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Poster #57 - Inflammation, Depression, and Neural Response to Reward in Adolescents of Depressed Parents

Thu, March 21, 2:15 to 3:30pm, Baltimore Convention Center, Floor: Level 1, Exhibit Hall B

Integrative Statement

Disrupted function in neural reward circuitry is a widely replicated biomarker of depression (e.g., Forbes & Dahl, 2012; Russo & Nelson, 2013), a disorder that is also marked by increased inflammation. Recently, alteration of reward circuitry has been postulated as a mechanism for the link between inflammation and depression. Understanding associations among inflammation, reward circuitry, and depression as they unfold with development is particularly important during adolescence, the period in which depression emerges, inflammation interacts with several aspects of changing physiology, and development in neural reward circuitry is underway (Mills et al., 2013). To investigate this potential pathway from inflammation to depression, we assessed circulating inflammatory markers, neural response to reward, and baseline and 6-month depression in adolescents of parents with depression, a population at especially high risk for depression. We hypothesized that 1) high levels of depression will be associated with high levels of inflammation; 2) high levels of depression and inflammation will be associated with altered neural response to reward and reward anticipation in regions including the medial-prefrontal cortex (mPFC) and striatum; and 3) altered neural activation in reward-related regions will predict depression 6 months later.
Participants were 45 adolescents (13-19 years old; 49% female) who were healthy but had a first-degree relative with depression. We assessed serum levels of 3 inflammatory markers: (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, and C-reactive protein [CRP]). Adolescents completed a monetary reward functional magnetic resonance imaging task on a 3T Siemens TIM Trio scanner. Adolescents completed the Center for Epidemiologic Studies Depression Scale (Radloff, 1977) at the time of scanning and again 6 months later. Preprocessing and analyses of imaging data were conducted in SPM12 (https://www.fil.ion.ucl.ac.uk/spm/doc/) using a threshold of p<.005 with family-wise-error cluster-level correction at p<.05.
Adolescents with higher depressive symptoms had higher C-reactive protein (CRP), even when controlling for BMI and age (F(1,37)=3.38, B=.38) (Figure 1)., and decreased mPFC response to reward anticipation (778 voxels, [-8, 60, 24], t=4.56). Adolescents with higher TNF-alpha had greater dmPFC response to reward anticipation (380 voxels, [-28, 52, 2], t=4.98 ). Greater response in the putamen (561 voxels, [-22, 0, 2], t = 5.09), post-central gyrus (322 voxels, [38, -22, 0], t= 5.61), medial temporal gyrus (307 voxels, [-54, -64, 8], t=5.33), and posterior insula (304 voxels, [38, -32, 18], t= 5.32) predicted higher depression severity 6 months later (Figure 2).
In adolescents of depressed parents, higher levels of two inflammatory markers were associated with depression and altered neural response to reward. In addition, altered response in several neural regions associated with reward processing was predictive of later depression. These findings suggest that in high-risk offspring, the presence of inflammation could create enhanced risk for depression, potentially through disrupted neural response to reward. These cross-sectional findings are a step toward understanding the mechanisms through which depression develops. Future work on the developmental psychopathology of depression should employ longitudinal, prospective research designs, a developmental neuroscience framework, and a focus on applications to prevention.

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