Increased cortical inhibition deficits in first-episode schizophrenia with comorbid cannabis abuse

There is a high prevalence of substance use disorder (SUD) in first-episode schizophrenia (SZ), but its contribution to the underlying SZ pathophysiology remains unclear. Several studies using transcranial magnetic stimulation (TMS) have observed abnormalities in human motor cortex (M1) excitability in SZ. Studies on cortical excitability comparing SZ patients with and without comorbid substance abuse are lacking. A total of 29 first-episode SZ patients participated in this study; 12 had a history of comorbid cannabis abuse (SZ-SUD) and 17 did not (SZ-NSUD). We applied TMS to right and left M1 areas to assess the resting motor threshold (RMT), short-interval cortical inhibition (SICI), intracortical facilitation (ICF), and the contralateral cortical silent period (CSP). In SICI and ICF conditions, right M1 stimulation led to significantly higher motor evoked potential ratios in SZ-SUD compared to SZ-NSUD. This suggests lower cortical inhibition and increased ICF in first-episode SZ with previous cannabis abuse. There were no group differences in RMT and CSP duration. Neither were there any significant correlations between psychopathology (as indexed by Positive and Negative Syndrome Scale), disease characteristics, the extent of cannabis abuse, and TMS parameters (SICI, ICF, and CSP). Comorbid cannabis abuse may potentiate the reduced intracortical inhibition and enhanced ICF observed in first-episode SZ patients in some previous studies. This finding suggests an increased alteration of GABA(A) and NMDA receptor activity in cannabis-abusing first-episode patients as compared to schizophrenia patients with no history of substance abuse. This may constitute a distinct vulnerability factor in this special population

A Similar but Distinctive Pattern of Impaired Cortical Excitability in First-Episode Schizophrenia and ADHD

Background: First-episode schizophrenia (FE-SZ) and attention deficithyperactivity disorder (ADHD) are both neuropsychiatric disordersassociated with an impaired dopaminergic transmission. Though displayingdifferent clinical phenotypes, a common pathophysiological pathway isdiscussed controversially. Several studies using transcranial magneticstimulation (TMS) revealed abnormalities in human motor cortexexcitability in both schizophrenia and ADHD patients. Studies oncortical excitability comparing these two diseases directly are lacking.Method: In this study, a total of 94 subjects were analyzed.Twenty-fiveFE-SZ patients were directly compared with 28 ADHD patients and 41healthy controls (HC). We investigated cortical excitability (inhibitoryand facilitatory networks) with single- and paired-pulse TMS to the leftand right motor cortex. Results: Compared to HC, FE-SZ/ADHD patientsdisplayed an impaired cortical inhibition over the left hemisphere.Apart from an enhanced intracortical facilitation, FE-SZ patients didnot differ compared to ADHD patients in the main outcome measures. Bothpatient groups presented a dysfunctional hemispheric pattern of corticalinhibition and facilitation in comparison with HC. Conclusion: Theresults of this study indicate a pattern of cortical disinhibition andabnormal hemispheric balance of intracortical excitability networks intwo different psychiatric diseases. These effects might be associatedwith an imbalance in GABAergic and dopaminergic transmission and mightprovide evidence for a common pathophysiological pathway of bothdiseases

Diretrizes da Federação Mundial das Sociedades de Psiquiatria Biológica para o tratamento biológico da esquizofrenia. Parte 2: tratamento de longo prazo

These guidelines for the biological treatment of schizophrenia were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal during the development of these guidelines was to review systematically all available evidence pertaining to the treatment of schizophrenia, and to reach a consensus on a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating people with schizophrenia. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for schizophrenia, as well as from meta-analyses, reviews and randomised clinical trials on the efficacy of pharmacological and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into four levels of evidence (A/D). This second part of the guidelines covers the long-term treatment as well as the management of relevant side effects. These guidelines are primarily concerned with the biological treatment (including antipsychotic medication, other pharmacological treatment options, electroconvulsive therapy, adjunctive and novel therapeutic strategies) of adults suffering from schizophrenia.Estas diretrizes para o tratamento biológico da esquizofrenia foram desenvolvidas pela Força-Tarefa da Federação Mundial das Sociedades de Psiquiatria Biológica (World Federation of Societies of Biological Psychiatry, WFSBP). As metas fixadas durante o desenvolvimento destas diretrizes foi a revisão sistemática de todas as evidências disponíveis referentes ao tratamento da esquizofrenia, tanto no âmbito clínico como no científico, e o estabelecimento de um consenso sobre as principais recomendações para a prática psiquiátrica. Estas diretrizes são destinadas a todos os médicos que atendem e tratam de pacientes portadores de esquizofrenia. Os dados usados para desenvolver estas diretrizes foram extraídos primariamente de vários painéis e diretrizes nacionais para o tratamento da esquizofrenia, assim como de metanálises, revisões e estudos clínicos randomizados sobre a eficácia do tratamento farmacológico e de outras intervenções terapêuticas biológicas, identificadas por uma busca nas bases de dados MedLine e na Biblioteca Cochrane. A literatura identificada foi avaliada quanto à solidez das evidências a favor da eficácia de determinada intervenção, sendo, então, categorizada em quatro níveis de evidência (de A a D). A segunda parte das diretrizes abrange o tratamento de longo prazo, bem como o controle dos efeitos colaterais relevantes. Essas diretrizes são primariamente relacionadas ao tratamento biológico de adultos esquizofrênicos, incluindo medicação antipsicótica, outras opções de tratamento farmacológico, eletroconvulsoterapia, estratégias terapêuticas recentes e complementares

Testing a motor score based on PANSS ratings: a proxy for comprehensive motor assessment

Background and Hypothesis Abnormal psychomotor behavior is a core schizophrenia symptom. However, assessment of motor abnormalities with expert rating scales is challenging. The Positive and Negative Syndrome Scale (PANSS) includes 3 items broadly related to hypokinetic motor behavior. Here, we tested whether a sum score of the PANSS items mannerisms and posturing (G5), motor retardation (G7), and disturbance of volition (G13) corresponds to expert ratings, potentially qualifying as a proxy-marker of motor abnormalities. Study Design Combining baseline datasets (n = 196) of 2 clinical trials (OCoPS-P, BrAGG-SoS), we correlated PANSS motor score (PANSSmot) and 5 motor rating scales. In addition, we tested whether the cutoff set at ≥3 on each PANSS motor item, ie, “mild” on G05, G07, and G13 (in total ≥9 on PANSSmot) would differentiate the patients into groups with high vs low scores in motor scales. We further sought for replication in an independent trial (RESIS, n = 102), tested the longitudinal stability using week 3 data of OCoPS-P (n = 75), and evaluated the validity of PANSSmot with instrumental measures of physical activity (n = 113). Study Results PANSSmot correlated with all motor scales (Spearman-Rho-range 0.19–0.52, all P ≤ .007). Furthermore, the cutoff set at ≥3 on each PANSS motor item was able to distinguish patients with high vs low motor scores in all motor scales except using Abnormal Involuntary Movement Scale (Mann-Whitney-U-Tests: all U ≥ 580, P ≤ .017). Conclusions Our findings suggest that PANSSmot could be a proxy measure for hypokinetic motor abnormalities. This might help to combine large datasets from clinical trials to explore whether some interventions may hold promise to alleviate hypokinetic motor abnormalities in psychosis

Prefrontal cortex gyrification index in twins: an MRI study

Cortical development and folding seems to be under environmental as well as genetic control. The aim of our study was to estimate the genetic influence on gyrification and cortical volumes, comparing prefrontal gyrification index (GI) in monozygotic (MZ) and dizygotic (DZ) twin pairs, and unrelated pairs. Twenty-four subjects (6 pairs of MZ and 6 pairs of DZ twins) were included in this study. Prefrontal cortical folding (gyrification) was measured by an automated and manual version of the gyrification index (A-GI, M-GI) according to previously published protocols. MR-imaging was performed and 3 representative slices were selected from coronar MR-imaging scans. The volumes of the total brain, temporal lobes, prefrontal lobes, and cerebellum were analyzed, too. To evaluate similarity in GI, absolute differences in GI, and brain volumes as well as intraclass correlations of twin pairs were compared with regard to twin status. Finally, a control group of unrelated pairs was assembled from the first two study groups and analyzed. Compared to unrelated pairs, twin pairs exhibited more similarity concerning different brain volumes and a trend to more similarity concerning A-GI. MZ twins did not present more similarity concerning GI (automatically and manually measured) and volume measurements compared to DZ twins. Different factors, like intrauterine factors, postnatal development conditions, and especially environmental factors might account for the differences between related and unrelated pairs. The nonexistence of a pronounced similarity in MZ twins compared to DZ twins concerning prefrontal GI raises questions about the extent of genetic influence on GI

Cognitive and functional deficits are associated with white matter abnormalities in two independent cohorts of patients with schizophrenia

BACKGROUND Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the relationship of these abnormalities with functional outcome remains unclear. METHODS In two independent cohorts (C1, C2), patients with SZ were divided into two subgroups: patients with higher cognitive performance (SZ-HCP-C1, n = 25; SZ-HCP-C2, n = 24) and patients with lower cognitive performance (SZ-LCP-C1, n = 25; SZ-LCP-C2, n = 24). Healthy controls (HC) were included in both cohorts (HC-C1, n = 52; HC-C2, n = 27). We compared fractional anisotropy (FA) of the whole-brain WM skeleton between the three groups (SZ-LCP, SZ-HCP, HC) by a whole-brain exploratory approach and an atlas-defined WM regions-of-interest approach via tract-based spatial statistics. In addition, we explored whether FA values were associated with Global Assessment of Functioning (GAF) scores in the SZ groups. RESULTS In both cohorts, mean FA values of whole-brain WM skeleton were significantly lower in the SCZ-LCP group than in the SCZ-HCP group. Whereas in C1 the FA of the frontal part of the left inferior fronto-occipital fasciculus (IFOF) was positively correlated with GAF score, in C2 the FA of the temporal part of the left IFOF was positively correlated with GAF score. CONCLUSIONS We provide robust evidence for WM microstructural abnormalities in SZ. These abnormalities are more prominent in patients with low cognitive performance and are associated with the level of functioning

Reduced prefrontal gyrification in obsessive–compulsive disorder

Structural magnetic resonance imaging (MRI) studies reveal evidence for brain abnormalities in obsessive–compulsive disorder (OCD), for instance, reduction of gray matter volume in the prefrontal cortex. Disturbances of gyrification in the prefrontal cortex have been described several times in schizophrenia pointing to a neurodevelopmental etiology, while gyrification has not been studied so far in OCD patients. In 26 OCD patients and 38 healthy control subjects MR-imaging was performed. Prefrontal cortical folding (gyrification) was measured bilaterally by an automated version of the automated-gyrification index (A-GI), a ratio reflecting the extent of folding, from the slice containing the inner genu of the corpus callosum up to the frontal pole. Analysis of covariance (ANCOVA, independent factor diagnosis, covariates age, duration of education) demonstrated that compared with control subjects, patients with OCD displayed a significantly reduced A-GI in the left hemisphere (p = 0.021) and a trend for a decreased A-GI in the right hemisphere (p = 0.076). Significant correlations between prefrontal lobe volume and A-GI were only observed in controls, but not in OCD patients. In conclusion, prefrontal hypogyrification in OCD patients may be a structural correlate of the impairment in executive function of this patient group and may point to a neurodevelopmental origin of this disease

Internal capsule size associated with outcome in first-episode schizophrenia

Subtle structural brain abnormalities are an established finding in first-episode psychosis. Nevertheless their relationship to the clinical course of schizophrenia is controversially discussed. In a multicentre study 45 first-episode schizophrenia patients (FE-SZ) underwent standardized MRI scanning and were followed up to 1 year. In 32 FE-SZ volumetric measurement of three regions of interests (ROIs) potentially associated with disease course, hippocampus, lateral ventricle and the anterior limb of the internal capsule (ALIC) could be performed. The subgroups of FE-SZ with good (12 patients) and poor outcome (11 patients), defined by a clinically relevant change of the PANSS score, were compared with regard to these volumetric measures. Multivariate analysis of covariance revealed a significant reduced maximal cross sectional area of the left ALIC in FE-SZ with clinically relevant deterioration compared to those with stable psychopathology. There were no differences in the other selected ROIs between the two subgroups. In conclusion, reduced maximal area of ALIC, which can be interpreted as a disturbance of fronto-thalamic connectivity, is associated with poor outcome during the 1 year course of first-episode schizophrenia