Abnormal hypothalamic response to light in seasonal affective disorder

Abstract

Background: Vulnerability to the reduction in natural light associated with fall/winter is generally accepted as the main trigger of seasonal affective disorder (SAD), whereas light therapy is a treatment of choice of the disorder. However, the relationship between exposure to light and mood regulation remains unclear. As compared with green light, blue light was shown to acutely modulate emotion brain processing in healthy individuals. Here, we investigated the impact of light on emotion brain processing in patients with SAD and healthy control subjects and its relationship with retinal light sensitivity.

Methods: Fourteen symptomatic untreated patients with SAD (34.5 ± 8.2 years; 9 women) and 16 healthy control subjects (32.3 ± 7.7 years; 11 women) performed an auditory emotional task in functional magnetic resonance imaging during the fall/winter season, while being exposed to alternating blue and green monochromatic light. Scotopic and photopic retinal light sensitivities were then evaluated with electroretinography.

Results: Blue light enhanced responses to auditory emotional stimuli in the posterior hypothalamus in patients with SAD, whereas green light decreased these responses. These effects of blue and green light were not observed in healthy control subjects, despite similar retinal sensitivity in SAD and control subjects.

Conclusions: These results point to the posterior hypothalamus as the neurobiological substrate involved in specific aspects of SAD, including a distinctive response to light and altered emotional responses.

Figure 1. experimental design

a. General protocol. Arrow: pupil dilator administration. Time relative to scheduled wake time (hr). Subject performed an emotional task in fMRI (see b. for details) before photopic and scotopic ERGs were recorded. b. Detailed fMRI procedures Time (s) relative to t0, a time point arbitrary chosen as a green light onset of the session. The task consisted in a gender discrimination of auditory vocalizations while exposed to alternating (480nm) and (550nm) monochromatic light (counter balanced order). Light exposures lasted 40s and were separated by 15-to-25s periods of darkness. Anger ( bars) and neutral (white bars) prosody vocalizations of the three pseudo-word type (“goster”, “niuvenci” or “figotleich”) were pseudo-randomly and evenly administered throughout each light conditions across the entire session (inter stimuli interval: 3 to 11s; mean: 4.8s).

Figure 2. behavioral results of the fMRI task

a. Accuracy (mean ± SD); b. Reaction times (mean ± SD). SAD: Patients with SAD patient; CON: Control subjects; NEU: Neutral prosody; ANG: Anger prosody; * significant differences (p ≤ 0.05); ns: non-significant difference (p > 0.05).

Figure 3. Significant differences between patients with SAD and healthy controls in the brain responses to all auditory stimulus types (irrespective of light and prosody condition)

a. Thalamus (dorsal and posterior); b. Brainstem (median-posterior, next to superior cerebellar peduncle). Results are overlaid over the mean structural image of all subjects. Insets: enlargements in representative subjects. Graphs: activity estimates (arbitrary unit – a.u. ± SEM) of the brain responses to all auditory stimulus types. # p_corrected ≤ 0.05 (group difference).

Figure 4. Significant differences between patients with SAD and healthy controls in the impact of blue and green light exposure on the brain responses to auditory emotional stimuli

Results are overlaid over the mean structural image of all subjects. Inset: enlargement in a representative subject. 3V: third ventricle; B: brainstem; CP: corpus collusum; F: fornix; MB: mammillary bodies; OT: optic tract; SC: superior colliculus; T: thalamus. Graphs: change in activity estimates (arbitrary unit – a.u. ± SEM) between the light condition (blue, green) and the darkness condition for the processing of auditory emotional stimuli. * p_corrected ≤ 0.05 (in SAD patients taken in isolation); ~ p_corrected = 0.07 (in SAD patients taken in isolation); ns p_uncorrected > 0.1 (in controls taken in isolation); # p_corrected ≤ 0.05 (group difference).