Citalopram Improves Obsessive-Compulsive Crossword Puzzling in Frontotemporal Dementia

Abstract

Behavioral variant frontotemporal dementia (bvFTD) is characterized by severe changes in personality/behavior. Recent studies have provided evidence that a decrease in serotonin receptors and neuronal loss in the raphe nuclei play a role in the bvFTD pathology. Serotonergic antidepressants have been reported to diminish behavioral disturbances in bvFTD, particularly repetitive behaviors, disinhibition, apathy, sexually inappropriate behaviors, and hyperorality. Here, we present the case of an 80-year-old Caucasian male patient with clinically and biomarker supported bvFTD ("probable" bvFTD; disease-specific alterations in ¹⁸F-fluorodesoxyglucose positron emission tomography and magnetic resonance imaging). The patient exhibited behavioral disinhibition, apathy, a loss of empathy, perseverative behavior during testing, hyperorality, changes in diet, and executive deficits in neuropsychological testing. Remarkably, he failed in solving crosswords by systematically filling in the blanks by letters in alphabetical order (A, B, C, D, etc.), indicating obsessive-compulsive behavior. One year later, the patient visited the clinic again for a follow-up investigation. He had taken 20 mg of citalopram per day for 1 consecutive year. Remarkably, he had regained the ability to fill in crossword puzzles correctly, although the neuropsychiatric inventory showed overall only small improvement in behavioral impairment. A regimen of 20 mg citalopram per day over the course of 1 year led to a specific improvement in one of the bvFTD core symptoms, obsessive-compulsive behavior, most pronounced in solving crossword puzzles. This case contributes to the understanding of the neuropharmacological correlates of bvFTD and supports the treatment of bvFTD's behavioral symptoms with selective serotonin reuptake inhibitors.

Keywords: Behavioral variant frontotemporal dementia; Citalopram; Obsessive-compulsive behavior; Selective serotonin reuptake inhibitors; Serotonin.

Fig. 1.

Two crossword puzzles filled in by the patient. a At baseline. b After consecutive treatment with 20 mg citalopram per day.

Fig. 2.

The patient's T1-MRI scans at baseline (a) and 1 year later at follow-up (b), showing subtle bifrontoparietal atrophy. Fast fluid-attenuated inversion recovery images at baseline (c) and at follow-up (d), showing punctual hyperintensities in white matter. T2*-MRI scan at baseline (e) showing no evidence of (micro-)bleeding. Fusion image of the patient's T1-MRI scan and ¹⁸F-FDG-PET scan at baseline (f), showing impaired glucose metabolism with a focus in the bilateral mediofrontal lobe. The relative quantitative analysis of FDG tracer uptake confirmed reduced tracer uptake in the bilateral mediofrontal lobe compared to a normal control group (25 normal subjects). g Representative transversal slice of the region-based evaluation using Hermes Brass software, and h using three-dimensional stereotactic surface projection analysis, bottom view. S.D., standard deviation.