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The role of dopamine in the pathophysiology of gambling disorder (GD) remains incompletely understood, with disparate research findings concerning presynaptic and postsynaptic structures and dopaminergic synthesis. The aim of this study was to investigate potential correlations between striatal dopamine transporter (DAT) lateralization and asymmetry index, as assessed by 123I-FP-CIT SPECT, and temperamental traits, as measured by Cloninger's Temperament and Character Inventory (TCI), in GD subjects. Significant associations were found between DAT binding asymmetries in the caudate and putamen and the temperamental dimensions of harm avoidance and novelty seeking. Specifically, high novelty seeking scores correlated with increased DAT binding in the left caudate relative to the right, whereas higher harm avoidance scores corresponded to increased DAT binding in the right putamen relative to the left. These observations potentially imply that the asymmetry in DAT expression in the basal ganglia could be an outcome of hemispheric asymmetry in emotional processing and behavioural guidance. In summary, our study provides evidence supporting the relationship between DAT asymmetries, temperamental dimensions and GD. Future investigations could be directed towards examining postsynaptic receptors to gain a more comprehensive understanding of dopamine's influence within the basal ganglia circuit in disordered gambling. If confirmed in larger cohorts, these findings could have substantial implications for the tailoring of individualized neuromodulation therapies in the treatment of behavioural addictions.
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INTRODUCTION: Dopaminergic transmission impairment has been identified as one of the main neurobiological correlates of both depression and clinical symptoms commonly associated with its spectrum such as anhedonia and psychomotor retardation. OBJECTIVES: We examined the relationship between dopaminergic deficit in the striatum, as measured by 123I-FP-CIT SPECT imaging, and specific psychopathological dimensions in patients with major depressive disorder. METHODS: To our knowledge this is the first study with a sample of >120 subjects. After check for inclusion and exclusion criteria, 121 (67 females, 54 males) patients were chosen retrospectively from an extensive 1106 patients database of 123I-FP-CIT SPECT scans obtained at the Nuclear Medicine Unit of Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome. These individuals had undergone striatal dopamine transporter (DAT) assessments based on the recommendation of their referring clinicians, who were either neurologists or psychiatrists. At the time of SPECT imaging, each participant underwent psychiatric and psychometric evaluations. We used the following psychometric scales: Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Snaith Hamilton Pleasure Scale, and Depression Retardation Rating Scale. RESULTS: We found a negative correlation between levels of depression (p = 0.007), anxiety (p = 0.035), anhedonia (p = 0.028) and psychomotor retardation (p = 0.014) and DAT availability in the left putamen. We further stratified the sample and found that DAT availability in the left putamen was lower in seriously depressed patients (p = 0.027) and in patients with significant psychomotor retardation (p = 0.048). CONCLUSION: To our knowledge this is the first study to have such a high number of sample. Our study reveals a pivotal role of dopaminergic dysfunction in patients with major depressive disorder. Elevated levels of depression, anxiety, anhedonia, and psychomotor retardation appear to be associated with reduced DAT availability specifically in the left putamen.
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Transtorno Depressivo Maior , Proteínas da Membrana Plasmática de Transporte de Dopamina , Putamen , Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/metabolismo , Feminino , Masculino , Putamen/diagnóstico por imagem , Putamen/metabolismo , Adulto , Pessoa de Meia-Idade , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Tropanos , Estudos Retrospectivos , Anedonia/fisiologia , Dopamina/metabolismo , Idoso , Escalas de Graduação PsiquiátricaRESUMO
BACKGROUND: Severe traumatic brain injury (TBI) is one of the most dramatic events in pediatric age and, despite advanced neuro-intensive care, the survival rate of these patients remains low. Children suffering from severe TBI show long-term sequelae, more pronounced in behavioral, neurological and neuropsychological functions leading to, in the most severe cases, an unresponsive wakefulness syndrome (UWS). Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. In experimental animal models, human- recombinant Nerve Growth Factor (hr-NGF) promotes neural recovery supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated processes. Only a few studies reported the efficacy of intranasal hr-NGF administration in children with post- traumatic UWS. METHODS: Children with the diagnosis of post-traumatic UWS were enrolled. These patients underwent a treatment with intranasal hr-NGF administration, at a total dose of 50 gamma/kg, three times a day for 7 consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. Neuroradiogical evaluation by Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG), and Power Spectral Density (PSD) was determined before the treatment and one month after the end. Neurological assessment was also deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale. RESULTS: Three children with post-traumatic UWS were treated. hr-NGF administration improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary movements, facial mimicry, attention and verbal comprehension, ability to cry, cough reflex, oral motility, and feeding capacity, with a significant improvement of their neurological scores. No side effects were reported. CONCLUSION: These promising results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from severe TBI and in patients with better baseline neurological conditions, to explore more thoroughly the benefits of this new approach on neuronal function recovery after traumatic brain damage.
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Fator de Crescimento Neural , Vigília , Animais , Humanos , Criança , Fator de Crescimento Neural/uso terapêutico , Fator de Crescimento Neural/metabolismo , Vigília/fisiologia , Encéfalo , Eletroencefalografia , Administração IntranasalRESUMO
BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is one of the most dramatic events in pediatric age and, despite advanced neurointensive care, the survival rate remains low. Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. Nerve Growth Factor (NGF) is a neurotrophin potentially able to counteract many of the deleterious effects triggered by OHCA. Transcranial Direct Current Stimulation (tDCS) has been reported to be neuroprotective in many neurological diseases, such as motor deficit and cognitive impairment. Children with the diagnosis of chronic vegetative state after OHCA were enrolled. These patients underwent a combined treatment of intranasal administration of human recombinant NGF (hr-NGF), at a total dose of 50 gamma/kg, and tDCS, in which current intensity was increased from zero to 2 mA from the first 5 s of stimulation and maintained constant for 20 min. The treatment schedule was performed twice, at one month distance each. Neuroradiogical evaluation with Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG) and Power Spectral Density of the brain (PSD) was determined before the treatment and one month after the end. Neurological assessment was deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale. RESULTS: Three children with a chronic vegetative state secondary to OHCA were treated. The combined treatment with hr-NGF and tDCS improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary finger movements, improved facial mimicry and reaction to painful stimuli. No side effects were reported. CONCLUSIONS: These promising preliminary results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from OHCA and in patients with better baseline neurological conditions, in order to explore more thoroughly the benefits of this new approach on neuronal function recovery after OHCA.
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Parada Cardíaca Extra-Hospitalar , Estimulação Transcraniana por Corrente Contínua , Humanos , Criança , Parada Cardíaca Extra-Hospitalar/terapia , Estado Vegetativo Persistente , Estimulação Transcraniana por Corrente Contínua/métodos , Fator de Crescimento Neural/uso terapêutico , EncéfaloRESUMO
BACKGROUND: There is increasing evidence that chronic endotheliopathy can play a role in patients with Post-Covid Condition (PCC, or Long Covid) by affecting peripheral vascularization. This pilot study aimed at assessing lung perfusion in children with Long-COVID with 99m Tc-MAA SPECT/CT. MATERIALS AND METHODS: lung 99m Tc-MAA SPECT/CT was performed in children with Long-COVID and a pathological cardiopulmonary exercise testing (CPET). Intravenous injections were performed on patients in the supine position immediately before the planar scan according to the EANM guidelines for lung scintigraphy in children, followed by lung SPECT/CT acquisition. Reconstructed studies were visually analyzed. RESULTS: Clinical and biochemical data were collected during acute infection and follow-up in 14 children (6 females, mean age: 12.6 years) fulfilling Long-COVID diagnostic criteria and complaining of chronic fatigue and postexertional malaise after mild efforts, documented by CPET. Imaging results were compared with clinical scenarios during acute infection and follow-up. Six out of 14 (42.8%) children showed perfusion defects on 99m Tc-MAA SPECT/CT scan, without morphological alterations on coregistered CT. CONCLUSIONS: This pilot investigation confirmed previous data suggesting that a small subgroup of children can develop lung perfusion defects after severe acute respiratory syndrome coronavirus 2 infection. Larger cohort studies are needed to confirm these preliminary results, providing also a better understanding of which children may deserve this test and how to manage those with lung perfusion defects.
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COVID-19 , Síndrome de COVID-19 Pós-Aguda , Feminino , Humanos , Criança , Projetos Piloto , Pulmão/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , PerfusãoRESUMO
BACKGROUND: Hereditary spastic paraplegia (HSP) include various sporadic and hereditary neurodegenerative disorders, characterized by progressive spasticity and weakness of lower limbs, possibly associated to additional features. CASE PRESENTATION: We report a male HPS patient in his 40 s, showing mental retardation associated with language impairment, dysarthria, and increased urinary frequency. Three months after treatment with electric chronic high-frequency cervical spinal cord stimulation (HF-SCS), he showed an amelioration of motor symptoms (lower limbs spasticity and gait), dysarthria, cognitive functioning (language and constructive praxic abilities), and urinary symptoms (decreased urinary frequency). Single-photon emission computed tomography (SPECT) showed a postoperative increase of cerebral perfusion in right frontal cortex and temporal cortex bilaterally. CONCLUSION: In our patient, HF-SCS might have induced an activation of ascending neural pathways, resulting in changes in activity in various cortical areas (including sensory-motor cortical areas), which may give rise to a modulation of activity in spared descending motor pathways and in neural networks involved in cognitive functions, including language. Although further studies in patients with HPS are needed to clarify whether HF-SCS can be a suitable treatment option in HSP, our observation suggests that HF-SCS, a minimally invasive neurosurgical procedure, might induce beneficial effects of on various symptoms of such orphan disease.
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Deficiência Intelectual , Paraplegia Espástica Hereditária , Estimulação da Medula Espinal , Humanos , Masculino , Paraplegia Espástica Hereditária/complicações , Paraplegia Espástica Hereditária/terapia , Paraplegia Espástica Hereditária/diagnóstico , Deficiência Intelectual/complicações , Deficiência Intelectual/terapia , Disartria , Cognição , Espasticidade Muscular , MarchaRESUMO
We describe 3 children with new-onset neurocognitive problems after coronavirus disease 2019 (COVID-19), that showed, at the brain [18F]-fluorodeoxyglucose positron emission tomography/computed tomography, hypometabolism in the left orbito-frontal region. The voxel-wise analysis confirmed a cluster of hypometabolic voxels in this region with a peak at -18/46/-4mm (179 voxels, T-Score 8.1). These findings may explain neurocognitive symptoms that some children develop after COVID-19 and require further investigations.
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COVID-19 , Encéfalo , COVID-19/complicações , COVID-19/diagnóstico por imagem , Criança , Fluordesoxiglucose F18 , Lobo Frontal/diagnóstico por imagem , Humanos , Tomografia por Emissão de Pósitrons/métodos , Síndrome de COVID-19 Pós-AgudaRESUMO
INTRODUCTION: Ischemic stroke is an important cause of death and long-term morbidity in children. Viral respiratory infections are emerging as important risk factors for ischemic stroke in this age group of patients. Direct action of virus against cerebral vessels, autoimmune reactivity, and an increased production of cytokines have all been advocated as main factors in determining ischemic stroke. CASE REPORT: We report the case of an EBV-induced ischemic stroke in a caucasian 2 year-old female. The cerebrospinal fluid samples showed positivity of polymerase chain reaction for EBV infection, also confirmed by pharyngeal swab culture. Increased levels of interleukin 6 and interleukin 1b were also detected in the cerebrospinal fluid. Discussion: EBV infection has been identified as an important cause of neurological involvement in children. Findings of increased levels of interleukin 6 and interleukin 1b in the cerebrospinal fluid of the child with EBV induced-ischemic stroke seems to validate the role of pro-inflammatory cytokines as crucial mediators of cerebral thrombus formation. Conclusions: We believe that this report can be useful to clarify some pathophysiological mechanisms related to ischemic stroke related to Epstein-Barr Virus (EBV) infection in children.
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Infecções por Vírus Epstein-Barr , Acidente Vascular Cerebral , Viroses , Pré-Escolar , Infecções por Vírus Epstein-Barr/complicações , Feminino , Herpesvirus Humano 4/genética , Humanos , Reação em Cadeia da Polimerase , Acidente Vascular Cerebral/etiologiaRESUMO
Neurotrophins are a family of proteins that support neuronal proliferation, survival, and differentiation in the central and peripheral nervous systems, and are regulators of neuronal plasticity. Nerve growth factor is one of the best-described neurotrophins and has advanced to clinical trials for treatment of ocular and brain diseases due to its trophic and regenerative properties. Prior trials over the past few decades have produced conflicting results, which have principally been ascribed to adverse effects of systemic nerve growth factor administration, together with poor penetrance of the blood-brain barrier that impairs drug delivery. Contrastingly, recent studies have revealed that topical ocular and intranasal nerve growth factor administration are safe and effective, suggesting that topical nerve growth factor delivery is a potential alternative to both systemic and invasive intracerebral delivery. The therapeutic effects of local nerve growth factor delivery have been extensively investigated for different ophthalmic diseases, including neurotrophic keratitis, glaucoma, retinitis pigmentosa, and dry eye disease. Further, promising pharmacologic effects were reported in an optic glioma model, which indicated that topically administered nerve growth factor diffused far beyond where it was topically applied. These findings support the therapeutic potential of delivering topical nerve growth factor preparations intranasally for acquired and degenerative brain disorders. Preliminary clinical findings in both traumatic and non-traumatic acquired brain injuries are encouraging, especially in pediatric patients, and clinical trials are ongoing. The present review will focus on the therapeutic effects of both ocular and intranasal nerve growth factor delivery for diseases of the brain and eye.
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Substance Use Disorder (SUD) is a chronic and relapsing disease characterized by craving, loss of control, tolerance and physical dependence. At present, the combination of pharmacotherapy and psychosocial intervention is the most effective management strategy in preventing relapse to reduce dropout rates and promote abstinence in SUD patients. However, only few effective medications are available. Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation technique that modulates the cellular activity of the cerebral cortex through a magnetic pulse applied on selected brain areas. Recently, the efficacy of TMS has been investigated in various categories of SUD patients. The present review analyzes the application of repetitive TMS in patients with alcohol, tobacco, and cocaine use disorder. Although the number of clinical studies is still limited, repetitive TMS yields encouraging results in these patients, suggesting a possible role of TMS in the treatment of SUD.
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Transtornos Relacionados ao Uso de Cocaína , Transtornos Relacionados ao Uso de Substâncias , Transtornos Relacionados ao Uso de Cocaína/terapia , Fissura , Humanos , Nicotiana , Estimulação Magnética TranscranianaRESUMO
Electric Extradural Motor Cortex Stimulation (EMCS) is a neurosurgical procedure suggested for treatment of patients with advanced Parkinson's disease (PD). We report two PD patients treated by EMCS, who experienced worsening of motor symptoms and cognition 5 years after surgery, when EMCS batteries became discharged. One month after EMCS restoration, they experienced a subjective improvement of motor symptoms and cognition. Neuropsychological assessments were carried out before replacement of batteries (off-EMCS condition) and 6 months afterward (on-EMCS condition). As compared to off-EMCS condition, in on-EMCS condition both patients showed an improvement on tasks of verbal episodic memory and backward spatial short-term/working memory task, and a decline on tasks of selective visual attention and forward spatial short-term memory. These findings suggest that in PD patients EMCS may induce slight beneficial effects on motor symptoms and cognitive processes involved in verbal episodic memory and in active manipulation of information stored in working memory.
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Background: Major depressive disorder (MDD) has different clinical presentations and is associated with neurobiological alterations. Hopelessness, anhedonia, and dissociation represent some of the most pervasive psychopathological symptoms that often lead to suicidal thoughts, attempts, and actions. To further research on the concept of depression endophenotypes, this study aimed to assess the possible relationships between hopelessness and other clinical and biological correlates (i.e., striatal dopaminergic dysfunction) in depressed patients. Methods: We recruited 51 subjects with MDD. All subjects underwent 123I-FP-CIT SPECT to assess striatal dopamine transporter (DAT) availability and a psychometric evaluation using the psychometric scale to assess depressive, anxious, dissociative, and hopelessness symptoms aside from suicidal ideation. Result: An inverse correlation between the hopelessness score and dopamine transporter availability in all basal ganglia was bilaterally found. (Right Putamen, r = -0.445, p < 0.01; Left Putamen, r = -0.454, p < 0.01; Right Caudate, r = -0.398, p < 0.01; Left Caudate, r = -0.467, p < 0.01) Moreover, a positive correlation was also found between hopelessness and dissociative symptoms. Conclusions: These results provide important evidence on the neurobiological and clinical correlates of different psychopathological symptoms of depression with potential implications in terms of devising more effective treatment programs.
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AIM: People experiencing homelessness are often excluded from treatment programs for alcohol use disorder (AUD). The goal of this study was to describe the impact of a multidisciplinary treatment program on alcohol consumption and social reintegration in individuals with AUD experiencing homelessness. METHODS: Thirty-one individuals with AUD experiencing homelessness were admitted to an inpatient unit for 5-6 days for clinical evaluation and to treat potential alcohol withdrawal syndrome. A group of volunteers, in collaboration with the Community of Sant'Egidio, provided social support aimed to reintegrate patients. After inpatient discharge, all patients were followed as outpatients. Alcohol intake (number drinks/day), craving and clinical evaluation were assessed at each outpatient visit. Biological markers of alcohol use were evaluated at enrollment (T0), at 6 months (T1) and 12 months (T2). RESULTS: Compared with T0, patients at T1 showed a significant reduction in alcohol consumption [10 (3-24) vs 2 (0-10); P = 0.015] and in γ-glutamyl-transpeptidase [187 (78-365) vs 98 (74-254); P = 0.0021]. The reduction in alcohol intake was more pronounced in patients with any housing condition [10 (3-20) vs 1 (0-8); P = 0.008]. Similarly, compared with T0, patients at T2 showed significant reduction in alcohol consumption [10 (3-24) vs 0 (0-15); P = 0.001], more pronounced in patients with any housing condition [10 (3-20) vs 0 (0-2); P = 0.006]. Moreover, at T2 patients showed a significant reduction in γ-glutamyl-transpeptidase [187 (78-365) vs 97 (74-189); P = 0.002] and in mean cell volume [100.2 (95-103.6) vs 98.3 (95-102); P = 0.042]. CONCLUSION: Patients experiencing homelessness may benefit from a multidisciplinary treatment program for AUD. Strategies able to facilitate and support their social reintegration and housing can improve treatment outcomes.
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Alcoolismo/terapia , Pessoas Mal Alojadas/psicologia , Equipe de Assistência ao Paciente , Adulto , Consumo de Bebidas Alcoólicas/terapia , Alcoolismo/sangue , Fissura , Índices de Eritrócitos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistemas de Apoio Psicossocial , Apoio Social , Síndrome de Abstinência a Substâncias/reabilitação , gama-Glutamiltransferase/sangueRESUMO
Second-generation antipsychotics (SGA) are a pharmacological class widely used in psychiatry thanks to their efficacy and good tolerability profile. One of the most used SGA is aripiprazole (ARI) because of its several formulations and safe metabolic and cardiac profile. As reported in a recent review, there are growing numbers of reports about ARI-induced gambling disorder (ARI-induced GD) which should encourage clinicians to use ARI more cautiously. Given the common genetic susceptibility of both GD and ARI's clinical response to a genetic polymorphism on the D2 receptor (DRD2/ANKK1 Taq1A; rs1800497), the hypothesis regarding the origin of this phenomenon could be found in the altered sensitization of dopamine's receptors that certain individuals carry genetically. The identification of a possible genetic susceptibility (detectable by genetic tests) could provide clinicians with an explanation for the ARI-induced GD and the possibility of using genetic screening tools for those cases of suspected predisposition; this would allow the clinician to prescribe ARI with less apprehension. The confirmation of this hypothesis through future pharmacogenetic studies may be useful for clinicians to have a correct understanding of the phenomenon.
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INTRODUCTION: Anhedonia is a transdiagnostic psychopathological dimension, consisting in the impaired ability to experience pleasure. In order to further our understanding of its neural correlates and to explore its potential relevance as a predictor of treatment response, in this article we systematically reviewed studies involving anhedonia and neuromodulation interventions, across different disorders. METHODS: We included seven studies fulfilling inclusion/exclusion criteria and involving different measures of anticipatory and consummatory anhedonia, as well as different noninvasive brain stimulation interventions (transcranial magnetic stimulation and transcranial direct current stimulation). Studies not exploring hedonic measures or not involving neuromodulation intervention were excluded. RESULTS: All the included studies entailed the use of rTMS protocols in one of the diverse prefrontal targets. The limited amount of studies and the heterogeneity of stimulation protocols did not allow to draw any conclusion with regard to the efficacy of rTMS in the treatment of transnosographic anhedonia. A potential for anhedonia in dissecting possible endophenotypes of different psychopathological conditions preliminarily emerged. CONCLUSIONS: Anhedonia is an underexplored condition in neuromodulation trials. It may represent a valuable transdiagnostic dimension that requires further examination in order to discover new clinical predictors for treatment response.
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Anedonia/fisiologia , Encéfalo/fisiologia , Transtornos Mentais/terapia , Recompensa , Estimulação Transcraniana por Corrente Contínua/tendências , Estimulação Magnética Transcraniana/tendências , Animais , Ensaios Clínicos como Assunto/métodos , Endofenótipos , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Estimulação Transcraniana por Corrente Contínua/métodos , Estimulação Magnética Transcraniana/métodosRESUMO
Repetitive Transcranial Magnetic Stimulation (rTMS) shows the potential to modulate local brain activity, thus resulting in a modulatory action on neurocircuitries implicated in the pathophysiology of Gambling Disorder (GD). We report the case of a GD patient treated with two weeks of high frequency (15â¯Hz) rTMS over the dorsolateral prefrontal cortex (DLPFC). At baseline and after rTMS treatment the patient underwent a SPECT examination with (123)I-FP-CIT tracer, to test changes in dopamine transporter (DAT) availability. The patient was followed up for six months, to explore safety and clinical correlates of a weekly high frequency rTMS maintenance treatment. Over the six-month follow-up the patient reported no episodes of gambling relapse. Also, the patient did not report craving for gambling or gambling-related symptoms. After two weeks of left DLPFC-rTMS treatment, we found a decrease in DAT availability in striatal regions, that represents a putative neurobiological substrate of dopaminergic pathways modulation. This study suggests that high frequency DLPFC-rTMS deserves further investigations in larger samples, using controlled study designs, to assess its real potential as a treatment for GD.
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Núcleo Caudado/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Jogo de Azar/terapia , Córtex Pré-Frontal , Putamen/diagnóstico por imagem , Estimulação Magnética Transcraniana/métodos , Adulto , Núcleo Caudado/metabolismo , Fissura , Jogo de Azar/diagnóstico por imagem , Jogo de Azar/metabolismo , Humanos , Masculino , Neostriado/diagnóstico por imagem , Neostriado/metabolismo , Putamen/metabolismo , Recidiva , Tomografia Computadorizada de Emissão de Fóton Único , TropanosRESUMO
Alcohol use disorders (AUDs) are one of the leading causes of mortality and morbidity worldwide. In spite of significant advances in understanding the neural underpinnings of AUDs, therapeutic options remain limited. Recent studies have highlighted the potential of repetitive transcranial magnetic stimulation (rTMS) as an innovative, safe, and cost-effective treatment for AUDs. Here, we summarize the fundamental principles of rTMS and its putative mechanisms of action via neurocircuitries related to alcohol addiction. We will also discuss advantages and limitations of rTMS, and argue that Hebbian plasticity and connectivity changes, as well as state-dependency, play a role in shaping some of the long-term effects of rTMS. Visual imaging studies will be linked to recent clinical pilot studies describing the effect of rTMS on alcohol craving and intake, pinpointing new advances, and highlighting conceptual gaps to be filled by future controlled studies.
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Alcoolismo/terapia , Estimulação Magnética Transcraniana , Alcoolismo/fisiopatologia , Dopamina/fisiologia , Humanos , Plasticidade NeuronalRESUMO
Although the involvement of dopamine in gambling disorder (GD) has long been hypothesized, its precise role remains unclear. The action of dopamine in the synapses is regulated by the dopamine transporter (DAT). We hereinafter present significant differences between a sample of 15 treatment-seeking GD subjects and 17 healthy controls in terms of striatal DAT availability, and we explore its association with reward-based decision making. We performed 123 I-FP-CIT Single-photon emission computed tomography (SPECT) and correlated DAT binding ratios in the bilateral caudate and putamen with gambling symptoms (G-SAS, PG-YBOCS) and behaviors, as well as other psychometric variables (anhedonia and impulsivity). Gambling disorder (GD) subjects were also administered a computerized version of the Iowa gambling task (IGT) to assess reward-based decision making. We found reduced DAT availability in GD subjects compared with healthy controls (-13.30% in right caudate, -11.11% in right putamen, -11.44% in left caudate, and -11.46% in the left putamen). We also found that striatal DAT availability was inversely correlated with days spent gambling and IGT performance in GD subjects. These results provide evidence for a presynaptic dopaminergic dysfunction in striatal regions of GD subjects. Functional DAT down-regulation possibly sustains the transition towards compulsive gambling addiction, characterized both by hyperdopaminergic and hypodopaminergic states in the context of a sensitized dopaminergic system.
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Corpo Estriado/química , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Jogo de Azar/fisiopatologia , Adolescente , Adulto , Idoso , Anedonia/fisiologia , Corpo Estriado/diagnóstico por imagem , Tomada de Decisões/fisiologia , Dopamina/metabolismo , Feminino , Humanos , Comportamento Impulsivo/fisiologia , Masculino , Pessoa de Meia-Idade , Psicometria , Compostos Radiofarmacêuticos , Recompensa , Transdução de Sinais/fisiologia , Sinapses/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos , Adulto JovemRESUMO
A 47-year-old man, with a history of anabolic steroid abuse, developed hepatic adenomatosis and multifocal hepatocellular carcinoma. He underwent ultrasound and CT follow-up, showing multiple solid and fluid hepatic lesions. Consequently, hospitalization was required because of high fever (up to 39°C), weakness, and anorexia. An abdominal CT scan revealed an enlargement of one of the intrahepatic fluid collections. Biochemical and microbiological analyses of a fluid sample showed bilirubin and bile acids as well as Streptococcus cristatus and Enterobacter cloacae. Thus, the patient underwent Tc-trimethylbromo-iminodiacetic acid scintigraphy, demonstrating bile collection in the lesion with a flow from a bile duct.