Table 2.

Summary of recent studies in the internalizing domain.

Study	Design	Participants	Behavioral/ Imaging Measures of Interest	Alcohol-Related Measures of Interest	Main Findings	Gender-Related Differences
Neuroimaging Studies of Emotional Control
Peraza et al., 2015	Cross-sectional	N=29; FH+ =14, (M=13.73 yrs, SD=1.49), FH− =15 (M=13.67 yrs, SD=1.60)	Adapted Masked Faces Task	FH+ vs. FH−	FH−: deactivated to both masked fearful and neutral faces in the left superior parietal lobule. FH+: only deactivated to masked fearful faces	41% female; Gender-related differences not assessed
Cservenka et al., 2014	Cross-sectional	N=36; FH+ =19 (M=14.92 yrs, SD 1.34), FH+ =17 (M=14.69 yrs, SD=1.10)	Emotional Go/No-Go Task; Resting state	FH+ vs. FH−	FH+: reduced activation during positive emotional contexts in left superior temporal cortex, reduced activation in frontal and striatal regions during emotionally-valenced inhibitory control trials; greater negative connectivity between left amygdala and left superior frontal gyrus	47% female; Gender-related differences not assessed
Hardee et al., 2017	Longitudinal; 3–4 fMRI scans per participant, 1–2 yrs between scans	N=36; age range 8.5–17.6 yrs (M=12.8 yrs, SD=2.3)	Emotional Word Task; Internalizing/externalizing	Family history of AUD	Males: internalizing symptoms significantly decreased with age; fMRI activation for negative vs. neutral words significantly decreased with age in right amygdala, right precentral gyrus. Females: internalizing symptoms significantly increased with age. No significant change for fMRI activation in two ROIs, but activation was sustained across age in both regions	50% female; Primary aim of study was gender-related differences
Considerations in Internalizing Research
Edwards et al., 2014	Longitudinal; Baseline internalizing then follow-up every 1.5–2 yrs	N=11,157; baseline internalizing M=3.9 yrs; T1=6.8 yrs; T2=8.1 yrs; T3=9.5 yrs; T4=11.7 yrs (no SD); alcohol use M=13.8 yrs SD=2.5 mos	Internalizing (maternal report)	Alcohol use; maternal depression	Children with elevated internalizing symptoms: less likely to use alcohol in early adolescence, both for those who displayed increasing levels of internalizing symptoms over time and those who had desisting symptoms over time	50% female; Gender used as a covariate in follow-up analyses
Cerda et al., 2013	Longitudinal; Baseline substance use and psychiatric disorder measures, then follow-up annually	N=460 (alcohol follow-up sample); baseline M=6.7 yrs (no SD); assessed annually until age 19	Depression, anxiety, conduct disorder symptoms	Alcohol and marijuana use	Recent anxiety and conduct disorder symptoms (year prior to measurement), as well as cumulative conduct disorder and depression symptoms (up to two years prior to measurement), were associated with earlier alcohol use onset	0% female
Hulvershorn et al., 2013	Cross-sectional	N=37; high risk=19 (M=12.2 yrs, SD 1.4), healthy controls=18 (M=11.9 yrs, SD=1.4)	Facial Emotion Matching Task; Emotional traits	FH+ & high externalizing (high risk) vs. FH− & no externalizing	High risk group: greater activation in right medial prefrontal cortex, left precuneus, right and left occipital cortex; occipital activation positively correlated with parent-report of emotional lability/negativity and emotional flatness	32% female; Groups matched on gender but gender-related differences were not assessed
Environmental Influences on Internalizing Pathways for AUD
Casement et al., 2015	Mediation	N=153; Stressful life events: 15–18 yrs, fMRI scan: 20 yrs (M=19.52, SD=0.51), alcohol dependence: 20 yrs	Reward Guessing Task; Stressful life events	Alcohol problems	Greater number of cumulative life stressors during adolescence associated with lower brain activation in mPFC during both reward anticipation and receipt. mPFC response to rewards significant mediator between adolescent life stress and symptoms of alcohol dependence measured at age 20	0% female
Nikolova et al., 2016	Prospective; Baseline fMRI and substance use follow-up 3 mos later	N=759; M=19.65 yrs, SD=1.24	Stressful life events; Number Guessing Reward Task	Alcohol problems	Positive correlation between stress and problem drinking; moderated by threat-related amygdala in individuals with high amygdala but low VS activation	56% female; Males showed greater activation in the amygdala and VS and higher AUDIT scores

Note. M mean age, SD standard deviation, FH+ family history positive, FH− family history negative, yrs years, AUD alcohol use disorder, fMRI functional magnetic resonance imaging, ROIs regions of interest, T time, mos months, mPFC medial prefrontal cortex, VS ventral striatum, AUDIT Alcohol Use Disorders Identification Test