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Aim: To date, despite possible neuroanatomical importance, no magnetic resonance spectroscopy (MRS) study on hippocampus has been performed in obsessive–compulsive disorder (OCD). The purpose of the present study was therefore to compare hippocampal chemicals in patients with OCD with those in healthy subjects with no psychopathology.
Methods: Eighteen patients meeting DSM-IV criteria for OCD and 18 healthy controls were studied. The patients and controls underwent proton magnetic resonance spectroscopy (1H-MRS), and measures of N-acetyl-l-aspartate (NAA), choline (CHO), and creatine (CRE) in hippocampal regions were obtained.
Results: Both NAA/CRE and NAA/CHO ratios in the hippocampus in patients with OCD were reduced relative to healthy controls. The anova showed a near-significant effect of diagnosis for NAA/CRE and a significant effect for NAA/CHO, but the anova did not show any significant effect even at a trend level for CHO/CRE. No main effect of hemisphere was found for any metabolite ratio.
Conclusions: The presence of neuronal degeneration is suggested in OCD. Future longitudinal neuroimaging and neuropsychological studies with larger patient samples are warranted in order to confirm these preliminary findings to better characterize the relevance of neurochemical abnormalities in hippocampus in the pathophysiology of OCD.
GROWING NEUROIMAGING STUDIES have the potential to increase our understanding of the connection between the clinical features and related neurobiology in obsessive–compulsive disorder (OCD). Magnetic resonance spectroscopy (MRS), an increasing trend in psychoneuroradiology, is a safe and non-invasive technique for the in vivo study of brain chemistry and metabolism. MRS has been used primarily to measure concentrations of metabolites in brain tissue such as N-acetyl-aspartate (NAA; a marker of neuronal viability), combined glutamate and glutamine, choline (CHO; a marker of cell membrane turnover), myo-inositol, and creatine–phosphocreatine (CRE; a marker of cellular energy). NAA has been reported to exist mainly intraneuronally. A reduction of NAA is considered to reflect a loss of neurons and axons and/or neural dysfunction.1 CHO, a marker of the membrane phospholipids, is increased in myelin breakdown. CRE is an energetic marker of cells. The majority of current functional and structural neuroimaging findings have emphasized abnormalities in fronto-striatal–thalamic–cortical circuits, but other candidate structures include the hippocampus–amygdala complex. Hippocampal and amygdalar abnormalities were emphasized in studies involving positron emission tomography or functional magnetic resonance imaging and authors commented that the region might play an important role in the pathophysiology of OCD.2,3 In contrast, it has been suggested that hippocampal structural alteration may play a role in the pathophysiology of OCD.3 Furthermore, the agents that are efficacious in the management of OCD (e.g. serotonergic re-uptake inhibitors [SSRI], and anti-anxiety drugs) have been shown to exert their effects on receptors in the amygdaloid.4–6 Although limited studies have been performed and no consensus has been established in MRS studies in OCD, some clues were obtained. Two studies found unilaterally decreased NAA in the striatum of adults with OCD,7,8 and two reported increased concentrations of CHO bilaterally in the medial thalami of children with OCD.9,10 In addition, in another study Rosenberg et al. found that increased glutamine concentrations in the left caudate decreased after management of pediatric OCD.11 In another study, absolute levels of NAA were shown to be increased in the right dorsolateral prefrontal cortex.12 Most recently, Sumitani et al. suggested that a subgroup of OCD patients who respond to an SSRI with an atypical antipsychotic had lower NAA levels in the anterior cingulate compared to those on SSRI treatment alone.13 To date, however, despite possible neuroanatomical importance, no MRS study on the hippocampus has been performed in OCD. The purpose of the present study was therefore to compare hippocampal chemicals in patients with OCD with those in healthy subjects with no psychopathology.
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As can be seen in Table 1, the patients and controls did not differ with regard to age, gender, intracranial volume, whole brain volume, gray or white matter volumes (P > 0.05).
Table 1. Subject characteristics
| ||OCD patients (n = 18)||Controls (n = 18)|
|Age (years)||28.1 ± 3.4||30.6 ± 4.2|
|Age at onset (years)||22.6 ± 4.2||–|
|Graduated from high school||11||13|
|Presence of family history||2||1|
|YBOCS score||17.2 ± 3.0||–|
|ICV (cm3)||1448.7 ± 180.5||1513.4 ± 206.2|
|Whole brain volume (cm3)||1251.1 ± 110.3||1194.9 ± 91.8|
|Gray matter volume (cm3)||847.6 ± 86.2||819.1 ± 90.4|
|White matter volume (cm3)||403.5 ± 36.1||375.8 ± 28.2|
|Hippocampus volume (mm3)|| || |
| Left||2339.7 ± 226.5||2681.8 ± 369.2*|
| Right||2289.9 ± 200.6||2711.3 ± 306.3*|
|NAA/CRE||1.16 ± 0.21||1.31 ± 0.28*|
|NAA/CHO||2.94 ± 0.29||3.99 ± 0.37**|
|CHO/CRE||0.39 ± 0.14||0.41 ± 0.11|
|NAA (mmol/kg)||8.62 ± 1.16||9.33 ± 0.93*|
|CHO (mmol/kg)||2.93 ± 0.38||2.33 ± 0.20*|
|CRE (mmol/kg)||7.45 ± 1.62||7.12 ± 1.48|
The anova showed a near-significant effect of diagnosis for NAA/CRE (F = 3.8, P = 0.06; mean ratio, 1.13 ± 0.21 for patients and 1.31 ± 0.28 for controls) and a significant effect for NAA/CHO (F = 6.8, P < 0.01; mean ratio, 2.87 ± 0.29 for patients 3.99 ± 0.37 for controls). But the anova did not indicate any significant effect even at trend level for CHO/CRE (F = 1.26, P > 0.05). No main effect of hemisphere was found for any metabolite ratio.
The Spearman correlation test did not find any relationship in either group between the NAA/CRE, NAA/CHO or CHO/CRE ratio of the hippocampus and age, years of education, age of onset, duration of illness, or total Y-BOCS score, except for a negative correlation between the NAA/CHO ratio and age (r = −0.53, P < 0.05).
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The present results show a decreases in both NAA/CRE and NAA/CHO ratios in the hippocampus in patients with OCD relative to healthy control subjects and also a relationship between NAA/CHO ratio and age in the patient group. Because NAA is thought to be a measure of neuronal integrity, these findings of decreased NAA/CRE and NAA/CHO may suggest decreased hippocampal neuronal density or at least neuronal dysfunction in patients with OCD. We did not evaluate other brain regions in this preliminary study, however, so we do not know exactly but it is possible that these findings are not specific for the hippocampus and that this finding may be generalized to other brain regions as well. It is unclear whether NAA/CRE decrease is due to an neurodegenerative process or to a trait characteristic of the disorder. The fact that there was a negative correlation between NAA/CHO ratio and age suggests that this may be a neurodegenerative process. In regard to CHO, we found increased concentrations in the patient group compared to healthy controls. There have been studies that did not report CHO changes in adult or pediatric patients with OCD.8 Recent proton MRS studies have found localized functional neurochemical marker alterations in the left and right medial but not the lateral thalamus.9,17 In another study, CHO concentrations were reported as significantly increased in the thalamus of 11 treatment-naive pediatric OCD patients. Likewise, Smith et al. found that localized functional neurochemical marker alterations in medial thalamic CHO differentiated patients with OCD from healthy control subjects and patients with major depressive disorder.10 It was suggested that the CHO signal rise might be an important biomarker in specific neuropsychiatric disorders,9,18 supporting our comment regarding possible neurodegeneration. Meanwhile phosphotidylcholine breakdown has been shown to play an important role in signal transduction,19 suggesting that altered CHO concentrations in patients with OCD may contribute to the pathophysiology of the disorder in this way. Similarly for NAA concentration, we did not evaluate other brain regions in this preliminary study, so we do not know exactly but it is possible that these findings are not specific for the hippocampus and that they may be generalized to other brain regions as well. To provide strong evidence, however, further investigation with more patients and in multiple brain regions are needed.
Some limitations of the present study should be taken in consideration. First, the relatively small sample size might have reduced the statistical power of the analysis, and small changes in the metabolite concentrations might not have been detected. Second, only the hippocampus was investigated, therefore the present findings cannot be extrapolated to other brain regions.
In conclusion, the present study found that both NAA/CRE and NAA/CHO ratios in the hippocampus in patients with OCD relative to healthy control subjects were reduced, thereby suggesting neuronal degeneration. Future longitudinal neuroimaging and neuropsychological studies with larger patient samples are warranted in order to confirm these preliminary findings to better characterize the relevance of neurochemical abnormalities in hippocampus in the pathophysiology of OCD.