Inflammatory cytokines and white matter microstructure in the acute phase of first-episode psychosis: A longitudinal study.

OBJECTIVES: Schizophrenia-related psychosis is associated with abnormalities in white matter (WM) microstructure and structural brain dysconnectivity. However, the pathological process underlying such changes is unknown. We sought to investigate the potential association between peripheral cytokine levels and WM microstructure during the acute phase of first-episode psychosis (FEP) in a cohort of drug-naïve patients. METHODS: Twenty-five non-affective FEP patients and 69 healthy controls underwent MRI scanning and blood collection at study entry. After achieving clinical remission, 21 FEP were reassessed; 38 age and biological sex-matched controls also had a second assessment. We measured fractional anisotropy (FA) of selected WM regions-of-interest (ROIs) and plasma levels of four cytokines (IL-6, IL-10, IFN-γ, and TNF-α). RESULTS: At baseline (acute psychosis), the FEP group showed reduced FA relative to controls in half the examined ROIs. Within the FEP group, IL-6 levels were negatively correlated with FA values. Longitudinally, patients showed increments of FA in several ROIs affected at baseline, and such changes were associated with reductions in IL-6 levels. CONCLUSIONS: A state-dependent process involving an interplay between a pro-inflammatory cytokine and brain WM might be associated with the clinical manifestation of FEP. This association suggests a deleterious effect of IL-6 on WM tracts during the acute phase of psychosis.

Increased platelet glycogen sysnthase kinase 3beta in first-episode psychosis.

Past studies have linked intracellular pathways related to psychotic disorders to the GSK3B enzyme. This study aimed to investigate GSK3B protein expression and phosphorylation in drug-naïve first-episode psychosis patients (n=43) at baseline and following symptom remission, and in healthy controls (n=77). At baseline GSK3B total level was higher in patients (p<0.001). In schizophrenia spectrum patients (n=25) GSK3B total and phosphorylated levels were higher than in controls and patients with other non-affective psychotic disorders (n=18) (p<0.001; p=0.027; p=0.05 respectively). No enzyme changes were found after clinical remission. The implication of this finding for the biology of psychoses warrants further studies to clarify whether increased GSK3B may be useful as a biomarker for psychosis in general, and schizophrenia in particular.

Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness.

BACKGROUND: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-based morphometry (VBM) study was carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertain which (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity. METHODS: We gathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) from four previous morphometric MRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General Linear Model Analysis of Co-variance (ANCOVA), always including total GM volume, scan protocol, age and gender as nuisance variables. Finally, correlation analyses were performed between the aforementioned clinical moderators and regional and global brain volumes. RESULTS: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume-corrected (SVC) analyses (p < 0.05, FWE-corrected), including the insula, temporolimbic structures and striatum. Chronic schizophrenia patients, on the other hand, demonstrated an extensive pattern of regional GM volume decreases relative to controls, involving bilateral superior, inferior and orbital frontal cortices, right middle frontal cortex, bilateral anterior cingulate cortices, bilateral insulae and right superior and middle temporal cortices (p < 0.05, FWE-corrected over the whole brain). GM volumes in several of those brain regions were directly correlated with age of disease onset on SVC analyses for conjoined (first-episode and chronic) schizophrenia groups. There were also widespread foci of significant negative correlation between duration of illness and relative GM volumes, but such findings remained significant only for the right dorsolateral prefrontal cortex after accounting for the influence of age of disease onset. Finally, significant negative correlations were detected between life-time cumulative exposure to antipsychotics and total GM and white matter volumes in schizophrenia patients, but no significant relationship was found between indices of antipsychotic usage and relative GM volume in any specific brain region. CONCLUSION: The above data indicate that brain changes associated with the diagnosis of schizophrenia are more widespread in chronic schizophrenia compared to first-episode patients. Our findings also suggest that relative GM volume deficits may be greater in (presumably more severe) cases with earlier age of onset, as well as varying as a function of illness duration in specific frontal brain regions. Finally, our results highlight the potentially complex effects of the continued use of antipsychotic drugs on structural brain abnormalities in schizophrenia, as we found that cumulative doses of antipsychotics affected brain volumes globally rather than selectively on frontal-temporal regions.

Aspectos do acompanhamento psiquiátrico de pacientes obesos sob tratamento bariátrico: revisão / Aspects of psychiatric care for obese patients under bariatric treatment: a review

CONTEXTO: Nas últimas décadas, diversos estudos longitudinais têm demonstrado a eficácia da cirurgia bariátrica no controle de peso em longo prazo e na redução da mortalidade resultante de complicações clínicas associadas à obesidade. Contudo, os estudos também revelam aumento significativo da mortalidade devida a suicídio e comportamento impulsivo, por razões largamente desconhecidas, o que demonstra a escassez de informações relativas ao manejo clínico de pacientes bariátricos. O presente estudo tem como objetivo sintetizar o estado atual de conhecimentos referentes ao acompanhamento psiquiátrico de pacientes bariátricos. MÉTODO: Revisão seletiva da literatura envolvendo artigos indexados no Medline e PubMed até junho de 2010, utilizando-se os termos: "bariatric surgery", "psychiatry", "binge eating", "follow-up" e "outcome". RESULTADOS: Há relativo consenso na literatura de que não haja contraindicação psiquiátrica absoluta para a cirurgia bariátrica, embora a avaliação pré-operatória seja de extrema importância para o diagnóstico e tratamento de eventuais transtornos psiquiátricos, objetivando assegurar aderência ao tratamento multidisciplinar, melhor qualidade de vida e, possivelmente, melhor prognóstico pós-cirúrgico. Entre os transtornos mais prevalentes nessa população, encontra-se o transtorno da compulsão alimentar periódica (TCAP), que está relacionado com menor perda ponderal e pior qualidade de vida, especialmente quando presente no pós-operatório. No acompanhamento pós-operatório, também se deve atentar para o surgimento de sintomas impulsivos, incluindo abuso de álcool e outras substâncias. CONCLUSÃO: Diversos estudos indicam elevada prevalência de transtornos mentais e alterações psicopatológicas na população de pacientes bariátricos. Embora a maioria dos pacientes apresente adequado controle ponderal e melhora na qualidade de vida em médio e longo prazo, alguns pacientes desenvolvem alterações relativas ao comportamento alimentar,...

BACKGROUND: In recent decades, several longitudinal studies show the efficacy of bariatric surgery on long-term weight control and reductions in mortality due to clinical complications associated with obesity. However, studies also show significantly increased mortality due to suicide and impulsive behavior, for reasons largely unknown, which demonstrates the paucity of information concerning the clinical management of bariatric patients. This study aims to synthesize the current state of knowledge regarding the psychiatric care of bariatric patients. METHOD: A selective review of literature involving articles indexed on Medline and PubMed up to June 2010, using the terms: "bariatric surgery", "psychiatry", "binge eating", "follow-up", and "outcome". RESULTS: The literature is somehow consensual in which there is no absolute psychiatric contraindication for bariatric surgery, although the preoperative evaluation is of extreme importance for the diagnosis and treatment of any psychiatric disorder, to assure adherence to the multidisciplinary approach, improved quality of life and possibly a better prognosis after surgery. Among the most prevalent disorders in this population is the binge-eating disorder (BED), which is associated with lower weight loss and poor quality of life, especially when present in the postoperative period. In the postoperative follow-up one should also be alert to the emergence of impulsive symptoms, including abuse of alcohol and other substances. DISCUSSION: Several studies indicate high prevalence of mental disorders and psychopathology in the population of bariatric patients. Although most patients experience adequate weight control and improved quality of life in the medium and long term, some patients develop abnormal behavior relating to dysfunctional eating patterns, abuse of alcohol and other substances, and complications associated with impulsive behavior, which suggests etiological hypotheses involving from...

Eating disorders in patients with obsessive-compulsive disorder: prevalence and clinical correlates.

OBJECTIVE: The objective is to evaluate the prevalence and associated clinical characteristics of eating disorders (ED) in patients with obsessive-compulsive disorder (OCD). METHOD: This is a cross-sectional study comparing 815 patients with OCD. Participants were assessed with structured interviews and scales: SCID-I, Y-BOCS, Dimensional Y-BOCS, BABS, Beck Depression and Anxiety Inventories. RESULTS: Ninety-two patients (11.3%) presented the following EDs: binge-eating disorders [= 59 (7.2%)], bulimia nervosa [= 16 (2.0%)], or anorexia nervosa [= 17 (2.1%)]. Compared to OCD patients without ED (OCD-Non-ED), OCD-ED patients were more likely to be women with previous psychiatric treatment. Mean total scores in Y-BOCS, Dimensional Y-BOCS, and BABS were similar within groups. However, OCD-ED patients showed higher lifetime prevalence of comorbid conditions, higher anxiety and depression scores, and higher frequency of suicide attempts than did the OCD-Non-ED group. Primarily diagnosed OCD patients with comorbid ED may be associated with higher clinical severity. DISCUSSION: Future longitudinal studies should investigate dimensional correlations between OCD and ED.

Polymorphisms in genes involved in neurodevelopment may be associated with altered brain morphology in schizophrenia: preliminary evidence.

An abnormality in neurodevelopment is one of the most robust etiologic hypotheses in schizophrenia (SZ). There is also strong evidence that genetic factors may influence abnormal neurodevelopment in the disease. The present study evaluated in SZ patients, whose brain structural data had been obtained with magnetic resonance imaging (MRI), the possible association between structural brain measures, and 32 DNA polymorphisms, located in 30 genes related to neurogenesis and brain development. DNA was extracted from peripheral blood cells of 25 patients with schizophrenia, genotyping was performed using diverse procedures, and putative associations were evaluated by standard statistical methods (using the software Statistical Package for Social Sciences - SPSS) with a modified Bonferroni adjustment. For reelin (RELN), a protease that guides neurons in the developing brain and underlies neurotransmission and synaptic plasticity in adults, an association was found for a non-synonymous polymorphism (Val997Leu) with left and right ventricular enlargement. A putative association was also found between protocadherin 12 (PCDH12), a cell adhesion molecule involved in axonal guidance and synaptic specificity, and cortical folding (asymmetry coefficient of gyrification index). Although our results are preliminary, due to the small number of individuals analyzed, such an approach could reveal new candidate genes implicated in anomalous neurodevelopment in schizophrenia.

Eating behavior as a prognostic factor for weight loss after gastric bypass.

BACKGROUND: Binge-eating disorder (BED) may be associated with unsatisfactory weight loss in obese patients submitted to bariatric procedures. This study aims to investigate whether the presence of binge eating before Roux-en-Y gastric bypass (RYGBP) influences weight outcomes. METHODS: In a prospective design, 216 obese patients (37 males, 178 females, BMI=45.9 +/- 6.0 kg/m2) were assessed for the lifetime prevalence of BED and classified at structured interview into 3 subgroups: no binge eating (NBE=43), sub-threshold binge eating (SBE=129), and binge-eating disorder (BED=44). All patients were encouraged to take part in a multidisciplinary program following surgery, and weight loss at follow-up was used as the outcome variable. RESULTS: At 1-year follow-up, NBE patients (n=41) showed percent excess BMI loss (%EBL) significantly higher than SBE patients (n=112) (P=0.027), although this effect was not significantly different between NBE and BED patients (n=44). At 2-year follow-up, NBE patients (n=33) showed %EBL higher than SBE (n=64) (P=-0.003) and BED patients (n=34) (P<0.001). Nevertheless, we found no significant weight loss differences between SBE (subclinical) and BED (full criteria) patients at any period of follow-up. Preliminary results at 3-year follow-up suggest that such an effect may be enduring. CONCLUSION: The presence of a history of binge eating prior to treatment is associated with poorer weight loss in obese patients submitted to RYGBP. Because BED is highly prevalent in obese patients seeking bariatric surgery, its early recognition and treatment may be of important clinical value.

Nogo CAA 3'UTR Insertion polymorphism is not associated with Schizophrenia nor with bipolar disorder.

The Nogo gene maps to 2p14-p13, a region consistently associated with schizophrenia and bipolar disorder. The association of a polymorphism in Nogo was previously investigated by two groups, with divergent results. In this report, using an alternative approach, we evaluated this same polymorphism in 725 individuals, including patients with schizophrenia, bipolar disorder, normal controls and non-human primate samples. Our results indicate that the polymorphism is not associated with any of these diseases, but has a remarkably biased distribution in ethnic groups. Genotyping of primate samples, suggest that this polymorphism is a recent event in human speciation.

Brazilian multicenter study of the intragastric balloon.

BACKGROUND: Intragastric balloons have been used in obese patients to provide early satiety and thereby induce weight loss. Several studies have reported promising results with a new balloon (BIB((R))) designed to overcome some of the technical pitfalls of earlier devices. We assessed both safety and effectiveness of the BIB((R)). METHOD: From November 2000 to February 2004, 483 overweight and obese patients were treated with the BIB((R)). 323 patients completed a 6-month follow-up, and 85 of them completed a 1-year follow-up. All patients took part in a multidisciplinary program involving clinical, psychiatric, physical training, and dietary approaches. RESULTS: Compared to baseline values, after a 6-month follow-up subjects showed significant reductions in weight (15.2 +/- 10.5 kg), percent excess weight loss (48.3 +/- 28.1), and BMI (-5.3 +/- 3.4 kg/m(2)) (P < 0.000). At 1-year follow-up, 85 patients have maintained more than 90% of their BMI reduction. The main side-effects were nausea/vomiting (40%), and epigastric pain (20%), requiring removal of the BIB (R) in 11 patients (3.4%). Minor complications were reflux esophagitis (12%) and symptomatic gastric stasis (9%). Balloon impaction occurred in 2 cases (0.6%), and in 1 patient (0.3%) there was spontaneous deflation of the balloon leading to a small-bowel obstruction solved by a surgical approach. CONCLUSION: The BIB((R)) has been effective to temporarily control obesity, inducing an excess weight loss of approximately 48%. It was not associated with mortality and showed minimal risk of major complications.

Reduced cortical folding in schizophrenia: an MRI morphometric study.

OBJECTIVE: Although well documented, regional brain structural abnormalities in schizophrenia are nonspecific, and morphometric parameters show significant overlapping between patients and healthy comparison subjects. An increasing number of studies have focused on supraregional models involving abnormalities of the neuronal circuitry between cortical regions in schizophrenia. The aim of the present study was to investigate cortical folding as an index of the neuronal wiring in different subtypes of schizophrenia. METHOD: Magnetic resonance imaging measures of gyrification index in intervals of 3.6 mm along the total cerebral cortex were compared in 40 patients with DSM-IV schizophrenia and 20 healthy subjects. Psychopathology was assessed with the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, and the Negative Symptom Rating Scale. RESULTS: The schizophrenia patients showed significantly reduced bilateral cortical folding relative to healthy comparison subjects. Such reductions were more pronounced in those with the disorganized subtype and showed an inverse correlation with negative symptoms and a positive correlation with positive symptoms. The paranoid subtype showed reduced cortical folding that was restricted to the left hemisphere. CONCLUSIONS: These results from a larger patient group confirm a previous report of reduced cortical folding in schizophrenia patients. They also suggest a distinct pattern of abnormality between schizophrenia subtypes regarding the process of cerebral lateralization and are in agreement with the neurodevelopmental hypothesis of schizophrenia.

Rightward cerebral asymmetry in subtypes of schizophrenia according to Leonhard's classification and to DSM-IV: a structural MRI study.

Although well documented, brain structural abnormalities in schizophrenia are non-specific, and morphometric parameters show significant overlap between patients and healthy controls. Such inconsistencies in neuroimaging findings could represent different levels of severity along a single pathogenic process or distinct clinical and etiopathological psychoses within a schizophrenic spectrum. The aim of the present study was the investigation of distinct brain abnormalities in different subtypes of schizophrenia. Forty patients were classified according to DSM-IV and Leonhard's classifications. Psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS) and the Negative Symptom Rating Scale (NSRS). Patients were compared to 20 healthy volunteers on volumetric measures of cerebral structures (hemisphere, hippocampus and planum temporale) and ventricular-brain ratio (VBR) obtained by magnetic resonance imaging. Patients showed rightward asymmetry of cerebral hemispheres and increased VBR. Rightward asymmetry correlated with severity of negative symptoms and prevailed in the systematic forms of Leonhard, suggesting a distinct pattern of left hemisphere abnormality in this subgroup of psychoses. Increased VBR values showed a single normal distribution in the subgroups, indicating that ventricular enlargement is not restricted to a subgroup but is present to a certain degree in all cases.