Preliminary communicationAssociation between depression severity and amygdala reactivity during sad face viewing in depressed preschoolers: An fMRI study
Introduction
The critical need for understanding functional and structural brain development abnormalities in very early onset mental illness is becoming increasingly clear (Davidson and Slagter, 2000, Pine et al., 2002). However, few studies to date have directly addressed this question due to greater diagnostic ambiguity in young children and the associated difficulty of translating developmentally appropriate tasks into an MRI environment. As such, the current study sought to begin filling this gap in the field by examining functional brain activation in the earliest empirically validated occurrence of depression, preschool onset major depressive disorder (PO-MDD).
Luby et al. (2002) have provided empirical evidence validating PO-MDD in a number of areas, including findings of symptom specificity discriminating PO-MDD from other early onset disorders, familial transmission (Luby et al., 2002), biological correlates (Luby et al., 2003), impairment across multiple contexts (Luby et al., 2009a), and longitudinal stability (Luby, 2009). Additionally, recent evidence has demonstrated continuity of PO-MDD with the well-known school age form of MDD, suggesting that depression identified during the preschool years is an earlier manifestation of MDD, rather than a transient or non-specific phenomenon (Luby et al., 2009b). This finding of homotypic continuity is of particular importance because it suggests that alterations in brain function that have already been documented in school age children (Zalsman et al., 2006) with depression may already be present earlier in development during the preschool period. The earliest possible detection of brain changes in depressive disorders is important to capture windows of opportunity for earlier interventions or prevention during periods of greater neuroplasticity.
Neurobiological models of depression have pointed to the importance of subcortical limbic structures, especially the amygdala, in the onset and course of the disorder. While our understanding of the amygdala is continually evolving, it is largely agreed that it plays a prominent role in the perception and expression of emotion (Phelps and LeDoux, 2005). Research into amygdala function in depression has been examined in a number of ways, including constrained (e.g., ‘How sad?’) or unconstrained (e.g., passive viewing) processing of human facial expressions of emotion (Peluso et al., 2009, Suslow et al., 2010). The frequent use of facial expressions in the study of MDD has been due in large part to their ecological validity as critical mediators of nonverbal communication across a large age range (Russell and Bullock, 1985, Birmaher et al., 2009, Ekman, 1993). Generally, studies incorporating these stimuli have indicated a heightened level of amygdala activity following exposure to facial expressions of negative emotion (e.g., sad) in MDD (Beesdo et al., 2009, Suslow et al., 2010). Additionally, individual differences in MDD severity and amygdala activity have been found to be positively related in both older children and adults during such tasks (Peluso et al., 2009, Belden et al., 2009).
Nevertheless, despite this growing body of literature on brain function in child, adolescent and adult MDD, data informing the neurodevelopmental course of brain function in general, and the function of the amygdala specifically, in PO-MDD has been unavailable to date. As an initial effort to begin addressing this need and stimulate further research, the current study reports on a group of young children with PO-MDD who underwent functional magnetic resonance imaging (fMRI) while viewing facial expressions of emotion. Following previous studies of emotion face processing in depressed adults using a region of interest approach (e.g., Sheline et al., 2001), we hypothesized that a positive relationship between MDD severity and amygdala activity would be found in children with PO-MDD when viewing facial expressions of sadness. Additionally, given the growing evidence supporting the involvement of cortical and subcortical areas in face processing, exploratory whole-brain analyses were conducted (Fusar-Poli et al., 2009). Based on previous research indicating a significant role for primary visual cortex during face viewing in similarly aged children (Gathers et al., 2004), it was hypothesized that functional activation within the occipital cortex would be found.
Section snippets
Participants
Participants included 14 preschool children with PO-MDD recruited as part of an ongoing federally funded treatment study (PI: J.L.). All children participated in the current imaging experiment prior to starting active treatment. Neurological disorders (e.g., seizure disorder, closed head injury, etc.), presence of an autism spectrum disorder, IQ < 70, and ongoing participation in psychotherapy and/or taking psychotropic medication acted as exclusionary criteria (due to the treatment aims). Of the
Behavioral
Due to inconsistent responding, behavioral data was unavailable for 1 participant. For the remaining participants (N = 10), the mean response time was 1337 ms (539) and the mean response rate was 98 (3.86) percent for the combined face viewing conditions (happy, sad, neutral).
Region of interest
The results from the ROI analyses indicated a strong positive relationship between MDD severity and level of activity in the right (r = .709, p = .007) but not left (r = .421, p = .099) amygdala during the viewing of sad faces (see
Discussion
The current study sought to examine the relationship between very early childhood depression and functional brain activity in the amygdala and other regions responsive to face processing. To our knowledge, this is the first investigation of brain function in depressed preschoolers. As hypothesized, the current study found a positive relationship between level of MDD severity and amygdala activation in depressed preschoolers while viewing sad faces, a relationship that remained even after
Role of funding source
The current study was supported by a grant from the CHADS Coalition for Mental Health (JL, DB) and grant number MH080163-03 from the National Institute of Mental Health (JL). Both CHADS and the NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Conflict of interest
Dr. Barch has received grants from the NIMH, NIA, NARSAD, Novartis, and the McDonnell Center for Systems Neuroscience. Dr. Luby has received grants from NIMH and NARSAD. Dr. Belden has received funding from the McDonnell Center for Systems Neuroscience and NIMH (1K01MH090515-01). Dr. Gaffrey has received funding from the Klingenstein Third Generation Foundation. The remaining authors declare that they have no conflicts of interest to report.
Acknowledgements
We wish to acknowledge the Early Emotional Development Program Staff, our preschool participants and their parents, and community recruiting sites whose participation and cooperation made this research possible.
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