role of mitochondria in many intracellular processes coupled to synaptic plasticity and cellular resilience. New insights in depression pathophysiology are revolving around the impairment of neuroplasticity. Mitochondria have potential role in ATP production, intracellular Ca²⁺ signalling to establish membrane stability, reactive oxygen species (ROS) balance and to execute the complex processes of neurotransmission and plasticity. So understanding the various concepts of mitochondrial dysfunction in pathogenesis of depression indubitably helps to generate novel and more targeted therapeutic approaches for depression treatment.
Objective
The review was aimed to give a comprehensive insight on role of mitochondrial dysfunction in depression.
Result
Targeting mitochondrial dysfunction and enhancing the mitochondrial functions might act as potential target for the treatment of depression.
Conclusion
Literature cited in this review highly supports the role of mitochondrial dysfunction in depression. As impairment in the mitochondrial functions lead to the generation of various insults that exaggerate the pathogenesis of depression. So, it is useful to study mitochondrial dysfunction in relation to mood disorders, synaptic plasticity, neurogenesis and enhancing the functions of mitochondria might show promiscuous effects in the treatment of depressed patients.
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.
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.
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.
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.
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.
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.
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.
Recent evidences include mitochondrial dysfunctions in pathophysiology of mood disorders. We examined association between depressive disorders and mitochondrial respiration using both intact and permeabilized blood platelets. In intact platelets, physiological respiration, maximal capacity of electron transport system and respiratory rate after complex I inhibition were decreased in depressive patients, who reached partial remission, compared to healthy controls. Respiratory rates were unchanged in several respiratory states in permeabilized platelets. Results indicate that changes in respiratory rate in intact platelets can be used as biological marker of depressive disorder. Hypothesis was supported that decreased mitochondrial respiratory rate participate in pathophysiology of depression.
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.