Research paperAmygdala response to emotional faces in seasonal affective disorder
Introduction
Seasonal affective disorder (SAD) is a type of major depressive disorder (MDD) or bipolar disorder characterized by seasonally recurring depression, commonly manifesting with fatigue, hypersomnia, hyperphagia with carbohydrate craving and weight gain (Magnusson and Partonen, 2005, Rosenthal et al., 1984). In most cases, depressive symptoms associated with SAD emerge in the winter, when daylight minutes decrease (Danilenko and Levitan, 2012). Pronounced seasonal fluctuations in daylight means that individuals living at extreme northern or southern latitudes are particularly prone to develop depressive symptoms in the winter (Hansen et al., 2016). In Copenhagen (55⁰ N latitude), about 12% of the population report symptoms of winter SAD and an additional 5% report sub-syndromal seasonal changes in mood and behavior that do not meet diagnostic criteria for SAD (Dam et al., 1998). Although risk factors for SAD have been identified (Magnusson and Partonen, 2005, Partonen, 1995, Rosenthal et al., 1998), the underlying neurobiological mechanisms distinguishing individuals suffering from SAD have only been explored to a very limited degree. Delineation of the neurobiological mechanisms underlying SAD may facilitate the identification of potential treatment targets and may elucidate mechanisms involved in remission. Considering the periodic emergence of SAD symptoms, a longitudinal study design wherein SAD individuals are evaluated during both symptomatic and asymptomatic phases may be particularly advantageous to identify neurobiological mechanisms associated with emergence of depressive symptoms.
Neuroimaging studies are well-suited for the evaluation of potential mechanisms underlying the emergence of depressive symptoms in SAD. Only two studies to date, including one from our own group, have used a seasonal longitudinal design to evaluate neurobiological changes in SAD individuals (Mc Mahon et al., 2016, Tyrer et al., 2016) and most neuroimaging studies of seasonality and SAD have focused on serotonergic dysfunction (Fisher et al., 2012, Kalbitzer et al., 2010, Mc Mahon et al., 2016, Praschak-Rieder and Willeit, 2012, Praschak-Rieder et al., 2008, Spindelegger et al., 2012, Tyrer et al., 2016, Willeit et al., 2000) with positron emission tomography (PET) and less attention to brain function. Resting-state functional magnetic resonance imaging (fMRI) studies in SAD individuals have reported increased connectivity in attention and vision networks (Abou Elseoud et al., 2014, Borchardt et al., 2015). However, effects on default mode network are equivocal with one report of increased functional connectivity of the network hub posterior cingulate cortex (Abou Elseoud et al., 2014), whereas another study found decreased role for posterior cingulate cortex based on graph theory metrics (Borchardt et al., 2015). Despite the substantial body of evidence for altered emotion processing in MDD, particularly increased amygdala activation to aversive stimuli (Stuhrmann et al., 2011), only one task-based fMRI study has evaluated emotion processing in SAD individuals. This study reported heightened thalamus response to auditory stimuli with angry prosody in SAD individuals during blue vs. green light exposure (Vandewalle et al., 2011). To the best of our knowledge, no studies have evaluated whether seasonally emergent changes in depressive symptoms are accompanied by changes in brain function.
In the current study, we evaluated amygdala activation to aversive faces in SAD individuals and healthy controls using a longitudinal study design previously described in Mc Mahon et al. (2016). Seventeen SAD individuals and 15 healthy controls completed an implicit emotional faces fMRI paradigm two times, once during winter, when depressive symptoms in SAD individuals were present, and once during summer, when both groups were euthymic. This allowed us to evaluate whether the emergence of SAD symptoms correlated with changes in amygdala activation to aversive faces. Consistent with elevated amygdala activation to aversive stimuli in MDD patients, we hypothesized that amygdala activation to aversive faces would increase in SAD individuals as symptoms emerged, that is, from summer to winter but remain unchanged in healthy controls (i.e., a season-by-group interaction).
Section snippets
Participants
Participants included in this study are described in detail elsewhere (Mc Mahon et al., 2016). Briefly, potential SAD individuals and healthy controls (sex, age and BMI matched) were recruited through online and newspaper advertisements for a research protocol approved by The Copenhagen Region Ethics Committee (H-1–2010-085 with amendments). All participants gave informed written consent prior to participation. Exclusion criteria included age < 18 or > 45 years, smoking, a history of
Demographics and emotional faces fMRI task performance
Healthy control and SAD groups were similar in age, sex and BMI. In addition, they had similar neuroticism and MDI scores in the summer (Table 1). Consistent with our observation in a larger cohort (Mc Mahon et al., 2016), depressive symptoms (SIGH-SAD and MDI score) emerged in SAD individuals during winter (SIGH-SAD season parameter estimate (SAD only): 21.6, 95% CI: [17.1; 26.1], p = 4 × 10–11, MDI interaction parameter estimate (all participants): −16.4, 95% CI: [−21.5; −11.3], p = 2 × 10−8
Discussion
Here, we report for the first time the amygdala response to an implicit emotional faces fMRI paradigm in SAD individuals, during their symptomatic and asymptomatic phases and compared with healthy controls. Inconsistent with our hypothesis, seasonal variation in amygdala activation to aversive stimuli did not differ between healthy controls and SAD individuals. However, analyses showed evidence for reduced amygdala activation in SAD individuals compared to healthy controls across angry, fearful
Acknowledgements
We thank Sussi Larsen, Julian Macoveanu, Pernille Iversen and Sofie Bech Andersen for assistance in data collection and Peter Jensen for assistance in data management. We thank Henrik Dam for assistance with clinical assessment. We thank the Hasholt-Nørremølle laboratory in the Section of Neurogenetics at the Department of Cellular and Molecular Medicine, University of Copenhagen, for their assistance with genotyping. We would like to acknowledge the Simon Spies Foundation for the donation of
Funding
This project was funded by the Lundbeck Foundation (R90-A7722). B.M.M. was funded by a scholarship from Dr. Ejlif Trier-Hansen and wife Ane Trier-Hansen and a scholarship from Brain Mind and Medicines. The funding sources had no influence on the collection, analysis and interpretation of data, nor on the writing and submission of the article.
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