Psychobiology of Stress and Adolescent Depression (PSY SAD) Study: Protocol overview for an fMRI-based multi-method investigation

Abstract

Depression is a common, often recurrent disorder that causes substantial disease burden worldwide, and this is especially true for women following the pubertal transition. According to the Social Signal Transduction Theory of Depression, stressors involving social stress and rejection, which frequently precipitate major depressive episodes, induce depressive symptoms in vulnerable individuals in part by altering the activity and connectivity of stress-related neural pathways, and by upregulating components of the immune system involved in inflammation. To test this theory, we recruited adolescent females at high and low risk for depression and assessed their psychological, neural, inflammatory, and genomic responses to a brief (10 minute) social stress task, in addition to trait psychological and microbial factors affecting these responses. We then followed these adolescents longitudinally to investigate how their multi-level stress responses at baseline were related to their biological aging at baseline, and psychosocial and clinical functioning over one year. In this protocol paper, we describe the theoretical motivations for conducting this study as well as the sample, study design, procedures, and measures. Ultimately, our aim is to elucidate how social adversity influences the brain and immune system to cause depression, one of the most common and costly of all disorders.

Neural and peripheral markers of reward during positive social evaluation are associated with less clinician-rated depression symptom severity in adolescence

“…None of the girls in the PSY SAD Study had yet experienced a lifetime MDE, but did exhibit some symptoms of depression [ 55 ]. As the K-SADS-PL is considered the gold-standard for childhood assessment of psychiatric symptoms [ 58 ], finding significant associations between a highly specified brain region and clinician-evaluated symptoms of depression may be useful in extending our understanding of how the brain processes reward, leading to depression.…”

“…Participants in the PSY SAD Study ( N = 52, M age = 14.90, SD = 1.35) were recruited from online advertisements, flyers posted in community locations, social media posts, word of mouth, and announcements made at middle and high schools in the greater Los Angeles area [ 55 ]. Inclusion and exclusion criteria included age between 12 and 16 years old, English-speaking, right-handed, not claustrophobic, free of bodily metal (except dental fillings) and other contraindications for MRI, living with their biological mother, and have no current or past history of any Diagnostic and Statistical Manual-IV (DSM-IV) Axis I disorder.…”

“…First, written informed consent and assent was obtained from mothers and daughters, respectively. Then, mothers and daughters were screened separately by trained diagnostic interviewers (all trained by GMS) to ensure they met all of the inclusion criteria, did not meet any of the exclusion criteria, and ascertain the daughter's maternal risk group, which was classified as either low-risk (i.e., mothers with no MDEs; N = 30) or high-risk (i.e., mothers with at least one MDE; N = 22) [ 55 ].…”

“…Afterward, daughters completed a 10-min video-recorded interview about their upbringing, opinions, feelings, and autobiographical memories in absence of their mothers (for complete procedural details, see Ref. [ 55 ]).…”

“…[ 10 ]), and evidence that blunted sensitivity to monetary reward is associated with depression [ 28 , 41 , [52] , [53] , [54] ], how neural and peripheral markers of social reward responsivity are related to depression in adolescence is unknown. To address this gap, we examined the extent to which risk for depression and current depression symptom severity were associated with differences in striatal activity to positive social evaluation and β-endorphin output following positive social reward in the context of the Psychobiology of Stress and Adolescent Depression (PSY SAD) Study [ 55 ]. We hypothesized that both risk for depression (i.e., having a positive maternal history of depression) and current depressive symptoms would be related to blunted striatal activity during positive (vs. neutral) social evaluation, as well as to blunted β-endorphin output following an acute, laboratory-based experience of social evaluation.…”