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Differential Pattern of Brain Metabolism in Drug-naive versus Refractory OCD using [18F]-FDG PET/MRI Brain
Address for correspondence: Dr. Amarnath Jena, Department of Molecular Imaging and Nuclear Medicine, PET Suite (Indraprastha Apollo Hospitals and House of Diagnostics), Indraprastha Apollo Hospitals, New Delhi, India. E-mail: drjena2002@gmail.com
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Received: ,
Accepted: ,
This article was originally published by Wolters Kluwer - Medknow and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Obsessive–compulsive disorder is among the most extensively researched mental health disorder. Various metabolic neuroimaging research findings are consistent but still nonconclusive. The major limitation is a homogeneous sample. There are research findings which have established the impact of treatment in changing brain metabolism. Therefore, it is important to highlight differential metabolic changes with respect to treatment staging and its outcome. It will also help to individualized neuromodulation protocol based on differential metabolic findings. This study highlights the distinct differential fluorodeoxyglucose metabolic changes among two distinct cases: drug-naïve and treatment-refractory.
Keywords
Drug naïve
obsessive–compulsive disorder
positron emission tomography magnetic resonance imaging
treatment refractory
Introduction
Obsessive–compulsive disorder (OCD) is among the most extensively researched mental health disorders. To date, there is various research on phenomenology, neuropathogenesis, and endophenotypes along with their clinical correlates, etc., Among various functional or metabolic neuroimaging studies on OCD, most of them have shown some commonality but are inconsistent in terms of sample selection, stage of treatment, cortical–subcortical distinction, and brain subregional structural or hypo/hypermetabolic patterns. To date, the majority of the work on the neurobiology of OCD has suggested corticobasal ganglia dysfunction,[1] but major limitations were in sample selection based on the stage of illness/treatment. There is also a need for uniformity among different brain templates or nomenclature.
Previous metabolic imaging studies have also found changing metabolic patterns in cortical and subcortical regions due to on-going treatment[2] but the findings were limited to only few brain subregions and samples were not from the same treatment staging;[34] these findings suggest the impact of pharmacological and nonpharmacological treatment on brain functional and metabolic pattern in patients with OCD.
To elicit the impact of treatment on brain metabolism, we conducted 18-F fluorodeoxyglucose (FDG) positron emission tomography (PET) magnetic resonance imaging (MRI) subregion description using Scenium software (based on the MNI template) in two cases with distinct clinical profiles of first case chronic OCD drug-naive and second case who was a treatment-refractory chronic OCD.
Case 1
A 52-year-old female, married, postgraduate, adequate social support admitted to tertiary care GHPU with complaints of panic attacks, aversion to food, excessive concerns about dirt and contamination, obsessive doubts, medicine phobia, aggressive obsessions, excessive concerns about body image, and weight gain with marked socioccupational decline with a total duration of illness more than 25 years. She had not taken any treatment in the past. Her medical investigation showed nutritional deficiency, anemia, hyponatremia, and hypocalcemia, which was corrected during the hospital stay. Her most of the other profiles such as liver function test (LFT), kidney function test (KFT), and hormone profile came out to be within range. She was considered for neuromodulation treatment after safety/suitability screening and informed consent. As a part of the neuromodulation protocol, she underwent pretreatment 18F-FDG PET MRI brain [Figure 1].
We observed that there was distinct regional hypermetabolism seen in b/l basal ganglia predominantly bilateral putamen and pallidum ranging from +4.3 to +6.0 with relative sparing of bilateral caudate nucleus and thalamus [Table 1 and Figure 2]. Distinct cortical hypermetabolism was seen in b/l mesial temporal (L > R; +4.3> +3.5), hippocampus (L > R; +5.2> +3.5), central region (L < R; +2.9< +4.4), and amygdala (L > R; +6> +5.3) with mild hypermetabolism in b/l supplementary motor area (SMA) (L < R; +2.3< +2.4) [Figure 2]. All lobes including b/l frontal lobes showed normal metabolism except right side temporal, parietal, and occipital lobes showed mild hypometabolism (−2.6, −2.7, and −3.4, respectively) [Figure 1] including b/l angular gyrus (L < R; +3< +3.1). At subregional level, overall all segments of inferior, middle, and superior frontal gyrus showed normal metabolism or borderline hypermetabolic except the left inferior frontal gyrus triangular part (L > R; −4.2> −1.8) which was hypometabolic and right superior frontal gyrus dorsolateral part (+3) hypermetabolic. All subsegments in the inferior, middle, and superior temporal lobes showed normal metabolism except the right inferior temporal gyrus (−3.5) and right middle temporal gyrus (−3) which were mildly hypometabolic. The MRI features of this patient were normal; there were no structural abnormalities such as ischemia/infarct or cortical atrophy and no volume loss in brainstem/hippocampus or cerebellum.
| Brain regions | Case 1 | Case 2 | ||
|---|---|---|---|---|
| Left | Right | Left | Right | |
| Frontal lobe | 0.5 | 1.2 | −9.1 | −5.1 |
| Temporal lobe | −1.1 | −2.6 | −9.3 | −6.2 |
| Parietal lobe | −1.6 | −2.7 | −4.2 | −2.5 |
| Cingulate and paracingulate gyri | 2 | 1.5 | −2.1 | −2 |
| Central region | 2.9 | 4.4 | 0 | 2 |
| Occipital lobe | −2.1 | −3.4 | 2.6 | 2.7 |
| Calcarine fissure and surrounding cortex | −2 | −3.1 | 6.5 | 5.1 |
| Basal ganglia | 4.5 | 2.9 | 2.2 | 2.7 |
| Mesial temporal lobe | 4.3 | 3.5 | 0.1 | −0.4 |
| Amygdala | 6 | 5.3 | 1.1 | 0.9 |
| Angular gyrus | −3 | −3.1 | −6.1 | −3.8 |
| Caudate nucleus | 2.1 | 1.1 | 0 | 0.3 |
| Gyrus rectus | 1.2 | 0.6 | −3.2 | −4.2 |
| Hippocampus | 5.2 | 3.5 | 0 | 0.5 |
| Superior frontal gyrus, dorsolateral | 0.8 | 3 | −6.7 | −4.6 |
| Superior frontal gyrus, medial | 1 | 2.1 | −5.1 | −3.2 |
| Superior frontal gyrus, medial orbital | 2.2 | 2.3 | −3.2 | −7 |
| Superior frontal gyrus, orbital part | 0.4 | −1.1 | −3 | −4.3 |
| Middle frontal gyrus | −1.9 | −1.2 | −6.6 | −5.9 |
| Middle frontal gyrus, orbital part | −0.6 | 1.6 | −2.9 | −0.7 |
| Middle cingulate and paracingulate gyri | 2.7 | 1.4 | −0.9 | −1.2 |
| Inferior frontal gyrus, opercular part | −1.8 | −1.3 | −3.4 | −2.5 |
| Inferior frontal gyrus, orbital part | 0.3 | 1.1 | −2.4 | −0.3 |
| Inferior frontal gyrus, triangular part | −4.2 | −1.8 | −6.3 | −3.4 |
| Inferior temporal gyrus | −1.7 | −3.5 | −8.2 | −7.1 |
| Supplementary motor area | 2.3 | 2.4 | 0.1 | 1.8 |
| Paracentral lobule | 4.4 | 1.4 | 2.9 | 4.7 |
| Olfactory cortex | 5.2 | 2.8 | 1.9 | 1.3 |
| Thalamus | 2.3 | 0.9 | 0.7 | 0.3 |
| Lenticular nucleus, pallidum | 6 | 4.3 | 1.1 | 1 |
| Lenticular nucleus, putamen | 5.5 | 5.2 | 3.4 | 4.4 |
| Cerebellum | 0 | 0.3 | −0.4 | −0.5 |
FDG: Fluorodeoxyglucose, PET: Positron emission tomography, MNI: Montreal neurological institute
Case 2
A 31-year-old female, unmarried, graduate, adequate social support presented in the psychiatry outpatient department tertiary care hospital, Delhi, with complaints of irritable mood, generalized anxiety, excessive concerns about dirt and contamination, obsessive doubts, obsessive thoughts and images of sexual content, aggressive obsessions, excessive concerns about body image and weight gain, and binge eating with marked socioccupational decline with total duration of illness more than 15 years. She had received adequate trial of two selective serotonin reuptake inhibitors, one serotonin & norepinephrine reuptake inhibitors in combination with lamotrigine and topiramate as adjuvant treatment in the past with minimal change on Yale–Brown Obsessive – Compulsive Scale. Her medical investigation showed deranged LFT and lipid profile which was corrected during the course of treatment. Her most of the other profiles such as KFT and hormone profile came out to be within range. She was considered for neuromodulation treatment after safety/suitability screening and informed consent. As a part of the neuromodulation protocol, she underwent pretreatment 18F-FDG PET MRI brain [Figure 1].
We observed that the metabolism of the bilateral caudate nucleus, pallidum, and thalamus was normal with hypermetabolism in the putamen (L < R; +3.4< +4.4) [Figure 2]. Frontal, temporal, and parietal lobes showed cortical hypometabolism that ranged from −2.5 to −9.3 [Table 1 and Figure 1] and in bilateral angular gyrus (L > R; −6.1> −3.8). While both central regions, mesial temporal lobes, hippocampus, and SMA showed cortical normal metabolism [Figure 2], hypermetabolism was seen in the bilateral occipital cortex [Figure 1] including calcarine fissure and surrounding cortex that ranged from (+2.6 to +6.5) more strikingly in the later (L + 5.1, R + 6.5). At subregional level, distinct hypometabolism was seen in all sub segments of superior frontal gyrus (i.e. dorsolateral, medial, medial orbital, and orbital part ranging from −3 to −7.3), b/l inferior frontal gyrus opercular and triangular part (ranging from −2.5 to −6.3), b/l middle frontal gyrus and right middle frontal gyrus orbital part (ranging from −2.9 to −6.6), and b/l gyrus rectus (L −3.2 and R −4.2). Furthermore, in the temporal lobe, b/l inferior and middle temporal gyrus were distinctly hypometabolic (ranging from −5.1 to −9.2). However, normal metabolism was seen in b/l superior temporal gyrus and temporal poles. The MRI features of this patient were normal, there were no structural abnormalities such as ischemia/infarct or cortical atrophy and no volume loss in brainstem/hippocampus or cerebellum.
Discussion
To date, so much have been studied on brain metabolic changes in OCD. However, one of the major limitations is the impact of treatment on brain metabolic findings. In most of the studies, the samples were taken from mixed groups includes patients coming from different stages of treatment. Previous metabolic imaging studies have also found changing metabolic patterns in cortical and subcortical regions due to on-going treatment[2] but the findings were limited to only few brain subregions and samples were not homogenize based on treatment staging.[34] In these two cases, we found a series of differences in brain metabolic patterns comparing drug-naive versus treatment-refractory.
In this study, there are some contrasting results seen. Unlike previous neuroimaging studies which have shown a significant reduction of gray matter volume in the inferior and medial frontal gyrus, cingulate gyrus, superior temporal gyrus, and insula,[2] In this study, no structural abnormalities such as ischemia/infarct or cortical atrophy and no volume loss in brainstem/hippocampus or cerebellum was seen.
Previous functional neuroimaging studies using 18F-FDG in patients with obsessive compulsive disorder suggested increased metabolism in the orbitofrontal cortex, anterior cingulate cortex, lenticular nucleus and thalamus and parietal cortex and caudate nucleus.[3] Another study using hexamethylpropyleneamine oxime-single-photon emission computerized tomography (SPECT) studies have demonstrated increased uptake in prefrontal region, medial frontal cortex, decreased uptake in the left basal ganglia, and decreased uptake in the right caudate nucleus.[4]
In this study, we can see different metabolic patterns such as predominant hypermetabolic changes in drug-naive chronic OCD mostly in subcortical regions sparing the thalamus and caudate nucleus. Major findings include hypermetabolic changes in basal ganglia left > right (4.5 vs. 2.9), mesial temporal lobe left > right (4.3; 3.5), amygdala left > right (6 vs. 5.3), hippocampus left > right (5.2 vs. 3.5), paracentral lobule left > right (4.4 vs. 1.4), olfactory cortex left > right (5.2 vs. 2.8), lenticular nucleus, pallidum left > right (6 vs. 4.3), and lenticular nucleus, putamen left > right (5.5 vs. 5.2).
No significant hypometabolic change in cortical subregions except inferior frontal gyrus, triangular part left > right (−4.2 vs. −1.8).
In the treatment-refractory chronic OCD, there are predominant hypometabolic changes in cortical subregions and normal metabolic patterns in subcortical regions including the thalamus and caudate nucleus. Major findings include frontal lobe left > right (−9.1 vs. −5.1), temporal lobe left > right (−9.3 vs. −6.2), superior frontal gyrus, dorsolateral left > right (−6.7 vs. −4.6), superior frontal gyrus, medial left > right (−5.1 vs. −3.2), middle frontal gyrus left > right (−6.6 vs. −5.9), inferior frontal gyrus, triangular part left > right (−6.3 vs. −3.4), and inferior temporal gyrus left > right (−8.2 vs. −7.1); whereas the hypermetabolic changes were seen in lenticular nucleus, putamen left < right (3.4 vs. 4.4), paracentral lobule left < right (2.9 vs. 4.7), and calcarine fissure and surrounding cortex left > right (6.5; 5.1).
These contrasting findings suggest the impact of treatment on brain metabolic patterns in patients with chronic OCD. These findings highlight the future direction of research for metabolic biomarkers and early predictors of treatment nonresponse. Like previous studies,[5] these findings would also be a way forward in identifying targets for various different neuromodulation protocols to improve overall clinical outcomes (high frequency vs. low frequency; hypometabolism vs. hypermetabolism).
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest
There are no conflicts of interest.
Nil.
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