Abstract
Several neuroimaging studies have investigated brain metabolite abnormalities in patients with obsessive–compulsive disorder (OCD) and also explored metabolic changes after OCD treatments using proton magnetic resonance spectroscopy (1H-MRS). The main objective of this study was to investigate the effects of a selective serotonin re-uptake inhibitor (SSRI) treatment on the neurochemical levels in patients with OCD. In the present study, levels of N-acetylaspartate (NAA), choline, and myo-Inositol were measured in terms of their ratios with creatine (Cr) using 1H-MRS. The ratios of metabolite levels in the three brain regions for 19 unmedicated patients with OCD, including 10 who were drug-naïve, at baseline and following 12 weeks of sertraline treatment and for 19 healthy control subjects were compared with ANOVA. In post hoc analysis, the NAA/Cr levels were significantly lower in patients with OCD at baseline than in healthy controls in the anterior cingulate and in the caudate. On the other hand, no significant differences were detected in terms of the NAA/Cr in the anterior cingulate, caudate, and putamen between the patients with OCD after 12 weeks of sertraline treatment and healthy controls. The paired t test revealed that NAA/Cr levels were significantly higher in patients with OCD after 12 weeks of sertraline treatment compared with those at baseline in the anterior cingulate and in the caudate. Our results suggest that reductions in NAA can be reversed with SSRI treatment, which may indicate an improvement in neuronal integrity.
Similar content being viewed by others
References
Baxter LR Jr, Phelps ME, Mazziotta JC, Guze BH, Schwartz JM, Selin CE (1987) Local cerebral glucose metabolic rates in obsessive–compulsive disorder. A comparison with rates in unipolar depression and in normal controls. Arch Gen Psychiatry 44:211–218
Nordahl TE, Benkelfat C, Semple WE, Gross M, King AC, Cohen RM (1989) Cerebral glucose metabolic rates in obsessive compulsive disorder. Neuropsychopharmacology 2:23–28
Swedo SE, Schapiro MB, Grady CL, Cheslow DL, Leonard HL, Kumar A et al (1989) Cerebral glucose metabolism in childhood-onset obsessive–compulsive disorder. Arch Gen Psychiatry 46:518–523
Rauch SL, Jenike MA, Alpert NM, Baer L, Breiter HC, Savage CR, Fischman AJ (1994) Regional cerebral blood flow measured during symptom provocation in obsessive–compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. Arch Gen Psychiatry 51:62–70
Breiter HC, Rauch SL, Kwong KK, Baker JR, Weisskoff RM, Kennedy DN et al (1996) Functional magnetic resonance imaging of symptom provocation in obsessive–compulsive disorder. Arch Gen Psychiatry 53:595–606
Adler CM, McDonough-Ryan P, Sax KW, Holland SK, Arndt S, Strakowski SM (2000) fMRI of neuronal activation with symptom provocation in unmedicated patients with obsessive compulsive disorder. J Psychiatr Res 34:317–324
Trzesniak C, Araujo D, Crippa JAS (2008) Magnetic resonance spectroscopy in anxiety disorders. Acta Neuropsychiatr 20:56–71
Brennan BP, Rauch SL, Jensen JE, Pope HG Jr (2013) A critical review of magnetic resonance spectroscopy studies of obsessive–compulsive disorder. Biol Psychiatry 73:24–31
Tsai G, Coyle JT (1995) N-acetylaspartate in neuropsychiatric disorders. Prog Neurobiol 46:531–540
Ebert D, Speck O, König A, Berger M, Hennig J, Hohagen F (1997) 1H-magnetic resonance spectroscopy in obsessive–compulsive disorder: evidence for neuronal loss in the cingulate gyrus and the right striatum. Psychiatry Res 74:173–176
Baslow MH (2010) Evidence that the tri-cellular metabolism of N-acetylaspartate functions as the brain’s “operating system”: how NAA metabolism supports meaningful intercellular frequency-encoded communications. Amino Acids 39:1139–1145
Jang JH, Kwon JS, Jang DP, Moon WJ, Lee JM, Ha TH et al (2006) A proton MRSI study of brain N-acetylaspartate level after 12 weeks of citalopram treatment in drug-naive patients with obsessive–compulsive disorder. Am J Psychiatry 163:1202–1207
Sumitani S, Harada M, Kubo H, Ohmori T (2007) Proton magnetic resonance spectroscopy reveals an abnormality in the anterior cingulate of a subgroup of obsessive–compulsive disorder patients. Psychiatry Res 154:85–92
Yücel M, Harrison BJ, Wood SJ, Fornito A, Wellard RM, Pujol J (2007) Functional and biochemical alterations of the medial frontal cortex in obsessive–compulsive disorder. Arch Gen Psychiatry 64:946–955
Whiteside SP, Abramowitz JS, Port JD (2012) The effect of behavior therapy on caudate N-acetyl-l-aspartic acid in adults with obsessive–compulsive disorder. Psychiatry Res 201:10–16
Bartha R, Stein MB, Williamson PC, Drost DJ, Neufeld RW, Carr TJ et al (1998) A short echo 1H spectroscopy and volumetric MRI study of the corpus striatum in patients with obsessive–compulsive disorder and comparison subjects. Am J Psychiatry 155:1584–1591
Mohamed MA, Smith MA, Schlund MW, Nestadt G, Barker PB, Hoehn-Saric R (2007) Proton magnetic resonance spectroscopy in obsessive–compulsive disorder: a pilot investigation comparing treatment responders and non-responders. Psychiatry Res 156:175–179
Fitzgerald KD, Moore GJ, Paulson LA, Stewart CM, Rosenberg DR (2000) Proton spectroscopic imaging of the thalamus in treatment-naive pediatric obsessive–compulsive disorder. Biol Psychiatry 47:174–182
Ohara K, Isoda H, Suzuki Y, Takehara Y, Ochiai M, Takeda H et al (1999) Proton magnetic resonance spectroscopy of lenticular nuclei in obsessive–compulsive disorder. Psychiatry Res 92:83–91
Fan Q, Tan L, You C, Wang J, Ross CA, Wang X et al (2010) Increased N-acetylaspartate/creatine ratio in the medial prefrontal cortex among unmedicated obsessive–compulsive disorder patients. Psychiatry Clin Neurosci 64:483–490
Aoki Y, Aoki A, Suwa H (2012) Reduction of N-acetylaspartate in the medial prefrontal cortex correlated with symptom severity in obsessive–compulsive disorder: meta-analyses of (1)H-MRS studies. Transl Psychiatry 2:e153. doi:10.1038/tp.2012.78
Whiteside SP, Port JD, Deacon BJ, Abramowitz JS (2006) A magnetic resonance spectroscopy investigation of obsessive–compulsive disorder and anxiety. Psychiatry Res 146:137–147
Lázaro L, Bargalló N, Andrés S, Falcón C, Morer A, Junqué C, Castro-Fornieles J (2012) Proton magnetic resonance spectroscopy in pediatric obsessive–compulsive disorder: longitudinal study before and after treatment. Psychiatry Res 201:17–24
Yücel M, Wood SJ, Wellard RM, Harrison BJ, Fornito A, Pujol J et al (2008) Anterior cingulate glutamate–glutamine levels predict symptom severity in women with obsessive–compulsive disorder. Aust N Z J Psychiatry 42:467–477
American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders (DSM-IV), 4th ed. American Psychiatric Press, Washington
First MB, Spitzer RL, Gibbon M, Williams JBW (1997) Structured Clinical Interview for DSM-IV Clinical Version (SCID-I/CV). American Psychiatric Press, Washington
Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL et al (1989) The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry 46:1006–1011
Goodman WK, Price LH, Rasmussen SA, Mazure C, Delgado P, Heninger GR, Charney DS (1989) The Yale-Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry 46:1012–1016
Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50–55
Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:278–296
Baslow MH (2002) Evidence supporting a role for N-acetyl-L-aspartate as a molecular water pump in myelinated neurons in the central nervous system. An analytical review. Neurochem Int 40:295–300
Baslow MH (2003) N-acetylaspartate in the vertebrate brain: metabolism and function. Neurochem Res 28:941–953
Barker PB (2001) N-acetyl aspartate—a neuronal marker? Ann Neurol 49:423–424
Maddock RJ, Buonocore MH (2012) MR spectroscopic studies of the brain in psychiatric disorders. In: Carter CS, Dalley JW (eds) Brain imaging in behavioral neuroscience. Springer, Berlin, pp 199–251
Baxter LR Jr, Schwartz JM, Mazziotta JC, Phelps ME, Pahl JJ, Guze BH, Fairbanks L (1988) Cerebral glucose metabolic rates in nondepressed patients with obsessive–compulsive disorder. Am J Psychiatry 145:1560–1563
Hollander E, Prohovnik I, Stein DJ (1995) Increased cerebral blood flow during m-CPP exacerbation of obsessive–compulsive disorder. J Neuropsychiatry Clin Neurosci 7:485–490
Baxter LR Jr, Schwartz JM, Bergman KS, Szuba MP, Guze BH, Mazziotta JC et al (1992) Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive–compulsive disorder. Arch Gen Psychiatry 49:681–689
Swedo SE, Pietrini P, Leonard HL, Schapiro MB, Rettew DC, Goldberger EL et al (1992) Cerebral glucose metabolism in childhood-onset obsessive–compulsive disorder. Revisualization during pharmacotherapy. Arch Gen Psychiatry 49:690–694
Perani D, Colombo C, Bressi S, Bonfanti A, Grassi F, Scarone S et al (1995) [18F]FDG PET study in obsessive–compulsive disorder. A clinical/metabolic correlation study after treatment. Br J Psychiatry 166:244–250
Rotge JY, Guehl D, Dilharreguy B, Cuny E, Tignol J, Bioulac B et al (2008) Provocation of obsessive–compulsive symptoms: a quantitative voxel-based meta-analysis of functional neuroimaging studies. J Psychiatry Neurosci 33:405–412
Del Casale A, Kotzalidis GD, Rapinesi C, Serata D, Ambrosi E, Simonetti A et al (2011) Functional neuroimaging in obsessive–compulsive disorder. Neuropsychobiology 64:61–85
Benazon NR, Moore GJ, Rosenberg DR (2003) Neurochemical analyses in pediatric obsessive–compulsive disorder in patients treated with cognitive-behavioral therapy. J Am Acad Child Adolesc Psychiatry 42:1279–1285
Acknowledgments
This work was supported by the Research Fund of the Istanbul University (BYP/12238).
Conflict of interest
All authors report no biomedical financial interests or potential conflict of interests.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tükel, R., Aydın, K., Ertekin, E. et al. 1H-magnetic resonance spectroscopy in obsessive–compulsive disorder: effects of 12 weeks of sertraline treatment on brain metabolites. Eur Arch Psychiatry Clin Neurosci 265, 219–226 (2015). https://doi.org/10.1007/s00406-014-0545-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00406-014-0545-1