Age-Normative Pathways of Striatal Connectivity Related to Clinical Symptoms in the General Population

Pediatric Imaging, Neurocognition, and Genetics (PING) Study Consortium

Research output: Contribution to journalArticle

Abstract

Background: Altered striatal development contributes to core deficits in motor and inhibitory control, impulsivity, and inattention associated with attention-deficit/hyperactivity disorder and may likewise play a role in deficient reward processing and emotion regulation in psychosis and depression. The maturation of striatal connectivity has not been well characterized, particularly as it relates to clinical symptomatology. Methods: Resting-state functional connectivity with striatal subdivisions was examined for 926 participants (8–22 years of age, 44% male) from the general population who had participated in two large cross-sectional studies. Developing circuits were identified and growth charting of age-related connections was performed to obtain individual scores reflecting relative neurodevelopmental attainment. Associations of clinical symptom scales (attention-deficit/hyperactivity disorder, psychosis, depression, and general psychopathology) with the resulting striatal connectivity age-deviation scores were then tested using elastic net regression. Results: Linear and nonlinear developmental patterns occurred across 231 striatal age-related connections. Both unique and overlapping striatal age-related connections were associated with the four symptom domains. Attention-deficit/hyperactivity disorder severity was related to age-advanced connectivity across several insula subregions, but to age-delayed connectivity with the nearby inferior frontal gyrus. Psychosis was associated with advanced connectivity with the medial prefrontal cortex and superior temporal gyrus, while aberrant limbic connectivity predicted depression. The dorsal posterior insula, a region involved in pain processing, emerged as a strong contributor to general psychopathology as well as to each individual symptom domain. Conclusions: Developmental striatal pathophysiology in the general population is consistent with dysfunctional circuitry commonly found in clinical populations. Atypical age-normative connectivity may thereby reflect aberrant neurodevelopmental processes that contribute to clinical risk.

Original languageEnglish (US)
JournalBiological psychiatry
DOIs
StatePublished - Jan 1 2019

Fingerprint

Corpus Striatum
Population
Attention Deficit Disorder with Hyperactivity
Psychotic Disorders
Depression
Prefrontal Cortex
Psychopathology
Impulsive Behavior
Temporal Lobe
Reward
Emotions
Cross-Sectional Studies
Pain
Growth

Keywords

  • ADHD
  • Depression
  • Development
  • General psychopathology
  • Psychosis
  • Striatum

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Age-Normative Pathways of Striatal Connectivity Related to Clinical Symptoms in the General Population. / Pediatric Imaging, Neurocognition, and Genetics (PING) Study Consortium.

In: Biological psychiatry, 01.01.2019.

Research output: Contribution to journalArticle

Pediatric Imaging, Neurocognition, and Genetics (PING) Study Consortium. / Age-Normative Pathways of Striatal Connectivity Related to Clinical Symptoms in the General Population. In: Biological psychiatry. 2019.
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abstract = "Background: Altered striatal development contributes to core deficits in motor and inhibitory control, impulsivity, and inattention associated with attention-deficit/hyperactivity disorder and may likewise play a role in deficient reward processing and emotion regulation in psychosis and depression. The maturation of striatal connectivity has not been well characterized, particularly as it relates to clinical symptomatology. Methods: Resting-state functional connectivity with striatal subdivisions was examined for 926 participants (8–22 years of age, 44{\%} male) from the general population who had participated in two large cross-sectional studies. Developing circuits were identified and growth charting of age-related connections was performed to obtain individual scores reflecting relative neurodevelopmental attainment. Associations of clinical symptom scales (attention-deficit/hyperactivity disorder, psychosis, depression, and general psychopathology) with the resulting striatal connectivity age-deviation scores were then tested using elastic net regression. Results: Linear and nonlinear developmental patterns occurred across 231 striatal age-related connections. Both unique and overlapping striatal age-related connections were associated with the four symptom domains. Attention-deficit/hyperactivity disorder severity was related to age-advanced connectivity across several insula subregions, but to age-delayed connectivity with the nearby inferior frontal gyrus. Psychosis was associated with advanced connectivity with the medial prefrontal cortex and superior temporal gyrus, while aberrant limbic connectivity predicted depression. The dorsal posterior insula, a region involved in pain processing, emerged as a strong contributor to general psychopathology as well as to each individual symptom domain. Conclusions: Developmental striatal pathophysiology in the general population is consistent with dysfunctional circuitry commonly found in clinical populations. Atypical age-normative connectivity may thereby reflect aberrant neurodevelopmental processes that contribute to clinical risk.",
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author = "{Pediatric Imaging, Neurocognition, and Genetics (PING) Study Consortium} and Barber, {Anita D.} and Sarpal, {Deepak K.} and Majnu John and Fales, {Christina L.} and Mostofsky, {Stewart H} and Malhotra, {Anil K.} and Karlsgodt, {Katherine H.} and Todd Lencz",
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AU - Pediatric Imaging, Neurocognition, and Genetics (PING) Study Consortium

AU - Barber, Anita D.

AU - Sarpal, Deepak K.

AU - John, Majnu

AU - Fales, Christina L.

AU - Mostofsky, Stewart H

AU - Malhotra, Anil K.

AU - Karlsgodt, Katherine H.

AU - Lencz, Todd

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AB - Background: Altered striatal development contributes to core deficits in motor and inhibitory control, impulsivity, and inattention associated with attention-deficit/hyperactivity disorder and may likewise play a role in deficient reward processing and emotion regulation in psychosis and depression. The maturation of striatal connectivity has not been well characterized, particularly as it relates to clinical symptomatology. Methods: Resting-state functional connectivity with striatal subdivisions was examined for 926 participants (8–22 years of age, 44% male) from the general population who had participated in two large cross-sectional studies. Developing circuits were identified and growth charting of age-related connections was performed to obtain individual scores reflecting relative neurodevelopmental attainment. Associations of clinical symptom scales (attention-deficit/hyperactivity disorder, psychosis, depression, and general psychopathology) with the resulting striatal connectivity age-deviation scores were then tested using elastic net regression. Results: Linear and nonlinear developmental patterns occurred across 231 striatal age-related connections. Both unique and overlapping striatal age-related connections were associated with the four symptom domains. Attention-deficit/hyperactivity disorder severity was related to age-advanced connectivity across several insula subregions, but to age-delayed connectivity with the nearby inferior frontal gyrus. Psychosis was associated with advanced connectivity with the medial prefrontal cortex and superior temporal gyrus, while aberrant limbic connectivity predicted depression. The dorsal posterior insula, a region involved in pain processing, emerged as a strong contributor to general psychopathology as well as to each individual symptom domain. Conclusions: Developmental striatal pathophysiology in the general population is consistent with dysfunctional circuitry commonly found in clinical populations. Atypical age-normative connectivity may thereby reflect aberrant neurodevelopmental processes that contribute to clinical risk.

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KW - Depression

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KW - General psychopathology

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KW - Striatum

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