Serotonin Transporter Occupancy and the Functional Neuroanatomic Effects of Citalopram in Geriatric Depression
ABSTRACT The functional neuroanatomic changes associated with selective serotonin reuptake inhibitor (SSRI) treatment have been the focus of positron emission tomography (PET) studies of cerebral glucose metabolism in geriatric depression.
To evaluate the underlying neurochemical mechanisms, both cerebral glucose metabolism and serotonin transporter (SERT) availability were measured before and during treatment with the SSRI, citalopram. It was hypothesized that SERT occupancy would be observed in cortical and limbic brain regions that have shown metabolic effects, as well as striatal and thalamic regions that have been implicated in prior studies in midlife patients.
Psychiatric outpatient clinic.
Seven depressed patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for current major depressive episode were enrolled.
Patients underwent a 12-week open-label trial of the SSRI, citalopram.
Patients underwent high-resolution research tomography PET scans to measure changes in cerebral glucose metabolism and SERT occupancy by citalopram treatment (after 8-10 weeks of treatment).
Three different tracer kinetic models were applied to the [¹¹C]-DASB region-of-interest data and yielded similar results of an average of greater than 70% SERT occupancy in the striatum and thalamus during citalopram treatment. Voxel-wise analyses showed significant SERT occupancy in these regions, as well as cortical (e.g., anterior cingulate, superior and middle frontal, precuneus, and limbic (parahippocampal gyrus) areas that also showed reductions in glucose metabolism.
The findings suggest that cortical and limbic SERT occupancy may be an underlying mechanism for the regional cerebral metabolic effects of citalopram in geriatric depression.
- SourceAvailable from: Amy Kathleen Wagner[Show abstract] [Hide abstract]
ABSTRACT: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the United States, and the incidence has been increasing within the geriatric age group as the population ages. There are many factors that are unique to this subgroup, including normal aging processes, differences in pathophysiology, and inherent medical comorbidities that affect their outcomes, treatment, and therefore, the allocation of medical and social services. The geriatric population has age-appropriate strength, coordination and balance deficits that make them predisposed to falls and subsequent TBI. The aging brain often has premorbid atrophy and increased susceptibility to the inflammatory, excitatory, and vascular processes that facilitate neurologic damage during the acute phases after injury. The aged also can have premorbid neurodegenerative and medical comorbidities that also affect their rehabilitation course, recovery, and outcomes once a TBI has occurred. Pharmacological strategies to maximize rehabilitation and recovery require specific considerations of the potential for adverse effects and contraindications specific to common comorbidities in the aged population. The management of geriatric TBI requires a coordinated effort between physicians and other healthcare providers with focus on risk factor modification, medical optimization, and successful return to the community by setting goals that emphasize level of function and quality of life.09/2012; 1(3). DOI:10.1007/s13670-012-0021-6
- The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 12/2011; 19(12):985-8. DOI:10.1097/JGP.0b013e31823922c9 · 3.52 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Older adults are among the most vulnerable to adverse cognitive effects of psychotropic medications and, therefore, the personalization of psychotropic treatment based on adverse drug reactions in this demographic is of great importance. We examined changes on neuropsychological tests of attention attributable to selective serotonin reuptake inhibitor (SSRI) treatment in anxious older adults. We also examined whether variation in serotonin receptor genes was associated with reduced attentional performance with SSRIs. We examined change from pre- to post-treatment in two attention measures - digit span and coding - in 133 adults aged ⩾60 yr with generalized anxiety disorder in a 12-wk trial of escitalopram vs. placebo. We also examined attentional change in relation to genetic variability in four central serotonin receptors: the serotonin transporter and serotonin 1A, 2A and 1B receptors. Digit span scores were significantly lowered in patients receiving escitalopram relative to placebo, indicating reduced attentional performance attributable to the SSRI. Individuals with high-transcription variants in the receptors 5-HTR2A rs6311 and 5-HTR1B rs11568817 had greater reductions in attention with SSRI treatment compared to placebo. We conclude that SSRIs reduce attention in older adults, particularly in those with high-expression genetic variants at the serotonin 2A and 1B receptors. Analysing neuropsychological changes with SSRIs in relation to genetic variation in the serotonin system may be a useful strategy for detecting subgroups of older adults who are more susceptible to side-effects of SSRIs. These results, if confirmed, could lead to the personalization of SSRI use to reduce adverse neurocognitive effects.The International Journal of Neuropsychopharmacology 04/2012; 16(2):1-10. DOI:10.1017/S1461145712000351 · 5.26 Impact Factor