Bilateral Amygdala Radio-Frequency Ablation for Refractory Aggressive Behavior Alters Local Cortical Thickness to a Pattern Found in Non-refractory Patients.

Aggressive behaviors comprise verbal and/or physical aggression directed toward oneself, others, or objects and are highly prevalent among psychiatric patients, especially patients diagnosed with autism spectrum disorder and severe intellectual disabilities. Some of these patients are considered refractory to treatment, and functional neurosurgery targeting the amygdala can result in widespread plastic brain changes that might reflect ceasing of some abnormal brain function, offering symptom alleviation. This study investigated cortical thickness changes in refractory aggressive behavior patients that were treated with bilateral amygdala ablation and compared to control patients presenting non-refractory aggressive behavior [three refractory and seven non-refractory patients, all males diagnosed with autism spectrum disorder (ASD) and intellectual disabilities]. The Overt Aggression Scale (OAS) was used to quantify behavior and magnetic resonance imaging was performed to investigate cortical thickness. Before surgery, both groups presented similar total OAS score, however refractory patients presented higher physical aggression against others. After surgery the refractory group showed 88% average reduction of aggressive behavior. Imaging analysis showed that while refractory patients present an overall reduction in cortical thickness compared to non-refractory patients across both timepoints, the local pattern of thickness difference found in areas of the neurocircuitry of aggressive behavior present before surgery is diminished and no longer detected after surgery. These results corroborate the hypotheses on induction of widespread neuronal plasticity following functional neurosurgical procedures resulting in modifications in brain morphology and improvement in behavior. Further studies are necessary to determine the underlying cause of these morphological changes and to better understand and improve treatment options.

Longitudinal Changes After Amygdala Surgery for Intractable Aggressive Behavior: Clinical, Imaging Genetics, and Deformation-Based Morphometry Study-A Case Series.

BACKGROUND: Intractable aggressive behavior (iAB) is a devastating behavioral disorder that may affect psychiatric patients. These patients have reduced quality of life, are more challenging to treat as they impose a high caregiver burden and require specialized care. Neuromodulatory interventions targeting the amygdala, a key hub in the circuitry of aggressive behavior (AB), may provide symptom alleviation. OBJECTIVE: To Report clinical and imaging findings from a case series of iAB patients treated with bilateral amygdala ablation. METHODS: This series included 4 cases (3 males, 19-32 years old) who underwent bilateral amygdala radiofrequency ablation for iAB hallmarked by life-threatening self-injury and social aggression. Pre- and postassessments involved full clinical, psychiatric, and neurosurgical evaluations, including scales quantifying AB, general agitation, quality of life, and magnetic resonance imaging (MRI). RESULTS: Postsurgery assessments revealed decreased aggression and agitation and improved quality of life. AB was correlated with testosterone levels and testosterone/cortisol ratio in males. No clinically significant side effects were observed. Imaging analyses showed preoperative amygdala volumes within normal populational range and confirmed lesion locations. The reductions in aggressive symptoms were accompanied by significant postsurgical volumetric reductions in brain areas classically associated with AB and increases in regions related to somatosensation. The local volumetric reductions are found in areas that in a normal brain show high expression levels of genes related to AB (eg, aminergic transmission) using gene expression data provided by the Allen brain atlas. CONCLUSION: These findings provide new insight into the whole brain neurocircuitry of aggression and suggest a role of altered somatosensation and possible novel neuromodulation targets.

Refractoriness of aggressive behaviour to pharmacological treatment: cortical thickness analysis in autism spectrum disorder.

Aggressive behaviour is a highly prevalent and devastating condition in autism spectrum disorder resulting in impoverished quality of life. Gold-standard therapies are ineffective in about 30% of patients leading to greater suffering. We investigated cortical thickness in individuals with autism spectrum disorder with pharmacological-treatment-refractory aggressive behaviour compared with those with non-refractory aggressive behaviour and observed a brain-wide pattern of local increased thickness in key areas related to emotional control and overall decreased cortical thickness in those with refractory aggressive behaviour, suggesting refractoriness could be related to specific morphological patterns. Elucidating the neurobiology of refractory aggressive behaviour is crucial to provide insights and potential avenues for new interventions.

Long-term outcome of children and adolescents with obsessive-compulsive disorder: a 7-9-year follow-up of a randomized clinical trial.

Pediatric obsessive-compulsive disorder (OCD) is an impairing disorder frequently associated with long-term persistence. Long-term follow-up studies that investigated psychopathological trajectories after initial treatment are scarce. The present study is a 7-9-year follow-up of a randomized clinical trial (RCT) that tested the efficacy of group cognitive-behavioral therapy (CBT) and sertraline for children with OCD (n = 40), and aimed to describe long-term outcomes of pediatric OCD and identify predictors of these outcomes. Thirty-five participants who were included in the original study were recruited for follow-up evaluations. Participants underwent a comprehensive assessment of demographic and clinical characteristics comprised of the Structured Clinical Interview for DSM Disorders (SCID) and/or Kiddie-Schedule of Affective Disorders and Schizophrenia Present-Lifetime (K-SADS-PL), and the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Thirty-three participants had a complete psychiatric assessment at follow-up (mean age 21 years, SD 3.2; 65% male). At follow-up, 13 (39.4%) participants had an OCD diagnosis, 10 (30.3%) had a diagnosis of any mental disorder (excluding OCD), and 10 (30.3%) did not have any diagnosis of mental disorder. In total, 23 participants (69.7%) had at least one mental disorder (including OCD). Among those without OCD (n = 20), 60.6% had a mental disorder. The following characteristics at follow-up were associated with OCD diagnosis: YBOCS total score (p < 0.001), global functioning (p = 0.008), and presence of any anxiety disorder (p = 0.027). Being treated with GCBT or sertraline during the original RCT did not predict OCD at follow-up. New treatment strategies should consider the role of psychopathological trajectories using a dynamic approach to combine or change interventions to enhance prognosis.

Amygdala and Hypothalamus: Historical Overview With Focus on Aggression.

Aggressiveness has a high prevalence in psychiatric patients and is a major health problem. Two brain areas involved in the neural network of aggressive behavior are the amygdala and the hypothalamus. While pharmacological treatments are effective in most patients, some do not properly respond to conventional therapies and are considered medically refractory. In this population, surgical procedures (ie, stereotactic lesions and deep brain stimulation) have been performed in an attempt to improve symptomatology and quality of life. Clinical results obtained after surgery are difficult to interpret, and the mechanisms responsible for postoperative reductions in aggressive behavior are unknown. We review the rationale and neurobiological characteristics that may help to explain why functional neurosurgery has been proposed to control aggressive behavior.

Oxytocin and Gynecomastia: Correlation or Causality?

Oxytocin has been administered to patients with autism spectrum disorder (ASD) in order to improve social skills, communication, and manage repetitive behaviors in the context of research trials. The majority of the studies focus on acute administration; thus, the effectiveness and potential side effects of chronic administration remain unknown. The main goal of this case report is to highlight the importance of the safety parameters for the chronic use of intranasal oxytocin administration. In a single case conducted in our outpatient clinic, one adolescent (15 years old) received intranasal oxytocin (24 IU) twice per day, in accordance with the recommended doses for this age group that varies from 8 - 25 IU twice per day. After three weeks of treatment, the patient presented with gynecomastia. While it is not certain that the gynecomastia was oxytocin-induced, this case highlights the importance of developing optimal regimens for chronic oxytocin administration, with a particular focus on safety parameters.

Reduced prefrontal activation in pediatric patients with obsessive-compulsive disorder during verbal episodic memory encoding.

OBJECTIVE: Patients with obsessive-compulsive disorder (OCD) often present with deficits in episodic memory, and there is evidence that these difficulties may be secondary to executive dysfunction, that is, impaired selection and/or application of memory-encoding strategies (mediation hypothesis). Semantic clustering is an effective strategy to enhance encoding of verbal episodic memory (VEM) when word lists are semantically related. Self-initiated mobilization of this strategy has been associated with increased activity in the prefrontal cortex, particularly the orbitofrontal cortex, a key region in the pathophysiology of OCD. We therefore studied children and adolescents with OCD during uncued semantic clustering strategy application in a VEM functional magnetic resonance imaging (fMRI)-encoding paradigm. METHOD: A total of 25 pediatric patients with OCD (aged 8.1-17.5 years) and 25 healthy controls (HC, aged 8.1-16.9) matched for age, gender, handedness, and IQ were evaluated using a block design VEM paradigm that manipulated semantically related and unrelated words. RESULTS: The semantic clustering strategy score (SCS) predicted VEM performance in HC (p < .001, R(2) = 0.635), but not in patients (p = .099). Children with OCD also presented hypoactivation in the dorsomedial prefrontal cortex (cluster-corrected p < .001). Within-group analysis revealed a negative correlation between Yale-Brown Obsessive Compulsive Scale scores and activation of orbitofrontal cortex in the group with OCD. Finally, a positive correlation between age and SCS was found in HC (p = .001, r = 0.635), but not in patients with OCD (p = .936, r = 0.017). CONCLUSION: Children with OCD presented altered brain activation during the VEM paradigm and absence of expected correlation between SCS and age, and between SCS and total words recalled. These results suggest that different neural mechanisms underlie self-initiated semantic clustering in OCD.

Comparison among clomipramine, fluoxetine, and placebo for the treatment of anxiety disorders in children and adolescents.

OBJECTIVE: The purpose of this study was to test the efficacy of clomipramine and fluoxetine, controlled by placebo, and compare their action in children and adolescents with anxiety disorders. METHOD: Thirty subjects (ages 7-17 years), who were diagnosed with generalized anxiety disorder and/or separation anxiety disorder and/or social phobia, were submitted to a 12 week double-blind, randomized, placebo-controlled trial of clomipramine and fluoxetine. The instruments included: the Schedule for Affective Disorders and Schizophrenia, the Multidimensional Anxiety Scale for Children, the Children's Depression Inventory, the Clinical Global Impressions, and the Children's Global Assessment Scale. RESULTS: All groups (clomipramine [n=9], fluoxetine [n=10], placebo [n=11]) showed a significant improvement after 12 weeks of treatment. There were significant differences between the fluoxetine and placebo groups in some ratings of anxiety severity and impairment. No significant differences were observed between clomipramine and placebo groups or between fluoxetine and clomipramine groups. CONCLUSIONS: Treatment with placebo showed an unusual high response rate. Clomipramine showed similar efficacy compared with fluoxetine, although it was not superior to placebo.

Ao sul do Equador: os relatórios médicos da Estação Naval Francesa no Brasil (1819-1870) / South of the Equator: medical reports of French Naval Station in Brazil (1819-1870)

Desde fins do século XVIII, as nações europeias perceberam a utilidade das estações navais. A organizaçãode expedições foi uma forma de desenvolver o comércio e de estreitar as relações políticas com regiõesextra-europeias. Em 1819, a França enviou as primeiras embarcações para o Brasil. Essas embarcações fizeramparte da Estação Naval do Brasil e do Prata que tinha a missão de realizar o mapeamento hidrográfico das costasbrasileiras. A partir de então, as embarcações da estação naval francesa, equipadas com um serviço médicoque tinha como obrigação principal a de zelar pela saúde da tripulação, não pararam de navegar pelas costasbrasileiras. O corpo de saúde elaborava também relatórios oficiais sobre os acontecimentos mais interessantese sobre os tratamentos contra doenças. Interessa-nos falar sobre esses relatos de viagens. Esses documentosmanuscritos são uma fonte autêntica indispensável para o conhecimento da patologia exótica e das condiçõesde saúde no Brasil. Os relatórios contêm informações que são muito mais do que simples registro de acontecimentos.Eles expõem as impressões dos médicos franceses sobre a paisagem local, impressões estas marcadaspelo determinismo racial e pelo pessimismo no que tange ao clima. (AU)

[Medical geography and the French expeditions to Brazil: a description of the naval station in Brazil and the Prata (1868-1870)]. / A geografia médica e as expedições francesas para o Brasil: uma descrição da estação naval do Brasil e da Prata (1868-1870). .

During the XIX century, medicine went through several etiological postulate changes. Medical geography, the discipline closely tied to the interests of the European colonialist enterprise, was in charge of mapping the diseases occurring all over the world. The physicians in European navies were in charge of this important mission. The greatest enemy of European troops and residents, in the colonies and in the hot climate regions were known to be the so-called tropical diseases. In this article, we analyze the official travel account by Bourel-Roncière, a French physician responsible for healthcare on the ship La Circé, from 1868 to 1870. Special attention is given to his personal point of view concerning the diseases and respective treatments, which he studied in collaboration with Brazilian physicians.

A geografia médica e as expedições francesas para o Brasil: uma descrição da estação naval do Brasil e da Prata (1868-1870) / Medical geography and the French expeditions to Brazil: a description of the naval station in Brazil and the Prata (1868-1870)

Durante o século XIX, a medicina passou por inúmeras mudanças em seus postulados etiológicos. A geografia médica, disciplina diretamente ligada aos interesses da empresa colonialista européia, coube o mapeamento das doenças em variadas partes do globo. Os médicos das marinhas européias foram encarregados dessa importante missão. Sabia-se que o maior inimigo das tropas e residentes europeus nas colônias e regiões de clima quente eram as doenças ditas tropicais. O artigo analisa o relatório oficial de viagem de Bourel-Roncière, médico francês responsável pela manutenção da saúde a bordo da embarcação La Circé, entre os anos 1868-1870. Ressalta o ponto de vista pessoal de Bourel-Roncière a respeito das doenças e seus tratamentos, que ele estudava em colaboração com médicos brasileiros.

During the XIX century, medicine went through several etiological postulate changes. Medical geography, the discipline closely tied to the interests of the European colonialist enterprise, was in charge of mapping the diseases occurring all over the world. The physicians in European navies were in charge of this important mission. The greatest enemy of European troops and residents, in the colonies and in the hot climate regions were known to be the so-called tropical diseases. In this article, we analyze the official travel account by Bourel-Roncière, a French physician responsible for healthcare on the ship La Circé, from 1868 to 1870. Special attention is given to his personal point of view concerning the diseases and respective treatments, which he studied in collaboration with Brazilian physicians.

A geografia médica e as expedições francesas para o Brasil: uma descrição da estação naval do Brasil e da Prata (1868-1870) / Medical geography and the French expeditions to Brazil: a description of the naval station in Brazil and the Prata (1868-1870)

Durante o século XIX, a medicina passou por inúmeras mudanças em seus postulados etiológicos. A geografia médica, disciplina diretamente ligada aos interesses da empresa colonialista européia, coube o mapeamento das doenças em variadas partes do globo. Os médicos das marinhas européias foram encarregados dessa importante missão. Sabia-se que o maior inimigo das tropas e residentes europeus nas colônias e regiões de clima quente eram as doenças ditas tropicais. O artigo analisa o relatório oficial de viagem de Bourel-Roncière, médico francês responsável pela manutenção da saúde a bordo da embarcação La Circé, entre os anos 1868-1870. Ressalta o ponto de vista pessoal de Bourel-Roncière a respeito das doenças e seus tratamentos, que ele estudava em colaboração com médicos brasileiros.(AU)

Medicina e sociedade no Brasil: a teoria microbiana em questão(1860-1890) / Medicine and society in Brasil: the microbian theory in question

Este trabalho tem o intuito de analisar a repercussão da teoria microbiana na comunidade médica brasileira oitocentista. Na segunda metade do século XIX, mais especificamente, ocorreu uma mudança nos postulados etiológicos: descobriu-se que muitas doenças eram causadas por micróbios

Medicina e sociedade no Brasil: a teoria microbiana em questäo (1860-1890) / Medicine and society in Brazil: the microbial theory (1860-1890)

Tem o intuito de analisar a repercussäo da teoria microbiana na comunidade médica brasileira oitocentista. Na segunda metade do século XIX, mais especificamente, ocorreu uma mudança nos postulados etiológicos: descobriu-se que muitas doenças eram causadas por micróbios. Com esta descoberta, ocorreram sensíveis transformaçöes no saber médico e na sociedade de modo geral. A arquitetura, as vestimentas, os hábitos alimentares e de higiene, tudo foi sendo lentamente modificado em funçäo da nova racionalidade. O interesse é justamente acompanhar esta trajetória no interior da comunidade médica brasileira, procurando apontar näo só os aspectos biológicos, mas inclusive os sociais e culturais da questäo.(AU)