Comorbidity between temporal lobe epilepsy and depression: a [18F]MPPF PET study

• Published in: Brain (London, England : 1878) Vol. 131; no. 10; pp. 2765 - 2782
• Main Authors: Lothe, A., Didelot, A., Hammers, A., Costes, N., Saoud, M., Gilliam, F., Ryvlin, P.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-10-2008
• Subjects: [18F]MPPF; Adult; Aminopyridines - metabolism; Biological and medical sciences; Brain - diagnostic imaging; Brain - metabolism; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - metabolism; Depression - complications; Depression - diagnostic imaging; Depression - metabolism; depressive symptoms; Epilepsy, Temporal Lobe - diagnostic imaging; Epilepsy, Temporal Lobe - metabolism; Epilepsy, Temporal Lobe - psychology; Female; Fluorodeoxyglucose F18; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - diagnostic imaging; Hippocampus - metabolism; Humans; Image Interpretation, Computer-Assisted; Male; Medical sciences; Middle Aged; Nervous system (semeiology, syndromes); Neurology; Original; Piperazines - metabolism; Positron-Emission Tomography - methods; Prospective Studies; Radiopharmaceuticals; Raphe Nuclei - diagnostic imaging; Raphe Nuclei - metabolism; Receptor, Serotonin, 5-HT1A - metabolism; Serotonin - metabolism; Serotonin 5-HT1 Receptor Antagonists; TLE; [; TLE; F]MPPF; depressive symptoms; Mood disorder; Nervous system diseases; Central nervous system disease; Complex partial epilepsy; Temporal lobe epilepsy; Depression; Positron emission tomography; [18F]MPPF; Cerebral disorder; Emission tomography
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awn194

Brain and brainstem changes of serotoninergic 5-hydroxytryptophan (5-HT)1A receptor density have been reported in patients with major depressive disorder as well as in patients with temporal lobe epilepsy (TLE), using PET and the selective antagonist radiotracers [11C]WAY-100635 or [18F]FC-WAY. We used a distinct 5-HT1A antagonist, [18F]MPPF, whose binding potential depends on both receptor density and extracellular serotonin concentration, in 24 patients with drug-resistant TLE and MRI evidence of hippocampal sclerosis but without prior antidepressant exposure. Their Beck Depression Inventory (BDI-2) score ranged from 0 to 34, with nine patients having a score >11. We used a simplified reference tissue model, statistical parametric mapping and anatomical regions of interest (ROIs) to correlate parametric images of [18F]MPPF BP with the total BDI score and its four subclasses. The total BDI score, as well as symptoms of psychomotor anhedonia and negative cognition, correlated positively with [18F]MPPF BP in the raphe nuclei and in the insula contralateral to seizure onset, whereas somatic symptoms correlated positively with [18F]MPPF binding potential in the hippocampal/parahippocampal region ipsilateral to seizure onset, the left mid-cingulate gyrus and the inferior dorsolateral frontal cortex, bilaterally. We confirm an association of depressive symptoms in TLE patients with changes of the central serotoninergic pathways, in particular within the raphe nuclei, insula, cingulate gyrus and epileptogenic hippocampus. These changes are likely to reflect lower extracellular serotonin concentration in more depressed patients, with an upregulation of receptors a less likely alternative.