Elsevier

Biological Psychiatry

Volume 74, Issue 4, 15 August 2013, Pages 296-304
Biological Psychiatry

Archival Report
Frontal Lobe γ-Aminobutyric Acid Levels During Adolescence: Associations with Impulsivity and Response Inhibition

https://doi.org/10.1016/j.biopsych.2013.01.033Get rights and content

Background

The brain undergoes major remodeling during adolescence, resulting in improved cognitive control and decision-making and reduced impulsivity, components of behavior mediated in part by the maturing frontal lobe. γ-Aminobutyric acid (GABA), the main inhibitory neurotransmitter system, also matures during adolescence, with frontal lobe GABA receptors reaching adult levels late in adolescence. Thus, the objective of this study was to characterize in vivo developmental differences in brain GABA levels.

Methods

Proton magnetic resonance spectroscopy was used at 4 T to acquire metabolite data from the anterior cingulate cortex (ACC) and the parieto-occipital cortex (POC) in adolescents (n=30) and emerging adults (n = 20).

Results

ACC GABA/creatine (Cr) levels were significantly lower in adolescents relative to emerging adults, whereas no age differences were observed in the POC. Lower ACC GABA/Cr levels were significantly associated with greater impulsivity and worse response inhibition, with relationships being most pronounced for ACC GABA/Cr and No-Go response inhibition in adolescent males.

Conclusions

These data provide the first human developmental in vivo evidence confirming frontal lobe GABA maturation, which was linked to impulsiveness and cognitive control. These findings suggest that reduced GABA may be an important neurobiological mechanism in the immature adolescent brain, contributing to the reduced yet rapidly developing ability to inhibit risky behaviors and to make suboptimal decisions, which could compromise adolescent health and safety.

Section snippets

Participants

Participants included 30 healthy ADO (12–14 years, 15 females) and 20 healthy EA (18–24 years, 10 females), with middle-upper class socioeconomic status (53) (Table 1). The clinical research protocol was approved by the Institutional Review Board of McLean Hospital. After complete study description, all subjects and ADO parent(s)/guardian(s) provided written informed assent/consent. Participants completed urine screening before scanning to rule out current psychoactive substance use and

Impulsivity

Significantly higher BIS impulsivity scores (Table 1) were observed for ADO versus EA on Motor [F1,48=26.97, p=.0001, ES=.77] and Non-Planning [F1,48=13.16, p=.001; ES=.51] subscales and total BIS [F1,48=15.70, p=.0001; ES = .57].

Response Inhibition

EA took significantly less time than ADO to complete each Stroop subtest: CN [F1,48=11.80, p=.001; ES=.49], WR [F1,48=8.66, p=.005; ES=.42], and INTF [F1,48=4.17, p=.047; ES=.29], although group differences for derived INTF were not significant (Table 2). Significantly

Discussion

This study provides the first in vivo human evidence of lower GABA in ADO relative to EA, which extends previous developmental findings 17, 18. Lower adolescent GABA/Cr was observed in ACC but not POC and was evident in the absence of tissue contribution differences. There were significant differences in POC tissue contributions but not tissue percentage, the relevance of which is unclear with regard to the use of the POC as a comparison region. Consistent with the a priori study hypotheses,

References (90)

  • F. Boy et al.

    Individual differences in subconscious motor control predicted by GABA concentration in SMA

    Curr Biol

    (2010)
  • L. van Leijenhorst et al.

    Neural correlates of developmental differences in risk estimation and feedback processing

    Neuropsychologia

    (2006)
  • L. Van Leijenhorst et al.

    Adolescent risky decision-making: neurocognitive development of reward and control regions

    Neuroimage

    (2010)
  • N.E. Adleman et al.

    A developmental fMRI study of the Stroop olor-Word Task

    Neuroimage

    (2002)
  • D.S. Leland et al.

    Anterior cingulate cortex and benefit of predictive cueing on response inhibition in stimulant dependent individuals

    Biol Psychiatry

    (2008)
  • I.Y. Choi et al.

    In vivo detection of gray and white matter differences in GABA concentration in the human brain

    Neuroimage

    (2006)
  • M.C. Stevens et al.

    Functional neural networks underlying response inhibition in adolescents and adults

    Behav Brain Res

    (2007)
  • C.N. Epperson et al.

    Sex, GABA, and nicotine: the impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy

    Biol Psychiatry

    (2005)
  • C.J. Stagg et al.

    The role of GABA in human motor learning

    Curr Biol

    (2011)
  • R. Goya-Maldonado et al.

    Motor impulsivity and the ventrolateral prefrontal cortex

    Psychiatry Res

    (2010)
  • J. Knight-Scott et al.

    Molality as a unit of measure for expressing 1H MRS brain metabolite concentrations in vivo

    Magn Reson Imaging

    (2003)
  • R. Gomez et al.

    Intravenous ethanol infusion decreases human cortical gamma-aminobutyric acid and N-acetylaspartate as measured with proton magnetic resonance spectroscopy at 4 tesla

    Biol Psychiatry

    (2012)
  • J.N. Giedd et al.

    Quantitative magnetic resonance imaging of human brain development: ages 4–18

    Cereb Cortex

    (1996)
  • E.R. Sowell et al.

    Mapping changes in the human cortex throughout the span of life

    Neuroscientist

    (2004)
  • B. Luna et al.

    The emergence of collaborative brain function: FMRI studies of the development of response inhibition

    Ann N Y Acad Sci

    (2004)
  • P.S. Goldman-Rakic

    Topography of cognition: Parallel distributed networks in primate association cortex

    Annu Rev Neurosci

    (1988)
  • R. Marsh et al.

    A developmental fMRI study of self-regulatory control

    Hum Brain Mapp

    (2006)
  • M.M. Silveri et al.

    Adolescents at risk for alcohol abuse demonstrate altered frontal lobe activation during stroop performance

    Alcohol Clin Exp Res

    (2011)
  • N. Gogtay et al.

    Dynamic mapping of human cortical development during childhood through early adulthood

    Proc Natl Acad Sci U S A

    (2004)
  • D.A. McCormick

    GABA as an inhibitory neurotransmitter in human cerebral cortex

    J Neurophysiol

    (1989)
  • M.V. Johnston et al.

    Development of central neurotransmitter systems

    Ciba Found Symp

    (1981)
  • J.M. Candy et al.

    The postnatal development of the benzodiazepine receptor in the cerebral cortex and cerebellum of rat

    J Neurochem

    (1979)
  • S.L. Erickson et al.

    Postnatal development of parvalbumin- and GABA transporter-immunoreactive axon terminals in monkey prefrontal cortex

    J Comp Neurol

    (2002)
  • B.W. Brooksbank et al.

    Biochemical development of the human brain, II: Some parameters of the GABA-ergic system

    Dev Neurosci

    (1981)
  • D.C. Chugani et al.

    Postnatal maturation of human GABAA receptors measured with positron emission tomography

    Ann Neurol

    (2001)
  • S.J. Fung et al.

    Expression of interneuron markers in the dorsolateral prefrontal cortex of the developing human and in schizophrenia

    Am J Psychiatry

    (2010)
  • H.P. Hetherington et al.

    Measurements of human cerebral GABA at 4.1 T using numerically optimized editing pulses

    Magn Reson Med

    (1998)
  • J.E. Jensen et al.

    Grey and white matter GABA level differences in the human brain using two-dimensional, J-resolved spectroscopic imaging

    NMR Biomed

    (2005)
  • J.R. Keltner et al.

    In vivo detection of GABA in human brain using a localized double-quantum filter technique

    Magn Reson Med

    (1997)
  • M. Mescher et al.

    Simultaneous in vivo spectral editing and water suppression

    NMR Biomed

    (1998)
  • D.L. Rothman et al.

    Localized 1H NMR measurements of (gamma)-aminobutyric acid in human brain in vivo

    Proc Natl Acad Sci U S A

    (1993)
  • J. Shen et al.

    In vivo chemical shift imaging of (gamma)-aminobutyric acid in the human brain

    Magn Reson Med

    (1999)
  • Z. Bhagwagar et al.

    Low GABA concentrations in occipital cortex and anterior cingulate cortex in medication-free, recovered depressed patients

    Int J Neuropsychopharmacol

    (2008)
  • L. Chang et al.

    Magnetic resonance spectroscopy studies of GABA in neuropsychiatric disorders

    J Clin Psychiatry

    (2003)
  • C.N. Epperson et al.

    Preliminary evidence of reduced occipital GABA concentrations in puerperal women: A 1H-MRS study

    Psychopharmacology (Berl)

    (2006)
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