روشن در مقابل نور محیط کم نور بهزیستی ذهنی را تحت تاثیر قرار می دهد اما بر عوامل مرتبط بیولوژیکی سروتونین تاثیر ندارد

Abstract Light falling on the retina is converted into an electrical signal which stimulates serotonin synthesis. Previous studies described an increase of plasma and CNS serotonin levels after bright light exposure. Ghrelin and leptin are peptide hormones which are involved in the regulation of hunger/satiety and are related to serotonin. Neopterin and kynurenine are immunological markers which are also linked to serotonin biosynthesis. In this study, 29 healthy male volunteers were exposed to bright (5000 lx) and dim (50 lx) light conditions for 120 min in a cross-over manner. Subjective well-being and hunger as well as various serotonin associated plasma factors were assessed before and after light exposure. Subjective well-being showed a small increase under bright light and a small decrease under dim light, resulting in a significant interaction between light condition and time. Ghrelin concentrations increased significantly under both light conditions, but there was no interaction between light and time. Correspondingly, leptin decreased significantly under both light conditions. Hunger increased significantly with no light–time interaction. We also found a significant decrease of neopterin, tryptophan and tyrosine levels, but no interaction between light and time. In conclusion, ambient light was affecting subjective well-being rather than serotonin associated biological factors.

Introduction Light is a potent synchronizer of the endogenous pacemaker in the hypothalamus (Boivin et al., 1996). Light impulses affect the suprachiasmatic nucleus (SCN) via the retinothalamic tract and photosensitive, melanopsin-expressing ganglions in the retina, where the light input is converted into an electrical signal by membrane potential changes (Lockley et al., 2003). These electrical signals are transmitted to the pineal gland which contains high levels of serotonin. Serotonin has an impact on numerous behavioral functions including mood, impulsivity, the sleep–wake rhythm, sexual behavior, nociception, body temperature, the immune system, hunger/satiety and energy balance (Jonnakuty and Gragnoli, 2008 and Marston et al., 2011). Previous studies have described an effect of bright light exposure on plasma and central nervous system (CNS) serotonin levels in depressed patients as well as in healthy subjects (Even et al., 2008, Neumeister et al., 1996 and Golden et al., 2005). Besides the well-known mood effects of bright light therapy (Neumeister et al., 1998 and Benedetti et al., 2003), a number of light-induced alterations in psychological and behavioral functions in humans including cognition, memory, agitation, sleep and others have been reported (Benedetti et al., 2003, Golden et al., 2005 and Lieverse et al., 2010). Recently, a 3-week treatment with bright light was found to reduce appetite and body fat in overweight women (Danilenko et al., 2013). All of these features are subject to complex mechanisms with serotonin as a major modulating factor. There are several other serotonin-related hormones and messenger molecules which may be photosensitive, thus being potential moderators between ambient light and human functioning. 1.1. Fat hormones and adipokines Ghrelin is a 28 amino-acid peptide, mainly produced in the stomach, but also in the CNS (Van der Lely et al., 2004 and Portelli et al., 2012). During food restriction plasma levels of ghrelin are high while they decrease after food intake. There is also evidence that ghrelin, as an orexigenic hormone, mediates food intake, increases appetite, decreases thermogenesis and causes a positive energy balance via the hypothalamus (Van der Lely et al., 2004). A number of other, partly serotonin mediated, physiological and behavioral functions of ghrelin have been described. E.g., ghrelin promotes slow wave sleep, is able to inhibit the expression of proinflammatory cytokines, stimulates neuroprotection and inhibits serotonin release in depolarized neurons (Weikel et al., 2003, Dixit and Taub, 2005, Frago et al., 2011 and Brunetti et al., 2002). Leptin is mainly produced in and released from the white adipose tissue and is considered an antagonist of ghrelin. Leptin is able to inhibit food intake via leptin receptors in the hypothalamus and affects meal size, food preference and glucose balance (Guo et al., 2012, Schoeller et al., 1997 and Gautron and Elmquist, 2011). Further, leptin increases thermogenesis and is able to bind immune cells such as leukocytes and natural killer cells (Bruno et al., 2005 and Carlton et al., 2012). Leptin has also a role in the stimulation of the serotonin synthesis. In turn, serotonin inhibits the leptin expression and secretion in adipocytes (Calapai et al., 1999). Several factors have an influence on ghrelin and leptin concentrations. These include circadian rhythmicity (Spiegel et al., 2004), sleep deprivation (Dzaja et al., 2004) and exercise (Shiiya et al., 2011). An interrelationship between ghrelin and serotonin involving melatonin and a potential alterability of ghrelin by photic signals have been suggested (Kirsz and Zieba, 2012). Adipokine is mainly produced in and released from adipocytes (Gelsinger et al., 2010). Decreased adiponectin levels have been found in patients with major depressive disorder (Cizza et al., 2010 and Lehto et al., 2010). 1.2. Immunological variables Neopterin is produced in human monocyte-derived macrophages. High neopterin plasma levels represent a sensitive marker for the activation of the immune system and may concur with tryptophan degradation as well as increased nitrite and phenylalanine levels in the incidence of psychological symptoms (Widner et al., 2002 and Capuron et al., 2011). Kynurenine is a metabolite of tryptophan. The conversion of tryptophan into kynurenine via indoleamine 2,3-dioxygenase (IDO) is facilitated by a variety of stimuli including IFN-γ and tumor necrosis factor (TNF)-α (Widner et al., 2002). Increased levels of phenylalanine have been reported in inflammation and immune activated conditions. Phenylalanine is the precursor amino acid of tyrosine which plays an important role in the biosynthesis of catecholamines (Neurauter et al., 2008). A correlation between phenylalanine and immune parameters such as interleukin-6 (IL-6) has been found (Haroon et al., 2012). In this pilot study, the effect of short-term bright versus dim light exposure on subjective well-being and feelings of hunger/satiety as well as on potentially photosensitive plasma markers was investigated in healthy male volunteers. The hypothesis of the study was that ghrelin levels decrease as an effect of bright light exposure and increase during dim light intervention. In contrast, leptin levels were expected to increase under bright light and decrease under dim light exposure. Further a decrease of neopterin as an effect of bright light exposure was hypothesized. A potential finding of an influence of light on the parameters studied may have clinical implications in terms of regulation of weight and inflammation.

. Results 3.1. Demographic variables A total of 29 male healthy subjects were included into the study. Table 1 illustrates the descriptive data of the participants. With regard to the MEQ, 19 (66%) described themselves as intermediate type, 5 (17%) as moderate eveningness type and 5 (17%) as moderate morningness type. As this was a cross-over study and as the distribution of age was the same in the two strata (mean age±SD: 26.3±5.7 in the stratum “dim l.-bright l.”, 26.5±4.5 in the stratum “bright l.-dim l.”, p=0.926, t=0.094), the results regarding the effect of light, time and the light-by-time interaction on the various dependent variables ( Table 2, Table 3 and Table 4) remain unchanged when adjusting for age. Table 1. Sample characteristics. Variable Mean±SD or n (%) Age (years) 26.4±5.1 Height (cm) 179.6±8.1 Weight (kg) 74.4±9.9 BMI (kg/m²) 23.0±2.0 Total body water (kg) 45.5±5.4 Skeletal muscle mass (kg) 35.1±4.4 Body fat mass (kg) 12.7±4.8 MEQ score 49.3±8.2 Sports (frequency per week) Never 2 (6.9%) Less than once per week 2 (6.9%) 1–2 times 8 (27.6%) 2–3 times 9 (31.0%) 3–4 times 8 (27.6%) Sports (minutes per week) None 2 (6.9%) 30–60 min 10 (34.5%) 60–90 min 12 (41.4%) 90–120 min 2 (6.9%) >120 min 2 (6.9%) Not specified 1 (3.4%) Table options Table 2. Effect of light condition and time on visual analog scales (well-being, hunger) and HFS. Variable Condition Statisticsa Bright light t0 Bright light t1 Dim light t0 Dim light t1 Light (bright versus dim) Time Light×Timeb Mean SD Mean SD Mean SD Mean SD F p F p F p VAS well-being 65.0 14.3 69.5 13.1 64.4 14.0 62.3 15.0 2.16 0.153 0.45 0.507 Difference t1−t0 +4.1±12.4 (n.s.)c −2.1±10.1 (n.s.)c 4.28 0.048 VAS hunger 51.4 20.5 63.2 19.1 54.0 15.8 62.9 17.0 0.15 0.703 18.4 0.000 Difference t1−t0 +11.8±20.1↑(p=0.004) c + 8.9±12.8↑(p=0.002) c 0.51 0.480 HFS 4.07 0.96 3.48 1.12 4.14 0.71 3.64 1.03 0.42 0.523 18.1 0.000 Difference t1−t0 −0.59±0.98↓(p=0.006) c −0.50±0.79↓(p=0.004) c 0.10 0.758 ↑/↓ Significant increase/decrease from t0 to t1. t0=baseline; t1=follow-up. VAS, Visual Analog Scale; HFS, Hunger Fullness Scale. a Repeated-measures ANOVA. b This column shows the statistics for the comparison of the differences “t1−t0” under the two light conditions bright and dim. c Comparison of t0 and t1 within light conditions (Wilcoxon matched-pairs test). Table options Table 3. Effect of light condition and time on ghrelin, adiponectin and leptin. Variable Condition Statisticsa Bright light t0 Bright light t1 Dim light t0 Dim light t1 Light (bright versus dim) Time Light×Timeb Mean SD Mean SD Mean SD Mean SD F p F p F p Ghrelin 480.0 164.0 522.0 214.2 512.8 198.1 539.9 233.7 1.09 0.304 9.20 0.005 Difference t1−t0 +42.0±71.9↑(p=0.002) c + 27.1±79.9↑(p=0.009) c 0.67 0.420 Leptin 2627.9 2612.1 2235.9 2022.8 2988.4 2861.4 2854.9 3155.4 3.74 0.064 7.35 0.012 Difference t1−t0 −469.1±1243.9↓(p<0.001) c −133.5±802.2↓(p=0.024) c 0.10 0.756 Adiponectin 9475.6 3604.5 9502.7 3511.2 8984.6 3174.7 9044.4 3085.9 1.14 0.294 0.08 0.798 Difference t1−t0 +27.1±1329.7 (n.s.)c +59.7±685.3 (n.s.)c 0.02 0.896 ↑/↓ Significant increase/decrease from t0 to t1. t0=baseline; t1=follow-up. a Repeated-measures ANOVA. b This column shows the statistics for comparison of the differences “t1−t0” under the two light conditions bright and dim. c Comparison of t0 and t1 within light conditions (Wilcoxon matched-pairs test). Table options Table 4. Effect of light condition and time on immune parameters. Variable Condition Statisticsa Bright light t0 Bright light t1 Dim light t0 Dim light t1 Light (bright versus dim) Time Light×Timeb Mean SD Mean SD Mean SD Mean SD F p F p F p Neopterin 5.84 2.21 5.51 1.77 5.27 1.01 5.07 0.90 1.81 0.189 9.30 0.005 Difference t1−t0 −0.33±0.79↓(p=0.009) c − 0.20±0.57↓(p=0.030) c 0.27 0.607 Tryptophan 64.62 7.33 61.93 8.05 67.20 7.52 63.60 8.37 2.86 0.102 8.30 0.008 Difference t1−t0 −2.69±9.20 (n.s.)c −3.60±7.09↓(p=0.023) c 0.18 0.674 Kynurenine 2.46 0.55 2.42 0.59 2.51 0.47 2.46 0.55 0.45 0.508 0.33 0.571 Difference t1−t0 −0.04 ±0.67 (n.s.)c −0.05±0.45 (n.s.)c 0.01 0.946 Kyn/tryp 38.18 8.59 38.90 8.13 37.69 7.46 39.08 9.07 0.02 0.898 1.56 0.222 Difference t1−t0 +0.73±7.87 (n.s.)c +1.38±5.45 (n.s.)c 0.12 0.727 Tyrosine 49.4 18.1 44.8 16.1 48.9 15.7 46.2 11.4 0.27 0.610 4.65 0.040 Difference t1−t0 −4.6±7.3↓(p=0.005) c −2.8±10.3↓(p=0.034) c 2.39 0.133 Phenylalanine 72.1 19.9 70.7 19.9 72.8 23.2 72.7 16.8 0.45 0.510 0.01 0.984 Difference t1−t0 −1.4±10.2 (n.s.)c −0.1±16.9 (n.s.)c 0.98 0.330 Phe/tyr 1.50 0.23 1.62 0.24 1.51 0.25 1.60 0.21 0.00 0.999 23.1 0.000 Difference t1−t0 +0.12±0.15↑(p=0.001) c +0.08±0.17↑(p=0.009) c 0.42 0.520 Nitrite 19.2 17.9 14.7 5.0 18.1 16.5 14.7 1.4 0.70 0.409 1.90 0.179 Difference t1−t0 −4.4±17.4 (n.s.)c −3.3±20.1 (n.s.)c 0.05 0.829 ↑/↓ Significant increase/decrease from t0 to t1. t0=baseline; t1=follow-up. Kyn, kynurenine; tryp, tryptophan; phe, phenylalanine; tyr, tyrosine. a Repeated-measures ANOVA. b This column shows the statistics for comparison of the differences “t1 – t0” under the two light conditions bright and dim. c Comparison of t0 and t1 within light conditions (Wilcoxon matched-pairs test). Table options 3.2. Scale results (HFS, VAS hunger, VAS well-being) Table 2 illustrates the results of the self-rating scales. VAS hunger and HFS values showed a significant increase during the intervention period (significant main effect of the factor time). However, this applied likewise for both light conditions, i.e., there was no significant interaction between light condition and time. In contrast, subjective well-being showed a small increase under exposure with bright light and a small decrease under dim light (both effects on its own being non-significant), resulting in a statistically significant interaction between light condition and time (p=0.048). 3.3. Ghrelin, leptin, and adiponectin Table 3 shows the results of the plasma concentrations of ghrelin, leptin and adiponectin. Ghrelin levels increased significantly during the intervention period under both light conditions (p=0.005), but there were no significant differences between the two conditions. Similarly, leptin concentrations decreased significantly under both light conditions (p=0.012), but there was again no significant interaction between light condition and time. Adiponectin showed no significant change under either light condition. 3.4. Immunological parameters Table 4 illustrates the effect of light condition and time on immune parameters. There was a significant decrease of neopterin, tryptophan and tyrosine plasma levels during both interventions, but again we did not observe a significant interaction between light condition and time. Similarly, the phenylalanine/tyrosine ratio showed a significant increase under both light conditions, but there were no significant differences between the two interventions. The other immune parameters did not exhibit a significant change under either light condition. 3.5. Results of correlation analyses Correlation analyses at fixed observation times (t0 and t1) did not reveal any significant associations after Bonferroni correction for multiple testing, neither for inter-correlations among laboratory parameters nor for correlations between these parameters and the VAS. Correlation analyses of changes from t0 to t1 showed significant associations between ΔTryptophan and ΔKynurenin, both under bright light (r=0.791, p<0.00001, pBonferroni<0.001) and under dim light (r=0.617, p=0.00037 pBonferroni=0.013), and also for ΔTyrosine and ΔPhenylalanine, again under bright light (r=0.657, p=0.00006, pBonferroni=0.002) and under dim light (r=0.596, p=0.00065, pBonferroni=0.023). No further significant correlations between changes of laboratory parameters were observed after Bonferroni correction for mutliple testing. The same applied for correlations between changes of laboratory parameters and changes of VAS scores.