RESUMEN
Ritualistic displays of aggressive intent are important social signals, often obviating physically dangerous engagement. To date, however, brain regions mediating such behaviors are not established. Here we used male Anolis carolinensis together with an in vivo 14C-2-deoxyglucose method to determine patterns of brain activation during elicitation of this animal's dominance displays vs. other behaviors. By patching one eye regional brain activation in the hemisphere receiving display-evocative visual stimuli ('seeing' side) was compared to activity in the contralateral brain that did not see specific stimuli ('patched' side); this was quantitated as the ratio of seeing/patched activity for brain regions of interest. Lone males displaying dominantly to mirrors activated dorsolateral basal ganglia (BG) in the seeing, compared to the patched hemisphere; this was not seen in various non-displaying controls. Degree of dorsolateral BG activation also correlated with a measure of dominant display activity, but not with locomotion. In socially stable pairs, displaying dominants showed similar activation of dorsolateral BG, but deactivated ventromedial BG; non-dominant cagemates displaying submissively had the opposite pattern. When cohabiting peacefully without displaying, paired dominants' and subordinates' brain activity patterns were similar to each other. Thus, different BG subsystems seem involved in dominant vs. submissive display behaviors. Given similarities in both social displays and BG organization, homologous brain systems might have similar functions in members of other amniote classes, including primates.
Asunto(s)
Agresión/fisiología , Ganglios Basales/fisiología , Dominación-Subordinación , Lagartos/fisiología , Percepción Visual/fisiología , Animales , Nivel de Alerta/fisiología , Autorradiografía , Ganglios Basales/anatomía & histología , Glucemia/metabolismo , Mapeo Encefálico , Dominancia Cerebral/fisiología , Masculino , Vías Visuales/anatomía & histología , Vías Visuales/fisiologíaRESUMEN
Serotonin (5-HT) functions are associated with social dominance status in diverse species, but to date the brain regions wherein 5-HT exerts such effects are uncertain. Here, we indexed 5-HT turnover in male Anolis carolinensis as the ratio of 5-HT to its metabolite, 5-hydroxy-indol-acetic acid, and also as the accumulation of the in vivo tracer 14C-alpha-methyl-tryptophan (14C-AMT). After patching one eye, displaying dominant animals increased both measures of 5-HT turnover in the forebrain hemisphere receiving display-evocative visual stimuli, compared to control, contralateral brain, whereas both 5-HT turnover indices were decreased when animals displayed submissively. In contrast, various non-displaying controls showed forebrain symmetry on both measures. Drugs that stimulate 5-HT(2C) receptors in mammals, and have 5-HT(2C)-like binding in A. carolinensis, evoked some elements of dominant display behaviors in non-dominant anole males and also activated dorsolateral basal ganglia as seen in non-medicated dominants when they display [Baxter et al., 2001]. Thus, acute changes in forebrain 5-HT output from baseline equilibrium, acting at 5-HT(2C)-like receptors, might effect some elements of the dominant vs. submissive male anoles' territorial displays. A mechanistic model of how this might occur is offered. Given similarities in 5-HT systems, forebrain functions, and territorial display routines, similar mechanisms might have similar functions in other amniotes, including primates.
Asunto(s)
Agresión/fisiología , Dominación-Subordinación , Lagartos/fisiología , Prosencéfalo/fisiología , Receptores de Serotonina/fisiología , Serotonina/metabolismo , Percepción Visual/fisiología , Animales , Nivel de Alerta/fisiología , Autorradiografía , Mapeo Encefálico , Dominancia Cerebral/fisiología , Masculino , Actividad Motora/fisiología , Prosencéfalo/anatomía & histología , TerritorialidadRESUMEN
Measures of serotonin (5-HT) turnover in A. carolinensis forebrain increase acutely when males exhibit dominant social/territorial display routines, but decrease during submissive displays [Baxter et al., 2001a, b]. The present investigation sought to determine whether a difference in presynaptic regulatory receptors - one that might affect 5-HT flux - distinguish dominant vs. submissive anoles. Both 5-HT(1B) and 5-HT(1D) receptors are presynaptic regulators of output; this role is prominent at 5-HT terminals, where stimulation inhibits 5-HT release. Here, 3H-sumatriptan binding at sites similar to mammalian 5-HT(1B/D) receptors was significantly higher in forebrain regions of submissive anoles than in dominant cagemates; this receptor site seemed pharmacologically more like a 5-HT(1B) than a 5-HT(1D) receptor. Higher densities of presynaptic 5-HT(1B) receptors in subordinates than in dominants might account for differences in 5-HT flux (lower in subordinates than in dominants) observed in displaying anoles of different status. Knockout mice missing the 5-HT(1B) receptor show heightened male territorial aggressiveness, thus similar 5-HT regulatory mechanisms might influence the likelihood of dominance in both mammals and reptiles.
Asunto(s)
Agresión/fisiología , Dominación-Subordinación , Lagartos/fisiología , Prosencéfalo/fisiología , Receptores de Serotonina/fisiología , Sumatriptán/farmacocinética , Territorialidad , Percepción Visual/fisiología , Animales , Autorradiografía , Unión Competitiva/fisiología , Mapeo Encefálico , Masculino , Prosencéfalo/anatomía & histología , Receptor de Serotonina 5-HT1B , Receptor de Serotonina 5-HT1D , Serotonina/metabolismoRESUMEN
BACKGROUND: The frequent comorbidity of major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) suggests a fundamental relationship between them. We sought to determine whether MDD and OCD have unique cerebral metabolic patterns that remain the same when they coexist as when they occur independently. METHODS: [18F]-fluorodeoxyglucose positron emission tomography (PET) brain scans were obtained on 27 subjects with OCD alone, 27 with MDD alone, 17 with concurrent OCD+MDD, and 17 normal control subjects, all in the untreated state. Regional cerebral glucose metabolism was compared between groups. RESULTS: Left hippocampal metabolism was significantly lower in subjects with MDD alone and in subjects with concurrent OCD+MDD than in control subjects or subjects with OCD alone. Hippocampal metabolism was negatively correlated with depression severity across all subjects. Thalamic metabolism was significantly elevated in OCD alone and in MDD alone. Subjects with concurrent OCD+MDD had significantly lower metabolism in thalamus, caudate, and hippocampus than subjects with OCD alone. CONCLUSIONS: Left hippocampal dysfunction was associated with major depressive episodes, regardless of primary diagnosis. Other cerebral metabolic abnormalities found in OCD and MDD occurring separately were not seen when the disorders coexisted. Depressive episodes occurring in OCD patients may be mediated by different basal ganglia-thalamic abnormalities than in primary MDD patients.
Asunto(s)
Encéfalo/metabolismo , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/metabolismo , Trastorno Obsesivo Compulsivo/complicaciones , Trastorno Obsesivo Compulsivo/metabolismo , Adulto , Encéfalo/anomalías , Encéfalo/fisiopatología , Núcleo Caudado/metabolismo , Trastorno Depresivo Mayor/diagnóstico , Femenino , Fluorodesoxiglucosa F18 , Lateralidad Funcional/fisiología , Glucosa/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Trastorno Obsesivo Compulsivo/diagnóstico , Radiofármacos , Tálamo/metabolismo , Tomografía Computarizada de EmisiónRESUMEN
BACKGROUND: Symptoms of major depressive disorder (MDD) have been linked to regional brain function through imaging studies of symptom provocation in normal control subjects and baseline studies of subjects with MDD. We examined associations between change in depressive symptom factors and change in regional brain metabolism from before to after treatment of MDD. METHODS: Thirty-nine outpatients with MDD underwent 18F-fluorodeoxyglucose positron emission tomography scanning before and after treatment with either paroxetine or interpersonal psychotherapy. Associations were determined between changes in regional brain metabolism and changes in four Hamilton Depression Rating Scale factors (anxiety/somatization [ANX], psychomotor retardation [PR], cognitive disturbance [COGN], and sleep disturbance) and two corresponding Profile of Mood States subscales (tension [TENS] and fatigue [FATIG]). RESULTS: Improvement in ANX, PR, TENS, and FATIG factors was associated with decreasing ventral frontal lobe metabolism. Improvement in ANX and TENS was also associated with decreasing ventral anterior cingulate gyrus (AC) and anterior insula activity, whereas improvement in PR was associated with increasing dorsal AC activity. COGN improvement was associated with increasing dorsolateral prefrontal cortex metabolism. CONCLUSIONS: Brain regions that show significant relationships with symptom provocation in normal control subjects have similar relationships with MDD symptoms as they improve with treatment.
Asunto(s)
Trastorno Depresivo Mayor/metabolismo , Corteza Prefrontal/metabolismo , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/terapia , Fluorodesoxiglucosa F18 , Giro del Cíngulo/metabolismo , Humanos , Paroxetina/uso terapéutico , Trastornos Psicomotores/metabolismo , Psicoterapia , Radiofármacos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Índice de Severidad de la Enfermedad , Tomografía Computarizada de EmisiónRESUMEN
BACKGROUND: In functional brain imaging studies of major depressive disorder (MDD), regional abnormalities have been most commonly found in prefrontal cortex, anterior cingulate gyrus, and temporal lobe. We examined baseline regional metabolic abnormalities and metabolic changes from pretreatment to posttreatment in subjects with MDD. We also performed a preliminary comparison of regional changes with 2 distinct forms of treatment (paroxetine and interpersonal psychotherapy). METHODS: Twenty-four subjects with unipolar MDD and 16 normal control subjects underwent resting F 18 ((18)F) fluorodeoxyglucose positron emission tomography scanning before and after 12 weeks. Between scans, subjects with MDD were treated with either paroxetine or interpersonal psychotherapy (based on patient preference), while controls underwent no treatment. RESULTS: At baseline, subjects with MDD had higher normalized metabolism than controls in the prefrontal cortex (and caudate and thalamus), and lower metabolism in the temporal lobe. With treatment, subjects with MDD had metabolic changes in the direction of normalization in these regions. After treatment, paroxetine-treated subjects had a greater mean decrease in Hamilton Depression Rating Scale score (61.4%) than did subjects treated with interpersonal psychotherapy (38.0%), but both subgroups showed decreases in normalized prefrontal cortex (paroxetine-treated bilaterally and interpersonal psychotherapy-treated on the right) and left anterior cingulate gyrus metabolism, and increases in normalized left temporal lobe metabolism. CONCLUSIONS: Subjects with MDD had regional brain metabolic abnormalities at baseline that tended to normalize with treatment. Regional metabolic changes appeared similar with the 2 forms of treatment. These results should be interpreted with caution because of study limitations (small sample size, lack of random assignment to treatment groups, and differential treatment response between treatment subgroups).
Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Trastorno Depresivo/metabolismo , Trastorno Depresivo/terapia , Glucosa/metabolismo , Paroxetina/uso terapéutico , Psicoterapia , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Tomografía Computarizada de Emisión/estadística & datos numéricos , Adulto , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/metabolismo , Trastorno Depresivo/diagnóstico por imagen , Femenino , Fluorodesoxiglucosa F18 , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/metabolismo , Tálamo/diagnóstico por imagen , Tálamo/metabolismo , Resultado del TratamientoRESUMEN
BACKGROUND: Human and animal studies point to 3 dimensions of personality that change during pharmacotherapy with a selective serotonin reuptake inhibitor (SSRI). Specifically, harm avoidance has been found to decrease, social dominance has been found to increase, and hostility in social situations has been found to decrease with SSRI treatment. We sought to determine personality changes in subjects with either major depressive disorder (MDD) or obsessive-compulsive disorder (OCD) treated with paroxetine. We also sought to determine whether or not these personality changes were associated with disease state (MDD vs. OCD) or treatment response (responders vs. nonresponders). METHOD: Thirty-seven subjects diagnosed with either MDD or OCD (according to DSM-IV criteria) completed the Cattell 16 Personality Factor Inventory (16-PF) before and after treatment with paroxetine. Treatment response was defined as a Clinical Global Impressions-Improvement rating of "much" or "very much" improved and a drop in Hamilton Rating Scale for Depression score of at least 50% for MDD or Yale-Brown Obsessive Compulsive Scale score of at least 30% for OCD. RESULTS: No significant differences were found between subjects with MDD and OCD in personality change with treatment. In the whole group, treatment responders had a greater decrease than nonresponders in 16-PF factors relating to harm avoidance. An increase in social dominance factors and a decrease in factors relating to hostility in social situations were found, but these changes were not significantly different between responders and nonresponders. CONCLUSION: These findings indicate that certain personality dimensions change with SSRI treatment and that some of these changes are independent of clinical treatment response.
Asunto(s)
Trastorno Depresivo/tratamiento farmacológico , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Paroxetina/efectos adversos , Trastornos de la Personalidad/inducido químicamente , Personalidad/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Adulto , Análisis de Varianza , Trastorno Depresivo/psicología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Análisis Factorial , Humanos , Masculino , Trastorno Obsesivo Compulsivo/psicología , Paroxetina/uso terapéutico , Trastornos de la Personalidad/diagnóstico , Inventario de Personalidad/estadística & datos numéricos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Resultado del TratamientoRESUMEN
Serotonin (5-HT) 5-HT(2A) and 5-HT(2C) receptors are thought to play important roles in the mammalian striatum. As basal ganglia functions in general are thought highly conserved among amniotes, we decided to use in situ autoradiographic methods to determine the occurrence and distribution of pharmacologically mammal-like 5-HT(2A) and 5-HT(2C) receptors in the lizard, Anolis carolinensis, with particular attention to the striatum. We also determined the distributions of 5-HT(1A), 5-HT(1B/D), 5 HT(3), and 5-HT(uptake) receptors for comparison. All 5-HT receptors examined showed pharmacological binding specificity, and forebrain binding density distributions that resembled those reported for mammals. Anolis 5 HT(2A/C) and 5-HT(1A) site distributions were similar in both in vivo and ex vivo binding experiments. 5-HT(2A & C) receptors occur in both high and low affinity states, the former having preferential affinity for (125)I-(+/-)-2,5-dimethoxy-4-iodo-amphetamine hydrochloride ((125)I-DOI). In mammals (125)I-DOI binding shows a patchy density distribution in the striatum, being more dense in striosomes than in surrounding matrix. There was no evidence of any such patchy density of (125)I-DOI binding in the anole striatum, however. As a further indication that anoles do not possess a striosome and matrix striatal organization, neither (3)H-naloxone binding nor histochemical staining for acetylcholinesterase activity (AChE) were patchy. AChE did show a band-like striatal distribution, however, similar to that seen in birds.
Asunto(s)
Cuerpo Estriado/anatomía & histología , Lagartos/anatomía & histología , Receptores de Serotonina/ultraestructura , Animales , Mapeo Encefálico , Masculino , Mamíferos , Especificidad de la EspecieRESUMEN
We used in situ autoradiographic ligand binding methods to determine the occurrence and distribution of dopamine D(1) and D(2) receptor sub-types in the anole lizard, Anolis carolinensis. Both were present and exhibited pharmacological specificity characteristics similar to those described for mammals. However, unlike in mammals where in the neostriatum [outside the nucleus accumbens/olfactory tubercle complex (NA/OT)] these receptors exhibit only slight dorsolateral (D(2) high, D(1) low) to ventromedial (D(1 )high, D(2) low) gradients that co mingle extensively, in the anole striatum outside the NA/OT there was a striking laminar pattern, with little if any overlap between D(2) (high in a dorsal band) and D(1) (high ventral to the D(2) band) distributions. As D(1) receptors are related to the direct and D(2) to the indirect basal ganglia (BG) subsystems in mammals, we also determined anole striatal distributions of pre-proenkephalin mRNA, a marker for striatal efferents to the indirect BG subsystem in mammals. Here, too, there was a striking laminar pattern, with pre-proenkephalin mRNA in a band similar to that seen for D(2) receptors. The crisp neuroanatomical separation between these classic BG subsystem markers in Anolis striatum make this species attractive for the study of such systems' functions during behavior.
Asunto(s)
Ganglios Basales/anatomía & histología , Cuerpo Estriado/anatomía & histología , Lagartos/anatomía & histología , Receptores de Dopamina D1/ultraestructura , Receptores de Dopamina D2/ultraestructura , Animales , Mapeo Encefálico , Mamíferos , Especificidad de la EspecieRESUMEN
Previous positron emission tomography (PET) studies of patients with obsessive-compulsive disorder (OCD) have found elevated glucose metabolic rates in the orbitofrontal cortex (OFC) and caudate nuclei that normalize with response to treatment. Furthermore, OCD symptom provocation differentially activates specific subregions of the OFC, which have distinct patterns of connectivity and serve different functions. Therefore, we sought to determine the role of specific subregions of the OFC and associated subcortical structures in mediating OCD symptoms, by determining how glucose metabolism in these structures changed with paroxetine treatment of OCD patients. We also sought to determine whether pretreatment OFC metabolism would predict response to paroxetine, as it has for other OCD treatments. Twenty subjects with OCD received [18F]-fluorodeoxyglucose (FDG)-PET scans before and after 8 to 12 weeks of treatment with paroxetine, 40 mg/day. In patients who responded to paroxetine, glucose metabolism decreased significantly in right anterolateral OFC and right caudate nucleus. Lower pretreatment metabolism in both left and right OFC predicted greater improvement in OCD severity with treatment. These results add to evidence indicating that orbitofrontal-subcortical circuit function mediates the symptomatic expression of OCD. Specific subregions of the OFC may be differentially involved in the pathophysiology of OCD and/or its response to pharmacotherapy.
Asunto(s)
Corteza Cerebral/metabolismo , Fluorodesoxiglucosa F18 , Lóbulo Frontal/metabolismo , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Trastorno Obsesivo Compulsivo/metabolismo , Paroxetina/uso terapéutico , Radiofármacos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Corteza Cerebral/diagnóstico por imagen , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Lóbulo Frontal/diagnóstico por imagen , Humanos , Masculino , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Valor Predictivo de las Pruebas , Radiofármacos/farmacocinética , Análisis de Regresión , Tomografía Computarizada de EmisiónRESUMEN
Functional brain imaging studies of subjects with Major Depressive Disorder (MDD) have suggested that decreased dorsolateral (DLPFC) and increased ventrolateral (VLPFC) prefrontal cortical activity mediate the depressed state. Pre- to post-treatment studies indicate that these abnormalities normalize with successful treatment. We performed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans on 16 outpatients with MDD before and after treatment with paroxetine (target dose = 40 mg/day). Regions of interest (ROIs) for this analysis were drawn by a rater blind to subject identity on the magnetic resonance image of each subject and transferred onto their coregistered PET scans. We hypothesized that DLPFC metabolism would increase, while ventral frontal metabolism [in the VLPFC, the orbitofrontal cortex (OFC), and the inferior frontal gyrus (IFG)] would decrease with successful treatment. Treatment response was defined as a decrease in the Hamilton Depression Rating Scale of > 50% and a Clinical Global Improvement Scale rating of 'much' or 'very much' improved. By these criteria, nine of the subjects were classified as treatment responders. These responders had significantly greater decreases in normalized VLPFC and OFC metabolism than did non-responders. There were no significant effects of treatment response on change in the DLPFC or IFG in this sample. However, there was a positive correlation between change in HAM-D scores and change in normalized IFG and VLPFC metabolism. There were no significant interactions with laterality. On pre-treatment scans, lower metabolism in the left ventral anterior cingulate gyrus was associated with better treatment response. These findings implicate ventral prefrontal-subcortical brain circuitry in the mediation of response to serotonin reuptake inhibitors in MDD.
Asunto(s)
Antidepresivos de Segunda Generación/uso terapéutico , Glucemia/metabolismo , Trastorno Depresivo Mayor/tratamiento farmacológico , Metabolismo Energético/efectos de los fármacos , Paroxetina/uso terapéutico , Corteza Prefrontal/efectos de los fármacos , Tomografía Computarizada de Emisión , Adulto , Antidepresivos de Segunda Generación/efectos adversos , Mapeo Encefálico , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/fisiopatología , Relación Dosis-Respuesta a Droga , Metabolismo Energético/fisiología , Femenino , Fluorodesoxiglucosa F18 , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/efectos de los fármacos , Giro del Cíngulo/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Paroxetina/efectos adversos , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Pronóstico , Resultado del TratamientoRESUMEN
In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this, [18F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale-Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (F = 6.07, d.f. = 1,17, P = 0.025). Correlations between normalized left OFC metabolism and treatment response revealed that higher normalized metabolism in this region was associated with greater improvement in the BT-treated group (tau = 0.35, P = 0.04), but worse outcome (tau = -0.57, P = 0.03) in the fluoxetine-treated group. These results suggest that subjects with differing patterns of metabolism preferentially respond to BT vs. medication.
Asunto(s)
Antidepresivos Tricíclicos/uso terapéutico , Terapia Conductista/métodos , Encéfalo/diagnóstico por imagen , Clomipramina/uso terapéutico , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/terapia , Tomografía Computarizada de Emisión , Adulto , Encéfalo/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Neuroimaging studies provide strong evidence that the pathophysiology of obsessive-compulsive disorder (OCD) involves abnormal functioning along specific frontal-subcortical brain circuits. METHOD: A literature search was carried out for all brain imaging studies of patients with OCD. We also reviewed the basic science literature on the functional neuroanatomy of cortico-basal ganglia circuits, and integrated this information with neuroimaging data in OCD to formulate a theoretical model of brain mediation of OCD symptoms and response to treatment. RESULTS: At least a subgroup of patients with OCD may have abnormal basal ganglia development. Functional neuroimaging studies indicate that OCD symptoms are associated with increased activity in orbitofrontal cortex, caudate nucleus, thalamus and anterior cingulate gyrus. CONCLUSIONS: OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, perhaps due to an imbalance of tone between direct and indirect striato-pallidal pathways. We present a model which describes how frontal-subcortical brain circuitry may mediate OCD symptomatology, and suggest a hypothesis for how successful treatments may ameliorate symptoms, via their effects on circuit activity.
Asunto(s)
Encefalopatías/fisiopatología , Circulación Cerebrovascular/fisiología , Trastorno Obsesivo Compulsivo/fisiopatología , Encefalopatías/complicaciones , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/fisiopatología , Humanos , Imagen por Resonancia Magnética/métodos , Trastorno Obsesivo Compulsivo/complicaciones , Tomografía Computarizada de Emisión/métodos , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
We describe a method of orally administering 18F-fluoro-2-deoxyglucose (FDG) for positron emission tomography (PET) scans to determine local cerebral metabolic rates for glucose (LCMRGlc), normalized to that of whole brain, in fully conscious, non-restrained primates. Oral FDG-PET studies were performed in both non-restrained and chaired monkeys, and in one human where results could be compared with traditional intravenous FDG administration. The oral route of FDG administration gave images and whole brain-normalized PET LCMRGlc results comparable to those obtained by the intravenous route. This oral FDG-PET method may provide a useful means by which to obtain measures of LCMRGlcs for brain structures, relative to each other, in non-restrained, non-drugged primates in field and laboratory studies. This method might also have clinical applications for PET studies of children.
Asunto(s)
Encéfalo/metabolismo , Desoxiglucosa/análogos & derivados , Radioisótopos de Flúor , Glucosa/metabolismo , Tomografía Computarizada de Emisión/veterinaria , Administración Oral , Animales , Encéfalo/diagnóstico por imagen , Desoxiglucosa/administración & dosificación , Desoxiglucosa/farmacocinética , Femenino , Radioisótopos de Flúor/administración & dosificación , Radioisótopos de Flúor/farmacocinética , Fluorodesoxiglucosa F18 , Inyecciones Intravenosas , Macaca mulatta , Masculino , Factores de Tiempo , Distribución Tisular , Tomografía Computarizada de Emisión/métodosRESUMEN
BACKGROUND: Reduced amplitude of the circadian temperature rhythm and elevated nocturnal body temperature normalize after successful pharmacotherapy of major depression. METHODS: Core body temperature was continually monitored in three groups: a) 6 depressed patients before an electroconvulsive therapy (ECT) course and b) after an ECT course; and c) 6 healthy, sex-matched controls of similar age. RESULTS: The 24-hour profile of temperature was significantly different in patients pre-ECT than in patients post-ECT or in controls. Post-ECT subjects and controls manifested 24-hour profiles similar to one another. Circadian temperature rhythm amplitude increased after ECT. The mean asleep and mean 24-hour temperatures were significantly higher in patients pre-ECT than post-ECT and controls. CONCLUSIONS: We find that ECT restores a disrupted circadian temperature rhythm in depressed patients.
Asunto(s)
Temperatura Corporal/fisiología , Ritmo Circadiano/fisiología , Trastorno Depresivo/fisiopatología , Trastorno Depresivo/terapia , Terapia Electroconvulsiva , Adulto , Afecto , Trastorno Depresivo/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración PsiquiátricaRESUMEN
BACKGROUND: Although serotonin reuptake inhibitors (SRIs) are the mainstay of pharmacologic treatment for obsessive-compulsive disorder (OCD), many patients do not have an adequate response to these medications. One approach to treating SRI-refractory OCD patients has been to add other classes of medications to the SRI. We predicted that augmentation with risperidone would alleviate symptoms in SRI-refractory OCD patients. METHOD: 21 patients were treated openly with the combination of an SRI and adjunctive risperidone (mean dose = 2.75 mg/day). All met DSM-IV criteria for obsessive-compulsive disorder and had a variety of comorbid disorders. Prior to addition of risperidone, all patients had failed to respond to at least one adequate trial of an SRI. Response was determined by clinical judgment and standardized rating scales. RESULTS: 5 (24%) of the 21 patients experienced side effects (most commonly, akathisia), which forced discontinuation of risperidone. Of the 16 patients who tolerated combined treatment, 14 (87%) had substantial reductions in obsessive-compulsive symptoms within 3 weeks. Patients with horrific mental imagery had the strongest and fastest response, often within a few days. Patients with comorbid psychotic disorders improved gradually over 2 to 3 weeks. Patients with comorbid tic disorders had the poorest rate of response and highest rate of akathisia. CONCLUSION: These results suggest that risperidone augmentation is effective and well tolerated in patients with SRI-refractory obsessive-compulsive disorder. Response to risperidone augmentation appears to be influenced by symptom subtypes and comorbid conditions. Controlled trials are required to confirm the efficacy of risperidone augmentation for refractory OCD.
Asunto(s)
Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Risperidona/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adulto , Acatisia Inducida por Medicamentos/etiología , Comorbilidad , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/psicología , Escalas de Valoración Psiquiátrica , Risperidona/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: We sought to determine in a new patient sample whether symptomatic improvement in obsessive-compulsive disorder treated with behavior modification is accompanied by significant changes in glucose metabolic rates in the caudate nucleus, measured with positron emission tomography, as seen in a previous study. Second, by combining samples from this and the previous study, we also examined whether there were pathologic correlational relationships among brain activity in the orbital cortex, caudate nucleus, and thalamus that obtained before behavioral treatment of obsessive-compulsive disorder, but that decreased significantly with symptom improvement. METHODS: Nine patients with obsessive-compulsive disorder were studied with positron emission tomography before and after 10 weeks of structured exposure and response prevention behavioral and cognitive treatment. Results were analyzed both alone and combined with those from nine similar subjects from the previous study. RESULTS: Behavior therapy responders had significant (P < .05) bilateral decreases in caudate glucose metabolic rates that were greater than those seen in poor responders to treatment. Before treatment, there were significant correlations of brain activity between the orbital gyri and the head of the caudate nucleus and the orbital gyri and the thalamus on the right. These correlations decreased significantly after effective treatment. CONCLUSIONS: These results replicate and extend previous findings of changes in caudate nucleus function with behavior therapy for obsessive-compulsive disorder. A prefrontal cortico-striato-thalamic brain system is implicated in mediation of symptoms of obsessive-compulsive disorder.
Asunto(s)
Terapia Conductista , Encéfalo/metabolismo , Glucosa/metabolismo , Trastorno Obsesivo Compulsivo/metabolismo , Trastorno Obsesivo Compulsivo/terapia , Adulto , Encéfalo/diagnóstico por imagen , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/metabolismo , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Femenino , Radioisótopos de Flúor/metabolismo , Fluorodesoxiglucosa F18 , Humanos , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/metabolismo , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Tálamo/metabolismo , Tomografía Computarizada de Emisión , Resultado del TratamientoRESUMEN
OBJECTIVE: Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 allele (APOE epsilon 4) is a risk factor for familial AD. To determine if APOE epsilon 4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4. We also compared them with seven patients with probable AD. DESIGN: After grouping subjects according to diagnosis and genotype, brain function measures were compared among groups. SETTING: University medical center. PATIENTS: At risk subjects had mild memory complaints, normal cognitive performance, and at least two relatives with AD. Subjects with APOE epsilon 4 did not differ from those without APOE epsilon 4 in mean age at examination (56.4 vs 55.5 years) or in neuropsychological performance (mean Mini-Mental State Examination score, 28.8 vs 29.3). MAIN OUTCOME MEASURES: Cerebral glucose metabolism was measured using positron emission tomography and fludeoxyglucose F 18. RESULTS: Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE epsilon 4 compared with those without APOE epsilon 4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE epsilon 4. CONCLUSIONS: These results suggest that the inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabolism and increased asymmetry in non-demented relatives at risk for probable AD. Longitudinal study will determine if glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder.
Asunto(s)
Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Apolipoproteínas E , Encéfalo/metabolismo , Glucosa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Enfermedad de Alzheimer/fisiopatología , Análisis de Varianza , Apolipoproteína E4 , Apolipoproteínas E/genética , Apolipoproteínas E/fisiología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiología , Desoxiglucosa/análogos & derivados , Familia , Femenino , Radioisótopos de Flúor , Fluorodesoxiglucosa F18 , Genotipo , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Modelos Teóricos , Pruebas Neuropsicológicas , Factores de Riesgo , Tomografía Computarizada de EmisiónRESUMEN
In the last 7 years, positron emission tomography (PET) scanning studies of obsessive compulsive disorder have given us new insights into misfunctionings of brain systems that may mediate the symptomatic expression of this classical "neurosis." Work by several PET groups indicates that a prefrontal cortex-basal ganglia-thalamic circuit may be the brain pathway leading to the broken record patterns of obsessions and compulsions.