Mania, glutamate/glutamine and risperidone in pediatric bipolar disorder: A proton magnetic resonance spectroscopy study of the anterior cingulate cortex

doi:10.1016/j.jad.2006.08.023

Journal of Affective Disorders

Volume 99, Issues 1–3, April 2007, Pages 19-25

https://doi.org/10.1016/j.jad.2006.08.023 Get rights and content

Abstract

Background

The purpose of this study was to investigate the anterior cingulate cortex (ACC) glutamate/glutamine (Glx) to creatine ratio (Glx/Cr) in two groups of children with Bipolar Disorder (BPD): those exhibiting manic symptoms requiring treatment and those being stably treated with the atypical antipsychotic risperidone. Atypical antipsychotics have been shown to increase serum glutamate levels and ACC Glx/Cr in subjects with schizophrenia. In this study, we hypothesized that the children with BPD in need of treatment would have lower Glx/Cr compared with the children with BPD being stably treated with risperidone.

Methods

Proton MR spectra were acquired, at 1.5 T, from the ACC of eighteen subjects with a DSM-IV diagnosis of BPD: ten (11.10 ± 3.48 years; five female) were manic and not medicated with any antipsychotic and eight (10.88 ± 2.99 years; one female) were medicated with the atypical antipsychotic risperidone.

Results

Children with BPD exhibiting manic symptoms requiring treatment had lower Glx/Cr than children with BPD being stably treated with the atypical antipsychotic risperidone. The children treated with risperidone also had significantly lower YMRS and CGI-Mania scores than the children not treated with risperidone. Both YMRS and CGI-Mania scores correlated negatively with ACC Glx/Cr levels.

Limitations

The cross-sectional design, small sample size, the use of Glx rather than glutamate or glutamine and the use of Cr ratios rather than absolute concentrations are limitations of this study.

Conclusions

Children with mania have lower Glx/Cr levels than children with BPD being stably treated with the atypical antipsychotic risperidone. Mania may be associated with reduced glutamate/glutamine levels in the ACC: other imaging studies have shown mania associated with hypometabolism in the ACC. These reductions in glutamate/glutamine may be increased following successful treatment with glutamatergic agents.

Section snippets

Background

The lifetime prevalence of bipolar disorder (BPD) is between 1% and 3%; and BPD can first manifest itself in childhood and adolescence (Geller et al., 1994, Lewinsohn et al., 1995). Glial cell abnormalities have been indicated in the prefrontal cortex and anterior cingulate cortex (ACC) in affective illnesses including BPD and major depression (MDD) (Rajkowska et al., 2001, Ongur et al., 1998). Glia provide a pathway for neuronal glutamate synthesis (Cooper et al., 2003, Sanacora et al., 2003)

Subjects

The Institutional Reviews Boards at McLean Hospital and Massachusetts General Hospital approved this study. All parents signed a written informed consent form and all children signed a written informed assent form. Subjects were recruited through the Pediatric Psychopharmacology Research Program at Massachusetts General Hospital.

To be included in the study subjects could be male or female aged between 6 and 17 years old. Each subject met criteria for DSM-IV TR Bipolar I Disorder, based on

Results

Eighteen subjects with a DSM-IV TR diagnosis of Bipolar 1 Disorder were recruited: ten (11.1 ± 1.0 years; 5 female) were not medicated with any antipsychotic and eight (10.9 ± 1.1 years; 1 female) were medicated with the atypical antipsychotic risperidone (see Table 1). The subjects with BPD, not treated with risperidone, were currently displaying manic or mixed symptoms (with or without psychotic features). All of these subjects had YMRS scores greater than 15. Of the BPD subjects treated with

Discussion

Children with BPD exhibiting manic symptoms requiring treatment had lower Glx/Cr than children with BPD being stably treated with the atypical antipsychotic risperidone. The children treated with risperidone also had significantly lower YMRS and CGI-Mania Severity scores than the children not treated with risperidone.

The Glx peak in proton MRS is composed primarily of glutamate (Glu) and glutamine (Gln): Glu is of the order of 8–13 μmol/g (Cooper et al., 2003); and the Glu to Gln ratio in vivo

Acknowledgements

The authors would like to acknowledge the following for support: National Institute of Mental Health (MH01798) and Johnson and Johnson.

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Moore and colleagues61 used 1H-MRS and found decreased levels of glutamine in the ACC in unmedicated youth with BD in comparison with healthy controls and medicated youth on a variety of different agents for BD. This group also found that unmedicated children with BD exhibiting manic symptoms severe enough to warrant treatment had lower Glx to creatine ratios in the ACC than children with BD who were stably treated with risperidone.62 Mania severity correlated negatively with ACC Glx/creatine levels.

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Research reportMania, glutamate/glutamine and risperidone in pediatric bipolar disorder: A proton magnetic resonance spectroscopy study of the anterior cingulate cortex

Abstract

Background

Methods

Results

Limitations

Conclusions

Section snippets

Background

Subjects

Results

Discussion

Acknowledgements

Journal of the American Academy of Child and Adolescent Psychiatry

Journal of the American Academy of Child and Adolescent Psychiatry

Biological Psychiatry

Journal of Affective Disorders

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Journal of the American Academy of Child and Adolescent Psychiatry

Biological Psychiatry

Biological Psychiatry

Biological Psychiatry

Biological Psychiatry

Neuroscience and Biobehavioral Reviews

Increased amygdala activation during mania: a functional magnetic resonance imaging study

American Journal of Psychiatry

An open-label trial of risperidone in children and adolescents with bipolar disorder

Journal of Child and Adolescent Psychopharmacology

A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices

Archives of General Psychiatry

Preliminary evidence for medication effects on functional abnormalities in the amygdala and anterior cingulate in bipolar disorder

Psychopharmacology

Glutamatergic changes with treatment in attention deficit hyperactivity disorder: a preliminary case series

Journal of Child and Adolescent Psychopharmacology

Research report
Mania, glutamate/glutamine and risperidone in pediatric bipolar disorder: A proton magnetic resonance spectroscopy study of the anterior cingulate cortex