Cortical surface abnormalities are different depending on the stage of schizophrenia: A cross-sectional vertexwise mega-analysis of thickness, area and gyrification.

BACKGROUND: Brain magnetic resonance imaging studies have not investigated the cortical surface comprehensively in schizophrenia subjects by assessing thickness, surface area and gyrification separately during the first-episode of psychosis (FEP) or chronic schizophrenia (ChSch). METHODS: We investigated cortical surface abnormalities in 137 FEP patients and 240 ChSch subjects compared to 297 Healthy Controls (HC) contributed by five cohorts. Maps showing results of vertexwise between-group comparisons of cortical thickness, area, and gyrification were produced using T1-weighted datasets processed using FreeSurfer 5.3, followed by validated quality control protocols. RESULTS: FEP subjects showed large clusters of increased area and gyrification relative to HC in prefrontal and insuli cortices (Cohen's d: 0.049 to 0.28). These between-group differences occurred partially beyond the effect of sample. ChSch subjects displayed reduced cortical thickness relative to HC in smaller fronto-temporal foci (d: -0.73 to -0.35), but not beyond the effect of sample. Differences between FEP and HC subjects were associated with male gender, younger age, and earlier illness onset, while differences between ChSch and HC were associated with treatment-resistance and first-generation antipsychotic (FGA) intake independently of sample effect. CONCLUSIONS: Separate assessments of FEP and ChSch revealed abnormalities that differed in regional distribution, phenotypes affected and effect size. In FEP, associations of greater cortical area and gyrification abnormalities with earlier age of onset suggest an origin on anomalous neurodevelopment, while thickness reductions in ChSch are at least partially explained by treatment-resistance and FGA intake. Associations of between-group differences with clinical variables retained statistical significance beyond the effect of sample.

Fully Automated Habenula Segmentation Provides Robust and Reliable Volume Estimation Across Large Magnetic Resonance Imaging Datasets, Suggesting Intriguing Developmental Trajectories in Psychiatric Disease.

Studies of habenula (Hb) function and structure provided evidence of its involvement in psychiatric disorders, including schizophrenia and bipolar disorder. Previous studies using magnetic resonance imaging (manual/semiautomated segmentation) have reported conflicting results. Aiming to improve Hb segmentation reliability and the study of large datasets, we describe a fully automated protocol that was validated against manual segmentations and applied to 3 datasets (childhood/adolescence and adult bipolar disorder and schizophrenia). It achieved reliable Hb segmentation, providing robust volume estimations across a large age range and varying image acquisition parameters. Applying it to clinically relevant datasets, we found smaller Hb volumes in the adult bipolar disorder dataset and larger volumes in the adult schizophrenia dataset compared with healthy control subjects. There are indications that Hb volume in both groups shows deviating developmental trajectories early in life. This technique sets a precedent for future studies, as it allows for fast and reliable Hb segmentation and will be publicly available.

An overlapping pattern of cerebral cortical thinning is associated with both positive symptoms and aggression in schizophrenia via the ENIGMA consortium.

BACKGROUND: Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample. METHOD: To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls. RESULTS: The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression. CONCLUSION: These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.

The role of neurocognitive functioning, substance use variables and the DSM-5 severity scale in cocaine relapse: A prospective study.

BACKGROUND: The severity of substance use disorder (SUD) is currently defined by the sum of DSM-5 criteria. However, little is known about the validity of this framework or the role of additional severity indicators in relapse prediction. This study aimed to investigate the relationship between DSM-5 criteria, neurocognitive functioning, substance use variables and cocaine relapse among inpatients with cocaine use disorder (CUD). METHODS: 128 adults aged between 18 and 45 years were evaluated; 68 (59 males, 9 females) had CUD and 60 (52 males, 8 females) were healthy controls. For the group with CUD, the use of other substances was not an exclusion criterion. Participants were tested using a battery of neurocognitive tests. Cocaine relapse was evaluated 3 months after discharge. RESULTS: Scores for attention span and working memory were worse in patients compared to controls. Earlier onset and duration of cocaine use were related to poorer inhibitory control and global executive functioning, respectively; recent use was related to worse performance in inhibitory control, attention span and working memory. More DSM-5 criteria at baseline were significantly associated with relapse. CONCLUSIONS: Recent cocaine use was the most predictive variable for neurocognitive impairments, while DSM-5 criteria predicted cocaine relapse at three months post treatment. The integration of neurocognitive measures, DSM-5 criteria and cocaine use variables in CUD diagnosis could improve severity differentiation. Longitudinal studies using additional biomarkers are needed to disentangle the different roles of severity indicators in relapse prediction and to achieve more individualized and effective treatment strategies for these patients.

Voxelwise evaluation of white matter volumes in first-episode psychosis.

The occurrence of white matter (WM) abnormalities in psychotic disorders has been suggested by several studies investigating brain pathology and diffusion tensor measures, but evidence assessing regional WM morphometry is still scarce and conflicting. In the present study, 122 individuals with first-episode psychosis (FEP) (62 fulfilling criteria for schizophrenia/schizophreniform disorder, 26 psychotic bipolar I disorder, and 20 psychotic major depressive disorder) underwent magnetic resonance imaging, as well as 94 epidemiologically recruited controls. Images were processed with the Statistical Parametric Mapping (SPM2) package, and voxel-based morphometry was used to compare groups (t-test) and subgroups (ANOVA). Initially, no regional WM abnormalities were observed when both groups (overall FEP group versus controls) and subgroups (i.e., schizophrenia/schizophreniform, psychotic bipolar I disorder, psychotic depression, and controls) were compared. However, when the voxelwise analyses were repeated excluding subjects with comorbid substance abuse or dependence, the resulting statistical maps revealed a focal volumetric reduction in right frontal WM, corresponding to the right middle frontal gyral WM/third subcomponent of the superior longitudinal fasciculus, in subjects with schizophrenia/schizophreniform disorder (n=40) relative to controls (n=89). Our results suggest that schizophrenia/schizophreniform disorder is associated with right frontal WM volume decrease at an early course of the illness.

Classificação automatizada de padrões morfológicos cerebrais complexos em indivíduos com primeiro episódio psicótico: avaliação de desempenho diagnóstico / Automated classification of complex morphological brain patterns in individuals with first-episode psychosis: assessment of diagnostic performance

INTRODUÇÃO: Os transtornos mentais psicóticos são condições frequentes na população em geral e estão associados à grande morbidade e elevadas taxas de comprometimento funcional, tornando-os um grave problema de saúde pública. O desenvolvimento de novos métodos de auxílio diagnóstico e prognóstico a pratica clínica psiquiátrica possibilitando que intervenções efetivas sejam feitas precocemente na história natural da doença são, dessa forma, desejáveis. A classificação de padrões neuroanatômicos é uma robusta técnica para processamento e análise de imagens médicas que permite tanto a realização de comparações voxel-a-voxel entre grupos com alta dimensionalidade de variáveis, como a classificação individualizada das imagens. OBJETIVOS: Avaliar o desempenho diagnóstico de um classificador de padrões morfológicos complexos baseado em support vector machine (SVM) na discriminação entre diferentes transtornos psicóticos no momento do primeiro episódio, utilizando-se uma abordagem epidemiológica para a seleção de casos e controles, bem como na determinação de prognóstico de 1 ano em pacientes com primeiro episódio de esquizofrenia. MÉTODOS: Uma amostra de 62 pacientes com primeiro episódio de esquizofrenia/ transtorno esquizofreniforme, 23 casos de primeiro episódio de mania psicótica (transtorno bipolar tipo I, TB-I), e 19 indivíduos com depressão maior (DM) psicótica foram estudados com ressonância magnética (RM) estrutural de 1.5T, assim como um total de 89 controles residentes na mesma região dos casos. As imagens T1 foram inicialmente registradas a uma imagem molde comum através de um método com preservação de massa, permitindo a obtenção de volumes cerebrais regionais. Um classificador neuroanatômico multivariado baseado em redução de dimensionalidade e SVM foi utilizado para identificar o melhor conjunto de características morfológicas que diferencia cada transtorno psicótico (esquizofrenia/ transtorno esquizofreniforme, TB-I e DM psicótica) de...

INTRODUCTION: Psychotic disorders are prevalent medical conditions in the general population, and are usually associated with high morbidity and functional impairment rates, which make them a major concern for public health. The development of new methods aiming to aid diagnostic and prognostic value in clinical psychiatric practice thus allowing effective interventions at an early course of the illness are, therefore, desirable. Neuroanatomical pattern classification is a powerful technique for image processing and analysis which allows both high-dimensional voxelwise group comparisons and classification of images at an individual basis. OBJECTIVES: To evaluate the diagnostic performance of a support vector machine (SVM)-based complex morphological pattern classifier was used to discriminate different non-affective and affective psychotic disorders at the first episode using a population-based approach to recruit both cases and healthy controls, and also to predict 1-year prognosis (i.e., remitting versus non-remitting course) in a group of patients with first-episode schizophrenia. METHODS: A sample of 62 patients with first-episode schizophrenia/ schizophreniform disorder, 23 cases presenting with their first-episode of psychotic mania (bipolar I disorder, BD-I) and 19 individuals with psychotic major depressive disorder (MDD) was studied with 1.5T structural magnetic resonance imaging (MRI), as well as a pool of 89 epidemiologically recruited controls. T1-weighted images were first registered to a common template through a robust mass-preserving routine allowing regional volumetric analysis. A high-dimensional multivariate classification method based on dimensionality reduction and SVM was employed to identify the best and most parsimonious set of morphological features that discriminate each psychotic group (schizophrenia/ schizophreniform disorder, BD-I & psychotic MDD) from subgroups of age, gender and educationally-matched healthy controls...

Coexistência das síndromes de Capgras e Frégoli associadas à redução de volume frontotemporal e hiperintensidades em substância branca cerebral

CONTEXTO: Transtornos delirantes de identificação são condições nas quais os pacientes identificam de maneira patologicamente equivocada pessoas, lugares, objetos ou eventos. Esses transtornos têm sido categorizados em quatro diferentes subtipos: Capgras, Frégoli, intermetamorfose e síndrome do duplo subjetivo. Tais síndromes podem estar presentes em diferentes transtornos psiquiátricos, como esquizofrenia e transtornos do humor, bem como em diferentes doenças neurológicas, como Alzheimer, Parkinson, lesões cerebrais traumáticas ou vasculares. OBJETIVOS: Descrever e discutir um caso de coexistência entre as síndromes de Capgras e Frégoli em uma paciente com esquizofrenia paranoide e com alterações cerebrais. MÉTODOS: Entrevista psiquiátrica e ressonância magnética de crânio. RESULTADOS: A paciente apresentava hiperintensidades periventriculares em aquisição flair e de substância branca subcortical concentradas principalmente na região frontotemporal direita, bem como perda do volume da região frontotemporal bilateral. DISCUSSÃO: As alterações descritas podem representar substrato orgânico das síndromes dos transtornos delirantes de identificação. Os delírios nas síndromes de Capgras e Frégoli podem ocorrer como resultado de uma desconexão têmporo-límbica-frontal direita, resultando em uma impossibilidade de associar memórias prévias a novas informações, levando consequentemente a alterações na capacidade de reconhecimento. Ademais, uma perda do volume de tais regiões cerebrais também pode desempenhar papel importante no desenvolvimento de tais síndromes delirantes de identificação.

BACKGROUND: Delusional misidentification syndromes are conditions in which the patients pathologically misidentify people, places, objects or events. They have been categorized in four subtypes: Capgras, Frégoli, intermetamorphosis and subjective double syndromes. Such syndromes may be present in patients with psychiatric disorders such as schizophrenia and mood disorders, and with neurological diseases such as Alzheimer, Parkinson and brain injury (trauma, vascular). OBJECTIVES: To describe and discuss a case of coexistent between Capgras and Frégoli syndromes in a female patient with paranoid schizophrenia and brain MRI findings. METHODS: Psychiatric interview and brain MRI scanning. RESULTS: The patient presented structural magnetic resonance imaging periventricular and subcortical white matter hyperintensities on flair images mainly concentrated in the right frontotemporal region and bilateral frontotemporal volume loss. DISCUSSION: The described neuroimaging findings may represent an organic substrate to the delusional misidentification syndromes of the present case. The delusional symptoms in Capgras and Frégoli syndromes could be the result of a right temporolimbic-frontal disconnection which results in impossibility to associate previous memories to new information and consequently misidentifying symptoms. Moreover a volume loss of such cerebral regions, as observed in the present case, may also play a significant role in the development of delusional misidentification syndromes.

Increased rates of white matter hyperintensities in late-onset bipolar disorder.

OBJECTIVES: Magnetic resonance imaging (MRI) studies have reported an increased frequency of white matter hyperintensities (WMH) in association with late-onset (LO) depression, and this has supported the notion that vascular-related mechanisms may be implicated in the pathophysiology of LO mood disorders. Recent clinical studies have also suggested a link between LO bipolar disorder (LO-BD) and cerebrovascular risk factors, but this has been little investigated with neuroimaging techniques. In order to ascertain whether there could be a specific association between WMH and LO-BD, we directly compared WMH rates between LO-BD subjects (illness onset >or= 60 years), early-onset BD subjects (EO-BD, illness onset <60 years), and elderly healthy volunteers. METHODS: T2-weighted MRI data were acquired in LO-BD subjects (n = 10, age = 73.60 +/- 4.09), EO-BD patients (n = 49, age = 67.78 +/- 4.44), and healthy subjects (n = 24, age = 69.00 +/- 7.22). WMH rates were assessed using the Scheltens scale. RESULTS: There was a greater prevalence of WMH in LO-BD patients relative to the two other groups in the deep parietal region (p = 0.018) and basal ganglia (p < 0.045). When between-group comparisons of mean WMH scores were conducted taking account of age differences (ANCOVA), there were more severe scores in LO-BD patients relative to the two other groups in deep frontal and parietal regions, as well as in the putamen (p < 0.05). CONCLUSIONS: Our results provide empirical support to the proposed link between vascular risk factors and LO-BD. If extended in future studies with larger samples, these findings may help to clarify the pathophysiological distinctions between bipolar disorder emerging at early and late stages of life.

Refractory psychotic symptoms in a patient with homozygous sickle cell disease: a 24-month follow-up.

The present report describes a case of a 33-year old male patient with homozygous sickle cell disease (SCD) with comorbid psychotic symptoms. The systematical evaluation revealed an intimate association between acute SCD complications, associated with hematological abnormalities, and psychotic symptoms worsening. Clozapine was effective in controlling psychotic symptoms refractory to previous antipsychotic trials.

Residência em psiquiatria no Brasil: análise crítica / Brazilian psychiatry medical residency programs: critical analysis

INTRODUÇÃO: A psiquiatria evoluiu muito nas últimas décadas e seu estudo tornou-se, conseqüentemente, mais complexo. Os avanços em neurociências, aliados aos estudos clássicos de psicopatologia, psicofarmacologia, psicoterapia e neurologia, influenciaram grandemente o diagnóstico e o tratamento psiquiátricos. Apesar disso, a residência em psiquiatria no Brasil não se adequou a essa nova realidade. OBJETIVOS E MÉTODO: Partindo das recomendações da World Psychiatry Association (WPA), pesquisamos na Internet programas de residências brasileiros e de países das Américas e Europa. Comparamos nosso programa com as recomendações e dados do Institutional Program on the Core Training Curriculum for Psychiatry da WPA e propusemos um currículo mínimo para a residência em psiquiatria. DISCUSSÃO: Na maioria dos programas pesquisados, alguns pontos se destacam: duração mínima de 3 anos; estágio integral em neurologia por no mínimo um mês; conteúdo programático contendo psicopatologia, psicofarmacologia, teorias psicoterápicas, emergências psiquiátricas entre outras disciplinas; ensino e prática das diversas linhas psicoterápicas; abrangência das várias etapas da vida (crianças, adultos e idosos); álcool e drogas; espaços livres de que o residente pode dispor para sua formação (terapia, estudo ou pesquisa). CONCLUSÃO: O modelo brasileiro de residência em psiquiatria encontra-se defasado em relação à formação proposta pela WPA (observada em diversos países, mesmo latino-americanos). A residência necessita, seguindo modelo referenciado pela WPA e respeitando as diferenças regionais de cada escola, prover o mínimo para uma boa formação do psiquiatra.

Intraventricular pressure monitoring in patients with thalamic and ganglionic hemorrhages.

In the present study, we have evaluated the use of intraventricular pressure catheters in thalamic and ganglionic hemorrhages. Ten patients admitted in our Emergency Department in Glasgow Coma Scale (GCS) equal or below 13 enrolled the study (at least one point should have been lost in the eye opening score to exclude purely aphasic patients that were fully alert). After a complete clinical and neurological evaluation, computed tomography scans were obtained and the volume of the hematomas, as well as presence or absence of hydrocephalus, were considered. Intraventricular pressure catheters connected in parallel to external derivation systems were implanted and patients were thereafter sent to the ICU. Patients that presented mass effect lesions with sustained increased ICP levels or clinical and neurological deterioration were submitted in addition, to the surgical evacuation of the hematomas. Clinical evolution, complications and the rehabilitation of the patients were recorded. Clinical outcome was assessed with the Glasgow Outcome Score. In all but three patients the initial intracranial pressure levels were bellow 20 mmHg (mean for all patients was 14.1 +/- 6.5 mmHg). Notwithstanding, these three patients were extremely difficult to treat. For this group of patients mortality was 100%. Among the patients that presented ICP levels bellow 20 mmHg, 04 developed hydrocephalus and 03 did not display ventricular dilation. As expected, the major benefits concerning the intraventricular pressure catheters connected in parallel with external derivation systems were observed in the group of patients that presented ICP levels bellow 20 mmHg and had hydrocephalus. Mild non-statistically significant correlations for all the three groups were achieved either when the initial GCS and ICP levels (r=-0.28, p=0.43) or when ICP levels and the volumes of the hematomas were compared (r=0.38, p=0.28). In addition, no significant correlations were observed concerning the final outcome of the patients and the variables previously evaluated.

Intraventricular pressure monitoring in patients with thalamic and ganglionic hemorrhages

In the present study, we have evaluated the use of intraventricular pressure catheters in thalamic and ganglionic hemorrhages. Ten patients admitted in our Emergency Department in Glasgow Coma Scale (GCS) equal or below 13 enrolled the study (at least one point should have been lost in the eye opening score to exclude purely aphasic patients that were fully alert). After a complete clinical and neurological evaluation, computed tomography scans were obtained and the volume of the hematomas, as well as presence or absence of hydrocephalus, were considered. Intraventricular pressure catheters connected in parallel to external derivation systems were implanted and patients were thereafter sent to the ICU. Patients that presented mass effect lesions with sustained increased ICP levels or clinical and neurological deterioration were submitted in addition, to the surgical evacuation of the hematomas. Clinical evolution, complications and the rehabilitation of the patients were recorded. Clinical outcome was assessed with the Glasgow Outcome Score. In all but three patients the initial intracranial pressure levels were bellow 20 mmHg (mean for all patients was 14.1 ± 6.5 mmHg). Notwithstanding, these three patients were extremely difficult to treat. For this group of patients mortality was 100 percent. Among the patients that presented ICP levels bellow 20 mmHg, 04 developed hydrocephalus and 03 did not display ventricular dilation. As expected, the major benefits concerning the intraventricular pressure catheters connected in parallel with external derivation systems were observed in the group of patients that presented ICP levels bellow 20 mmHg and had hydrocephalus. Mild non-statistically significant correlations for all the three groups were achieved either when the initial GCS and ICP levels (r=-0.28, p=0.43) or when ICP levels and the volumes of the hematomas were compared (r=0.38, p=0.28). In addition, no significant correlations were observed concerning the final outcome of the patients and the variables previously evaluated

Acute neurogenic pulmonary edema: case reports and literature review.

Neurogenic pulmonary edema (NPE) is an underdiagnosed clinical entity. Its pathophysiology is multifactorial but largely unknown. We report two cases of NPE and review the literature on NPE cases reported since 1990. A 21-year-old man had a seizure episode following cranioplasty. He became increasingly dyspneic, and clinical and laboratory signs of respiratory failure were evident. Chest radiography and computed tomography showed bilateral diffuse infiltrates. After supportive measures were taken, complete respiratory recovery occurred in 72 hours. A 52-year-old woman had several seizure episodes following subarachnoid hemorrhage due to a cavernoma. She became increasingly dyspneic upon arrival at the hospital. After tracheostomy and oxygen support were established, chest radiography showed bilateral diffuse infiltrates. Respiratory recovery was excellent, and the patient was eupneic with normal results of chest radiography 48 hours later. Fourteen reports (21 cases) were found. Thirteen patients were female, and the mean age of the patients was 31.6 years. The most frequent underlying factor was subarachnoid hemorrhage (42.9%). Symptom onset occurred <4 hours after the neurologic event in 71.4% of cases. One third of the patients presented with pink frothy sputum. Chest radiography showed bilateral diffuse infiltrates in 90.5% of cases. Supportive measures included oxygen support and vasoactive drugs. Recovery was usually very rapid: 52.4% of patients recovered in <72 hours. Almost 10% of patients died of NPE. Our two cases had clinical and laboratory features in common with most NPE cases. Physicians should remember NPE when neurologic patients suddenly become dyspneic. The mortality rate is high, but surviving patients usually recover very quickly.

Neurovascular compression associated with trigeminal neuralgia and systemic arterial hypertension: surgical treatment.

OBJECTIVE AND IMPORTANCE: To highlight arterial hypertension as an additional factor favoring surgical indication in neurovascular compression syndromes such as trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia. CLINICAL PRESENTATION: A 52-year-old woman with trigeminal neuralgia concomitant with systemic arterial hypertension, submitted initially to unsatisfactory conservative treatment, presents tortuousness and enlargement of the vertebral artery (VA) topography on magnetic resonance imaging (MRI). A microsurgical neurovascular decompression of the trigeminal nerve and the medulla was performed, revealing that the compression was due to the superior cerebellar artery instead of the VA. Both the neuralgia and the hypertension were controlled with no need of medication during a 1-year follow-up. CONCLUSION: Surgical indication in neurovascular compression disorders should be reinforced in the presence of concomitant arterial hypertension and a compatible MRI examination.

Anterior tarsal tunnel syndrome: case repot

The anterior tarsal syndrome, a compression of the deep fibular nerve under the inferior extensor retinaculum, is a very rare entrapment neuropathy. Its most important symptom is nocturnal pain on the dorsum of the foot. The distal motor latency of the deep fibular nerve is prolonged, and the EMG demonstrates an active and chronic denervation of the extensor digitorum brevis muscle. One case of complete lesion of the deep fibular nerve in the anterior tarsal tunnel is presented as well as a discussion of its physiopathology.