RESUMO
The pathogenetic role of central serotonin transporters (SERT) in obsessive-compulsive disorder (OCD) has been investigated in vivo by positron emission tomography (PET) or single-photon emission computed tomography (SPECT) studies with inconsistent results. This might reflect methodological differences but possibly also the pathophysiological heterogeneity of the disorder, i.e. the age at onset of OCD. The aim of our study was to compare SERT availability in patients with OCD to healthy controls (HC) taking into account the onset type, other factors and covariates (e.g. SERT genotype, age, depression level, gender). We studied 19 drug-naive OCD patients (36±13 yr, eight females) with early onset (EO-OCD, n=6) or with late onset (LO-OCD, n=13), and 21 HC (38±8 yr, nine females) with PET and the SERT-selective radiotracer [11C]DASB. Statistical models indicated that a variety of covariates and their interaction influenced SERT availability measured by distribution volume ratios (DVR). These models revealed significant effects of onset type on DVR with lower values in LO-OCD (starting at age 18 yr) compared to EO-OCD and HC in limbic (e.g. the amygdala), paralimbic brain areas (the anterior cingulate cortex), the nucleus accumbens and striatal regions, as well as borderline significance in the thalamus and the hypothalamus. The putamen, nucleus accumbens and hypothalamus were found with significant interaction between two SERT gene polymorphisms (SERT-LPR and VNTR). These findings suggest that late but not early onset of OCD is associated with abnormally low SERT availability. In part, functional polymorphisms of the SERT gene might determine the differences.
Assuntos
Transtorno Obsessivo-Compulsivo/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Adulto , Envelhecimento , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/patologia , Feminino , Genótipo , Humanos , Hipotálamo/diagnóstico por imagem , Hipotálamo/patologia , Masculino , Pessoa de Meia-Idade , Núcleo Accumbens/diagnóstico por imagem , Núcleo Accumbens/patologia , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/genética , Polimorfismo Genético , Cintilografia , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Tálamo/diagnóstico por imagem , Tálamo/patologia , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: It is an open question whether cognitive processes of auditory perception that are mediated by functionally different cortices exhibit the same sensitivity to sedation. The auditory event-related potentials P1, mismatch negativity (MMN), and early right anterior negativity (ERAN) originate from different cortical areas and reflect different stages of auditory processing. The P1 originates mainly from the primary auditory cortex. The MMN is generated in or in the close vicinity of the primary auditory cortex but is also dependent on frontal sources. The ERAN mainly originates from frontal generators. The purpose of the study was to investigate the effects of increasing propofol sedation on different stages of auditory processing as reflected in P1, MMN, and ERAN. METHODS: The P1, the MMN, and the ERAN were recorded preoperatively in 18 patients during four levels of anesthesia adjusted with target-controlled infusion: awake state (target concentration of propofol 0.0 microg/ml), light sedation (0.5 microg/ml), deep sedation (1.5 microg/ml), and unconsciousness (2.5-3.0 microg/ml). Simultaneously, propofol anesthesia was assessed using the Bispectral Index. RESULTS: Propofol sedation resulted in a progressive decrease in amplitudes and an increase of latencies with a similar pattern for MMN and ERAN. MMN and ERAN were elicited during sedation but were abolished during unconsciousness. In contrast, the amplitude of the P1 was unchanged by sedation but markedly decreased during unconsciousness. CONCLUSION: The results indicate differential effects of propofol sedation on cognitive functions that involve mainly the auditory cortices and cognitive functions that involve the frontal cortices.