Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety

Fredric Schiffer, Andrea L Johnston, Caitlin Ravichandran, Ann Polcari, Martin H Teicher, Robert H Webb, Michael R Hamblin, Fredric Schiffer, Andrea L Johnston, Caitlin Ravichandran, Ann Polcari, Martin H Teicher, Robert H Webb, Michael R Hamblin

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT00961454.

Figures

Figure 1
Figure 1
Near infrared treatment. The NIR LED array is a few millimeters from the skin beneath a heat sink and cooling fan at F3. Somanetics "SomaSensors" with NIR photon emitters and detectors are applied just above each eyebrow to measure left- and right-sided total hemoglobin.
Figure 2
Figure 2
Pre-frontal blood flow, "NIR on" versus "placebo". A comparison of the mean left-, right-sided, and left + right pre-frontal total hemoglobin (cHb) measurements (arbitrary, relative units) recorded during the two 4-minuted NIR treatments (F3 and F4), light on conditions, and during the two 4-minute placebo (LED off) conditions (F3 and F4). cHb is an index of regional cerebral blood flow (rCBF). Mean rCBf across hemispheres (left + right/2) increased from 0.011 units in the sham condition to 0.043 units in the treatment condition, for a difference of 0.032 (95% CI: -0.016, 0.080) units, though this result did not reach statistical significance (t9 = 1.52, p = 0.16). The increase with treatment was 0.046 (95% CI: -0.004, 0.097; t9 = 2.07, p = 0.07) units in the left hemisphere and 0.018 (95% CI: -0.033, 0.069; t9 = 0.80, p = 0.44) units in the right hemisphere, but the difference between hemispheres was also not statistically significant (95% CI for difference: -0.01, 0.063; t9 = 1.83; p = 0.10). Error bars represent 1 standard error from the mean.
Figure 3
Figure 3
Initial, 2-week, and 4-week HAM-D scores. The individual patient's Hamilton Depression Rating Scores at Baseline, 2-weeks, and at 4-weeks. A high score suggests more depression. Fifteen or above is suggestive of a clinical depression and below 8 is suggestive of a remission. The legend numbers correspond to the patient numbers. The mean scores are indicated.
Figure 4
Figure 4
Initial, 2-week, and 4-week HAM-A scores. The individual patient's Hamilton Anxiety Rating Scores at Baseline, 2-weeks, and at 4-weeks. A high score suggests more anxiety. Fifteen or above is suggestive of a clinical anxiety disorder and below 8 is suggestive of a remission. The legend numbers correspond to the patient numbers. The mean scores are indicated.

References

    1. Kessler R, McGonagle K, Swartz M, Blazer D, Nelson C. Sex and depression in the National Comorbidity Survey. I: Lifetime prevalence, chronicity and recurrence. J Affect Disord. 1993;29:85–96. doi: 10.1016/0165-0327(93)90026-G.
    1. Doris A, Ebmeier K, Shajahan P. Depressive illness. Lancet. 1999;354:1369–1375. doi: 10.1016/S0140-6736(99)03121-9.
    1. Murray C, Lopez A. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet. 1997;349:1436–1442. doi: 10.1016/S0140-6736(96)07495-8.
    1. Slade T, Johnston A, Browne MO, Andrews G, Whiteford H. 2007 National Survey of Mental Health and Wellbeing: methods and key findings. Aust N Z J Psychiatry. 2009;43:594–605. doi: 10.1080/00048670902970882.
    1. Yu W, Naim J, McGowan M, Ippolito K, Lanzafame R. Photomodulation of oxidative metabolism and electron chain enzymes in rat liver mitochondria. Photochem Photobiol. 1997;66:866–871. doi: 10.1111/j.1751-1097.1997.tb03239.x.
    1. Mochizuki-Oda N, Kataoka Y, Cui Y, Yamada H, Heya M, Awazu K. Effects of near-infra-red laser irradiation on adenosine triphosphate and adenosine diphosphate contents of rat brain tissue. Neurosci Lett. 2002;323:207–210. doi: 10.1016/S0304-3940(02)00159-3.
    1. Oron U, Ilic S, Taboada LD, Streeter J. Ga-As (808 nm) laser irradiation enhances ATP production in human neuronal cells in culture. Photomed Laser Surg. 2007;25:180–182. doi: 10.1089/pho.2007.2064.
    1. Chen ACH, Huang YY, Arany PR, Hamblin MR. In: Mechanisms for Low-Light Therapy IV; San Jose. Hamblin MR, Anders JJ, Waynant RW, editor. The International Society for Optical Engineering, Bellingham, WA; 2009. Role of reactive oxygen species in low level light therapy. doi: 10.1117/1112.814890.
    1. Zhang Y, Song S, Fong CC, Tsang CH, Yang Z, Yang M. cDNA microarray analysis of gene expression profiles in human fibroblast cells irradiated with red light. J Invest Dermatol. 2003;120:849–857. doi: 10.1046/j.1523-1747.2003.12133.x.
    1. Oron A, Oron U, Chen J, Eilam A, Zhang C, Sadeh M, Lampl Y, Streeter J, DeTaboada L, Chopp M. Low-level laser therapy applied transcranially to rats after induction of stroke significantly reduces long-term neurological deficits. Stroke. 2006;37:2620–2624. doi: 10.1161/01.STR.0000242775.14642.b8.
    1. Conlan M, Rapley J, Cobb C. Biostimulation of wound healing by low-energy laser irradiation. A review. J Clin Periodontol. 1996;23:492–496. doi: 10.1111/j.1600-051X.1996.tb00580.x.
    1. Castano AP, Dai T, Yaroslavsky I, Cohen R, Apruzzese WA, Smotrich MH, Hamblin MR. Low-level laser therapy for zymosan-induced arthritis in rats: Importance of illumination time. Lasers Surg Med. 2007;39:543–550. doi: 10.1002/lsm.20516.
    1. Oron U. Photoengineering of tissue repair in skeletal and cardiac muscles. Photomed Laser Surg. 2006;24:111–120. doi: 10.1089/pho.2006.24.111.
    1. Oron U, Yaakobi T, Oron A, Hayam G, Gepstein L, Rubin O, Wolf T, Haim SB. Attenuation of infarct size in rats and dogs after myocardial infarction by low-energy laser irradiation. Lasers Surg Med. 2001;28:204–211. doi: 10.1002/lsm.1039.
    1. Lapchak P, Salgado K, Chao C, Zivin J. Transcranial near-infrared light therapy improves motor function following embolic strokes in rabbits: an extended therapeutic window study using continuous and pulse frequency delivery modes. Neuroscience. 2007;148:907–914. doi: 10.1016/j.neuroscience.2007.07.002.
    1. Michalikova S, Ennaceur A, Rensburg Rv, Chazot P. Emotional responses and memory performance of middle-aged CD1 mice in a 3D maze: Effects of low infrared light. Neurobiol Learn Mem. 2007;187:312–326.
    1. Lampl Y, Zivin J, Fisher M, Lew R, Welin L, Dahlof B, Borenstein P, Andersson B, Perez J, Caparo C. Infrared Laser Therapy for Ischemic Stroke: A New Treatment Strategy. Results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1) Stroke. 2007.
    1. Zivin J, Albers G, Bornstein N, Chippendale T, Dahlof B, Devlin T, Fisher M, Hacke W, Holt W, Ilic S. Effectiveness and safety of transcranial laser therapy for acute ischemic stroke. Stroke. 2009;40:1359–1364. doi: 10.1161/STROKEAHA.109.547547.
    1. Fahim C, Stip E, Mancini-Marie A, Mensour B, Leroux J, Beaudoin G, Bourgouin P, Beauregard M. Abnormal prefrontal and anterior cingulate activation in major depressive disorder during episodic memory encoding of sad stimuli. Brain Cogn. 2004;54:161–163.
    1. Keedwell P, Andrew C, Williams S, Brammer M, Phillips M. The neural correlates of anhedonia in major depressive disorder. Biol Psychiatry. pp. 843–853.
    1. Phillips L, Drevets W, Rauch S, Lane R. Neurobiology of emotion perception II: Implications for major psychiatric disorders. Biol Psychiatry. 2003;54:515–528. doi: 10.1016/S0006-3223(03)00171-9.
    1. al-Awami M, Schillinger M, Maca T, Pollanz S, Minar E. Low level laser therapy for treatment of primary and secondary Raynaud's phenomenon. Vasa. 2004;33:25–28. doi: 10.1024/0301-1526.33.1.25.
    1. Hirschl M, Katzenschlager R, Francesconi C, Kundi M. Low level laser therapy in primary Raynaud's phenomenon--results of a placebo controlled, double blind intervention study. J Rheumatol. 2004;31:2408–2412.
    1. Kubota J. Effects of diode laser therapy on blood flow in axial pattern flaps in the rat model. Lasers Med Sci. 2002;17:146–153. doi: 10.1007/s101030200024.
    1. Schaffer M, Bonel H, Sroka R, Schaffer P, Busch M, Reiser M, Dühmke E. Effects of 780 nm diode laser irradiation on blood microcirculation: preliminary findings on time-dependent T1-weighted contrast-enhanced magnetic resonance imaging (MRI) J Photochem Photobiol B. 2000;54:55–60. doi: 10.1016/S1011-1344(99)00155-4.
    1. Avery D, Holtzheimer P, Fawaz W, Russo J, Neumaier J, Dunner D, Haynor D, Claypoole K, Wajdik C, Roy-Byrne P. A controlled study of repetitive transcranial magnetic stimulation in medication-resistant major depression. Biol Psychiatry. 2006;59:187–194. doi: 10.1016/j.biopsych.2005.07.003.
    1. Mayberg H, Lozano A, Voon V, McNeely H, Seminowicz D, Hamani C, Schwalb J, Kennedy S. Deep brain stimulation for treatment-resistant depression. Neuron. 2005;45:651–660. doi: 10.1016/j.neuron.2005.02.014.
    1. Eschweiler GW, Vonthein R, Bode R, Huell M, Conca A, Peters O, Mende-Lechler S, Peters J, Klecha D, Prapotnik M. Clinical efficacy and cognitive side effects of bifrontal versus right unilateral electroconvulsive therapy (ECT): A short-term randomised controlled trial in pharmaco-resistant major depression. J Affect Disord. 2007;101(1-3):149–57. doi: 10.1016/j.jad.2006.11.012.
    1. Nitsche M, Boggio P, Fregni F, Pascual-Leone A. Treatment of depression with transcranial direct current stimulation (tDCS): A Review. Exp Neurol. 2009;219(1):14–9. doi: 10.1016/j.expneurol.2009.03.038.
    1. Boggio P, Rigonatti S, Ribeiro R, Myczkowski M, Nitsche M, Pascual-Leone A, Fregni F. A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression. Int J Neuropsychopharmacol. 2008;11:249–254. doi: 10.1017/S1461145707007833.
    1. Ilic S, Leichliter S, Streeter J, Oron A, DeTaboada L, Oron U. Effects of power densities, continuous and pulse frequencies, and number of sessions of low-level laser therapy on intact rat brain. Photomed Laser Surg. 2006;24:458–466. doi: 10.1089/pho.2006.24.458.
    1. Spitzer R, Williams J, Gibbon M, First M. The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Arch Gen Psychiatry. 1992;49:624–629.
    1. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62. doi: 10.1136/jnnp.23.1.56.
    1. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50–5.
    1. Watson D, Clark L, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988;54:1063–1070. doi: 10.1037/0022-3514.54.6.1063.
    1. Schiffer F. Affect changes observed with right versus left lateral visual field stimulation in psychotherapy patients: possible physiological, psychological, and therapeutic implications. Compr Psychiatry. 1997;38:289–295. doi: 10.1016/S0010-440X(97)90062-6.
    1. Schiffer F. Of Two Minds: The Revolutionary Science of Dual-Brain Psychology. New York: The Free Press; 1998.
    1. Schiffer F, Anderson C, Teicher M. EEG, bilateral ear temperature, and affect changes induced by lateral visual field stimulation. Compr Psychiatry. 1999;40:221–225. doi: 10.1016/S0010-440X(99)90007-X.
    1. Schiffer F, Teicher M, Anderson C, Tomoda A, Polcari A, Navalta C, Andersen S. Determination of hemispheric emotional valence in individual subjects: a new approach with research and therapeutic implications. Behav Brain Funct. 2007;3:13. doi: 10.1186/1744-9081-3-13. Highly accessed.
    1. Schiffer F, Mottaghy F, Vimal RP, PF PR, Cowan R, Pascual-Leone A, Teicher M, Valente E, Rohan M. Lateral visual field stimulation reveals extrastriate cortical activation in the contralateral hemisphere: an fMRI study. Psychiatry Res. 2004;131:1–9. doi: 10.1016/j.pscychresns.2004.01.002.
    1. Schiffer F, Glass I, Lord J, Teicher M. Prediction of clinical outcomes from rTMS in depressed patients with lateral visual field stimulation: A replication. J Neuropsychiatry Clin Neurosci. 2008;2008:194–200.
    1. Schiffer F, Stinchfield Z, Pascual-Leone A. Prediction of clinical response to transcranial magnetic stimulation for depression by baseline lateral visual stimulation. Neuropsychiatry, Neuropsychology, and Behavioral Neurology. 2002;15:18–27.
    1. Stern W, Tormos J, Press D, Pearlman C, Pascual-Leone A. Antidepressant effects of high and low frequency repetitive transcranial magnetic stimulation to the dorsolateral prefrontal cortex: a double-blind, randomized, placebo-controlled trial. J Neuropsychiatry Clin Neurosci. 2007;19:179–186.
    1. Conlan MJ, Rapley JW, Cobb CM. Biostimulation of wound healing by low-energy laser irradiation. A review. J Clin Periodontol. 1996;23:492–496. doi: 10.1111/j.1600-051X.1996.tb00580.x.
    1. Moshkovska T, Mayberry J. It is time to test low level laser therapy in Great Britain. Postgrad Med J. 2005;81:436–441. doi: 10.1136/pgmj.2004.027755.
    1. Reddy GK. Photobiological basis and clinical role of low-intensity lasers in biology and medicine. J Clin Laser Med Surg. 2004;22:141–150. doi: 10.1089/104454704774076208.
    1. Gershon A, Dannon P, L LG. Transcranial magnetic stimulation in the treatment of depression. Am J Psychiatry. 2003;160:835–845. doi: 10.1176/appi.ajp.160.5.835.
    1. Loo C, Mitchell P, McFarquhar T, Malhi G, Sachdev P. A sham-controlled trial of the efficacy and safety of twice-daily rTMS in major depression. Psychol Med. 2007;37:341–349. doi: 10.1017/S0033291706009597.
    1. Grunhaus L, Schreiber S, Dolberg O, Polak D, Dannon P. A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant nonpsychotic major depression. Biol Psychiatry. 2003;53:324–331. doi: 10.1016/S0006-3223(02)01499-3.
    1. Janicak P, Dowd S, Martis B, Alam D, Beedle D, Krasuski J, Strong M, Sharma R, Rosen C, Viana M. Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: preliminary results of a randomized trial. Biol Psychiatry. 2002;52:1032–1033. doi: 10.1016/S0006-3223(02)01497-X.
    1. Pridmore S, Bruno R, Turnier-Shea Y, Reid P, Rybak M. Comparison of unlimited numbers of rapid transcranial magnetic stimulation (rTMS) and ECT treatment sessions in major depressive episode. Int J Neuropsychopharmacol. 2000;3:129–134. doi: 10.1017/S1461145700001784.
    1. Eschweiler G, Vonthein R, Bode R, Huell M, Conca A, Peters O, Mende-Lechler S, Peters J, Klecha D, Prapotnik M. Clinical efficacy and cognitive side effects of bifrontal versus right unilateral electroconvulsive therapy (ECT): a short-term randomised controlled trial in pharmaco-resistant major depression. J Affect Disord. 2007;101:149–157. doi: 10.1016/j.jad.2006.11.012.
    1. Tadiæ A, Helmreich I, Mergl R, Hautzinger M, Kohnen R, Henkel V, Hegerl U. Early improvement is a predictor of treatment outcome in patients with mild major, minor or subsyndromal depression. J Affect Disord. 2009. in press .
    1. Katz M, Tekell J, Bowden C, Brannan S, Houston J, Berman N, Frazer A. Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression. Neuropsychopharmacology. 2004;29:566–579. doi: 10.1038/sj.npp.1300341.
    1. Bech P, Cialdella P, Haugh M, Birkett M, Hours A, Boissel J, Tollefson G. Meta-analysis of randomised controlled trials of fluoxetine v. placebo and tricyclic antidepressants in the short-term treatment of major depression. Br J Psychiatry. 2000;176:421–428. doi: 10.1192/bjp.176.5.421.
    1. Leichsenring F, Salzer S, Jaeger U, Kächele H, Kreische R, Leweke F, Rüger U, Winkelbach C, Leibing E. Short-Term Psychodynamic Psychotherapy and Cognitive-Behavioral Therapy in Generalized Anxiety Disorder: A Randomized, Controlled Trial. Am J Psychiatry. 2009. in press .
    1. Montgomery S, Herman B, Schweizer E, Mandel F. The efficacy of pregabalin and benzodiazepines in generalized anxiety disorder presenting with high levels of insomnia. Int Clin Psychopharmacol. 2009;24:214–222. doi: 10.1097/YIC.0b013e32832dceb9.
    1. Kubota J. Effects of diode laser therapy on blood flow in axial pattern flaps in the rat model. Lasers Med Sci. 2002;17:146–153. doi: 10.1007/s101030200024.

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