Fronto-limbic dysfunction in mania pre-treatment and persistent amygdala over-activity post-treatment in pediatric bipolar disorder

Alessandra M. Passarotti, John A. Sweeney, Mani N. Pavuluri

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Rationale: Neural deficits at the interface of affect and cognition may improve with pharmacotherapy in pediatric bipolar disorder (PBD). Objectives: We examined lamotrigine treatment impact on the neural interface of working memory and affect in PBD. Methods: Un-medicated, acutely ill, patients with mania and hypomania (n=17), and healthy controls (HC; n=13; mean age=13.36±2.55) performed an affective two-back functional magnetic resonance imaging task with blocks of angry vs neutral faces (i.e., angry face condition) or happy vs neutral faces (i.e., happy face condition) before treatment and at follow-up, after 8-week treatment with second-generation antipsychotics followed by 6 weeks of lamotrigine monotherapy. Results: At baseline, for the angry face condition, PBD, relative to HC, showed reduced activation in the left ventrolateral prefrontal cortex (VLPFC) and right caudate; for the happy face condition, PBD showed increased activation in bilateral PFC and right amygdala and middle temporal gyrus. Post-treatment, PBD showed greater activation in right amygdala relative to HC for both conditions. Patients, relative to HC, exhibited greater changes over time in the right VLPFC and amygdala, left subgenual anterior cingulate cortex and left caudate for the angry face condition, and in right middle temporal gyrus for the happy face condition. Conclusions: Pharmacotherapy resulted in symptom improvement and normalization of higher cortical emotional and cognitive regions in patients relative to HC, suggesting that the VLPFC dysfunction may be state-specific in PBD. Amygdala was overactive in PBD, relative to HC, regardless of reduction in manic symptoms, and may be a trait marker of PBD.

Original languageEnglish (US)
Pages (from-to)485-499
Number of pages15
JournalPsychopharmacology
Volume216
Issue number4
DOIs
StatePublished - Aug 2011

Fingerprint

Amygdala
Bipolar Disorder
Pediatrics
Prefrontal Cortex
Therapeutics
Temporal Lobe
Drug Therapy
Gyrus Cinguli
Short-Term Memory
Cognition
Antipsychotic Agents
Magnetic Resonance Imaging

Keywords

  • Adolescent
  • Bipolar
  • Brain imaging
  • Child
  • Emotion
  • Face emotion
  • Functional magnetic resonance imaging (fMRI)
  • Lamotrigine
  • State
  • Trait
  • Working memory

ASJC Scopus subject areas

  • Pharmacology

Cite this

Fronto-limbic dysfunction in mania pre-treatment and persistent amygdala over-activity post-treatment in pediatric bipolar disorder. / Passarotti, Alessandra M.; Sweeney, John A.; Pavuluri, Mani N.

In: Psychopharmacology, Vol. 216, No. 4, 08.2011, p. 485-499.

Research output: Contribution to journalArticle

@article{efa8b615e3074921a2937470a47f7985,
title = "Fronto-limbic dysfunction in mania pre-treatment and persistent amygdala over-activity post-treatment in pediatric bipolar disorder",
abstract = "Rationale: Neural deficits at the interface of affect and cognition may improve with pharmacotherapy in pediatric bipolar disorder (PBD). Objectives: We examined lamotrigine treatment impact on the neural interface of working memory and affect in PBD. Methods: Un-medicated, acutely ill, patients with mania and hypomania (n=17), and healthy controls (HC; n=13; mean age=13.36±2.55) performed an affective two-back functional magnetic resonance imaging task with blocks of angry vs neutral faces (i.e., angry face condition) or happy vs neutral faces (i.e., happy face condition) before treatment and at follow-up, after 8-week treatment with second-generation antipsychotics followed by 6 weeks of lamotrigine monotherapy. Results: At baseline, for the angry face condition, PBD, relative to HC, showed reduced activation in the left ventrolateral prefrontal cortex (VLPFC) and right caudate; for the happy face condition, PBD showed increased activation in bilateral PFC and right amygdala and middle temporal gyrus. Post-treatment, PBD showed greater activation in right amygdala relative to HC for both conditions. Patients, relative to HC, exhibited greater changes over time in the right VLPFC and amygdala, left subgenual anterior cingulate cortex and left caudate for the angry face condition, and in right middle temporal gyrus for the happy face condition. Conclusions: Pharmacotherapy resulted in symptom improvement and normalization of higher cortical emotional and cognitive regions in patients relative to HC, suggesting that the VLPFC dysfunction may be state-specific in PBD. Amygdala was overactive in PBD, relative to HC, regardless of reduction in manic symptoms, and may be a trait marker of PBD.",
keywords = "Adolescent, Bipolar, Brain imaging, Child, Emotion, Face emotion, Functional magnetic resonance imaging (fMRI), Lamotrigine, State, Trait, Working memory",
author = "Passarotti, {Alessandra M.} and Sweeney, {John A.} and Pavuluri, {Mani N.}",
year = "2011",
month = "8",
doi = "10.1007/s00213-011-2243-2",
language = "English (US)",
volume = "216",
pages = "485--499",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "4",

}

TY - JOUR

T1 - Fronto-limbic dysfunction in mania pre-treatment and persistent amygdala over-activity post-treatment in pediatric bipolar disorder

AU - Passarotti, Alessandra M.

AU - Sweeney, John A.

AU - Pavuluri, Mani N.

PY - 2011/8

Y1 - 2011/8

N2 - Rationale: Neural deficits at the interface of affect and cognition may improve with pharmacotherapy in pediatric bipolar disorder (PBD). Objectives: We examined lamotrigine treatment impact on the neural interface of working memory and affect in PBD. Methods: Un-medicated, acutely ill, patients with mania and hypomania (n=17), and healthy controls (HC; n=13; mean age=13.36±2.55) performed an affective two-back functional magnetic resonance imaging task with blocks of angry vs neutral faces (i.e., angry face condition) or happy vs neutral faces (i.e., happy face condition) before treatment and at follow-up, after 8-week treatment with second-generation antipsychotics followed by 6 weeks of lamotrigine monotherapy. Results: At baseline, for the angry face condition, PBD, relative to HC, showed reduced activation in the left ventrolateral prefrontal cortex (VLPFC) and right caudate; for the happy face condition, PBD showed increased activation in bilateral PFC and right amygdala and middle temporal gyrus. Post-treatment, PBD showed greater activation in right amygdala relative to HC for both conditions. Patients, relative to HC, exhibited greater changes over time in the right VLPFC and amygdala, left subgenual anterior cingulate cortex and left caudate for the angry face condition, and in right middle temporal gyrus for the happy face condition. Conclusions: Pharmacotherapy resulted in symptom improvement and normalization of higher cortical emotional and cognitive regions in patients relative to HC, suggesting that the VLPFC dysfunction may be state-specific in PBD. Amygdala was overactive in PBD, relative to HC, regardless of reduction in manic symptoms, and may be a trait marker of PBD.

AB - Rationale: Neural deficits at the interface of affect and cognition may improve with pharmacotherapy in pediatric bipolar disorder (PBD). Objectives: We examined lamotrigine treatment impact on the neural interface of working memory and affect in PBD. Methods: Un-medicated, acutely ill, patients with mania and hypomania (n=17), and healthy controls (HC; n=13; mean age=13.36±2.55) performed an affective two-back functional magnetic resonance imaging task with blocks of angry vs neutral faces (i.e., angry face condition) or happy vs neutral faces (i.e., happy face condition) before treatment and at follow-up, after 8-week treatment with second-generation antipsychotics followed by 6 weeks of lamotrigine monotherapy. Results: At baseline, for the angry face condition, PBD, relative to HC, showed reduced activation in the left ventrolateral prefrontal cortex (VLPFC) and right caudate; for the happy face condition, PBD showed increased activation in bilateral PFC and right amygdala and middle temporal gyrus. Post-treatment, PBD showed greater activation in right amygdala relative to HC for both conditions. Patients, relative to HC, exhibited greater changes over time in the right VLPFC and amygdala, left subgenual anterior cingulate cortex and left caudate for the angry face condition, and in right middle temporal gyrus for the happy face condition. Conclusions: Pharmacotherapy resulted in symptom improvement and normalization of higher cortical emotional and cognitive regions in patients relative to HC, suggesting that the VLPFC dysfunction may be state-specific in PBD. Amygdala was overactive in PBD, relative to HC, regardless of reduction in manic symptoms, and may be a trait marker of PBD.

KW - Adolescent

KW - Bipolar

KW - Brain imaging

KW - Child

KW - Emotion

KW - Face emotion

KW - Functional magnetic resonance imaging (fMRI)

KW - Lamotrigine

KW - State

KW - Trait

KW - Working memory

UR - http://www.scopus.com/inward/record.url?scp=79961166039&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79961166039&partnerID=8YFLogxK

U2 - 10.1007/s00213-011-2243-2

DO - 10.1007/s00213-011-2243-2

M3 - Article

VL - 216

SP - 485

EP - 499

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 4

ER -