RESUMEN
Serotonin receptor 6 (5-hydroxytrypamine-6, or 5-HT6) is a potential therapeutic target given its distribution in brain regions that are important in depression, anxiety, and cognition. This study sought to investigate the effects of age on 5-HT6 receptor availability using 11C-GSK215083, a PET ligand with affinity for 5-HT6 in the striatum and 5-HT2A in the cortex. Methods: Twenty-eight healthy male volunteers (age range, 23-52 y) were scanned with 11C-GSK215083 PET. Time-activity curves in regions of interest were fitted using a multilinear analysis method. Nondisplaceable binding potential (BPND) was calculated using the cerebellum as the reference region and corrected for partial-volume effects. Results: In 5-HT6-rich areas, regional 11C-GSK215083 showed a negative correlation between BPND and age in the caudate (r = -0.41, P = 0.03) (14% change per decade) and putamen (r = -0.30, P = 0.04) (11% change per decade) but not in the ventral striatum or pallidum. A negative correlation with age was also seen in cortical regions (r = -0.41, P = 0.03) (7% change per decade), consistent with the literature on 5-HT2A availability. Conclusion: To our knowledge, this was the first in vivo study on humans to examine the effect of age on 5-HT6 receptor availability. The study demonstrated a significant age-related decline in 5-HT6 availability (BPND) in the caudate and putamen.
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Envejecimiento/metabolismo , Voluntarios Sanos , Tomografía de Emisión de Positrones , Quinolinas , Receptores de Serotonina/metabolismo , Sulfonas , Adulto , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
PURPOSE: [(18)F]FPEB is a promising PET radioligand for the metabotropic glutamate receptor 5 (mGluR5), a potential target for the treatment of neuropsychiatric diseases. The purpose of this study was to evaluate the test-retest reproducibility of [(18)F]FPEB in the human brain. METHODS: Seven healthy male subjects were scanned twice, 3 - 11 weeks apart. Dynamic data were acquired using bolus plus infusion of 162 ± 32 MBq [(18)F]FPEB. Four methods were used to estimate volume of distribution (V T): equilibrium analysis (EQ) using arterial (EQA) or venous input data (EQV), MA1, and a two-tissue compartment model (2 T). Binding potential (BP ND) was also estimated using cerebellar white matter (CWM) or gray matter (CGM) as the reference region using EQ, 2 T and MA1. Absolute test-retest variability (aTRV) of V T and BP ND were calculated for each method. Venous blood measurements (C V) were compared with arterial input (C A) to examine their usability in EQ analysis. RESULTS: Regional V T estimated by the four methods displayed a high degree of agreement (r (2) ranging from 0.83 to 0.99 among the methods), although EQA and EQV overestimated V T by a mean of 9 % and 7 %, respectively, compared to 2 T. Mean values of aTRV of V T were 11 % by EQA, 12 % by EQV, 14 % by MA1 and 14 % by 2 T. Regional BP ND also agreed well among the methods and mean aTRV of BP ND was 8 - 12 % (CWM) and 7 - 9 % (CGM). Venous and arterial blood concentrations of [(18)F]FPEB were well matched during equilibrium (C V = 1.01 · C A, r (2) = 0.95). CONCLUSION: [(18)F]FPEB binding shows good TRV with minor differences among analysis methods. Venous blood can be used as an alternative for input function measurement instead of arterial blood in EQ analysis. Thus, [(18)F]FPEB is an excellent PET imaging tracer for mGluR5 in humans.
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Encéfalo/metabolismo , Imagen Molecular/métodos , Nitrilos/administración & dosificación , Nitrilos/farmacocinética , Tomografía de Emisión de Positrones/métodos , Piridinas/administración & dosificación , Piridinas/farmacocinética , Receptor del Glutamato Metabotropico 5/metabolismo , Adulto , Encéfalo/diagnóstico por imagen , Humanos , Infusiones Intravenosas , Masculino , Radiofármacos/administración & dosificación , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Distribución Tisular , Adulto JovenRESUMEN
The Radiotracer [(11)C]OMAR was developed for positron emission tomography (PET) imaging of cannabinoid type-1 receptors (CB1R). The objectives of the present study were to evaluate kinetic analysis methods, determine test-retest reliability, and assess gender differences in receptor availability. Dynamic PET data were acquired in 10 human subjects, and analyzed with one-tissue (1T) and two-tissue (2T) compartment models and by the Logan and multilinear analysis (MA1) methods to estimate regional volume of distribution (VT). The 2T model inclusive of a vascular component (2TV) and MA1 were the preferred techniques. Test-retest reliability of VT was good (mean absolute deviation ~9%; intraclass correlation coefficient ~0.7). Tracer parent fraction in plasma was lower in women (P<0.0001). Cerebral uptake normalized by body weight and injected dose was higher in men by 17% (P<0.0001), but VT was significantly greater in women by 23% (P<0.0001). These findings show that [(11)C]OMAR binding can be reliably quantified by the 2T model or MA1 method and demonstrate the utility of this tracer for in vivo imaging of CB1R. In addition, results from the present study indicate that gender difference in receptor binding should be taken into consideration when [(11)C]OMAR is used to quantify CB1R availability in neuropsychiatric disorders.
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Encéfalo , Angiografía Cerebral/métodos , Tomografía de Emisión de Positrones/métodos , Radiofármacos/administración & dosificación , Receptor Cannabinoide CB1/metabolismo , Caracteres Sexuales , Adolescente , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Isótopos de Carbono/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Evidence from animal models and postmortem human studies points to the importance of the dopamine D3 receptor (D3R) in cocaine dependence (CD). The objective of this pilot study was to use the D3R-preferring radioligand [(11)C](+)PHNO to compare receptor availability in groups with and without CD. METHODS: Ten medically healthy, non-treatment seeking CD subjects (mean age 41 ± 8) in early abstinence were compared to 10 healthy control (HC) subjects (mean age 41 ± 6) with no history of cocaine or illicit substance abuse. Binding potential (BPND), a measure of available receptors, was determined with parametric images, computed using the simplified reference tissue model (SRTM2) with the cerebellum as the reference region. RESULTS: BPND in CD subjects was higher in D3R-rich areas including the substantia nigra ((SN) 29%; P=0.03), hypothalamus (28%; P=0.02) and amygdala (35%; P=0.03). No between-group differences were observed in the striatum or pallidum. BPND values in the SN (r=+0.83; P=0.008) and pallidum (r=+0.67; P=0.03) correlated with years of cocaine use. CONCLUSIONS: Between-group differences suggest an important role for dopaminergic transmission in the SN, hypothalamus and amygdala in CD. Such findings also highlight the potential relevance of D3R as a medication development target in CD.
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Encéfalo/efectos de los fármacos , Trastornos Relacionados con Cocaína/metabolismo , Receptores de Dopamina D3/metabolismo , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/patología , Estudios de Casos y Controles , Trastornos Relacionados con Cocaína/diagnóstico por imagen , Trastornos Relacionados con Cocaína/patología , Femenino , Globo Pálido/diagnóstico por imagen , Globo Pálido/efectos de los fármacos , Globo Pálido/metabolismo , Humanos , Masculino , Neuroimagen , Oxazinas , Tomografía de Emisión de Positrones/métodos , Sustancia Negra/diagnóstico por imagen , Sustancia Negra/efectos de los fármacos , Sustancia Negra/metabolismoRESUMEN
[(11)C]AFM, or [(11)C]2-[2-(dimethylaminomethyl)phenylthio]-5-fluoromethylphenylamine, is a new positron emission tomography (PET) radioligand with high affinity and selectivity for the serotonin transporter (SERT). The purpose of this study was to determine the most appropriate kinetic model to quantify [(11)C]AFM binding in the healthy human brain. Positron emission tomography data and arterial input functions were acquired from 10 subjects. Compartmental modeling and the multilinear analysis-1(MA1) method were tested using the arterial input functions. The one-tissue model showed a lack of fit in low-binding regions, and the two-tissue model failed to estimate parameters reliably. Regional time-activity curves were well described by MA1. The rank order of [(11)C]AFM binding potential (BPND) matched well with the known regional SERT densities. For routine use of [(11)C]AFM, several noninvasive methods for quantification of regional binding were evaluated, including simplified reference tissue models (SRTM and SRTM2), and multilinear reference tissue models (MRTM and MRTM2). The best methods for region of interest (ROI) analysis were MA1, MRTM2, and SRTM2, with fixed population kinetic values ( or b') for the reference methods. The MA1 and MRTM2 methods were best for parametric imaging. These results showed that [(11)C]AFM is a suitable PET radioligand to image and quantify SERT in humans.
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Compuestos de Anilina/farmacocinética , Encéfalo/diagnóstico por imagen , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Adulto , Compuestos de Anilina/metabolismo , Encéfalo/metabolismo , Radioisótopos de Carbono/metabolismo , Radioisótopos de Carbono/farmacocinética , Femenino , Humanos , Cinética , Masculino , Persona de Mediana Edad , Modelos Biológicos , Tomografía de Emisión de Positrones/métodos , Radiofármacos/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/análisis , Adulto JovenRESUMEN
BACKGROUND: The amygdala is a key site where alterations in the regulation of the serotonin transporter (5-HTT) may alter stress response. Deficient 5-HTT function and abnormal amygdala activity have been hypothesized to contribute to the pathophysiology of posttraumatic stress disorder (PTSD), but no study has evaluated the 5-HTT in humans with PTSD. On the basis of translational models, we hypothesized that patients diagnosed with PTSD would exhibit reduced amygdala 5-HTT expression as measured with positron emission tomography and the recently developed 5-HTT-selective radiotracer [(11)C]AFM. METHODS: Fifteen participants with PTSD and 15 healthy control (HC) subjects without trauma history underwent a resting-state positron emission tomography scan. RESULTS: [(11)C]AFM binding potential (BP(ND)) within the combined bilateral amygdala region of interest was significantly reduced in the PTSD group compared with the HC group (p = .027; 16.3% reduction), which was largely driven by the between-group difference in the left amygdala (p = .008; 20.5% reduction). Furthermore, amygdala [(11)C]AFM BP(ND) was inversely correlated with both Hamilton Rating Scale for Anxiety scores (r = -.55, p = .035) and Montgomery-Åsberg Depression Rating Scale scores (r = -.56, p = .029). CONCLUSIONS: Our findings of abnormally reduced amygdala 5-HTT binding in PTSD and its association with higher anxiety and depression symptoms in PTSD patients support a translational neurobiological model of PTSD directly implicating dysregulated 5-HTT signaling within neural systems underlying threat detection and fear learning.
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Amígdala del Cerebelo/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Trastornos por Estrés Postraumático/patología , Adolescente , Adulto , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/efectos de los fármacos , Compuestos de Anilina/farmacocinética , Mapeo Encefálico , Estudios de Casos y Controles , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Unión Proteica , Adulto JovenRESUMEN
BACKGROUND: Attention-deficit/hyperactivity disorder is a psychiatric disorder that starts in childhood. The mechanism of action of methylphenidate, the most common treatment for attention deficit hyperactivity disorder, is unclear. In vitro, the affinity of methylphenidate for the norepinephrine transporter (NET) is higher than that for the dopamine transporter (DAT). The goal of this study was to use positron emission tomography to measure the occupancy of brain norepinephrine transporter by methylphenidate in vivo in humans. METHODS: We used (S,S)-[¹¹C] methylreboxetine ([¹¹C]MRB) to determine the effective dose 50 (ED50) of methylphenidate for NET. In a within-subject design, healthy subjects (n = 11) received oral, single-blind placebo and 2.5, 10, and 40 mg of methylphenidate 75 min before [¹¹C]MRB injection. Dynamic positron emission tomography imaging was performed for 2 hours with the High Resolution Research Tomograph. The multilinear reference tissue model with occipital cortex as the reference region was used to estimate binding potential non-displaceable (BP(ND)) in the thalamus and other NET-rich regions. RESULTS: BP(ND) was reduced by methylphenidate in a dose-dependent manner in thalamus and other NET-rich regions. The global ED50 was estimated to be .14 mg/kg; therefore, the average clinical maintenance dose of methylphenidate (.35-.55 mg/kg) produces 70% to 80% occupancy of NET. CONCLUSIONS: For the first time in humans, we demonstrate that oral methylphenidate significantly occupies NET at clinically relevant doses. The ED50 is lower than that for DAT (.25 mg/kg), suggesting the potential relevance of NET inhibition in the therapeutic effects of methylphenidate in attention-deficit/hyperactivity disorder.
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Encéfalo/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Metilfenidato/farmacología , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/efectos de los fármacos , Adulto , Encéfalo/diagnóstico por imagen , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Metilfenidato/administración & dosificación , Morfolinas/farmacología , Tomografía de Emisión de Positrones/métodos , Ensayo de Unión Radioligante/métodos , ReboxetinaRESUMEN
[(11)C]P943 is a new radioligand recently developed to image and quantify serotonin 5-Hydroxytryptamine (5-HT(1B)) receptors with positron emission tomography (PET). The purpose of this study was to evaluate [(11)C]P943 for this application in humans, and to determine the most suitable quantification method. Positron emission tomography data and arterial input function measurements were acquired in a cohort of 32 human subjects. Using arterial input functions, compartmental modeling, the Logan graphical analysis, and the multilinear method MA1 were tested. Both the two tissue-compartment model and MA1 provided good fits of the PET data and reliable distribution volume estimates. Using the cerebellum as a reference region, BP(ND) binding potential estimates were computed. [(11)C]P943 BP(ND) estimates were significantly correlated with in vitro measurements of the density of 5-HT(1B) receptors, with highest values in the occipital cortex and pallidum. To evaluate noninvasive methods, two- and three-parameter graphical analyses, Simplified Reference Tissue Models (SRTM and SRTM2), and Multilinear Reference Tissue Models (MRTM and MRTM2) were tested. The MRTM2 model provided the best correlation with MA1 binding-potential estimates. Parametric images of the volume of distribution or binding potential of [(11)C]P943 could be computed using both MA1 and MRTM2. The results show that [(11)C]P943 provides quantitative measurements of 5-HT(1B) binding potential.
Asunto(s)
Piperazinas , Pirrolidinonas , Radiofármacos , Receptor de Serotonina 5-HT1B/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia por Spin del Electrón , Humanos , Procesamiento de Imagen Asistido por Computador , Marcaje Isotópico , Modelos Lineales , Imagen por Resonancia Magnética , Trastornos Mentales/diagnóstico por imagen , Trastornos Mentales/metabolismo , Modelos Estadísticos , Piperazinas/síntesis química , Tomografía de Emisión de Positrones , Pirrolidinonas/síntesis química , Radiofármacos/síntesis químicaRESUMEN
OBJECTIVES: The role of the norepinephrine transporter (NET) in cocaine dependence has never been demonstrated via in vivo imaging due to the lack of suitable NET radioligands. Here we report our preliminary studies evaluting the NET in individuals with cocaine dependence (COC) in comparison to healthy controls (HC) using (S,S)-[(11)C]methylreboxetine ([(11)C]MRB), the most promising C-11 labeled positron-emission tomography (PET) radioligand for NET developed to date. METHODS: Twenty two human volunteers (10 COC and 12 HC) underwent dynamic (11)C-MRB-PET acquisition using a High Resolution Research Tomograph (HRRT). Binding potential (BP(ND)) parametric images were computed using the simplified reference tissue model (SRTM2) with occipital cortex as reference region. BP(ND) values were compared between the two groups. RESULTS: Locus coeruleus (LC), hypothalamus, and pulvinar showed a significant inverse correlation with age among HC (age range = 25-54 years; P = 0.04, 0.009, 0.03 respectively). The BP(ND) was significantly increased in thalamus (27%; P < 0.02) and dorsomedial thalamic nuclei (30%; P < 0.03) in COC as compared to HC. Upon age normalization, the upregulation of NET in COC also reached significance in LC (63%, P < 0.01) and pulvinar (55%, P < 0.02) regions. CONCLUSION: Our results suggest that (a) brain NET concentration declines with age in HC, and (b) there is a significant upregulation of NET in thalamus and dorsomedial thalamic nucleus in COC as compared to HC. Our results also suggest that the use of [(11)C]MRB and HRRT provides an effective strategy for studying alterations of the NET system in humans.
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Encéfalo/diagnóstico por imagen , Trastornos Relacionados con Cocaína/metabolismo , Morfolinas , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/metabolismo , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Adulto , Envejecimiento/fisiología , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Cocaína/efectos adversos , Inhibidores de Captación de Dopamina/efectos adversos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , ReboxetinaRESUMEN
OBJETIVO: Revisar os artigos sobre substratos neurobiológicos dos transtornos do controle dos impulsos. O jogo patológico é o foco central desta revisão na medida em que a maioria dos estudos biológicos dos formalmente classificados como transtornos do controle dos impulsos examinou este transtorno. MÉTODO: Foi feita uma busca no banco de dados Medline de artigos publicados de 1966 até o presente para identificar aqueles relevantes para serem revisados neste artigo. DESFECHOS: Estudos pré-clínicos sugerem que a neuromodulação das monoaminas cerebrais está associada à tomada de decisões impulsivas e aos comportamentos de risco. Os estudos clínicos implicam diversos sistemas de neurotransmissores (serotoninérgico, dopaminérgico, adrenérgico e opióide) na fisiopatologia do jogo patológico e de outros transtornos do controle dos impulsos. Estudos de neuroimagem preliminares têm indicado o córtex pré-frontal ventromedial e o estriato ventral como atuantes na fisiopatologia do jogo patológico e de outros transtornos do controle dos impulsos. As contribuições genéticas para o jogo patológico parecem substanciais e os estudos iniciais têm relacionado esse transtorno a polimorfismos alélicos específicos, ainda que os achados de varredura genômica ainda tenham que ser publicados. CONCLUSÃO: Mesmo que tenham sido logrados avanços significativos em nossa compreensão sobre os transtornos do controle dos impulsos, mais pesquisas são necessárias para ampliar o conhecimento existente e traduzir esses achados em avanços clínicos.
OBJECTIVE: To review the neurobiological substrates of impulse control disorders. Pathological gambling is a main focus of the review in that most biological studies of the formal impulse control disorders have examined this disorder. METHOD: The medical database Medline from 1966 to present was searched to identify relevant articles that were subsequently reviewed to generate this manuscript. RESULTS: Preclinical studies suggest that differential brain monoamine neuromodulation is associated with impulsive decision-making and risk-taking behaviors. Clinical studies implicate multiple neurotransmitter systems (serotonergic, dopaminergic, adrenergic, and opioidergic) in the pathophysiology of pathological gambling and other impulse control disorders. Initial neuroimaging studies have implicated the ventromedial prefrontal cortex and ventral striatum in the pathophysiology of pathological gambling and other impulse control disorders. Genetic contributions to pathological gambling seem substantial and initial studies have implicated specific allelic polymorphisms, although genome-wide analyses have yet to be published. CONCLUSION: Although significant advances have been made in our understanding of the neurobiology of impulse control disorders, more research is needed to extend existing knowledge and translate these findings into clinical advances.
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Humanos , Trastornos Disruptivos, del Control de Impulso y de la Conducta/fisiopatología , Corteza Cerebral/fisiopatología , Dopamina/fisiología , Juego de Azar , Predisposición Genética a la Enfermedad/genética , Trastornos Disruptivos, del Control de Impulso y de la Conducta/genética , Monoaminooxidasa/fisiología , Neurotransmisores/fisiología , Norepinefrina/fisiología , Serotonina/fisiologíaRESUMEN
OBJECTIVE: To review the neurobiological substrates of impulse control disorders. Pathological gambling is a main focus of the review in that most biological studies of the formal impulse control disorders have examined this disorder. METHOD: The medical database Medline from 1966 to present was searched to identify relevant articles that were subsequently reviewed to generate this manuscript. RESULTS: Preclinical studies suggest that differential brain monoamine neuromodulation is associated with impulsive decision-making and risk-taking behaviors. Clinical studies implicate multiple neurotransmitter systems (serotonergic, dopaminergic, adrenergic, and opioidergic) in the pathophysiology of pathological gambling and other impulse control disorders. Initial neuroimaging studies have implicated the ventromedial prefrontal cortex and ventral striatum in the pathophysiology of pathological gambling and other impulse control disorders. Genetic contributions to pathological gambling seem substantial and initial studies have implicated specific allelic polymorphisms, although genome-wide analyses have yet to be published. CONCLUSION: Although significant advances have been made in our understanding of the neurobiology of impulse control disorders, more research is needed to extend existing knowledge and translate these findings into clinical advances.
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Trastornos Disruptivos, del Control de Impulso y de la Conducta/fisiopatología , Corteza Cerebral/fisiopatología , Trastornos Disruptivos, del Control de Impulso y de la Conducta/genética , Dopamina/fisiología , Juego de Azar , Predisposición Genética a la Enfermedad/genética , Humanos , Monoaminooxidasa/fisiología , Neurotransmisores/fisiología , Norepinefrina/fisiología , Serotonina/fisiologíaRESUMEN
Depression is a major psychiatric disorder. It affects millions of people worldwide and inflicts tremendous economic burden on societies. The advent of selective serotonin re-uptake inhibitors as antidepressants has been a revolutionary advance in the treatment of depression and related disorders. However, selective serotonin re-uptake inhibitors are also associated with several undesirable properties, such as delayed onset of action, low response rate and side effects. The present search for a newer generation of antidepressants is focused on overcoming these issues. The patent literature covered in this review, during 2004 - 2006, illustrates several strategies employed by the pharmaceutical industry in the development of enhanced serotonin re-uptake inhibitors. Encouraged by the success of venlafaxine and duloxetine, several companies have pursued dual-acting serotonin and noradrenaline re-uptake inhibitors as drug candidates for depression treatment. Molecules with combined serotonin re-uptake inhibitor and 5-HT autoreceptor (5-HT(1A) and/or 5-HT(1B)) antagonist properties are being developed. In particular, recent research suggests that serotonin 5-HT(1B) antagonists alone or combined with selective serotonin re-uptake inhibitors might hold unique promise as efficacious antidepressants. Finally, efforts are underway to formulate new drug candidates with both serotonin re-uptake inhibitor and neurokinin 1 (NK(1)) antagonist activities. Despite mixed results from clinical trials with several NK(1) antagonists, effective therapeutic agents for depression may still emerge from compounds with combined serotonin reuptake inhibitor/NK(1) antagonist properties.
RESUMEN
In an earlier study, we reported that some perpetrators of domestic violence evidenced exaggerated fear-related responses to the panicogenic agent sodium lactate. In the current study, we employed positron emission tomography (PET) to investigate our hypothesis that there are differences in the neural structures and/or pathways that mediate and control the expression of fear-induced aggression in perpetrators of domestic violence. Regional cerebral glucose metabolism was measured in eight male perpetrators of domestic violence who fulfilled DSM-III-R criteria for alcohol dependence (DV-ALC), 11 male participants who fulfilled DSM-III-R criteria for alcohol dependence and had no history of interpersonal aggression (ALC) and 10 healthy male participants who did not fulfill criteria for any DSM-III-R axis I diagnosis and had no history of interpersonal aggression (HCS). DV-ALC had a significantly lower mean glucose uptake in the right hypothalamus compared to ALC and HCS. Correlations were performed between measures of glucose utilization in the brain structures involved in fear-induced aggression. The comparison of DV-ALC to HCS and to ALC differed in six and seven comparisons, respectively, involving various cortical and subcortical structures. HCS and ALC differed between the left thalamus and the left posterior orbitofrontal cortex. These PET findings show that some perpetrators of domestic violence differ from control participants in showing lower metabolism in the right hypothalamus and decreased correlations between cortical and subcortical brain structures. A possible psychological covariate of these changes in regional activity might be fear-induced aggression, but this hypothesis should be examined in larger study groups that undergo provocation during imaging.
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Violencia Doméstica/psicología , Lateralidad Funcional/fisiología , Hipotálamo/metabolismo , Tomografía Computarizada de Emisión , Adulto , Agresión/psicología , Alcoholismo/diagnóstico , Amígdala del Cerebelo/metabolismo , Ganglios Basales/metabolismo , Corteza Cerebral/metabolismo , Depresión/diagnóstico , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Miedo , Fluorodesoxiglucosa F18 , Humanos , Masculino , Radiofármacos , Encuestas y CuestionariosRESUMEN
We measured the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF), regional cerebral glucose uptake (rCMRglc) as assessed with positron emission tomography in the medial prefrontal cortex (PFC) and severity of clinical depression (Beck's Depression Inventory, BDI) in detoxified male alcoholics and age-matched healthy men. In alcoholics, the severity of clinical depression was negatively correlated with rCMRglc in the medial PFC and positively with CSF 5-HIAA concentrations. A voxel-based analysis showed that the strongest correlation between CSF 5-HIAA levels and rCMRglc was found in alcoholics in the left orbitofrontal and medial PFC (BA10 and BA11); no significant correlations were observed among healthy control subjects. This pilot study indicates that a dysfunction of medial PFC may interact with central serotonin turnover and negative mood states during early abstinence.