OBJECTIVE:Affective disorder during pregnancy is a common condition requiring careful judgment to treat the depression while minimizing risk to the fetus. Following up on promising pilot trials, we studied the efficacy of light therapy.

METHOD:Twenty-seven pregnant women with nonseasonal major depressive disorder according to DSM-IV (outpatients, university polyclinic) were randomly assigned to 7,000 lux fluorescent bright white or 70 lux dim red (placebo) light administered at home in the morning upon awakening for 1 h/d in a 5-week double-blind trial carried out between October 2004 and October 2008. Clinical state was monitored weekly with the 29-item Structured Interview Guide for the Hamilton Depression Rating Scale (HDRS) with Atypical Depression Supplement (SIGH-ADS). Changes of rating scale scores over time were analyzed with the general linear model. Differences from baseline of SIGH-ADS and 17-item HDRS scores at every time point were the dependent variables, time was the within-subjects factor, and treatment was the between-subjects factor. The model also included baseline score of depression and gestational age at intervention start.

RESULTS:The superiority of bright light over dim light placebo was shown for both SIGH-ADS (R² = 0.251; F(3,23) = 3.91; P<.05) and HDRS (R² = 0.338; F(3,23) = 5.42; P<.01) when analyzing the week-by-week change from baseline, and HDRS scores showed a significant interaction of treatment with time (F(4,92) = 2.91; P<.05). Categorical analysis revealed that the response rate (HDRS≥ 50% improvement) at week 5 was significantly greater for bright light (81.3%, n = 16) than for placebo light (45.5%, n = 11) (P<.05). Remission (final score≤ 8) was attained by 68.6% versus 36.4%, respectively (P<.05). Expectation ratings did not differ significantly between groups.

CONCLUSIONS:Bright white light treatment for 5 weeks improved depression during pregnancy significantly more than placebo dim red light. The study provides evidence that light therapy, a simple, cost-effective antidepressant modality with minimal side effects for the mother and no known risk for the unborn child, may be a useful nonpharmacologic approach in this difficult situation.

TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01043289.

BACKGROUND:The aim of the study was to examine the efficacy and safety of morning bright light therapy (BLT) in the treatment of patients with a current major depressive episode (MDE) in bipolar and unipolar disorder without a seasonal pattern. It was a randomized, sham-controlled trial.

METHODS:Adults, ages 18-70 years were randomized to treatment either with BLT or a sham negative ion generator (as a placebo control). The subjects were required to be on a stable and therapeutic dose of psychotropic medication for at least 4 weeks prior to enrollment and their treatment had to be insufficiently effective. Their clinical state was monitored at the baseline and at the end of treatment. The Hamilton Depression Rating Scale-21 items (HDRS-21), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI-II), Clinical Global Impression-Severity (CGI-S) and Patient Global Impression (PGI) were used. The results were analyzed with an intention-to-treat (ITT) analysis.

RESULTS:Ninety-five patients were enrolled (50 diagnosed with bipolar disorder and 45 with unipolar depression). Fifty-two patients were randomized to treatment with BLT and forty-three were in the placebo group (ITT population). Eighty-three subjects completed the study. There were 12 dropouts (5 in the light group and 7 in the placebo group). After 14 days of treatment, a significant improvement was found in all groups (p<0.001). The subjects treated with BLT did not significantly differ in terms of improvement in HDRS-21 scores at the endpoint when compared to patients treated with placebo (p=0.2). However, further analysis demonstrated significantly higher response (50% v. 27.9%, p=0.02) and remission rates (28.8% v. 11.6%, p=0.04) among patients treated with morning BLT when compared to placebo group. It should be noted that in the population of drug-resistant patients, BLT was more efficacious than placebo. There were no statistically significant differences between unipolar and bipolar disorders (p=0.4).

CONCLUSION:Although overall improvement in HDRS-21 scores were not superior in the BLT group, both response and remission rates were significantly higher among patients treated with BLT relative to those receiving the sham intervention. BLT was also more efficacious than placebo in the population of patients with drug-resistant depression. Further studies to define the subpopulation of patients with non-seasonal depression who may benefit the most from BLT are needed.

Objective:Bright light therapy is a noninvasive biological intervention for disorders with nonnormative circadian features. Eating disorders, particularly those with binge-eating and night-eating features, have documented nonnormative circadian eating and mood patterns, suggesting that bright light therapy may be an efficacious stand-alone or adjunctive intervention. The purpose of this systematic literature review, using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, was (1) to evaluate the state of the empirical treatment outcome literature on bright light therapy for eating disorders and (2) to explore the timing of eating behavior, mood, and sleep-related symptom change so as to understand potential mechanisms of bright light therapy action in the context of eating disorder treatment.

Data Sources:A comprehensive literature search using PsycInfo and PubMed/MEDLINE was conducted in April 2016 with no date restrictions to identify studies published using bright light therapy as a treatment for eating disorders. Keywords included combinations of terms describing disordered eating (eating disorder, anorexia nervosa, bulimia nervosa, binge eating, binge, eating behavior, eating, and night eating) and the use of bright light therapy (bright light therapy, light therapy, phototherapy). After excluding duplicates, 34 articles were reviewed for inclusion.

Study Selection and Data Extraction:14 published studies of bright light therapy for eating disorders met inclusion criteria (included participants with an eating disorder/disordered-eating behaviors; presented as a case study, case series, open-label clinical trial, or randomized/nonrandomized controlled trial; written in English; and published and available by the time of manuscript review).

Results:Results suggest that bright light therapy is potentially effective at improving both disordered-eating behavior and mood acutely, although the timing of symptom response and the duration of treatment effects remain unknown.

Conclusions:Future research should systematically control for placebo response, assess symptom change frequently and across a broad range of systems, and evaluate the longer-term efficacy of bright light therapy for eating disorders.

We sought to establish the feasibility and preliminary effects of home-wearable light therapy for postpartum depression, and its effects on circadian measures. Eight women within 6 months postpartum were prescribed 60 min of daily morning light therapy for 5 weeks. The device was well tolerated. Significant improvements were observed in self-report and clinician-rated depression symptoms, with little change in objective circadian measures. Home-wearable light therapy is feasible for postpartum women and may be a promising treatment for postpartum depression. Clinicaltrials.gov Identifier: NCT02769858.

OBJECTIVES:We investigated the clinical benefits of bright light therapy (BLT) as an adjunct treatment to ongoing psychopharmacotherapy, both in unipolar and bipolar difficult-to-treat depressed (DTD) outpatients.

METHODS:In an open-label study, 31 depressed outpatients (16 unipolar and 15 bipolar) were included to undergo 3 weeks of BLT. Twenty-five completed the treatment and 5-week follow-up.

MAIN OUTCOME MEASURES:Clinical outcomes were evaluated by the Hamilton Depression Rating Scale (HDRS). The Snaith-Hamilton Pleasure Scale and the Depression Retardation Rating Scale were used to assess changes in anhedonia and psychomotor retardation, respectively.

RESULTS:The adjunctive BLT seemed to influence the course of the depressive episode, and a statistically significant reduction in HDRS scores was reported since the first week of therapy. The treatment was well-tolerated, and no patients presented clinical signs of (hypo)manic switch during the overall treatment period. At the end of the study (after 5 weeks from BLT discontinuation), nine patients (36%, eight unipolar and one bipolar) still showed a treatment response. BLT augmentation also led to a significant improvement of psychomotor retardation.

CONCLUSION:BLT combined with the ongoing pharmacological treatment offers a simple approach, and it might be effective in rapidly ameliorating depressive core symptoms of vulnerable DTD outpatients. These preliminary results need to be confirmed in placebo-controlled, randomized, double-blind clinical trial on larger samples.

OBJECTIVES:We investigated the clinical benefits of bright light therapy (BLT) as an adjunct treatment to ongoing psychopharmacotherapy, both in unipolar and bipolar difficult-to-treat depressed (DTD) outpatients.

METHODS:In an open-label study, 31 depressed outpatients (16 unipolar and 15 bipolar) were included to undergo 3 weeks of BLT. Twenty-five completed the treatment and 5-week follow-up.

MAIN OUTCOME MEASURES:Clinical outcomes were evaluated by the Hamilton Depression Rating Scale (HDRS). The Snaith-Hamilton Pleasure Scale and the Depression Retardation Rating Scale were used to assess changes in anhedonia and psychomotor retardation, respectively.

RESULTS:The adjunctive BLT seemed to influence the course of the depressive episode, and a statistically significant reduction in HDRS scores was reported since the first week of therapy. The treatment was well-tolerated, and no patients presented clinical signs of (hypo)manic switch during the overall treatment period. At the end of the study (after 5 weeks from BLT discontinuation), nine patients (36%, eight unipolar and one bipolar) still showed a treatment response. BLT augmentation also led to a significant improvement of psychomotor retardation.

CONCLUSION:BLT combined with the ongoing pharmacological treatment offers a simple approach, and it might be effective in rapidly ameliorating depressive core symptoms of vulnerable DTD outpatients. These preliminary results need to be confirmed in placebo-controlled, randomized, double-blind clinical trial on larger samples.

Background:Bright light therapy has demonstrated efficacy and is an accepted treatment for seasonal depression. It has been suggested that bright light therapy may have efficacy in nonseasonal depressions. Also, there is evidence that bright light therapy may improve responsiveness to antidepressant pharmacotherapy.

Data Sources:We searched PubMed/MEDLINE, PsycINFO, PsycARTICLES, CINAHL, EMBASE, Scopus, and Academic OneFile for English-language literature published between January 1998 and April 2016, using the keywords bright light therapy AND major depression, bright light therapy AND depress*, bright light therapy AND bipolar depression, bright light therapy AND affective disorders, circadian rhythm AND major depression, circadian rhythm AND depress*, and circadian rhythm AND affective disorder.

Study Selection and Data Extraction:Studies that reported randomized trials comparing antidepressant pharmacotherapy with bright light therapy≥ 5,000 lux for ≥ 30 minutes to antidepressant pharmacotherapy without bright light therapy for the treatment of nonseasonal depression were included. Studies of seasonal depression were excluded. Following review of the initial 112 returns, 2 of the authors independently judged each trial, applying the inclusionary and exclusionary criteria. Ten studies were selected as meeting these criteria. Subjects in these studies were pooled using standard techniques of meta-analysis.

Results:Ten studies involving 458 patients showed improvement using bright light therapy augmentation versus antidepressant pharmacotherapy alone. The effect size was similar to that of other accepted augmentation strategies, roughly 0.5.

Conclusions:Analysis of pooled data from randomized trials provides evidence for the efficacy of use of bright light therapy≥ 5,000 lux for periods ≥ 30 minutes when used as augmentation to standard antidepressant pharmacotherapy in the treatment of major depressive disorder and bipolar depression without a seasonal pattern.

Background:Bright light therapy has demonstrated efficacy and is an accepted treatment for seasonal depression. It has been suggested that bright light therapy may have efficacy in nonseasonal depressions. Also, there is evidence that bright light therapy may improve responsiveness to antidepressant pharmacotherapy.

Data Sources:We searched PubMed/MEDLINE, PsycINFO, PsycARTICLES, CINAHL, EMBASE, Scopus, and Academic OneFile for English-language literature published between January 1998 and April 2016, using the keywords bright light therapy AND major depression, bright light therapy AND depress*, bright light therapy AND bipolar depression, bright light therapy AND affective disorders, circadian rhythm AND major depression, circadian rhythm AND depress*, and circadian rhythm AND affective disorder.

Study Selection and Data Extraction:Studies that reported randomized trials comparing antidepressant pharmacotherapy with bright light therapy≥ 5,000 lux for ≥ 30 minutes to antidepressant pharmacotherapy without bright light therapy for the treatment of nonseasonal depression were included. Studies of seasonal depression were excluded. Following review of the initial 112 returns, 2 of the authors independently judged each trial, applying the inclusionary and exclusionary criteria. Ten studies were selected as meeting these criteria. Subjects in these studies were pooled using standard techniques of meta-analysis.

Results:Ten studies involving 458 patients showed improvement using bright light therapy augmentation versus antidepressant pharmacotherapy alone. The effect size was similar to that of other accepted augmentation strategies, roughly 0.5.

Conclusions:Analysis of pooled data from randomized trials provides evidence for the efficacy of use of bright light therapy≥ 5,000 lux for periods ≥ 30 minutes when used as augmentation to standard antidepressant pharmacotherapy in the treatment of major depressive disorder and bipolar depression without a seasonal pattern.

The study objective was to determine the effect of winter bright light therapy on binge and purge frequencies and depressive symptoms in subjects with bulimia nervosa. Thirty-four female bulimic outpatients were treated with either 10,000 lux bright white light or 50 lux dim red light (placebo control) during the winter months. In this double-blind study, the placebo group (n = 18) and the bright light group (n = 16) were matched for age, degree of seasonality (measured by the Seasonal Patterns Assessment Questionnaire [SPAQ]), and concurrent depression (measured by Structured Clinical Interview for DSM-IV [SCID]). Three weeks of baseline data collection were followed by 3 weeks of half-hour daily morning light treatment and 2 weeks of follow-up evaluation. There was a significant light-treatment by time interaction (Wilks' lambda = .81, F(2,28) = 3.31, P = .05). The mean binge frequency decreased significantly more from baseline to the end of treatment for the bright light group (F(1,29) = 6.41, P = .017) than for the placebo group. The level of depression (measured by daily Beck Depression Inventory [BDI] scores) did not significantly differ between the groups during any phase, and neither depression nor seasonality affected the response to light treatment. In this double-blind study, bulimic women who received 3 weeks of winter bright light treatment reported a reduced binge frequency between baseline and the active treatment period in comparison to subjects receiving dim red light.

CONTEXT:Major depressive disorder (MDD) in elderly individuals is prevalent and debilitating. It is accompanied by circadian rhythm disturbances associated with impaired functioning of the suprachiasmatic nucleus, the biological clock of the brain. Circadian rhythm disturbances are common in the elderly. Suprachiasmatic nucleus stimulation using bright light treatment (BLT) may, therefore, improve mood, sleep, and hormonal rhythms in elderly patients with MDD.

OBJECTIVE:To determine the efficacy of BLT in elderly patients with MDD.

DESIGN:Double-blind, placebo-controlled randomized clinical trial.

SETTING:Home-based treatment in patients recruited from outpatient clinics and from case-finding using general practitioners' offices in the Amsterdam region.

PARTICIPANTS:Eighty-nine outpatients 60 years or older who had MDD underwent assessment at baseline (T0), after 3 weeks of treatment (T1), and 3 weeks after the end of treatment (T2). Intervention Three weeks of 1-hour early-morning BLT (pale blue, approximately 7500 lux) vs placebo (dim red light, approximately 50 lux).

MAIN OUTCOME MEASURES:Mean improvement in Hamilton Scale for Depression scores at T1 and T2 using parameters of sleep and cortisol and melatonin levels.

RESULTS:Intention-to-treat analysis showed Hamilton Scale for Depression scores to improve with BLT more than placebo from T0 to T1 (7%; 95% confidence interval, 4%-23%; P = .03) and from T0 to T2 (21%; 7%-31%; P = .001). At T1 relative to T0, get-up time after final awakening in the BLT group advanced by 7% (P<.001), sleep efficiency increased by 2% (P = .01), and the steepness of the rise in evening melatonin levels increased by 81% (P = .03) compared with the placebo group. At T2 relative to T0, get-up time was still advanced by 3% (P = .001) and the 24-hour urinary free cortisol level was 37% lower (P = .003) compared with the placebo group. The evening salivary cortisol level had decreased by 34% in the BLT group compared with an increase of 7% in the placebo group (P = .02).

CONCLUSIONS:In elderly patients with MDD, BLT improved mood, enhanced sleep efficiency, and increased the upslope melatonin level gradient. In addition, BLT produced continuing improvement in mood and an attenuation of cortisol hyperexcretion after discontinuation of treatment.

TRIAL REGISTRATION:clinicaltrials.gov Identifier NCT00332670.

BACKGROUND: Postherpetic neuralgia (PHN) is one of the common complications of herpes zoster infection, particularly in the elderly. Current therapeutic measures are only partially effective in the affected patients. As inflammatory mediators released by different cells play an important role in the pathogenesis of this neuropathic pain and with regard to the immunomodulatory effects of ultraviolet B (UVB) spectrum, we presumed that UVB phototherapy might be effective in the prevention of PHN. METHOD: This study was performed in two phases. Phase I was a prospective open controlled trial. Twenty-five patients with severe pain in the first 7 days of zoster rash were divided into two groups: the prevention group (n=12) received oral acyclovir (800 mg five times a day for 10 days) plus broad-band UVB to the affected dermatomes, starting with 20 mJ/cm(2) and gradually increasing the dose by 10 mJ/cm(2) each session to a maximum dose of 100 mJ/cm(2). Treatment sessions were repeated three times a week until pain relief or to a maximum of 15 sessions. The control group (n=13), who had disease characteristics similar to the prevention group, received only oral acyclovir with the same dose. All patients reported their severity of pain on a verbal rating scale (VRS, score 0-4) before treatment and at 1 and 3 months' follow-up. In phase II of the study, five patients with established PHN (more than 3 months after rash onset) received UVB with the above-mentioned protocol. RESULTS: A total of 17 patients older than 40 (10 females, seven males; mean age, 65.5 years; range: 47-82 years) who had intractable pain due to zoster infection received UVB in two phases of the study. In patients who received phototherapy in the first 7 days of rash, 58.33% and 83.33% were completely pain free at 1-and 3-month follow-up, respectively. The corresponding figure in the control group was significantly lower (38.46% at 1 month and 53.85% at 3 months). The severity of pain was also lower in the phototherapy group than the control group (mean VRS 2.50 vs. 3.28 at 3 months). None of the patients who were treated more than 3 months after rash onset (established PHN) experienced significant (more than 50%) pain relief. CONCLUSION: UVB phototherapy in the acute stage of zoster rash might reduce the incidence and severity of PHN. Treatment after 3 months does not seem to have a significant beneficial effect.

Background::C-reactive protein is an inflammatory biomarker and its level increases in the serum of psoriatic patients. Its level is also associated with Psoriasis Area and Severity Index score.

Objective::The aim of this study was to assess the decrement of serum C-reactive protein level with narrow-band ultraviolet B (NB-UVB) therapy.

Methods::C-reactive protein serum levels in psoriasis patients were measured before and after treatment with NB-UVB and the data were analyzed in relation to the Psoriasis Area and Severity Index score improvement.

Results::Baseline C-reactive protein levels among psoriatic patients were higher than normal. These levels decreased significantly after treatment (P<0.001). At the beginning of the study, patients with higher levels of C-reactive protein also had more extensive and severe skin involvement. The highest decrease in C-reactive protein was observed in patients who responded better to the treatment and achieved a higher Psoriasis Area and Severity Index 75%. There was an association between baseline Psoriasis Area and Severity Index scores and C-reactive protein levels.

Conclusion::Patients with moderate to severe plaque-type psoriasis had active systemic inflammation, which was demonstrated by increased levels of C-reactive protein. Furthermore, skin disease severity was correlated with C-reactive protein levels. Phototherapy healed the psoriatic skin lesions and reduced inflammation, while decreasing C-reactive protein levels.

Glycyrrhizin has been used clinically for several years due to its beneficial effect on immunoglobulin E (IgE)-induced allergic diseases, alopecia areata and psoriasis. In this study, glycyrrhizin, ultraviolet B light (UVB) or a combination of both were used to treat active-stage generalized vitiligo. One hundred and forty-four patients between the ages of 3 and 48 years were divided into three groups: group A received oral compound glycyrrhizin (OCG); group B received UVB applications twice weekly, and group C received OCG+UVB. Follow-ups were performed at 2, 4, and 6 months after the treatment was initiated. The Vitiligo Area Scoring Index (VASI) and the Vitiligo Disease Activity (VIDA) instrument were used to assess the affected body surface, at each follow-up. Results showed that 77.1, 75.0 and 87.5% in groups A, B and C, respectively, presented repigmentation of lesions. Responsiveness to therapy seemed to be associated with lesion location and patient compliance. Adverse events were limited and transient. This study showed that, although the three treatment protocols had positive results, OCG and UVB combination therapy was the most effective and led to improvement in disease stage from active to stable.

Glycyrrhizin has been used clinically for several years due to its beneficial effect on immunoglobulin E (IgE)-induced allergic diseases, alopecia areata and psoriasis. In this study, glycyrrhizin, ultraviolet B light (UVB) or a combination of both were used to treat active-stage generalized vitiligo. One hundred and forty-four patients between the ages of 3 and 48 years were divided into three groups: group A received oral compound glycyrrhizin (OCG); group B received UVB applications twice weekly, and group C received OCG+UVB. Follow-ups were performed at 2, 4, and 6 months after the treatment was initiated. The Vitiligo Area Scoring Index (VASI) and the Vitiligo Disease Activity (VIDA) instrument were used to assess the affected body surface, at each follow-up. Results showed that 77.1, 75.0 and 87.5% in groups A, B and C, respectively, presented repigmentation of lesions. Responsiveness to therapy seemed to be associated with lesion location and patient compliance. Adverse events were limited and transient. This study showed that, although the three treatment protocols had positive results, OCG and UVB combination therapy was the most effective and led to improvement in disease stage from active to stable.

INTRODUCTION: Perinatal Major Depressive Disorder (MDD) is common and poses particular treatment dilemmas. Complementary and Alternative Medicine (CAM) treatments are widely used, accessible, and understudied for well-defined psychiatric indications. Women are more likely than men to both suffer from MDD and use CAM.

METHODS: A PubMed/Medline search was conducted to assess the evidence base for commonly utilized CAM treatments, MDD, and perinatal depression. RESULTS: Among CAM treatments, omega-3 fatty acids have received the most specific study in terms of epidemiological, preclinical, and clinical research for perinatal depression. Three randomized placebo-controlled trials have been conducted in which investigators assessed omega-3 fatty acids vs. placebo for perinatal depression, with conflicting results. CAM interventions that can be easily added to a treatment plan with little risk and general health benefits for most women include omega-3 fatty acids, exercise, and folate, although data are insufficient at this time to recommend any of these as monotherapy for perinatal depression. S-adenosyl-methionine (SAMe) and bright light therapy may be reasonable to consider based on the evidence in MDD. St. John's Wort requires further study with regard to safety in pregnancy, and drug interactions can be a potential problem.

DISCUSSION: Further study is required to elucidate the role of CAM treatments for perinatal depression, and the clinical context of perinatal depression requires safe, effective, and accessible treatment options.

It is known that curcumin, a dietary pigment from the plant Curcuma longa, inhibits cell proliferation and induces apoptosis in different cell lines; however, the therapeutic benefit is hampered by very low absorption after transdermal or oral application. Recent studies from our laboratory have demonstrated that curcumin at low concentrations (0.2-1 microg/ml) offered the described effects only when applied with UVA or visible light. Nevertheless, the in vivo efficacy of this combination is lacking. In the present study, we used a xenograft tumor model with human epithelial carcinoma A431 cells to test the effect of curcumin and visible light on tumor growth. It was found that tumor growth was significantly inhibited in mice that were i.p. injected with curcumin and consecutively irradiated with visible light. Furthermore, immunohistochemistry showed a reduction of Ki 67 expression, indicating a decrease of cycling cells and induction of apoptotic bodies. The effect on apoptosis was further confirmed by Western blot analysis showing enhanced activation of caspases-9. Vice versa inhibition of extracellular regulated kinases (ERK) 1/2 and epidermal growth factor receptor (EGF-R) was observed which may aid inhibition of proliferation and induction of apoptosis. In summary, the present findings suggest a combination of curcumin and light as a new therapeutic concept to increase the efficacy of curcumin in the treatment of cancer.

Light controls pineal melatonin production and temporally coordinates circadian rhythms of metabolism and physiology in normal and neoplastic tissues. We previously showed that peak circulating nocturnal melatonin levels were 7-fold higher after daytime spectral transmittance of white light through blue-tinted (compared with clear) rodent cages. Here, we tested the hypothesis that daytime blue-light amplification of nocturnal melatonin enhances the inhibition of metabolism, signaling activity, and growth of prostate cancer xenografts. Compared with male nude rats housed in clear cages under a 12:12-h light:dark cycle, rats in blue-tinted cages (with increased transmittance of 462-484 nm and decreased red light greater than 640 nm) evinced over 6-fold higher peak plasma melatonin levels at middark phase (time, 2400), whereas midlight-phase levels (1200) were low (less than 3 pg/mL) in both groups. Circadian rhythms of arterial plasma levels of linoleic acid, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were disrupted in rats in blue cages as compared with the corresponding entrained rhythms in clear-caged rats. After implantation with tissue-isolated PC3 human prostate cancer xenografts, tumor latency-to-onset of growth and growth rates were markedly delayed, and tumor cAMP levels, uptake-metabolism of linoleic acid, aerobic glycolysis (Warburg effect), and growth signaling activities were reduced in rats in blue compared with clear cages. These data show that the amplification of nighttime melatonin levels by exposing nude rats to blue light during the daytime significantly reduces human prostate cancer metabolic, signaling, and proliferative activities.

Our research objective was to increase isoflavone content in the germinated soybean seeds of four different varieties (Pungsannamulkong, Cheongjakong, Aga4, and Aga3) by optimizing light treatments (dark, greenhouse, fluorescent, incandescent, and ultraviolet lamps). The results demonstrated that the highest isoflavone content was produced from the Aga3 variety, which was developed by an interspecific cross between Eunhakong (Glycine max) and KLG10084 (G. soja) at the Plant Genetic Laboratory, Kyunpook National University. Aga3 is known to have one of the highest isoflavone content in the world at present. Our results recommend exposure of 7-day-old Aga3 sprouts to a combined light treatment of greenhouse lamps (12 h per day) and ultraviolet light (40 min per day) for maximum isoflavone production. Aga3 produced high levels of isoflavone because, in part, it contained very high isoflavone levels within the seed as compared with the other varieties. Under stress conditions, Aga3 could produce over 1.90 times more isoflavone than its seed content and 1.53 times more isoflavone than when grown under dark conditions.

STUDY OBJECTIVES:Chronic sleep onset insomnia with late melatonin onset is prevalent in childhood, and has negative daytime consequences. Melatonin treatment is known to be effective in treating these sleep problems. Bright light therapy might be an alternative treatment, with potential advantages over melatonin treatment. In this study, we compare the effects of melatonin and bright light treatment with a placebo condition in children with chronic sleep onset insomnia and late melatonin onset.

METHODS:84 children (mean age 10.0 years, 61% boys) first entered a baseline week, after which they received melatonin (N=26), light (N=30), or placebo pills (N=28) for three to four weeks. Sleep was measured daily with sleep diaries and actigraphy. Before and after treatment children completed a questionnaire on chronic sleep reduction, and Dim Light Melatonin Onset (DLMO) was measured. Results were analysed with linear mixed model analyses.

RESULTS:Melatonin treatment and light therapy decreased sleep latency (sleep diary) and advanced sleep onset (sleep diary and actigraphy), although for sleep onset the effects of melatonin were stronger. In addition, melatonin treatment advanced DLMO and had positive effects on sleep latency and sleep efficiency (actigraphy data), and sleep time (sleep diary and actigraphy data). However, wake after sleep onset (actigraphy) increased with melatonin treatment. No effects on chronic sleep reduction were found.

CONCLUSIONS:We found positive effects of both melatonin and light treatment on various sleep outcomes, but more and stronger effects were found for melatonin treatment.

NEDERLANDS TRIAL REGISTER (NTR):NTR4045 (http://www.trialregister.nl).

IMPORTANCE:Bright light therapy is an evidence-based treatment for seasonal depression, but there is limited evidence for its efficacy in nonseasonal major depressive disorder (MDD).

OBJECTIVE:To determine the efficacy of light treatment, in monotherapy and in combination with fluoxetine hydrochloride, compared with a sham-placebo condition in adults with nonseasonal MDD.

DESIGN, SETTING, AND PARTICIPANTS:Randomized, double-blind, placebo- and sham-controlled, 8-week trial in adults (aged 19-60 years) with MDD of at least moderate severity in outpatient psychiatry clinics in academic medical centers. Data were collected from October 7, 2009, to March 11, 2014. Analysis was based on modified intent to treat (randomized patients with≥1 follow-up rating).

INTERVENTIONS:Patients were randomly assigned to (1) light monotherapy (active 10,000-lux fluorescent white light box for 30 min/d in the early morning plus placebo pill); (2) antidepressant monotherapy (inactive negative ion generator for 30 min/d plus fluoxetine hydrochloride, 20 mg/d); (3) combination light and antidepressant; or (4) placebo (inactive negative ion generator plus placebo pill).

MAIN OUTCOMES AND MEASURES:Change score on the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to the 8-week end point. Secondary outcomes included response (≥50% reduction in MADRS score) and remission (MADRS score ≤10 at end point).

RESULTS:A total of 122 patients were randomized (light monotherapy, 32; fluoxetine monotherapy, 31; combination therapy, 29; placebo, 30). The mean (SD) changes in MADRS score for the light, fluoxetine, combination, and placebo groups were 13.4 (7.5), 8.8 (9.9), 16.9 (9.2), and 6.5 (9.6), respectively. The combination (effect size [d] = 1.11; 95% CI, 0.54 to 1.64) and light monotherapy (d = 0.80; 95% CI, 0.28 to 1.31) were significantly superior to placebo in the MADRS change score, but fluoxetine monotherapy (d = 0.24; 95% CI, -0.27 to 0.74) was not superior to placebo. For the respective placebo, fluoxetine, light,and combination groups at the end point, response was achieved by 10 (33.3%), 9 (29.0%), 16 (50.0%), and 22 (75.9%) and remission was achieved by 9 (30.0%), 6 (19.4%), 14 (43.8%), and 17 (58.6%). Combination therapy was superior to placebo in MADRS response (β = 1.70; df = 1; P = .005)and remission (β = 1.33; df = 1; P = .02), with numbers needed to treat of 2.4 (95% CI, 1.6 to 5.8) and 3.5 (95% CI, 2.0 to 29.9), respectively. All treatments were generally well tolerated, with few significant differences in treatment-emergent adverse events.

CONCLUSIONS AND RELEVANCE:Bright light treatment, both as monotherapy and in combination with fluoxetine, was efficacious and well tolerated in the treatment of adults with nonseasonal MDD. The combination treatment had the most consistent effects.

TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00958204.