RESUMEN
Patients with posttraumatic stress disorder (PTSD) experience psychological and physiological distress. However, imaging research has mostly focused on the psychological aspects of the disorder. Considered an expression of distress, heart rate (HR) in PTSD is often elevated. In the current study, we sought to identify brain regions associated with increased HR in PTSD. Nine patients with PTSD and six healthy trauma survivors were scanned while resting, clenching teeth, and listening to neutral and traumatic scripts. Brain function was evaluated using H2O15 positron emission tomography (PET). HR was monitored by electrocardiogram. Data were analyzed using statistical parametric mapping (SPM). Subjects with PTSD exhibited a significant increase in HR upon exposure to traumatic scripts, while trauma survivors did not. Correlations between regional cerebral blood flow and HR were found only in patients with PTSD, in orbitofrontal, precentral and occipital regions. Neither group showed correlation between rCBF and HR in the amygdala or hippocampus. These preliminary results indicate that "top down" central nervous system regulation of autonomic stress response in PTSD may involve associative, sensory and motor areas in addition to regions commonly implicated in fear conditioning.
Asunto(s)
Encéfalo/patología , Frecuencia Cardíaca/fisiología , Imágenes en Psicoterapia/métodos , Trastornos por Estrés Postraumático/patología , Trastornos por Estrés Postraumático/rehabilitación , Adulto , Análisis de Varianza , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Flujo Sanguíneo Regional/fisiología , Estadística como Asunto , Índices de Gravedad del TraumaRESUMEN
BACKGROUND: Recent studies indicate that modulation of glutamate neurotransmission is associated with antidepressant response. Lamotrigine, an anticonvulsant which decreases presynaptic glutamate release, has been shown to be effective in the depressive phase of bipolar disorder (BD-D); however, only 40-50% of patients have a full response. This pilot study investigated whether memantine, a low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist approved for Alzheimer's disease, can augment the effects of lamotrigine. METHODS: BD-D outpatients in a major depressive episode on a stable dose of lamotrigine (100 mg or more) were randomized to either memantine (starting dose of 5 mg increased up to 20 mg over four weeks, then 20 mg stable dose from four to eight weeks) or matching pill placebo for eight weeks. Patients were rated on the 17-item Hamilton Depression Rating Scale (HDRS) and other behavioral measures weekly. RESULTS: The eight-week repeated-measures mixed-effect model for HDRS was not significant for memantine (n = 14) versus placebo (n = 15). Exploratory mixed-effect analyses for the first four weeks, while the memantine dose was being titrated up every week, revealed a significant decrease in HDRS scores from baseline (p = 0.007). CONCLUSION: This proof-of-concept study failed to show a statistically significant benefit of memantine augmentation of lamotrigine for patients with BD-D over eight weeks. However, memantine had an antidepressant effect early on in the treatment while its dose was being titrated up. Larger placebo-controlled studies are needed to ascertain optimal timing and dosing for memantine augmentation of lamotrigine in BD-D.
Asunto(s)
Antidepresivos/uso terapéutico , Antimaníacos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Depresión/tratamiento farmacológico , Dopaminérgicos/administración & dosificación , Memantina/administración & dosificación , Triazinas/uso terapéutico , Adulto , Método Doble Ciego , Quimioterapia Combinada , Femenino , Ácido Glutámico/efectos de los fármacos , Humanos , Lamotrigina , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del TratamientoRESUMEN
OBJECTIVES: Dopamine transmission abnormalities have been implicated in the etiology of bipolar disorder (BPD). However, there is a paucity of receptor imaging studies in BPD, and little information is available about the dopamine system in BPD. Reuptake of synaptic dopamine by the dopamine transporter (DAT) is the principal mechanism regulating dopamine neurotransmission, and is often used as a marker for presynaptic dopamine function. This positron emission tomography (PET) study investigated whether DAT availability differed between BPD and healthy control subjects. METHODS: A total of 11 unmedicated BPD patients in either the euthymic or depressed phase and 13 closely matched healthy subjects underwent PET imaging with the DAT-selective radiotracer [(11) C]CFT and a structural magnetic resonance imaging (MRI) scan. Striatal binding potential (BP(ND) ) was estimated using the multilinear reference tissue model. Region of interest and analyses were conducted to test for differences in [(11) C]CFT BP(ND) between groups. RESULTS: Unmedicated BPD subjects had significantly lower DAT availability relative to healthy controls in bilateral dorsal caudate. CONCLUSIONS: The results of this study support the hypothesis that there are abnormalities in the dopaminergic system in BPD, and suggest that DAT availability may be related to the neuropathology of BPD. Future studies are needed to determine if DAT availability cycles with disease phase.