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1.
Psychiatry Res ; 211(3): 251-6, 2013 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-23158972

RESUMO

Impulsivity characterises various psychiatric disorders, particularly attention-deficit/hyperactivity disorder (ADHD). Evidence shows that ADHD symptoms are associated with dopamine dysfunction and alleviated with methylphenidate, a drug that reduces dopamine transporter availability. ADHD-like symptoms and impulsive traits are continuously distributed across the general population. Here, we aimed to investigate the dopaminergic basis of impulsivity and other ADHD-related traits in healthy individuals by studying the association of these traits with striatal dopamine transporter availability. Single-photon emission computed tomography with [(123)I] FP-CIT was performed on 38 healthy males. Impulsivity was measured using the Barratt Impulsiveness Scale (BIS) and hyperactivity-impulsivity and inattention using the Adult ADHD Self-Report Scale (ASRS). We found that greater dopamine transporter availability was associated with higher BIS impulsivity but not with ADHD-related traits. The association with BIS was significant after accounting for individual differences in age and neuroticism. These results suggest that individual differences in the dopamine system may be a neural correlate of trait impulsivity in healthy individuals.


Assuntos
Corpo Estriado/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Comportamento Impulsivo/diagnóstico , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Corpo Estriado/diagnóstico por imagem , Humanos , Comportamento Impulsivo/diagnóstico por imagem , Masculino , Escalas de Graduação Psiquiátrica , Psicometria , Análise de Regressão , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos , Adulto Jovem
2.
Psychiatry Res ; 212(2): 125-31, 2013 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-23137806

RESUMO

Numerous studies indicate that the serotonergic (5-HT) transmitter system is involved in the regulation of impulsive aggression and there is from post-mortem, in vivo imaging and genetic studies evidence that the 5-HT2A receptor may be involved. We investigated 94 healthy individuals (60 men, mean age 47.0±18.7, range 23-86) to determine if trait aggression and trait impulsivity were related to frontal cortex 5-HT2A receptor binding (5-HT2AR) as measured with [18F]-altanserin PET imaging. Trait aggression and trait impulsivity were assessed with the Buss-Perry Aggression Questionnaire (AQ) and the Barratt Impulsiveness Scale 11 (BIS-11). Statistical analyses were conducted using a multiple linear regression model and internal consistency reliability of the AQ and BIS-11 was evaluated by Cronbach's alpha. Contrary to our hypothesis, results revealed no significant associations between 5-HT2AR and the AQ or BIS-11 total scores. Also, there was no significant interaction between gender and frontal cortex 5-HT2AR in predicting trait aggression and trait impulsivity. This is the first study to examine how 5-HT2AR relates to trait aggression and trait impulsivity in a large sample of healthy individuals. Our findings are not supportive of a selective role for 5-HT2AR in mediating the 5-HT related effects on aggression and impulsivity in psychiatrically healthy individuals.


Assuntos
Agressão/fisiologia , Lobo Frontal/metabolismo , Comportamento Impulsivo/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Lobo Frontal/diagnóstico por imagem , Hormônios/metabolismo , Humanos , Comportamento Impulsivo/diagnóstico por imagem , Ketanserina/análogos & derivados , Ketanserina/farmacocinética , Masculino , Pessoa de Meia-Idade , Personalidade , Inventário de Personalidade , Tomografia por Emissão de Pósitrons , Antagonistas da Serotonina/farmacocinética , Estatísticas não Paramétricas , Adulto Jovem
3.
Biol Psychiatry ; 72(12): 1004-11, 2012 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-22835812

RESUMO

BACKGROUND: Impulsive aggression (IA) in adults is associated with brain serotonin (5-HT) system abnormalities and is more common following childhood adversity. Within aggressive behavior, IA and callous unemotional (CU) traits are core components of differentiable factors with opposing 5-HT abnormalities. We aimed to investigate 5-HT abnormalities in IA and potential correlations with severity of childhood adversity while controlling for confounding 5-HT effects of high CU traits and mental disorders. METHODS: Healthy male subjects (mean age 34 ± 9 years) without high CU traits were recruited with IA ratings in the high (n = 14) and low (n = 13) population extremes. Serotonin transporter (SERT) and 5-HT(2A) receptor availability was measured in multiple brain regions using positron emission tomography with (11)C-DASB and (11)C-MDL100907, respectively, and compared between high-IA and low-IA groups. Correlations were measured between SERT and 5-HT(2A) receptor availability, impulsivity and aggression, and childhood adversity. RESULTS: Compared with the low-IA group, SERT were significantly higher in brainstem regions in the high-IA group (by 29.0% ± 11.4%) and modestly lower across cortical regions (by 11.1% ± 6.0%), whereas 5-HT(2A) receptors were also modestly lower (by 8.6% ± 4.0%). Across all subjects, brainstem SERT were significantly positively correlated with impulsivity, aggression, and childhood trauma ratings. Within the high-IA group, higher brainstem SERT was most strongly predicted by severity of childhood trauma (r = .76 in midbrain). CONCLUSIONS: Pre-and postsynaptic 5-HT differences are present in men with high levels of IA and are strongly suggestive of a persisting effect of childhood adversity on serotonergic neurodevelopment and emotional-behavioral control.


Assuntos
Agressão/fisiologia , Agressão/psicologia , Compostos de Anilina , Fluorbenzenos , Comportamento Impulsivo/metabolismo , Comportamento Impulsivo/psicologia , Piperidinas , Compostos Radiofarmacêuticos , Serotonina/fisiologia , Sulfetos , Sinapses/diagnóstico por imagem , Sinapses/fisiologia , Adulto , Criança , Maus-Tratos Infantis/psicologia , Emoções/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Comportamento Impulsivo/diagnóstico por imagem , Testes de Inteligência , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Receptor 5-HT2A de Serotonina/metabolismo , Serotonina/metabolismo , Antagonistas da Serotonina , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Adulto Jovem
4.
Psychiatry Res ; 202(1): 60-4, 2012 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-22595510

RESUMO

Positron emission tomography (PET) studies have reported an association between reduced striatal dopamine D2/3 receptor availability and higher scores on self-report measures of trait impulsivity in healthy adults. However, impulsivity is a multi-faceted construct, and it is unclear which aspect(s) of impulsivity might be driving these associations. The current study aimed to investigate the relationship between limbic (ventral) striatal D2/3 receptor availability and individual components of impulsivity (attentional, motor and non-planning) using the Barratt Impulsiveness Scale (BIS-11) and [(11)C]raclopride PET in 23 healthy volunteers. A partial correlational analysis showed a significant association between non-planning impulsiveness (lack of forethought or 'futuring') and limbic D2/3 receptor availability, which was only apparent after the exclusion of potential dissimulators (indexed by high scores on impression management). Our findings suggest that non-planning impulsiveness is associated with individual variation in limbic striatal D2/3 receptor availability and that different facets of impulsivity may have specific neurochemical correlates. Future studies that combine D2/3 receptor imaging with behavioral measures of impulsivity are required to further elucidate the precise relationship between individual components of trait impulsivity and brain dopaminergic function.


Assuntos
Corpo Estriado/metabolismo , Comportamento Impulsivo/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Adulto , Corpo Estriado/diagnóstico por imagem , Dopamina/metabolismo , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Comportamento Impulsivo/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neostriado/diagnóstico por imagem , Neostriado/metabolismo , Testes Neuropsicológicos , Personalidade , Cintilografia
5.
Brain Stimul ; 5(2): 116-23, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22494829

RESUMO

Decision making is a cognitive function relaying on a complex neural network. In particular, the right dorsolateral prefrontal cortex (DLPFC) plays a key role within this network. We used positron emission tomography (PET) combined with continuous theta burst transcranial magnetic stimulation (cTBS) to investigate neuronal and behavioral changes in normal volunteers while performing a delay discounting (DD) task. We aimed to test whether stimulation of right DLPFC would modify the activation pattern of the neural circuit underlying decision making during the DD task and influence discounting behavior. We found that cTBS of the right DLPFC influenced decision making by reducing impulsivity and inducing participants to favor large but delayed rewards instead of immediate but small rewards. Stimulation also affected activation in several prefrontal areas associated with DD. In particular, we observed a reduced regional cerebral blood flow (rCBF) in the ipsilateral DLPFC (BA 46) extending into the rostral part of the prefrontal cortex (BA 10) as well as a disrupted relationship between impulsivity (k-value) and rCBF in these and other prefrontal areas. These findings suggest that transcranial magnetic stimulation of the DLPFC influences the neural network underlying impulsive decision making behavior.


Assuntos
Tomada de Decisões/fisiologia , Córtex Pré-Frontal/irrigação sanguínea , Córtex Pré-Frontal/fisiologia , Estimulação Magnética Transcraniana/psicologia , Adulto , Feminino , Humanos , Comportamento Impulsivo/diagnóstico por imagem , Comportamento Impulsivo/fisiopatologia , Masculino , Radioisótopos de Oxigênio , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/psicologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Desempenho Psicomotor/fisiologia , Estimulação Magnética Transcraniana/métodos
7.
Psychiatry Res ; 193(2): 80-4, 2011 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-21689908

RESUMO

The construct of impulsivity is considered as a major trait of personality. There is growing evidence that the mesolimbic dopamine system plays an important role in the modulation of impulsivity and venturesomeness, the two key components within the impulsivity-construct. The aim of the present study was to explore an association between trait impulsivity measured with self-assessment and the dopaminergic neurotransmission as measured by positron emission tomography (PET) in a cohort of healthy male subjects. In vivo D2/D3 receptor availability was determined with [(18)F]fallypride PET in 18 non-smoking healthy subjects. The character trait impulsivity was measured using the Impulsiveness-Venturesomeness-Empathy questionnaire (I7). Image processing and statistical analysis was performed on a voxel-by-voxel basis using statistical parametric mapping (SPM) software. The I7 subscale venturesomeness correlated positively with the D2/D3 receptor availability within the left temporal cortex and the thalamus. Measures on the I7 subscale impulsiveness and empathy did not correlate with the D2/D3 receptor availability in any brain region investigated. Our results suggest the involvement of extrastriatal dopaminergic neurotransmission in venturesomeness, a component of impulsivity.


Assuntos
Comportamento Impulsivo/diagnóstico por imagem , Comportamento Impulsivo/metabolismo , Receptores de Dopamina D2/metabolismo , Assunção de Riscos , Adulto , Benzamidas , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Estudos de Coortes , Humanos , Masculino , Testes Neuropsicológicos , Determinação da Personalidade , Tomografia por Emissão de Pósitrons/métodos , Pirrolidinas , Autoavaliação (Psicologia) , Estatística como Assunto , Inquéritos e Questionários , Adulto Jovem
8.
Brain ; 134(Pt 4): 969-78, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21349901

RESUMO

Impulsive-compulsive behaviours are a significant source of morbidity for patients with Parkinson's disease receiving dopaminergic therapy. The development of these behaviours may reflect sensitization of the neural response to non-drug rewards, similar to that proposed for sensitization to drug rewards in addiction. Here, by using (11)C-raclopride positron emission tomography imaging, we investigated the effects of reward-related cues and L-dopa challenge in patients with Parkinson's disease with and without impulsive-compulsive behaviours on striatal levels of synaptic dopamine. Eighteen patients (11 with and seven without impulsive-compulsive behaviours) underwent three (11)C-raclopride positron emission tomography scans. The impulsive-compulsive behaviours included hypersexuality, binge eating, punding, compulsive use of dopamine replacement therapy, compulsive buying and pathological gambling, with eight patients exhibiting more than one impulsive-compulsive behaviour. There were no significant differences in baseline dopamine D2 receptor availability between the Parkinson's disease groups. No differences were found when comparing the percentage change of raclopride binding potential between the two Parkinson's disease groups following L-dopa challenge with neutral cues. The group with Parkinson's disease with impulsive-compulsive behaviours had a greater reduction of ventral striatum (11)C-raclopride binding potential following reward-related cue exposure, relative to neutral cue exposure, following L-dopa challenge (16.3% compared with 5.8% in Parkinson's disease controls, P = 0.016). The heightened response of striatal reward circuitry to heterogeneous reward-related visual cues among a group of patients with different impulsive-compulsive behaviours is consistent with a global sensitization to appetitive behaviours with dopaminergic therapy in vulnerable individuals. Our findings are relevant for the broader debate on the relation between impulsive-compulsive behaviours and addictions and may have important implications with regards to advertisement legislation in an effort to prevent the onset of behavioural addictions.


Assuntos
Comportamento Compulsivo/metabolismo , Corpo Estriado/metabolismo , Dopamina/metabolismo , Comportamento Impulsivo/metabolismo , Doença de Parkinson/metabolismo , Idoso , Mapeamento Encefálico , Comportamento Compulsivo/complicações , Comportamento Compulsivo/diagnóstico por imagem , Corpo Estriado/diagnóstico por imagem , Sinais (Psicologia) , Feminino , Humanos , Comportamento Impulsivo/complicações , Comportamento Impulsivo/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Cintilografia
9.
Psychiatry Res ; 184(3): 151-6, 2010 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-20971619

RESUMO

Repetitive questioning is among the most common and burdensome of the behavioral and psychological symptoms of Alzheimer's disease (AD). Regardless of the clinical significance of the repetitive questioning, the neural substrates involved remain unclear. Fifty-eight consecutive patients with AD participated in this study. The score of repetitive questioning behavior was evaluated by multiplying the severity by the frequency of the behavior. They underwent brain SPECT with (99m)Tc-ethylcysteinate dimer. Scores of repetitive questioning behavior had a significant positive correlation with regional cerebral blood flow (rCBF) in the bilateral pericallosal regions. After removing the effect of memory test scores, we found a significant positive correlation of scores of repetitive questioning behavior to rCBF in the left pericallosal region. The pericallosal region includes the upper precuneus, cingulate, and posterior cingulate cortices on 3DSRT. Repetitive questioning behavior among AD patients might be a manifestation of mental state associated with a relative increase or preservation of rCBF in the left pericallosal region.


Assuntos
Doença de Alzheimer/complicações , Mapeamento Encefálico , Córtex Cerebral/irrigação sanguínea , Comportamento Impulsivo/etiologia , Comportamento Impulsivo/fisiopatologia , Fluxo Sanguíneo Regional/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Córtex Cerebral/diagnóstico por imagem , Feminino , Lateralidade Funcional , Humanos , Imageamento Tridimensional , Comportamento Impulsivo/diagnóstico por imagem , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estatísticas não Paramétricas , Tecnécio Tc 99m Exametazima , Tomografia Computadorizada de Emissão de Fóton Único/métodos
10.
Biol Psychiatry ; 67(12): 1154-62, 2010 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-20434136

RESUMO

BACKGROUND: Impulsive physical aggression is a common and problematic feature of many personality disorders. The serotonergic system is known to be involved in the pathophysiology of aggression, and multiple lines of evidence have implicated the serotonin 2A receptor (5-HT(2A)R). We sought to examine the role of the 5-HT(2A)R in impulsive aggression specifically in the orbitofrontal cortex (OFC), given that our own studies and an extensive literature indicate that serotonergic disturbances in the OFC are linked to aggression. We have previously hypothesized that increased 5-HT(2A)R function in the OFC is a state phenomenon that promotes impulsive aggression. METHODS: Serotonin 2A receptor availability was measured with positron emission tomography and the selective 5-HT(2A)R antagonist radioligand [(11)C]MDL100907 in two groups of impulsively aggressive personality disordered patients-14 with current physical aggression, and 15 without current physical aggression-and 25 healthy control subjects. Clinical ratings of various symptom dimensions were also obtained. RESULTS: Orbitofrontal 5-HT(2A)R availability was greater in patients with current physical aggression compared with patients without current physical aggression and healthy control subjects; no differences in OFC 5-HT(2A)R availability were observed between patients without current physical aggression and healthy control subjects. No significant differences in 5-HT(2A)R availability were observed in other brain regions examined. Among both groups of impulsively aggressive personality disordered patients combined, OFC 5-HT(2A)R availability was correlated, specifically, with a state measure of impulsive aggression. CONCLUSIONS: These findings are consistent with our previously described model in which impulsive aggression is related to dynamic changes in 5-HT(2A)R function in the OFC.


Assuntos
Agressão/psicologia , Lobo Frontal/metabolismo , Comportamento Impulsivo/metabolismo , Transtornos da Personalidade/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Adulto , Radioisótopos de Carbono/análise , Feminino , Fluorbenzenos/análise , Humanos , Comportamento Impulsivo/complicações , Comportamento Impulsivo/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Transtornos da Personalidade/complicações , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/diagnóstico por imagem , Piperidinas/análise , Tomografia por Emissão de Pósitrons/métodos , Ensaio Radioligante/métodos , Antagonistas da Serotonina/análise
11.
Psychiatry Res ; 181(1): 77-84, 2010 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-19959344

RESUMO

The vulnerability to mood disorders, impulsive-aggression, eating disorders, and suicidal behavior varies greatly with gender, and may reflect gender differences in central serotonergic function. We investigated the relationships of gender, mood, impulsivity, aggression and temperament to 5HT(2A) receptor binding in 21 healthy subjects using [18F]altanserin and PET neuroimaging. Binding potentials in pre-defined regions-of-interest (ROI) were calculated using the Logan graphical method, corrected for partial volume effects, and compared by gender with age co-varied. SPM analysis was used for voxel level comparisons. Altanserin binding (BP(P)) was greater in male than female subjects in the following nine ROIs: hippocampus (HIP) and Lt. HIP, lateral orbital frontal cortex (LOF) and Lt. LOF, left medial frontal cortex (Lt. MFC), left medial temporal cortex (Lt. MTC), left occipital cortex (Lt. OCC), thalamus (THL) and Lt. THL. Differences in Lt. HIP and Lt. MTL remained significant after Bonferroni correction. Gender differences were noted in the co-variation of psychological traits with BP(P) values in specific ROIs. Among males alone, aggression was negatively correlated with BP(P) values in Lt. LOF and Lt. MFC, and Suspiciousness positively correlated in LOF, Lt. LOF and Lt. MFC. Among female subjects alone, Negativism was positively correlated with BP(P) values in HIP, and Verbal Hostility in Lt. HIP. Altanserin binding in Lt. MTC was positively correlated with Persistence, with no significant gender effect. Gender differences in 5HT(2A) receptor function in specific ROIs may mediate expression of psychological characteristics such as aggression, suspiciousness and negativism. Future studies of 5HT(2A) receptor function and its relationship to behavior should control for gender.


Assuntos
Encéfalo/metabolismo , Personalidade/fisiologia , Receptor 5-HT2A de Serotonina/metabolismo , Caracteres Sexuais , Adolescente , Adulto , Agressão/fisiologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Feminino , Nível de Saúde , Humanos , Comportamento Impulsivo/diagnóstico por imagem , Comportamento Impulsivo/metabolismo , Ketanserina/análogos & derivados , Ketanserina/metabolismo , Masculino , Pessoa de Meia-Idade , Testes de Personalidade , Tomografia por Emissão de Pósitrons , Temperamento/fisiologia , Adulto Jovem
12.
Ann Neurol ; 66(6): 817-24, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20035509

RESUMO

OBJECTIVE: In Parkinson disease (PD) patients, deep brain stimulation (DBS) of the subthalamic nucleus (STN) may contribute to certain impulsive behavior during high-conflict decisions. A neurocomputational model of the basal ganglia has recently been proposed that suggests this behavioral aspect may be related to the role played by the STN in relaying a "hold your horses" signal intended to allow more time to settle on the best option. The aim of the present study was 2-fold: 1) to extend these observations by providing evidence that the STN may influence and prevent the execution of any response even during low-conflict decisions; and 2) to identify the neural correlates of this effect. METHODS: We measured regional cerebral blood flow during a Go/NoGo and a control (Go) task to study the motor improvement and response inhibition deficits associated with STN-DBS in patients with PD. RESULTS: Although it improved Unified Parkinson Disease Rating Scale motor ratings and induced a global decrease in reaction time during task performance, STN-DBS impaired response inhibition, as revealed by an increase in commission errors in NoGo trials. These behavioral effects were accompanied by changes in synaptic activity consisting of a reduced activation in the cortical networks responsible for reactive and proactive response inhibition. INTERPRETATION: The present results suggest that although it improves motor functions in PD patients, modulation of STN hyperactivity with DBS may tend at the same time to favor the appearance of impulsive behavior by acting on the gating mechanism involved in response initiation.


Assuntos
Comportamento de Escolha/fisiologia , Estimulação Encefálica Profunda/métodos , Comportamento Impulsivo/terapia , Núcleo Subtalâmico/fisiologia , Idoso , Mapeamento Encefálico , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Comportamento Impulsivo/diagnóstico por imagem , Comportamento Impulsivo/etiologia , Inibição Psicológica , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/terapia , Tomografia por Emissão de Pósitrons/métodos , Tempo de Reação/fisiologia , Índice de Gravidade de Doença , Estatística como Assunto
13.
Biol Psychiatry ; 66(12): 1107-14, 2009 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-19748078

RESUMO

BACKGROUND: Borderline personality disorder (BPD) is often associated with symptoms of impulsive aggression, which poses a threat to patients themselves and to others. Preclinical studies show that orbital frontal cortex (OFC) plays a role in regulating impulsive aggression. Prior work has found OFC dysfunction in BPD. METHODS: We employed a task to provoke aggressive behavior, the Point Subtraction Aggression Paradigm (PSAP), which has never previously been used during functional brain imaging. Thirty-eight BPD patients with intermittent explosive disorder (BPD-IED) and 36 age-matched healthy control subjects (HCs) received (18)fluoro-deoxyglucose positron emission tomography ((18)FDG-PET) on two occasions with a provocation and nonprovocation version of the PSAP. Mean relative glucose metabolism was measured throughout the cortex, and difference scores (provoked - nonprovoked) were calculated. A whole brain exploratory analysis for the double difference of BPD-IED - HC for provoked - nonprovoked was also conducted. RESULTS: BPD-IED patients were significantly more aggressive than HCs on the PSAP. BPD-IED patients also increased relative glucose metabolic rate (rGMR) in OFC and amygdala when provoked, while HCs decreased rGMR in these areas. However, HCs increased rGMR in anterior, medial, and dorsolateral prefrontal regions during provocation more than BPD-IED patients. CONCLUSIONS: Patients responded aggressively and showed heightened rGMR in emotional brain areas, including amygdala and OFC, in response to provocation but not in more dorsal brain regions associated with cognitive control of aggression. In contrast, HCs increased rGMR in dorsal regions of PFC during aggression provocation, brain regions involved in top-down cognitive control of aggression, and, more broadly, of emotion.


Assuntos
Agressão , Transtorno da Personalidade Borderline/complicações , Transtorno da Personalidade Borderline/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adulto , Agressão/psicologia , Análise de Variância , Transtorno da Personalidade Borderline/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Mapeamento Encefálico , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Fluordesoxiglucose F18 , Humanos , Comportamento Impulsivo/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Mov Disord ; 24(12): 1803-10, 2009 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-19562769

RESUMO

We aimed to assess whether allelic variants of dopamine receptor, glutamate receptor, and serotonin transporter genes are associated with the appearance of impulse control and related behaviors (ICRB) in Parkinson's disease (PD) with dopamine replacement therapy (DRT). We surveyed ICRB in consecutive Korean patients with PD who were treated with stable DRT using modified Minnesota Impulsive Disorders Interview over a period of 4 months. In the 404 patients who completed the interview and the 559 Korean healthy normal controls, genotyping was performed for variants of the DRD3 p.S9G, DRD2 Taq1A, GRIN2B c.366C>G, c.2664C>T and c.-200T>G, and the promoter region of the serotonin transporter gene (5-HTTLPR). Behavioral abnormalities suggestive of ICRB including compulsive buying, gambling, sexual behavior and eating, and punding, were present in 14.4% of the patients. Variants of DRD2 and 5-HTTLPR were not associated with the risk of developing ICRB. However, the AA genotype of DRD3 p.S9G and the CC genotype of GRIN2B c.366C>G were more frequent in patients with ICRB than in nonaffected patients (odds ratio [OR] = 2.21, P = 0.0094; and 2.14, P = 0.0087, after adjusting for age and sex). After controlling for clinical variables in the multivariate analysis, carriage of either AA genotype of DRD3 or CC genotype of GRIN2B was identified as an independent risk factor for ICRB (adjusted OR: 2.57, P = 0.0087). Variants of DRD3 p.S9G and GRIN2B c.366C>G may be associated with the appearance of ICRB in PD.


Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Predisposição Genética para Doença , Comportamento Impulsivo/etiologia , Doença de Parkinson/complicações , Doença de Parkinson/genética , Receptores de Dopamina D3/genética , Receptores de N-Metil-D-Aspartato/genética , Idoso , Mapeamento Encefálico , Isótopos de Carbono , Transtornos Disruptivos, de Controle do Impulso e da Conduta/diagnóstico por imagem , Transtornos Disruptivos, de Controle do Impulso e da Conduta/genética , Saúde da Família , Feminino , Fluordesoxiglucose F18 , Dosagem de Genes , Frequência do Gene , Genótipo , Humanos , Comportamento Impulsivo/diagnóstico por imagem , Comportamento Impulsivo/genética , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética
15.
Neuroimage ; 46(1): 23-30, 2009 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-19457377

RESUMO

Manipulations of the serotonin levels in the brain can affect impulsive behavior and influence our reactivity to conditioned reinforcers. Eating, tobacco smoking, and alcohol consumption are reinforcers that are influenced by serotonergic neurotransmission; serotonergic hypofunction leads to increased food and alcohol intake, and conversely, stimulation of the serotonergic system induces weight reduction and decreased food/alcohol intake as well as tobacco smoking. To investigate whether body weight, alcohol intake and tobacco smoking were related to the regulation of the cerebral serotonin 2A receptor (5-HT(2A)) in humans, we tested in 136 healthy human subjects if body mass index (BMI), degree of alcohol consumption and tobacco smoking was associated to the cerebral in vivo 5-HT(2A) receptor binding as measured with (18)F-altanserin PET. The subjects' BMI's ranged from 18.4 to 42.8 (25.2+/-4.3) kg/m(2). Cerebral cortex 5-HT(2A) binding was significantly positively correlated to BMI, whereas no association between cortical 5-HT(2A) receptor binding and alcohol or tobacco use was detected. We suggest that our observation is driven by a lower central 5-HT level in overweight people, leading both to increased food intake and to a compensatory upregulation of cerebral 5-HT(2A) receptor density.


Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Índice de Massa Corporal , Encéfalo/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Fumar/metabolismo , Adulto , Consumo de Bebidas Alcoólicas/genética , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Comportamento Impulsivo/diagnóstico por imagem , Comportamento Impulsivo/genética , Comportamento Impulsivo/metabolismo , Masculino , Obesidade/diagnóstico por imagem , Obesidade/genética , Obesidade/metabolismo , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Tomografia por Emissão de Pósitrons , Regiões Promotoras Genéticas/genética , Ligação Proteica/fisiologia , Receptor 5-HT2A de Serotonina/genética , Fumar/genética
16.
J Neuropsychiatry Clin Neurosci ; 19(3): 304-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17827416

RESUMO

The authors explored differences in regional cerebral blood flow in 11 impulsive murderers and 11 healthy comparison subjects using single photon emission computed tomography. The authors assessed subjects at rest and during a computerized go/no-go concentration task. Using statistical parametric mapping software, the authors performed voxel-by-voxel t tests to assess significant differences, making family-wide error corrections for multiple comparisons. Murderers were found to have significantly lower relative rCBF during concentration, particularly in areas associated with concentration and impulse control. These results indicate that nonemotionally laden stimuli may result in frontotemporal dysregulation in people predisposed to impulsive violence.


Assuntos
Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Homicídio , Comportamento Impulsivo/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Adolescente , Adulto , Idoso , Encéfalo/fisiopatologia , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Comportamento Impulsivo/metabolismo , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional/fisiologia , Estudos Retrospectivos
17.
Biol Psychiatry ; 62(6): 580-7, 2007 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-17448449

RESUMO

BACKGROUND: Postmortem studies in suicide victims demonstrate an increase in the number of post-synaptic 5-HT(2A) receptor binding sites in ventral lateral and orbital frontal cortex. Diminished metabolic responses to serotonergic activation are noted in these areas in impulsive subjects with borderline personality disorder (BPD), a group at high risk for suicidal behaviors. We examined 5HT(2A) receptor binding potential (BP) in impulsive subjects with BPD, with positron emission tomography neuroimaging with [(18)F] altanserin. METHODS: Fourteen female subjects with BPD were assessed for Axis I comorbidity, depressed mood, impulsivity, aggression, suicidality, childhood abuse, and compared with 11 healthy female control subjects. The 5HT(2A) receptor binding was evaluated in prefrontal cortex, anterior cingulate, hippocampus, temporal lobe, occipital cortex, and thalamus. Data were analyzed with Logan graphical analysis and a four-compartment (4C) model. RESULTS: Hippocampal 5HT(2A) receptor binding was significantly increased in BPD subjects compared with control subjects in both Logan and 4C analyses, covarying for age. Hippocampal BP values were related to comorbid major depressive episode, with highest values found in non-depressed BPD subjects and lowest in healthy control subjects. The BP values were not related to depressed mood, impulsivity, aggression, suicidality, or childhood abuse. CONCLUSIONS: 5HT(2A) receptor binding is increased in the hippocampus of BPD subjects independent of depressed mood, impulsivity, aggression, suicidality, or childhood abuse. Dysregulation of serotonergic function in hippocampus might contribute to affective and behavioral symptoms in BPD.


Assuntos
Transtorno da Personalidade Borderline/metabolismo , Encéfalo/metabolismo , Hipocampo/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Adulto , Agressão/psicologia , Transtorno da Personalidade Borderline/diagnóstico por imagem , Transtorno da Personalidade Borderline/genética , Encéfalo/diagnóstico por imagem , Criança , Maus-Tratos Infantis/psicologia , Maus-Tratos Infantis/estatística & dados numéricos , Depressão/diagnóstico por imagem , Depressão/metabolismo , Feminino , Fluordesoxiglucose F18 , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/metabolismo , Hipocampo/diagnóstico por imagem , Humanos , Comportamento Impulsivo/diagnóstico por imagem , Comportamento Impulsivo/metabolismo , Ketanserina/análogos & derivados , Tomografia por Emissão de Pósitrons , Fatores de Risco , Suicídio/estatística & dados numéricos
18.
Neuroimage ; 36(1): 153-66, 2007 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-17433881

RESUMO

A challenging question that continues to plague the field of addiction is why some individuals are more vulnerable for substance use disorders than others. Several important risk factors for substance abuse have been identified in clinical studies, including trait impulsivity and environmental stress. However, the neurobiological mechanisms that underlie the relationships remain poorly understood. The purpose of this study was to examine associations among impulsivity, stress, and striatal dopamine (DA) responses to amphetamine (AMPH) in humans. Forty healthy M, F adults, ages 18-29 years, completed self-report measures of trait impulsivity, life events stress, and perceived stress. Subjects subsequently underwent two consecutive 90-min positron emission tomography (PET) studies with high specific activity [11C]raclopride. The first scan was preceded by an intravenous injection of saline; the second was preceded by 0.3 mg/kg AMPH. Findings showed that high impulsivity was associated with blunted right ventral striatal DA release. However, effects were modified by a significant interaction with life events stress. Dopamine release was greater in low vs. high impulsivity subjects under conditions of low or moderate stress. Under conditions of high stress, both groups had low DA release. Subjects with high impulsivity reported more pleasant effects with AMPH than subjects with low impulsivity. In contrast, stress was negatively associated with pleasant drug effects. No associations were observed between impulsivity or stress and cortisol responses to AMPH. The findings are consistent with notions that blunted DA responses represent an endophenotype for substance use disorders.


Assuntos
Anfetamina/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Corpo Estriado/efeitos dos fármacos , Dopamina/metabolismo , Processamento de Imagem Assistida por Computador , Comportamento Impulsivo/diagnóstico por imagem , Acontecimentos que Mudam a Vida , Tomografia por Emissão de Pósitrons , Adulto , Radioisótopos de Carbono , Doença Crônica , Corpo Estriado/diagnóstico por imagem , Dominância Cerebral/fisiologia , Feminino , Humanos , Hidrocortisona/sangue , Individualidade , Masculino , Racloprida
19.
Neuropsychopharmacology ; 32(7): 1629-40, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17203018

RESUMO

Abnormal fronto-amygdala circuitry has been implicated in impulsive aggression, a core symptom of borderline personality disorder (BPD). We examined relative glucose metabolic rate (rGMR) at rest and after m-CPP (meta-chloropiperazine) with (18)fluorodeoxyglucose (FDG) with positron emission tomography (PET) in 26 impulsive aggressive (IED)-BPD patients and 24 controls. Brain edges/amygdala were visually traced on MRI scans co-registered to PET scans; rGMR was obtained for ventral and dorsal regions of the amygdala and Brodmann areas within the prefrontal cortex (PFC). Correlation coefficients were calculated between rGMR for dorsal/ventral amygdala regions and PFC. Additionally, amygdala volumes and rGMR were examined in BPD and controls. Correlations PFC/amygdala Placebo: Controls showed significant positive correlations between right orbitofrontal (OFC) and ventral, but not dorsal, amygdala. Patients showed only weak correlations between amygdala and the anterior PFC, with no distinction between dorsal and ventral amygdala. Correlations PFC/amygdala: m-CPP response: Controls showed positive correlations between OFC and amygdala regions, whereas patients showed positive correlations between dorsolateral PFC and amygdala. Group differences between interregional correlational matrices were highly significant. Amygdala volume/metabolism: No group differences were found for amygdala volume, or metabolism in the placebo condition or in response to meta-chloropiperazine (m-CPP). We demonstrated a tight coupling of metabolic activity between right OFC and ventral amygdala in healthy subjects with dorsoventral differences in amygdala circuitry, not present in IED-BPD. We demonstrated no significant differences in amygdala volumes or metabolism between BPD patients and controls.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtorno da Personalidade Borderline/fisiopatologia , Vias Neurais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Adulto , Agressão/fisiologia , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/patologia , Atrofia/diagnóstico por imagem , Atrofia/patologia , Atrofia/fisiopatologia , Transtorno da Personalidade Borderline/diagnóstico por imagem , Transtorno da Personalidade Borderline/metabolismo , Emoções/fisiologia , Metabolismo Energético/fisiologia , Feminino , Fluordesoxiglucose F18 , Glucose/metabolismo , Humanos , Comportamento Impulsivo/diagnóstico por imagem , Comportamento Impulsivo/metabolismo , Comportamento Impulsivo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/metabolismo , Piperazinas , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/metabolismo , Agonistas do Receptor de Serotonina
20.
Psychiatry Res ; 148(2-3): 195-203, 2006 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17085020

RESUMO

To study different aspects of regional pre-synaptic brain (123)I-beta-CIT uptake on serotonin and dopamine re-uptake sites in drug-free suicide attempters in comparison with age- and sex matched control subjects, single photon emission computed tomography (SPECT) measurements were analysed for regional serotonin re-uptake (5HTT) and dopamine re-uptake (DAT) capacity (binding potential, BP()) after i.v. (123)I-beta-CIT administration. All suicide attempters were examined concerning seriousness of the attempt, and DSM-IV diagnosis. Both suicide attempters and control subjects were tested for psychotropic drugs, and completed the Marke-Nyman Temperament (MNT) test, including solidity (level of impulsiveness/initiative) and validity (level of mental energy). We found no significant difference between suicide attempters and control subjects concerning the regional levels of 5HTT BP() or DAT BP(). However, in suicide attempters, but not controls, we found significant regional correlations between MNT variables and SPECT results. We interpret the discrepant findings in suicide attempters and control subjects to be due to a disability of the suicide attempters to regulate their serotonin and dopamine levels, e.g. in response to external stress.


Assuntos
Transtornos de Adaptação/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtorno Depressivo/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Comportamento Impulsivo/diagnóstico por imagem , Motivação , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Tentativa de Suicídio/psicologia , Tomografia Computadorizada de Emissão de Fóton Único , Transtornos de Adaptação/fisiopatologia , Adulto , Idoso , Cocaína/análogos & derivados , Cocaína/farmacocinética , Transtorno Depressivo/fisiopatologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Dopamina/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Pré-Sinápticos/metabolismo , Serotonina/metabolismo , Estresse Psicológico/complicações , Temperamento
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