Neural Mechanisms of Family-Focused Treatment for Youth Depression

Childhood-onset depression is impairing, often recurrent and persistent, and negatively impacts development, resulting in high personal, social, and economic costs. Family-Focused Treatment for Childhood-Depression (FFT-CD) was developed to address the needs of depressed youth. In a large, randomized controlled trial, FFT-CD was superior to individual therapy in promoting recovery from depression.

Despite its promise, there was high variability in degree of improvement in FFT-CD. Our long-term goal is to integrate parenting, neuroimaging and clinical measures to a) reveal the parenting, emotional and neural mechanisms of clinical benefit for FFT-CD and (b) examine what parent and child characteristics predict immediate and long-term benefit. The proposed study will provide groundwork for this larger study by providing preliminary data.

This study will enroll 40 children (ages 7-12) - 20 with current depressive disorder and 20 with no history of mental health disorder -- and their parents (40 parents total). At baseline parents and children will participate in (a) an evaluation of clinical state and family functioning, (b) functional neuroimaging procedures to evaluate neural response to emotional cues (faces), potential reward, and parent-child relations, and resting state-connectivity, and (c) structural imaging (MRI and diffusion tensor imaging). Participants with depressive disorders and their parents will then be provided a 12-session course of FFT-CD. Brief clinical and parenting data will be collected at two points during treatment; baseline procedures will be repeated at 4 months (post-treatment). The participants will engage in briefer clinical evaluation via telehealth 6 and 9 months post-treatment.

Goals include: 1) To examine differences between depressed and non-depressed participants in baseline neural and parenting. 2) To examine baseline neural functioning, emotional experience, and parenting as predictors of FFT-CD outcome in our depressed group. 3) To evaluate parenting and emotional experience across treatment and neural functioning measures at the end of treatment as mediators of change in depression from baseline to final follow-up.

The neuroimaging hypotheses include:

• Naturalistic Videos Task: Children with depression will display greater amygdala and insula activation to negatively vs. neutrally valenced video clips. There will be less striatal activation to positively vs. neutrally valenced video clips in the depressed group compared to the n on-depressed group. Dyads of depressed children and their parents will show less functional similarity while viewing naturalistic clips of parent-child interactions compared to healthy control dyads.

• Face Matching Task: Depressed children will show amygdala and insula hyperactivation in response to negative faces and striatum hypoactivation in response to positive faces compared to healthy controls.

• Reward Processing Task: Depressed children will show reduced striatal activation in response to reward anticipation and receipt relative to healthy controls.

• Evaluative Comments Task: Depressed children will display higher activation in the default mode network during self-evaluation relative to non-depressed control children across both conditions. We further expect a greater heightened Default Mode Network (DMN) response in the depressed group to negative words relative to positive words.

• Rest: Dyads of depressed children and their parents will show less functional similarity in the resting state functional connectome relative to non-depressed control dyads. Greater DMN connectivity will be observed at rest in depressed children relative to non-depressed control children.

• Magnetic Resonance Spectroscopy: Depressed children will show elevated levels of glutamate, aspartate, choline, and lactate and lower levels of ascorbate, glutathione, myo-inositol, and N-acetyl aspartate relative to non-depressed controls, consistent with neuroinflammation and excitotoxicity/oxidative stress.