Cingulate and thalamic metabolites in obsessive-compulsive disorder

Abstract

Focal brain metabolic effects detected by proton magnetic resonance spectroscopy (MRS) in obsessive-compulsive disorder (OCD) represent prospective indices of clinical status and guides to treatment design. Sampling bilateral pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and thalamus in 40 adult patients and 16 healthy controls, we examined relationships of the neurometabolites glutamate+glutamine (Glx), creatine+phosphocreatine (Cr), and choline-compounds (Cho) with OCD diagnosis and multiple symptom types. The latter included OC core symptoms (Yale-Brown Obsessive-Compulsive Scale - YBOCS), depressive symptoms (Montgomery-Åsberg Depression Rating Scale - MADRS), and general functioning (Global Assessment Scale - GAS). pACC Glx was 9.7% higher in patients than controls. Within patients, Cr and Cho correlated negatively with YBOCS and MADRS, while Cr correlated positively with the GAS. In aMCC, Cr and Cho correlated negatively with MADRS, while Cr in thalamus correlated positively with GAS. These findings present moderate support for glutamatergic and cingulocentric perspectives on OCD. Based on our prior metabolic model of OCD, we offer one possible interpretation of these group and correlational effects as consequences of a corticothalamic state of elevated glutamatergic receptor activity alongside below-normal glutamatergic transporter activity.

Fig. 1

[A] sample MR spectrum from left pregenual anterior cingulate cortex (pACC) with principal resonances for N-acetyl-aspartate+N-acetyl-aspartylyglutamate (NAA+NAAG = tNAA), glutamate+glutamine (Glu+Gln = Glx), creatine+phosphocreatine (Cr), choline-compounds (Cho), and myo-inositol (mI). [B] parasagittal, coronal and axial-oblique T1w MRI sections showing position of MRS acquisition volume (“voxel”) for left pACC. [C] the same for left anterior middle cingulate cortex (aMCC) voxel. [D] The same for left thalamus voxel. Voxels were acquired at homologous sites in the right cerebral hemisphere.

Fig. 2

Elevated levels of glutamate+glutamine measured by magnetic resonance spectroscopy (MRS) in pregenual anterior cingulate cortex (pACC) of OCD patients relative to healthy controls. Levels did not differ significantly for patients treated and not-treated with serotonin reuptake inhibitors. (SRIs). IU=Institutional Units

Fig. 3

MRS Cr and Cho drop with increasing OCD symptoms; Cr rises with increasing functioning. pACC Cr and Cho levels in OCD are close to normal means (horizontal solid blue bars), yet vary significantly with psychiatric symptoms. Symptoms themselves are outside normal ranges, indicated by vertical dashed blue bars marking measured control (GAS) or standard subclinical (YBOCS) ranges. [A] Cr and [B] Cho in pACC drop with increasing obsessive-compulsive symptoms. Cr in pACC [C] and thalamus [D] rises with increasing global functioning. (Not shown) Cr and Cho in pregenual cingulate and also anterior middle cingulate similarly drop with increasing depressive symptoms. For abbreviations, see Figs. 1–2.