Altered resting-state activity in seasonal affective disorder.

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.

Can transcranial brain-targeted bright light treatment via ear canals be effective in relieving symptoms in seasonal affective disorder? A pilot study.

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<0.001). The HAMA mean sum score at screening was 20.5 ± 5.4. During the study period, 12 out of 13 (92.3%) patients achieved at least 50% reduction in their HAMA sum scores, and in 10 out of 13 patients (76.9%), the HAMA sum score was <7. In conclusion, it is hard to believe that our findings could be explained solely by placebo effect. Consequently, the basic assumptions underlying extraocular photoreception in humans deserve to be reconsidered. Given that a proper placebo treatment can be implemented via ear canals, further investigations with randomized placebo-controlled and/or dose-finding study designs regarding the extraocular transcranial bright light in the treatment of SAD are called for.