Balancing act: Neural correlates of affect dysregulation in youth depression and substance use - A systematic review of functional neuroimaging studies

Abstract

Both depression and substance use problems have their highest incidence during youth (i.e., adolescence and emerging adulthood), and are characterized by emotion regulation deficits. Influential neurodevelopmental theories suggest that alterations in the function of limbic and frontal regions render youth susceptible to these deficits. However, whether depression and substance use in youth are associated with similar alterations in emotion regulation neural circuitry is unknown. In this systematic review we synthesized the results of functional magnetic resonance imaging (fMRI) studies investigating the neural correlates of emotion regulation in youth depression and substance use. Resting-state fMRI studies focusing on limbic connectivity were also reviewed. While findings were largely inconsistent within and between studies of depression and substance use, some patterns emerged. First, youth depression appears to be associated with exaggerated amygdala activity in response to negative stimuli; second, both depression and substance use appear to be associated with lower functional connectivity between the amygdala and prefrontal cortex during rest. Findings are discussed in relation to support for existing neurodevelopmental models, and avenues for future work are suggested, including studying neurodevelopmental trajectories from a network perspective.

Keywords: Emotion processing; Emotion regulation; Systematic review; Youth depression; Youth substance use.

Fig. 1

Regions involved in emotion generation, processing and regulation. Regions colored orange and red (EG1: amygdala, EG2: insula and EG3: basal ganglia) are regions involved in emotion generation and processing; regions depicted in blue and purple are top-down regulatory structures (ER1: dmPFC, dACC, SMA, pre-SMA, ER2: dlPFC, lOFC, vlPFC, ER3: rACC, vmPFC, sgACC, HPC). Abbreviations: EG = emotion generating, ER = emotion regulating. Brain regions: ACC = anterior cingulate cortex, AMG = amygdala, dACC = dorsal ACC, dmPFC = dorsomedial prefrontal cortex, dlPFC = dorsolateral prefrontal cortex, HPC = hippocampus, lOFC = lateral orbitofrontal cortex, mOFC = medial orbitofrontal cortex, pgACC = perigenual ACC, preSMA = presupplementary motor area, rACC = rostral ACC, SMA = supplementary motor area, sgACC = subgenual ACC, vlPFC = ventrolateral prefrontal cortex, vmPFC = ventromedial prefrontal cortex. (For interpretation of the references to colour in the Figure, the reader is referred to the web version of this article). Brain Images were downloaded from BioRender.

Fig. 2

Stacked histograms illustrating the number of studies that showed depression (A,C,E) and substance use (B,D,F) associated aberrant activation of EG1 (amygdala), EG2 (insula), EG3 (basal ganglia), ER1 (dmPFC/dACC/SMA/Pre-SMA), ER2 (dlPFC/vlPFC/lOFC), ER3 (rACC/vmPFC/mOFC/hippocampus) and other regions in A,B) tasks of affective reactivity and modulation for positive, negative and all emotion (all-emotions) contrasts in depression (A) and substance use (B). C, D) behavioral control for positive and negative emotions in depression (C) and substance use (D) and E, F) cognitive modulation (reappraisal and acceptance) of negative affect in depression (E) and substance use (F).

Fig. 3

Aberrant resting state functional connectivity. Histograms illustrating the number of studies that showed depression (A) and substance use (B) associated aberrant resting state functional connectivity between seed regions and EG1 (amygdala), EG2 (insula), EG3 (basal ganglia), ER1 (dmPFC/dACC/SMA/Pre-SMA), ER2 (dlPFC/vlPFC/lOFC), ER3 (rACC/vmPFC/mOFC/hippocampus) and other regions. Orange bars represent higher connectivity and blue bars represent lower connectivity. Gray bars represent null findings for each seed region. (For interpretation of the references to colour in the Figure, the reader is referred to the web version of this article).

Fig. 4

Aberrant resting state functional connectivity. Chord diagrams depicting the number of instances reported for depression (A) and substance use (B) associated aberrant resting state functional connectivity between seed regions and EG1 (amygdala), EG2 (insula), EG3 (basal ganglia), ER1 (dmPFC/dACC/SMA/Pre-SMA), ER2 (dlPFC/vlPFC/lOFC), ER3 (rACC/vmPFC/mOFC/hippocampus) and other regions in A) depression and B substance use (multiple findings of increased or reduced seed-group rsFC within the same study were counted as separate instances). Regions in blue depict seed regions and regions in orange represent target groups. Blue chords represent decreased connectivity; red chords represented increased connectivity. (For interpretation of the references to colour in the Figure, the reader is referred to the web version of this article). Brain regions: ACC = anterior cingulate cortex, dACC = dorsal ACC, dlPFC = dorsolateral prefrontal cortex, dmPFC = dorsomedial PFC, HPC = hippocampus, mOFC = medial orbitofrontal cortex, NAcc = nucleus accumbens, PCC = posterior cingulate cortex, pgACC = perigenual ACC, sgACC = subgenual ACC.