Skip to main content
Top
Published in: Magnetic Resonance Materials in Physics, Biology and Medicine 5/2014

01-10-2014 | Research Article

Neurochemicals measured by 1H-MR spectroscopy: putative vulnerability biomarkers for obsessive compulsive disorder

Authors: Sundar Gnanavel, Pratap Sharan, Sudhir Khandelwal, Uma Sharma, Naranamangalam R. Jagannathan

Published in: Magnetic Resonance Materials in Physics, Biology and Medicine | Issue 5/2014

Login to get access

Abstract

Object

Obsessive compulsive disorder (OCD) is the fourth most common psychiatric disorder characterized by recurrent, intrusive thoughts and repetitive, ritualistic behaviors that are debilitating to the patient. Despite its high prevalence and the attendant morbidity, the pathophysiology of OCD remains unclear. Magnetic resonance spectroscopy (MRS) provides a noninvasive method to characterize the molecular biochemistry that may contribute to the pathophysiology of OCD. This study aimed to identify alterations in neurochemical measures that are specific to OCD using in vivo proton (1H) MRS of the caudate nucleus, anterior cingulate cortex, and medial thalamus in these patients, and to identify their role as vulnerability markers by comparing them with the healthy first degree relatives of these patients and healthy controls.

Materials and methods

Appropriate psychometric instruments were applied in the study population followed by 1H- MRS. The absolute neurochemical measures were quantified using a linear combination model.

Results

Significant differences in neurochemical measures were demonstrated in two of the three candidate regions (except the medial thalamus) between the three study groups.

Conclusions

Our results lend support to the neurodegenerative hypothesis of OCD, and also raise the possibility of exploring these neurochemical measures (as measured by MRS) as putative vulnerability biomarkers in OCD that may aid in early identification and devising early prevention or management strategies for the population vulnerable to OCD.
Literature
1.
go back to reference Jenike M, Breiter H, Baer L (1996) Cerebral structural abnormalities in obsessive compulsive disorder: a quantitative morphometric magnetic resonance spectroscopy. Arch Gen Psychiatry 53:625–632PubMedCrossRef Jenike M, Breiter H, Baer L (1996) Cerebral structural abnormalities in obsessive compulsive disorder: a quantitative morphometric magnetic resonance spectroscopy. Arch Gen Psychiatry 53:625–632PubMedCrossRef
2.
go back to reference Ferrari MCF, Busatto GF, McGuire PK, Crippa JA (2008) Structural magnetic resonance imaging in anxiety disorders: an update of research findings. Rev Bras Psiquiatr 30(3):123–126CrossRef Ferrari MCF, Busatto GF, McGuire PK, Crippa JA (2008) Structural magnetic resonance imaging in anxiety disorders: an update of research findings. Rev Bras Psiquiatr 30(3):123–126CrossRef
3.
go back to reference Matsumoto R, Ito H, Takahashi H, Ando T, Fujimura Y, Nakayama K, Okubo Y, Obata T, Fukui K, Suhara T (2010) Reduced gray matter volume of dorsal cingulate cortex in patients with obsessive-compulsive disorder: a voxel-based morphometric study. Psychiatry Clin Neurosci 64:541–547PubMedCrossRef Matsumoto R, Ito H, Takahashi H, Ando T, Fujimura Y, Nakayama K, Okubo Y, Obata T, Fukui K, Suhara T (2010) Reduced gray matter volume of dorsal cingulate cortex in patients with obsessive-compulsive disorder: a voxel-based morphometric study. Psychiatry Clin Neurosci 64:541–547PubMedCrossRef
4.
go back to reference Alexander GE, Delong MR, Strick PL (1986) Parallel organisation of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 9:357–381PubMedCrossRef Alexander GE, Delong MR, Strick PL (1986) Parallel organisation of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 9:357–381PubMedCrossRef
5.
go back to reference Saxena S, Raunch SL (2000) Functional neuroimaging and neuroanatomy of obsessive compulsive disorder. Psychiatry Clin N Am 23:623–641CrossRef Saxena S, Raunch SL (2000) Functional neuroimaging and neuroanatomy of obsessive compulsive disorder. Psychiatry Clin N Am 23:623–641CrossRef
6.
go back to reference Murad A, Yikkum H, Huayin O, Koc M, Ozleus S, Tezcan E (2009) Neurochemistry of the hippocampus in patients with obsessive compulsive disorder. Psychiatry Clin Neuro 63:486–490CrossRef Murad A, Yikkum H, Huayin O, Koc M, Ozleus S, Tezcan E (2009) Neurochemistry of the hippocampus in patients with obsessive compulsive disorder. Psychiatry Clin Neuro 63:486–490CrossRef
7.
go back to reference Arnold PD, Sicard T, Burroughs E, Richter MA, Kennedy JL (2006) Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry 63:769–776PubMedCrossRef Arnold PD, Sicard T, Burroughs E, Richter MA, Kennedy JL (2006) Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry 63:769–776PubMedCrossRef
8.
go back to reference Bédard MJ, Chantal S (2011) Brain magnetic resonance spectroscopy in obsessive-compulsive disorder: the importance of considering subclinical symptoms of anxiety and depression. Psychiatry Res 192:45–54PubMedCrossRef Bédard MJ, Chantal S (2011) Brain magnetic resonance spectroscopy in obsessive-compulsive disorder: the importance of considering subclinical symptoms of anxiety and depression. Psychiatry Res 192:45–54PubMedCrossRef
9.
go back to reference Brennan BP, Raunch SL, Jensen JE, Pope HG (2013) A critical review of magnetic resonance spectroscopy studies of obsessive-compulsive disorder. Biol Psychiatry 73:24–31PubMedCrossRefPubMedCentral Brennan BP, Raunch SL, Jensen JE, Pope HG (2013) A critical review of magnetic resonance spectroscopy studies of obsessive-compulsive disorder. Biol Psychiatry 73:24–31PubMedCrossRefPubMedCentral
10.
go back to reference Nestadt G, Samuels J, Riddle M (2000) A family study of obsessive-compulsive disorder. Arch Gen Psychiatry 57:358–363PubMedCrossRef Nestadt G, Samuels J, Riddle M (2000) A family study of obsessive-compulsive disorder. Arch Gen Psychiatry 57:358–363PubMedCrossRef
11.
go back to reference Inouye E (1965) Similar and dissimilar manifestations of obsessive-compulsive neurosis in monozygotic twins. Am J Psychiatry 121:1171–1173PubMed Inouye E (1965) Similar and dissimilar manifestations of obsessive-compulsive neurosis in monozygotic twins. Am J Psychiatry 121:1171–1173PubMed
12.
go back to reference Gilbert AR, Keshavan MS, David V, Mitatin J, Macmaker F, Easter PC, Buhagiar C, Rosenberg D (2008) Grey matter differences between paediatric OCD patients and high risk siblings: a preliminary voxel-based morphometry study. Neurosci Lett 19:45–50CrossRef Gilbert AR, Keshavan MS, David V, Mitatin J, Macmaker F, Easter PC, Buhagiar C, Rosenberg D (2008) Grey matter differences between paediatric OCD patients and high risk siblings: a preliminary voxel-based morphometry study. Neurosci Lett 19:45–50CrossRef
13.
go back to reference De Wit SJ, De Vries FE, Van der Werf YD, Cath DC, Heslenfeld DJ, Veltman EM, Van Balkom AJ, Veltman DJ, Van den Heuvel OA (2012) Pre-supplementary motor area hyperactivity during response inhibition: a candidate endophenotypic of obsessive-compulsive disorder. Am J Psychiatry 69(10):1100–1108 De Wit SJ, De Vries FE, Van der Werf YD, Cath DC, Heslenfeld DJ, Veltman EM, Van Balkom AJ, Veltman DJ, Van den Heuvel OA (2012) Pre-supplementary motor area hyperactivity during response inhibition: a candidate endophenotypic of obsessive-compulsive disorder. Am J Psychiatry 69(10):1100–1108
14.
go back to reference Provencher SW (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672–679PubMedCrossRef Provencher SW (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672–679PubMedCrossRef
15.
go back to reference Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LC Model. NMR Biomed 14:260–264PubMedCrossRef Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LC Model. NMR Biomed 14:260–264PubMedCrossRef
16.
go back to reference Ebert D, Spelli O, Kinig A, Berga M, Hering J, Hohagen F (1997) 1H-Magnetic resonance spectroscopy in obsessive compulsive disorder: evidence for the neuronal; loss in the cingulate gyrus and the right striatum. Psychiatry Res 74:173–176PubMedCrossRef Ebert D, Spelli O, Kinig A, Berga M, Hering J, Hohagen F (1997) 1H-Magnetic resonance spectroscopy in obsessive compulsive disorder: evidence for the neuronal; loss in the cingulate gyrus and the right striatum. Psychiatry Res 74:173–176PubMedCrossRef
17.
go back to reference Bédard MJ, Chantal S (2011) Brain magnetic resonance spectroscopy in obsessive-compulsive disorder: the importance of considering subclinical symptoms of anxiety and depression. Psychiatry Res 192(1):45–54PubMedCrossRef Bédard MJ, Chantal S (2011) Brain magnetic resonance spectroscopy in obsessive-compulsive disorder: the importance of considering subclinical symptoms of anxiety and depression. Psychiatry Res 192(1):45–54PubMedCrossRef
18.
go back to reference Yucel M, Wood SJ, Wellard RM, Harrison BJ, Fornito A, Pijol J, Velakoulis D, Pantelis C (2007) Anterior cingulate glutamate-glutamine levels predict symptom severity in women with obsessive compulsive disorder. Psychiatry Res 156:175–179CrossRef Yucel M, Wood SJ, Wellard RM, Harrison BJ, Fornito A, Pijol J, Velakoulis D, Pantelis C (2007) Anterior cingulate glutamate-glutamine levels predict symptom severity in women with obsessive compulsive disorder. Psychiatry Res 156:175–179CrossRef
19.
go back to reference Braber AD, Ent DV, Gabriella AMB, Grootheest DSV, Dapelle CC, Dick JV, Veltman DJ, De Ruiter MB, Boomsma DI (2008) A f-MRI study in monozygotic twins discordant for OCD. Biol Psychol 79:91–102CrossRef Braber AD, Ent DV, Gabriella AMB, Grootheest DSV, Dapelle CC, Dick JV, Veltman DJ, De Ruiter MB, Boomsma DI (2008) A f-MRI study in monozygotic twins discordant for OCD. Biol Psychol 79:91–102CrossRef
20.
go back to reference Mirza Y, O’Neill J, Smith EA, Russell A, Smith JM, Banerjee SP, Bhandari R, Boyd C, Rose M, Ivey J, Renshaw PF, Rosenberg DR (2006) Increased medial thalamic creatine-phosphocreatine found by proton magnetic resonance spectroscopy in children with obsessive-compulsive disorder versus major depression and healthy controls. J Child Neurol 21:106–111PubMedCrossRef Mirza Y, O’Neill J, Smith EA, Russell A, Smith JM, Banerjee SP, Bhandari R, Boyd C, Rose M, Ivey J, Renshaw PF, Rosenberg DR (2006) Increased medial thalamic creatine-phosphocreatine found by proton magnetic resonance spectroscopy in children with obsessive-compulsive disorder versus major depression and healthy controls. J Child Neurol 21:106–111PubMedCrossRef
21.
go back to reference Bartha R, Stein MB, Williamson PC, Drost DJ, Neufield RWJ, Cain TJ, Canaran G, Densmore M, Anderson G, Siddiqui AR (1998) A short echo H1-spectroscopy and volumetric MRI study of the corpus striatum in patients with obsessive compulsive disorder and comparison subjects. Am J Psychiatry 155:11–14 Bartha R, Stein MB, Williamson PC, Drost DJ, Neufield RWJ, Cain TJ, Canaran G, Densmore M, Anderson G, Siddiqui AR (1998) A short echo H1-spectroscopy and volumetric MRI study of the corpus striatum in patients with obsessive compulsive disorder and comparison subjects. Am J Psychiatry 155:11–14
22.
go back to reference Whiteside SP, Abramowitz JS, Port JD (2004) A meta–analysis of functional neuroimaging in obsessive–compulsive disorder. Psychiatry Res 132:69–79PubMedCrossRef Whiteside SP, Abramowitz JS, Port JD (2004) A meta–analysis of functional neuroimaging in obsessive–compulsive disorder. Psychiatry Res 132:69–79PubMedCrossRef
23.
go back to reference Whiteside SP, Abramowitz JS, Port JD (2012) Decreased caudate N-acetyl-l-aspartic acid in pediatric obsessive-compulsive disorder and the effects of behaviour therapy. Psychiatry Res 202:53–59PubMedCrossRef Whiteside SP, Abramowitz JS, Port JD (2012) Decreased caudate N-acetyl-l-aspartic acid in pediatric obsessive-compulsive disorder and the effects of behaviour therapy. Psychiatry Res 202:53–59PubMedCrossRef
24.
go back to reference Lázaro L, Bargalló N, Andrés S, Falcón C, Morer A, Junqué C, Castro-Fornieles J (2012) Proton magnetic resonance spectroscopy in paediatric obsessive-compulsive disorder: longitudinal study before and after treatment. Psychiatry Res 201:17–24PubMedCrossRef Lázaro L, Bargalló N, Andrés S, Falcón C, Morer A, Junqué C, Castro-Fornieles J (2012) Proton magnetic resonance spectroscopy in paediatric obsessive-compulsive disorder: longitudinal study before and after treatment. Psychiatry Res 201:17–24PubMedCrossRef
25.
go back to reference Szeszko PR, MacMillan S, McMeniman M, Lorch E, Madden R, Ivey J, Banerjee SP, Moore GJ, Rosenberg DR (2004) Amygdala volume reductions in paediatric patients with obsessive compulsive disorder treated with paroxetine-preliminary findings. Neuropsychopharmcol 29:826–832CrossRef Szeszko PR, MacMillan S, McMeniman M, Lorch E, Madden R, Ivey J, Banerjee SP, Moore GJ, Rosenberg DR (2004) Amygdala volume reductions in paediatric patients with obsessive compulsive disorder treated with paroxetine-preliminary findings. Neuropsychopharmcol 29:826–832CrossRef
26.
go back to reference Fitzgerald KD, Moore GJ, Paulson LA, Stewart CM, Rosenberg DR (2004) Proton spectroscopic imaging of the thalamus in treatment-naive pediatric obsessive–compulsive disorder. Biol Psychiatry 47:174–182CrossRef Fitzgerald KD, Moore GJ, Paulson LA, Stewart CM, Rosenberg DR (2004) Proton spectroscopic imaging of the thalamus in treatment-naive pediatric obsessive–compulsive disorder. Biol Psychiatry 47:174–182CrossRef
27.
go back to reference Mohamed MA, Smith MA, Schlund MW, Gerald N, Parker PB, Hoehn RS (2007) Proton magnetic resonance spectroscopy in obsessive-compulsive disorder: a pilot investigation comparing treatment responders and non-responders. Psychiatry Res 156:175–179PubMedCrossRef Mohamed MA, Smith MA, Schlund MW, Gerald N, Parker PB, Hoehn RS (2007) Proton magnetic resonance spectroscopy in obsessive-compulsive disorder: a pilot investigation comparing treatment responders and non-responders. Psychiatry Res 156:175–179PubMedCrossRef
28.
go back to reference Insel TR (1992) Towards a neuroanatomy of obsessive compulsive disorder. Arch Gen Psychiatry 49:739–745PubMedCrossRef Insel TR (1992) Towards a neuroanatomy of obsessive compulsive disorder. Arch Gen Psychiatry 49:739–745PubMedCrossRef
29.
go back to reference Scott LR (2003) Neuroimaging and neurocircuitry models pertaining to the neurological treatment of psychiatric disorders. Neurosurg Clin N Am 14:223–225 Scott LR (2003) Neuroimaging and neurocircuitry models pertaining to the neurological treatment of psychiatric disorders. Neurosurg Clin N Am 14:223–225
30.
go back to reference Kitamura H, Shion T, Kimura T, Someya T (2006) Parietal white matter abnormalities in obsessive compulsive disorder: a magnetic resonance spectroscopy study at 3 Tesla. Acta Psychiatry Scand 114:101–108CrossRef Kitamura H, Shion T, Kimura T, Someya T (2006) Parietal white matter abnormalities in obsessive compulsive disorder: a magnetic resonance spectroscopy study at 3 Tesla. Acta Psychiatry Scand 114:101–108CrossRef
31.
go back to reference Rosenberg DR, Mirza Y, Russell A, Tang J, Smith JM, Banerjee SP, Bhandari R, Rose M, Ivey J, Boyd C, Moore GJ (2004) Reduced anterior cingulate glutamatergic concentrations in childhood OCD and major depression versus healthy controls. J Am Acad Child Adolesc Psychiatry 43:1146–1153PubMedCrossRef Rosenberg DR, Mirza Y, Russell A, Tang J, Smith JM, Banerjee SP, Bhandari R, Rose M, Ivey J, Boyd C, Moore GJ (2004) Reduced anterior cingulate glutamatergic concentrations in childhood OCD and major depression versus healthy controls. J Am Acad Child Adolesc Psychiatry 43:1146–1153PubMedCrossRef
Metadata
Title
Neurochemicals measured by 1H-MR spectroscopy: putative vulnerability biomarkers for obsessive compulsive disorder
Authors
Sundar Gnanavel
Pratap Sharan
Sudhir Khandelwal
Uma Sharma
Naranamangalam R. Jagannathan
Publication date
01-10-2014
Publisher
Springer Berlin Heidelberg
Published in
Magnetic Resonance Materials in Physics, Biology and Medicine / Issue 5/2014
Print ISSN: 0968-5243
Electronic ISSN: 1352-8661
DOI
https://doi.org/10.1007/s10334-013-0427-y

Other articles of this Issue 5/2014

Magnetic Resonance Materials in Physics, Biology and Medicine 5/2014 Go to the issue