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Until now, melanopsin (OPN4) - a specialized photopigment being responsive especially to blue light wavelengths - has not been found in the human brain at protein level outside the retina. More specifically, OPN4 has only been found in about 2% of retinal ganglion cells (i.e. in intrinsically photosensitive retinal ganglion cells), and in a subtype of retinal cone-cells. Given that Allen Institute for Brain Science has described a wide distribution of OPN4 mRNA in two human brains, we aimed to investigate whether OPN4 is present in the human brain also at protein level. Western blotting and immunohistochemistry, as well as immunoelectron microscopy, were used to analyse the existence and distribution of OPN4 protein in 18 investigated areas of the human brain in samples obtained in forensic autopsies from 10 male subjects (54 ± 3.5 years). OPN4 protein expression was found in all subjects, and, furthermore, in 5 out of 10 subjects in all investigated brain areas localized in membranous compartments and cytoplasmic vesicles of neurons. To our opinion, the wide distribution of OPN4 in central areas of the human brain evokes a question whether ambient light has important straight targets in the human brain outside the retinohypothalamic tract (RHT). Further studies are, however, needed to investigate the putative physiological phototransductive actions of inborn OPN4 protein outside the RHT in the human brain.

Seasonal affective disorder (SAD) is a subtype of recurrent unipolar or bipolar depressive disorder with a higher prevalence in winter than in summer. The biological underpinnings of SAD are so far poorly understood. Studies examining SAD have found disturbances between the molecular and connectivity scales. The aim of the study was to explore changes in functional connectivity typical for SAD.We investigated unmedicated, untreated SAD patients and healthy controls using resting-state functional magnetic resonance imaging (rs-fMRI) utilizing graph theory, a data driven and hypothesis free approach, to model functional networks of the brain.Comparing whole brain network properties using graph theory we observed globally affected network topologies with increasing pathlength in SAD. Nodal changes, however, were highly restricted to bilateral inferior occipital cortex. Interestingly, we found a lateralization where hyper-connectedness was restricted to right inferior occipital cortex and hyper-efficiency was found in the left inferior occipital cortex. Furthermore, we found these nodes became more "hub like" in patients, suggesting a greater functional role.Our work stresses the importance of abnormal intrinsic processing during rest, primarily affecting visual areas and subsequently changing whole brain networks, and thus providing an important hint towards potential future therapeutic approaches.

The purpose of this study was to compare hormonal, neuromuscular, and aerobic performance changes between a constant 2-minute interset recovery time and an interset recovery time based on individual heart rate (HR) responses during a 7-week (3 sessions per week, 3 × 10 repetition maximum [RM]) hypertrophic strength training period. The HR-dependent recovery time was determined with a Polar FT80 HR monitor, whereas the control groups used constant 2-minute periods between sets. From 24 male subjects who were divided in 2 equal groups, 21 completed the study (FT80, n = 12; CONTROL, n = 9). Serum blood samples analyzed for testosterone (TES) and cortisol (COR) were taken before and after the 7-week training period at rest. Concentric knee extension 1RM was measured before, after 4 weeks, and at the end of the training period. Concentric knee extension and knee flexion 10RM, central activation ratio (CAR), and max[latin capital V with dot above]o2 were measured before and after the training. Serum TES concentrations were significantly higher after the training period in FT80 (p < 0.001), whereas no significant changes were observed in the CONTROL. Serum COR and max[latin capital V with dot above]o2 were unchanged in both groups. In FT80 (p < 0.001), the increase in 10RM was higher (p < 0.05) than in CONTROL (p < 0.001). Central activation ratio increased in both groups, with the significant increase observed in FT80 (p < 0.05). The higher TES responses, 10RM, and CAR development in FT80 suggest that an HR-based recovery period system of the FT80 may be more efficient in this type of hypertrophic strength training (3 × 10RM). The protocol in this study may be considered as a metabolic training cycle that coaches and trainers can use within a longer periodized training program.

The purpose was (a) to study the effect of an 8-week Finnish military basic training period (BT) on physical fitness, body composition, mood state, and serum biochemical parameters among new conscripts; (b) to determine the incidence of overreaching (OR); and (c) to evaluate whether initial levels or training responses differ between OR and noOR subjects. Fifty-seven males (19.7 ± 0.3 years) were evaluated before and during BT. Overreaching subjects had to fulfill 3 of 5 criteria: decreased aerobic physical fitness (VO2max), increased rating of perceived exertion (RPE) in 45-minute submaximal test at 70% of VO2max or sick absence from these tests, increased somatic or emotional symptoms of OR, and high incidence of sick absence from daily service. VO2max improved during the first 4 weeks of BT. During the second half of BT, a stagnation of increase in VO2max was observed, basal serum sex hormone-binding globulin (SHBG) increased, and insulin-like growth factor-1 and cortisol decreased. Furthermore, submaximal exercise-induced increases in cortisol, maximum heart rate, and postexercise increase in blood lactate were blunted. Of 57 subjects, 33% were classified as OR. They had higher basal SHBG before and after 4 and 7 weeks of training and higher basal serum cortisol at the end of BT than noOR subjects. In addition, in contrast to noOR, OR subjects exhibited no increase in basal testosterone/cortisol ratio but a decrease in maximal La/RPE ratio during BT. As one-third of the conscripts were overreached, training after BT should involve recovery training to prevent overtraining syndrome from developing. The results confirm that serum SHBG, cortisol, and testosterone/cortisol and maximal La/RPE ratios could be useful tools to indicate whether training is too strenuous.

The present study examined whether activity energy expenditure related to body mass (AEE/kg) is associated with maximal aerobic fitness (VO(2max)), energy balance, and body mass index (BMI) during the 2 hardest weeks of the military basic training season (BT). An additional purpose was to study the accuracy of the pre-filled food diary energy intake. Energy expenditure (EE) with doubly labeled water, energy intake (EI), energy balance, and mis-recording was measured from 24 male conscripts with varying VO(2max). AEE/kg was calculated as (EE x 0.9-measured basal metabolic rate)/body mass. The reported EI was lower (P

We investigated whether transcranial bright light (TBL) affects nocturnal melatonin and cortisol secretion in sham-controlled crossover trial. Young healthy adults were exposed in random order to 24 minutes of TBL or sham exposure via ear canals at 01:10 h. Saliva and urine samples were collected hourly between 21 h-03 h and 06 h-09 h. There were no significant differences in melatonin or cortisol concentrations between TBL and sham exposures at any sampling point indicating that TBL via ear canals does not suppress nocturnal melatonin secretion. Thus, non-visual effects of TBL are mediated via a pathway not involving melatonin suppression.

Bright light therapy (BLT) is widely accepted as first-line treatment of seasonal affective disorder (SAD). However, the mechanism of action of BLT is still widely unknown. On the other hand, in mammals, light penetrates the skull bone and reaches the brain, and extra ocular transcranial phototransduction has physiological influences such as changed reproductive cycles and increased brain serotonin levels. Therefore, we challenged the existing conceptual framework that light therapy would only be mediated through the eyes. Consequently, we run a pilot study on the putative effect of transcranial bright light in the treatment of SAD. The light was produced using light-emitting diodes (LEDs), which were attached to earplugs. The amount of photic energy was 6.0-8.5 lumens in both ear canals, and the length of treatment was 8 or 12 min five times a week during a four-week study period. Subjects were recruited through advertisements in the city of Oulu, Finland (latitude 65°01'N) during 14 January 2009-03 February 2009. The final patient series consisted of 13 (aged 37.1 ± 7.2 years) physically healthy indoor workers suffering from SAD according to DSM-IV-TR criteria. Severity of depressive symptoms was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) and Beck Depression Inventory (BDI)-21. Furthermore, severity of anxiety symptoms was measured by the 14-item Hamilton Anxiety Rating Scale (HAMA). The HAMD-17 mean sum score at screening was 23.1 ± 1.6. Ten out of 13 SAD patients (76.9%) achieved full remission (i.e., HAMD-17 sum score ≤ 7), and 92.3% (12/13) at least 50% reduction in HAMD-17 sum scores at "Week 4". By using a mixed regression model of repeated measures (AR-1) controlling for age, gender, and HAMD-17 mean sum score at screening, significant differences were found comparing the HAMD-17 mean sum scores of "Week 0" with the corresponding scores at the "Week 3" (t=-2.05, p=0.045) and "Week 4" visit (t=-2.77, p=0.008). Correspondingly, significant differences were found comparing the BDI-21 mean sum scores (15.2 ± 6.7) of "Week 0" with the corresponding scores at the "Week 3" (t=-2.37, p=0.021) and "Week 4" visit (t=-3.65, p

At present, our knowledge about seasonal affective disorder (SAD) is based mainly up on clinical symptoms, epidemiology, behavioral characteristics and light therapy. Recently developed measures of resting‐state functional brain activity might provide neurobiological markers of brain disorders. Studying functional brain activity in SAD could enhance our understanding of its nature and possible treatment strategies. Functional network connectivity (measured using ICA‐dual regression), and amplitude of low‐frequency fluctuations (ALFF) were measured in 45 antidepressant‐free patients (39.78 ± 10.64, 30 ♀, 15 ♂) diagnosed with SAD and compared with age‐, gender‐ and ethnicity‐matched healthy controls (HCs) using resting‐state functional magnetic resonance imaging. After correcting for Type 1 error at high model orders (inter‐RSN correction), SAD patients showed significantly increased functional connectivity in 11 of the 47 identified RSNs. Increased functional connectivity involved RSNs such as visual, sensorimotor, and attentional networks. Moreover, our results revealed that SAD patients compared with HCs showed significant higher ALFF in the visual and right sensorimotor cortex. Abnormally altered functional activity detected in SAD supports previously reported attentional and psychomotor symptoms in patients suffering from SAD. Further studies, particularly under task conditions, are needed in order to specifically investigate cognitive deficits in SAD. Hum Brain Mapp 35:161–172, 2014. © 2012 Wiley Periodicals, Inc.

Purpose: To test the utility of HR variability (HRV) in daily exercise prescription in moderately active (approximately two exercises per week) men and women. Methods: A total of 21 men and 32 women were divided into standard training (ST: males = 7 and females = 7), HRV-guided training (HRV-I: males = 7 and females = 7; HRV-II: females = 10), and control (males = 7 and females = 8) groups. The 8-wk aerobic training period included 40-min exercises at moderate and vigorous intensities (70% and 85% of maximal HR). The ST group was instructed to perform two or more sessions at moderate and three or more sessions at vigorous intensity weekly. HRV-I and HRV-II groups trained on the basis of changes in HRV, measured every morning. In the HRV-I group, an increase or no change in HRV resulted in vigorous-intensity training on that day. Moderate-intensity exercise or rest was prescribed if HRV had decreased. The HRV-II group performed a vigorous-intensity exercise only when HRV had increased. Peak oxygen consumption (V[spacing dot above]O2peak) and maximal workload (Loadmax) were measured by a maximal bicycle ergometer test before and after the intervention. Results: The changes in V[spacing dot above]O2peak did not differ between the training groups either in men or in women. In men, the change in Loadmax was higher in the HRV-I group than in the ST group (30 +/- 8 vs 18 +/- 10 W, P = 0.033). In women, no differences were found in the changes in Loadmax between the training groups (18 +/- 10, 15 +/- 11, and 18 +/- 5 W for ST, HRV-I, and HRV-II, respectively). The HRV-II group performed fewer vigorous-intensity exercises than the ST and HRV-I groups (1.8 +/- 0.3 vs 2.8 +/- 0.6 and 3.3 +/- 0.2 times per week, respectively, P < 0.01 for both). Conclusions: HRV measurements are beneficial in exercise training prescription in moderately active men and women. Women benefit from HRV guidance by achieving significant improvement in fitness with a lower training load

Bright light treatment is effective for seasonal affective disorder (SAD), although the mechanisms of action are still unknown. We investigated whether transcranial bright light via the ear canals has an antidepressant effect in the treatment of SAD. During the four-week study period, 89 patients (67 females; 22 males, aged 22-65, mean ± SD age: 43.2 ± 10.9 years) suffering from SAD were randomized to receive a 12-min daily dose of photic energy of one of three intensities (1 lumen/0.72 mW/cm2; 4 lumens/2.881 mW/cm2; 9 lumens/6.482 mW/cm2) via the ear canals. The light was produced using light-emitting diodes. The severity of depressive symptoms was assessed with the Hamilton Depression Rating Scale – Seasonal Affective Disorder (SIGH-SAD), the Hamilton Anxiety Rating Scale (HAMA), and the Beck Depression Inventory (BDI). Cognitive performance was measured by the Trail Making Test (TMT). The within-group and between-group changes in these variables throughout the study were analysed with a repeated measures analysis of variance (ANOVA), whereas gender differences at baseline within the light groups were analysed using Student’s t-tests. Patients in all three groups showed significant decreases in their BDI, HAMA, and SIGH-SAD scores. Response rates, i.e., an at least 50% decrease of symptoms as measured by the BDI, were 74%-79% in the three treatment groups. Corresponding variations for the SIGH-SAD and the HAMA were 35-45% and 47-62%, respectively. No intensity-based dose-response relationships in the improvement of anxiety and depressive symptoms or cognitive performance between treatment groups were observed. Approximately one in four patients experienced mild adverse effects, of which the most common were headache, insomnia, and nausea. These results suggests that transcranial bright light treatment may have antidepressant and anxiolytic effect in SAD patients, as both self- and psychiatrist-rated depressive and anxiety symptoms decreased in all treatment groups. These improvements are comparable to findings of earlier bright light studies that used conventional devices. The lack of dose response may be due to a saturation effect above a certain light intensity threshold. Further studies on the effects of transcranial bright light with an adequate placebo condition are needed. NCT01293409 , ClinicalTrials.gov