Striatal Activity to Reward Anticipation as a Moderator of the Association Between Early Behavioral Inhibition and Changes in Anxiety and Depressive Symptoms From Adolescence to Adulthood

Abstract

ImportanceThe early childhood temperament of behavioral inhibition (BI), characterized by inhibited and fearful behaviors, has been associated with heightened risk for anxiety and depression across the lifespan. Although several neurocognitive correlates underlying vulnerability to the development of anxiety among inhibited children have been identified, little is known about the neurocognitive correlates underlying vulnerability to the development of depression.ObjectiveTo examine whether blunted striatal activation to reward anticipation, a well-documented neurocognitive vulnerability marker of depression, moderates the association between early BI and the developmental changes in depression and anxiety from adolescence to adulthood.Design, Setting, and ParticipantsParticipants in this prospective longitudinal study were recruited at age 4 months between 1989 and 1993 in the US. Follow-up assessments extended into 2018 (age 26 years). Data were analyzed between September 2021 to March 2022.Main Outcomes and MeasuresBI was measured through an observation paradigm in infancy (ages 14 and 24 months). Neural activity to anticipated rewards during a monetary incentive delay task was measured using functional magnetic resonance imaging in adolescence (between ages 15-18 years; 83 individuals had usable data). Anxiety and depressive symptoms were self-reported across adolescence to young adulthood (ages 15 and 26 years; n = 108). A latent change score model, accounting for the interdependence between anxiety and depression, tested the moderating role of striatal activity to reward anticipation in the association between early BI and changes in anxiety and depressive symptoms. A region of interest approach limited statistical tests to regions within the striatum (ie, nucleus accumbens, caudate head, caudate body, putamen).ResultsOf 165 participants, 84 (50.1%) were female and 162 (98%) were White. Preliminary analyses revealed significant increases in anxiety and depressive symptoms across ages 15 to 26 years, as well as individual variation in the magnitude of changes. Main analyses showed that reduced activity in the nucleus accumbens to reward anticipation moderated the association between early BI and increases in depressive (β = −0.32; b = −4.23; 95% CI, −7.70 to −0.76; P = .02), and more depressive symptoms at age 26 years (β = −0.47; b = −5.09; 95% CI, −7.74 to −2.43; P < .001). However, there were no significant interactions associated with latent changes in anxiety across age nor anxiety at age 26 years. Activity in the caudate and putamen did not moderate these associations.Conclusions and RelevanceBlunted reward sensitivity in the ventral striatum may be a developmental risk factor connecting an inhibited childhood temperament and depression over the transition to adulthood. Future studies should examine the efficacy of prevention programs, which target maladaptive reward processing and motivational deficits among anxious youths, in reducing risks for later depression.

Prenatal maternal immune activation predicts observed fearfulness in infancy.

“…Fear reactivity and behavioral inhibition are reliably assessed early markers of important behavioral and health outcomes, notably anxiety (Kagan, 2002;Tang et al, 2022). Kagan and others (Kagan et al, 1987(Kagan et al, , 1988 have added substantially to our understanding of its assessment in early infancy and its biological and environmental origins.…”

Chronic Pb Exposure Induces Anxiety and Depression-like Behaviors in Mice via Excitatory Neuronal Hyperexcitability in Ventral Hippocampal Dentate Gyrus

“…12 week-old mice were used in our experiments to enable the modeling of young adults in human. Young adults have recently emerged as a vulnerable group more likely to be associated with mental disorders. − Hence, finding possible mechanisms and targeted interventions for young adults are urgently needed and may lead to earlier detection and treatment. In the first step, we detected anxiety and depression-like behaviors in adult mice under Pb exposure through several behavioral studies.…”

Prenatal Maternal Immune Activation Predicts Observed Fearfulness in Infancy

“…Fear reactivity and behavioral inhibition are reliably assessed early markers of important behavioral and health outcomes, notably anxiety (Kagan, 2002;Tang et al, 2022). Kagan andothers (Kagan et al, 1987, 1988) have added substantially to our understanding of its assessment in early infancy and its biological and environmental origins.…”