Effect of treatment with paliperidone palmitate versus oral antipsychotics on frontal lobe intracortical myelin volume in participants with recent-onset schizophrenia: Magnetic resonance imaging results from the DREaM study.

OBJECTIVE: We investigated changes in brain intracortical myelin (ICM) volume in the frontal lobe after 9 months of treatment with paliperidone palmitate (PP) compared with 9 months of treatment with oral antipsychotics (OAP) in participants with recent-onset schizophrenia or schizophreniform disorder from the Disease Recovery Evaluation and Modification (DREaM) study, a randomized, open-label, delayed-start trial. METHODS: DREaM included 3 phases: Part I, a 2-month oral run-in; Part II, a 9-month disease progression phase (PP or OAP); and Part III, 9 months of additional treatment (participants receiving PP continued PP [PP/PP] and participants receiving OAP were rerandomized to receive either PP [OAP/PP] or OAP [OAP/OAP]). In Part II, magnetic resonance imaging (MRI) and functional and symptomatic assessment was performed at baseline, day 92, and day 260. ICM volume as a fraction of the entire brain volume was quantified by subtraction of a proton density image from an inversion recovery image. Within-treatment-group changes from baseline were assessed by paired t-tests. Analysis of covariance was used to analyze ICM volume changes between treatment groups, adjusting for country. RESULTS: The MRI analysis sample size included 71 DREaM participants (PP, 23; OAP, 48) and 64 healthy controls. At baseline, mean adjusted ICM fraction values did not differ between groups (PP, 0.057; OAP, 0.058, p = 0.79). By day 92, the adjusted ICM fraction in the OAP group had decreased significantly (change from baseline, -0.002; p = 0.001), whereas the adjusted ICM fraction remained unchanged from baseline in the PP group (0.000; p = 0.80). At day 260, the change from baseline in adjusted ICM fraction was -0.004 (p = 0.004) in the OAP group and -0.001 (p = 0.728) in the PP group. The difference between treatment groups did not reach statistical significance (p = 0.147). CONCLUSIONS: In participants with recent-onset schizophrenia or schizophreniform disorder, frontal ICM volume was preserved at baseline levels in those treated with PP over 9 months. However, a decrease of frontal ICM volume was observed among participants treated with OAPs. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT02431702.

[Sociodemographic features related to violent behavior in schizophrenia]. / Características sociodemográficas asociadas a la conducta violenta en la esquizofrenia.

INTRODUCTION: It has been proposed that some sociodemographic variables may predict violent behavior in schizophrenic patients. The aim of this study was to investigate the relationship of violent behavior with sociodemographic and clinical features in schizophrenic patients. METHOD: We included 106 schizophrenic patients. Sociodemographic and clinical characteristics of each patient were recorded in a previously designed record. Violent behaviors were assessed with the Overt Aggression Scale (OAS). RESULTS: From the total sample, 49.1 % of the patients were classified as violent. Marital status, alcohol abuse, number of previous psychiatric hospitalizations and age of first hospitalization were predictive variables for violent behavior in schizophrenia. DISCUSSION: Predictive sociodemographic variables for violence in schizophrenia are easy to measure during the first interview with the patient and can be useful for the prevention of future violence.

[Replication of a computer model of auditory hallucinations in schizophrenia]. / Reproducción de un modelo informático de las alucinaciones auditivas en la esquizofrenia.

INTRODUCTION: Abnormal synaptic pruning has been proposed by some authors as a theory to explain schizophrenia. It has been studied in different ways, some of which are computerized models. METHODS: A PC computer with MATLAB version 5.3 and Neural Networks Toolbox programs were used. To reproduce the model we used Elman's network for neuronal unit and McGlashan and Hoffman's network. RESULTS: The corrected percentage of detection improved as synapses were prunned. It increased from 68% to 91 %, reaching the highest detection level when 60% of the synapses were eliminated. Detection capacity was reduced when synaptic elimination continued and the program started detecting words in the absence of input. This was considered as a hallucination. When pruning reached from 80% to 95%, hallucinations occurred more frequently. CONCLUSIONS: The computer simulation model provides a symptom formation model, and also a way of understanding pruning's adaptative utility. When the neuronal units were eliminated (instead of connections), there was only progressive worsening in word perception. This confirms the hypothesis proposed that schizophrenia pathophysiology underlies neuronal connections, not the neurons.

Frontal and limbic metabolic differences in subjects selected according to genetic variation of the SLC6A4 gene polymorphism.

Allelic variants in the promoter region of the serotonin transporter (5-HTT) gene have been implicated in several psychiatric disorders and personality traits. In particular, two common alleles in a variable repeat sequence of the promoter region (SLC6A4) have been differentially associated with a display of abnormal levels of anxiety and affective illness in individuals carrying the "s" allele. The aim of this study was to compare the basal cerebral metabolic activity of non-psychiatric subjects in fronto-limbic structures to determine whether differences exist in basal metabolic activity within this functional polymorphism. PET scans with fluorine-18 fluorodeoxyglucose as radiotracer were performed in 71 non-psychiatric subjects previously screened for psychopathology and subsequently genotyped for SLC6A4; PET images were compared with SPM2 according to s/s (n = 27), s/l (n = 25), and l/l (n = 19) groups considering a significance threshold in a priori selected areas of P < 0.001 and an extent threshold > or =5 voxels. The analysis showed an effect of interest among the three genotype groups in right anterior cingulate gyrus (ACC), left middle frontal gyrus, and left posterior cingulate gyrus (PCC). Comparison between l/l vs. s/s showed increased metabolism for l/l in left middle frontal gyrus and an increase for s/s in right ACC and left PCC. Comparison between s/s vs. s/l showed an increase for s/s in left PCC and right ACC. Increased basal metabolism in fronto-limbic structures for the s/s group may be conceived as an "overactive metabolic state" of these structures, possibly related to an increased susceptibility for developing an anxiety-depression spectrum disorder.

A forced five-dimensional factor analysis and concurrent validity of the Positive and Negative Syndrome Scale in Mexican schizophrenic patients.

UNLABELLED: The heterogeneity of schizophrenic symptomatology is well documented. The positive-negative distinction is limited to cover the entire spectrum of schizophrenic psychopathology in order to describe the various clinical aspects of the disorder. METHOD: We recruited 150 schizophrenic patients between May 2002 and September 2003. Diagnoses were based on a structured clinical interview. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate general psychopathology and symptom severity. For the concurrent validity of the pentagonal model of the PANSS, the BPRS, the CDSS, the OAS and the MMSE were used. RESULTS: The forced five-factor principal-component analysis explained 53.4% of the total variance. There were significant correlations between the clinical rating scales and the five components of the PANSS. DISCUSSION: Our data support a pentagonal model underlying the multidimensional schizophrenic symptomatology as assessed by the PANSS. The five-factor structure of the PANSS in Mexican schizophrenic patients enables further elucidation of the various clinical aspects of schizophrenia.

Premorbid adjustment and violent behavior in schizophrenic patients.

UNLABELLED: We examined the influence of premorbid adjustment on violent behavior in schizophrenic patients. There is some evidence that poor premorbid adjustment predicts violent behavior, then we decided to examine this hypothesis further. METHOD: We recruited 72 schizophrenic patients without concomitant substance abuse 6 months prior to the assessment. Diagnoses were based on the SCID-I. Premorbid adjustment was evaluated with the Premorbid Adjustment Scale and violent behaviors with the Overt Aggression Scale. RESULTS: Violent schizophrenic patients showed an overall worse premorbid adjustment during childhood. In addition, the area of "peer relationships" was significantly diminished in several life period sections such as childhood, early and late adolescence in violent patients. DISCUSSION: Our data indicate that difficulties in social relationships during early stages of life may increase the risk of future violent behavior among schizophrenic patients.

[Sensitivity and specificity of the Overt Aggression Scale in schizophrenic patients]. / Sensibilidad y especificidad de la Escala de Agresión Explícita en pacientes con esquizofrenia.

INTRODUCTION: Research focused on the assessment of violent behavior in schizophrenic patients has been hindered by the lack of clinical instruments adapted to the Mexican psychiatric population. This study aimed to obtain sensitivity and specificity data as well as the most adequate cutoff point of the Overt Aggression Scale (OAS). METHOD: 137 schizophrenic patients were included. A clinical evaluation was performed with the PANSS subscale of excitability and the OAS. Diagnosis of violent behavior was obtained with the PANSS and clinical consensus of two psychiatrists. RESULTS: 66.4% of the sample was considered as nonviolent patients. A cutoff point of 7 points in the OAS showed sensitivity of 0.80 and specificity of 0.97, with adequate positive and negative predictive power. DISCUSSION: The objective assessment of violent behavior in schizophrenic patients can contribute to the development of new lines of research. Adaptation of the OAS for the assessment of violent behavior will encourage the development of better strategies for the detection and intervention of violent behavior in schizophrenia.