Transitional and translational studies of risk for anxiety

Casey, B. J.; Ruberry, Erika J.; Libby, Victoria; Glatt, Charles E.; Hare, Todd A.; Soliman, F. S. G.; Duhoux, Stéphanie; Frielingsdorf, Helena; Tottenham, Nim

doi:10.1002/da.20783

Cited by 36 publications

(27 citation statements)

References 91 publications

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“…First, a broad age range in the current study may obscure developmentally-sensitive processes (35). For example, evidence suggests that it may be more difficult to extinguish conditioned fear in early- relative to late-adolescence (34).…”

Section: Discussionmentioning

confidence: 99%

Response to Learned Threat: An fMRI Study in Adolescent and Adult Anxiety

Britton¹,

Grillon²,

Lissek³

et al. 2013

AJP

160

216

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Objective Poor threat-safety discrimination reflects prefrontal cortex dysfunction in adult anxiety disorders. While adolescent anxiety disorders are impairing and predict high risk for adult anxiety disorders, no prior study examines neural correlates of threat-safety discrimination in this group. The current study compares prefrontal cortex function in anxious and healthy adolescents and adults following conditioning and extinction, processes requiring threat-safety learning. Method Anxious and healthy adolescents and adults (n=114) completed fear conditioning and extinction in the clinic. Conditioned stimuli (CS+) were neutral faces, paired with an aversive scream. Physiological and subjective data were acquired. Several weeks later, 82 participants viewed the CS+ and morphed images resembling the CS+ in a magnetic resonance imaging (MRI) scanner. During scanning, participants made difficult threat-safety discriminations while appraising threat and explicit memory of the CS+. Results During conditioning and extinction, anxious groups reported more fear than healthy groups, but patient groups did not differ on physiology. During imaging, both anxious adolescents and adults exhibited lower sub-genual anterior cingulate (sgACC) activation than healthy peers, specifically when appraising threat. In ventromedial prefrontal cortex (vmPFC), relative to their age-matched peer groups, anxious adults exhibited reduced activation when appraising threat, whereas anxious adolescents exhibited a U-shaped pattern of activation, with greater activation to the most extreme CS and CS−. Conclusions Two regions of the prefrontal cortex are involved in anxiety disorders. Reduced sgACC engagement is a shared feature in adult and adolescent anxiety disorders, but vmPFC dysfunction is age-specific. The unique U-shaped pattern of vmPFC activation in many anxious adolescents could reflect heightened sensitivity to threat and safety conditions. How variations in the pattern relate to later risk for adult illness remains to be determined.

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Section: Discussionmentioning

confidence: 99%

Response to Learned Threat: An fMRI Study in Adolescent and Adult Anxiety

Britton¹,

Grillon²,

Lissek³

et al. 2013

AJP

160

216

View full text Add to dashboard Cite

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“…Compared to both children and adults, neurological circuits responsible for emotionally-salient cue responses are more active among adolescents, including an elevated amygdala response to threat [29••, 57] and elevated ventral striatum activity in response to rewards [3••]. Adolescents with a positive family history of SUD (i.e., at least one parent with an SUD) also show greater amygdala activation in response to emotional stimuli [46].…”

Section: Emotion Regulation Developmentmentioning

confidence: 99%

Adolescent Substance Use and Comorbid Psychopathology: Emotion Regulation Deficits as a Transdiagnostic Risk Factor

Shadur

Lejuez

2015

Curr Addict Rep

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Rates of substance use and comorbid psychopathology peak during adolescence, highlighting the need to identify transdiagnostic risk processes that cut across conditions and elucidate early embedded risk factors for comorbidity across development. The current review highlights emotion regulation deficits as a core transdiagnostic risk factor underlying the development of substance use, addiction, and comorbid psychopathology in adolescence. We present the dual systems model of neurological development to highlight adolescence as a critical period of increased risk for emotion regulation difficulties, corresponding risk behaviors, and psychopathology. We describe malfunction in the neurobiological regulation system underlying the relationship between emotion regulation and risk for addiction and comorbidity. We pull from two established developmental theories including both the externalizing pathway and the internalizing pathway to substance use disorders, which together highlight how early embedded risk in the form of emotion regulation deficits can explain mechanisms underlying the development of addiction and comorbid psychiatric disorders.

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“…Human adolescents exhibit greater stress reactivity than non-adolescents (Dahl and Gunnar, 2009) and PA stress can trigger the onset of neuropsychiatric disorders, most prominently schizophrenia and substance abuse (Hoffman and Dobscha, 1989). Furthermore, chronic stress during adolescence impacts PFC development (Casey et al, 2010(Casey et al, , 2011Hoftman and Lewis, 2011;Lupien et al, 2009;Selemon, 2013) and is associated with lower cognitive performance in adulthood, both in humans (Casey et al, 2010;Rahdar and Galvan, 2014) and rodents (Lukkes et al, 2009). Interestingly, although the DA system undergoes a transient expansion phase of high plasticity during adolescence (Figure 1), stress exposure can influence its maturation.…”

Section: Pa Adversity and Monoamine Perturbationmentioning

confidence: 99%

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Suri

Teixeira

Cagliostro

et al. 2014

Neuropsychopharmacol

145

125

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Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system development, such sensitive periods shape the formation of neurocircuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint as well as the environmental context. While allowing for adaptation, such sensitive periods are also vulnerability windows during which external and internal factors can confer risk to disorders by derailing otherwise resilient developmental programs. Here we review developmental periods that are sensitive to monoamine signaling and impact adult behaviors of relevance to psychiatry. Specifically, we review (1) a serotonin-sensitive period that impacts sensory system development, (2) a serotonin-sensitive period that impacts cognition, anxiety-and depressionrelated behaviors, and (3) a dopamine-and serotonin-sensitive period affecting aggression, impulsivity and behavioral response to psychostimulants. We discuss preclinical data to provide mechanistic insight, as well as epidemiological and clinical data to point out translational relevance. The field of translational developmental neuroscience has progressed exponentially providing solid conceptual advances and unprecedented mechanistic insight. With such knowledge at hand and important methodological innovation ongoing, the field is poised for breakthroughs elucidating the developmental origins of neuropsychiatric disorders, and thus understanding pathophysiology. Such knowledge of sensitive periods that determine the developmental trajectory of complex behaviors is a necessary step towards improving prevention and treatment approaches for neuropsychiatric disorders.

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Transitional and translational studies of risk for anxiety

Cited by 36 publications

References 91 publications

Response to Learned Threat: An fMRI Study in Adolescent and Adult Anxiety

Response to Learned Threat: An fMRI Study in Adolescent and Adult Anxiety

Adolescent Substance Use and Comorbid Psychopathology: Emotion Regulation Deficits as a Transdiagnostic Risk Factor

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

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