Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia.

We here present data on immune gene expression of chemokines, chemokine receptors, cytokines and regulatory T-cell (T-reg) markers in chronic patients suffering from either schizophrenia (SCZ, N=20) or bipolar disorder (BD=20) compared with healthy controls (HCs, N=20). We extracted RNA from peripheral blood mononuclear cells and performed real-time (RT)-PCR to measure mRNA levels of chemokines, chemokine receptors, cytokines and T-reg markers. All the analyses were Bonferroni-corrected. The classical monocyte activation (M1) markers il6, ccl3 were significantly increased in BD as compared with both HC and SCZ patients (P=0.03 and P=0.002; P=0.024 and P=0.021, respectively), whereas markers of alternative (M2) monocyte activation ccl1, ccl22 and il10 were coherently decreased (controls: P=0.01, P=0.001 and P=0.09; SCZ subjects: P=0.02, P=0.05 and P=0.011, respectively). Concerning T-cell markers, BD patients had compared with HC downregulated ccr5 (P=0.02) and upregulated il4 (P=0.04) and compared with both healthy and SCZ individuals downregulated ccl2 (P=0.006 and P=0.003) and tgfß (P=0.004 and P=0.007, respectively). No significant associations were found between any immune gene expression and clinical variables (prior hospitalizations, Brief Psychiatric Rating Scale, medications' dosages and lifetime administration). Although some markers are expressed by different immune cell types, these findings suggest a coherent increased M1/decrease M2 signature in the peripheral blood of BD patients with potential Th1/Th2 shift. In contrast, all the explored immune marker levels were preserved in SCZ. Further larger studies are needed to investigate the relevance of inflammatory response in BD, trying to correlate it to psychopathology, treatment and outcome measures and, possibly, to brain connectivity.

The impact of non-adherence to medication in patients with schizophrenia on health, social care and societal costs. Analysis of the QUATRO study.

Aims. For people with schizophrenia, non-adherence to antipsychotic medications may result in high use of health and other services. The objective of our research was to examine the economic consequences of non-adherence in patients with schizophrenia taking antipsychotic medication. Methods. Data were taken from QUATRO, a randomized controlled trial that drew a sample of adults with schizophrenia receiving psychiatric services in four European cities: Amsterdam, Leipzig, London and Verona. Trial inclusion criteria were a clinical diagnosis of schizophrenia, requiring on-going antipsychotic medication for at least 1-year following baseline assessment, and exhibiting evidence of clinical instability in the year prior to baseline. The patient-completed Medication Adherence Questionnaire (MAQ) was used to calculate the 5-point Morisky index of adherence. Generalized linear models (GLM) were developed to determine the effect of adherence on (i) health and social care and (ii) societal costs before and after treatment, taking into account other potential cost-influencing factors. Results. The effect of non-adherence on costs was mixed. For different groups of services, and according to treatment group assignment, non-adherence was both negatively and positively associated with costs. Conclusions. The impact of non-adherence on costs varies across the types of services used by individuals with schizophrenia.

Schizophrenia severity, social functioning and hippocampal neuroanatomy: three-dimensional mapping study.

BACKGROUND: Hippocampal shrinkage is commonly reported in schizophrenia, but its role in the illness is still poorly understood. In particular, it is unclear how clinical and psychosocial variables relate to hippocampal volumes. AIMS: To investigate neuroanatomic differences in the hippocampus using three-dimensional (3D) computational image analysis. METHOD: We used high-resolution magnetic resonance imaging and surface-based modelling to map the 3D profile of hippocampal differences in adults with schizophrenia (n = 67) and a healthy control group (n = 72). Manual tracings were used to create 3D parametric mesh models of the hippocampus. Regression models were used to relate diagnostic measures to maps of radial distance, and colour-coded maps were generated to show the profile of associations. RESULTS: There was no detectable difference between the schizophrenia and control groups in hippocampal radial distance. In the schizophrenia group, however, bilateral shape deflation was associated with greater illness severity (length of illness, positive and negative symptoms) and with poorer social functioning (educational level, quality of life and health status), which survived Bonferroni correction. CONCLUSIONS: Illness severity and poor social functioning may be associated with hippocampal deflation in schizophrenia. As a structural sign of poor outcome, imaging measures might help to identify a subgroup of patients who may need specific treatment to resist hippocampal shrinkage, such as cognitive rehabilitation or physical exercise.

The balanced care model for global mental health.

BACKGROUND: For too long there have been heated debates between those who believe that mental health care should be largely or solely provided from hospitals and those who adhere to the view that community care should fully replace hospitals. The aim of this study was to propose a conceptual model relevant for mental health service development in low-, medium- and high-resource settings worldwide. Method We conducted a review of the relevant peer-reviewed evidence and a series of surveys including more than 170 individual experts with direct experience of mental health system change worldwide. We integrated data from these multiple sources to develop the balanced care model (BCM), framed in three sequential steps relevant to different resource settings. RESULTS: Low-resource settings need to focus on improving the recognition and treatment of people with mental illnesses in primary care. Medium-resource settings in addition can develop 'general adult mental health services', namely (i) out-patient clinics, (ii) community mental health teams (CMHTs), (iii) acute in-patient services, (iv) community residential care and (v) work/occupation. High-resource settings, in addition to primary care and general adult mental health services, can also provide specialized services in these same five categories. CONCLUSIONS: The BCM refers both to a balance between hospital and community care and to a balance between all of the service components (e.g. clinical teams) that are present in any system, whether this is in low-, medium- or high-resource settings. The BCM therefore indicates that a comprehensive mental health system includes both community- and hospital-based components of care.

Increased salience of gains versus decreased associative learning differentiate bipolar disorder from schizophrenia during incentive decision making.

BACKGROUND: Abnormalities in incentive decision making, typically assessed using the Iowa Gambling Task (IGT), have been reported in both schizophrenia (SZ) and bipolar disorder (BD). We applied the Expectancy-Valence (E-V) model to determine whether motivational, cognitive and response selection component processes of IGT performance are differentially affected in SZ and BD. METHOD: Performance on the IGT was assessed in 280 individuals comprising 70 remitted patients with SZ, 70 remitted patients with BD and 140 age-, sex- and IQ-matched healthy individuals. Based on the E-V model, we extracted three parameters, 'attention to gains or loses', 'expectancy learning' and 'response consistency', that respectively reflect motivational, cognitive and response selection influences on IGT performance. RESULTS: Both patient groups underperformed in the IGT compared to healthy individuals. However, the source of these deficits was diagnosis specific. Associative learning underlying the representation of expectancies was disrupted in SZ whereas BD was associated with increased incentive salience of gains. These findings were not attributable to non-specific effects of sex, IQ, psychopathology or medication. CONCLUSIONS: Our results point to dissociable processes underlying abnormal incentive decision making in BD and SZ that could potentially be mapped to different neural circuits.

Psychosis Incident Cohort Outcome Study (PICOS). A multisite study of clinical, social and biological characteristics, patterns of care and predictors of outcome in first-episode psychosis. Background, methodology and overview of the patient sample.

AIMS: This paper aims at providing an overview of the background, design and initial findings of Psychosis Incident Cohort Outcome Study (PICOS). METHODS: PICOS is a large multi-site population-based study on first-episode psychosis (FEP) patients attending public mental health services in the Veneto region (Italy) over a 3-year period. PICOS has a naturalistic longitudinal design and it includes three different modules addressing, respectively, clinical and social variables, genetics and brain imaging. Its primary aims are to characterize FEP patients in terms of clinical, psychological and social presentation, and to investigate the relative weight of clinical, environmental and biological factors (i.e. genetics and brain structure/functioning) in predicting the outcome of FEP. RESULTS: An in-depth description of the research methodology is given first. Details on recruitment phase and baseline and follow-up evaluations are then provided. Initial findings relating to patients' baseline assessments are also presented. Future planned analyses are outlined. CONCLUSIONS: Both strengths and limitations of PICOS are discussed in the light of issues not addressed in the current literature on FEP. This study aims at making a substantial contribution to research on FEP patients. It is hoped that the research strategies adopted in PICOS will enhance the convergence of methodologies in ongoing and future studies on FEP.

Linguistic production and syntactic comprehension in schizophrenia and bipolar disorder.

OBJECTIVE: To explore linguistic abilities in schizophrenia and bipolar disorder. Specifically, the aims of this study were to: i) investigate microlinguistic (lexicon, morphology, syntax) and macrolinguistic (discourse coherence, pragmatics) dimensions of speech production and ii) evaluate syntactic comprehension skills in both schizophrenia and bipolar disorder. METHOD: Linguistic performance of 30 Italian-speaking patients with schizophrenia, 30 participants with bipolar disorder and 30 healthy controls comparable for age and educational level has been assessed using a story-telling task and a computer-based test of syntactic comprehension. RESULTS: In narrative production, compared with healthy participants, those with schizophrenia had slight problems in speech rate and deficits at both local and global discourse coherence, whereas patients with bipolar disorder showed reduced mean length of utterance. As regards syntactic comprehension, both groups of patients collected more grammatical errors than controls, but they differed with regard to the number and kind of grammatical construction they missed. CONCLUSION: Linguistic deficits have been detected in both groups of patients, being, however, more severe and generalized in schizophrenia than in bipolar disorder. Such results help us in improving our understanding of the potential psychopathological overlapping between these disorders.

EPA guidance on the quality of mental health services.

The main aim of this guidance of the European Psychiatric Association is to provide evidence-based recommendations on the quality of mental health services in Europe. The recommendations were derived from a systematic search of the best available evidence in the scientific literature, supplemented by information from documents retrieved upon reviewing the identified articles. While most recommendations could be based on empirical studies (although of varying quality), some had to be based on expert opinion alone, but were deemed necessary as well. Another limitation was that the wide variety of service models and service traditions for the mentally ill worldwide often made generalisations difficult. In spite of these limitations, we arrived at 30 recommendations covering structure, process and outcome quality both on a generic and a setting-specific level. Operationalisations for each recommendation with measures to be considered as denominators and numerators are given as well to suggest quality indicators for future benchmarking across European countries. Further pan-European research will need to show whether the implementation of this guidance will lead to improved quality of mental healthcare, and may help to develop useful country-specific cutoffs for the suggested quality indicators.

The influence of gender on clinical and social characteristics of patients at psychosis onset: A report from the Psychosis Incident Cohort Outcome Study (PICOS).

BACKGROUND. This paper examined the hypothesis that males with first-episode psychosis (FEP) experience lower pre-morbid adjustment, greater social disability and more self-perceived needs at illness onset than females(by controlling for duration of untreated psychosis, diagnosis, age and symptoms at onset). Results disconfirming this hypothesis were thought to suggest the potentially mediating role of social context in determining the impact of symptoms and disability on the everyday lives of male patients in the early phase of psychosis. METHOD. A large epidemiologically representative cohort of FEP patients (n=517) was assessed within the Psychosis Incident Cohort Outcome Study (PICOS) framework ­ a multi-site research project examining incident cases of psychosis in Italy's Veneto region. RESULTS. Despite poorer pre-morbid functioning and higher social disability at illness onset, males reported fewer unmet needs in the functioning domain than females did. An analysis of help provided by informal care givers showed that males received more help from their families than females did. This finding led us to disconfirm the second part of the hypothesis and suggest that the impact of poorer social performance and unmet needs on everyday life observed in male patients might be hampered by higher tolerance and more support within the family context.CONCLUSIONS. These findings shed new light on rarely investigated sociocultural and contextual factors that may account for the observed discrepancy between social disability and needs for care in FEP patients. They also point to a need for further research on gender differences, with the ultimate aim of delivering gender-sensitive effective mental health care.

Classification of schizophrenia using feature-based morphometry.

The objective of this study was to use a combined local descriptor, namely scale invariance feature transform (SIFT), and a non linear support vector machine (SVM) technique to automatically classify patients with schizophrenia. The dorsolateral prefrontal cortex (DLPFC), considered a reliable neuroanatomical marker of the disease, was chosen as region of interest (ROI). Fifty-four schizophrenia patients and 54 age- and gender-matched normal controls were studied with a 1.5T MRI (slice thickness 1.25 mm). Three steps were conducted: (1) landmark detection and description of the DLPFC, (2) feature vocabulary construction and Bag-of-Words (BoW) computation for brain representation, (3) SVM classification which adopted the local kernel to implicitly implement the feature matching. Moreover, a new weighting approach was proposed to take into account the discriminant relevance of the detected groups of features. Substantial results were obtained for the classification of the whole dataset (left side 75%, right side 66.38%). The performances were higher when females (left side 84.09%, right side 77.27%) and seniors (left side 81.25%, right side 70.83%) were considered separately. In general, the supervised weighed functions increased the efficacy in all the analyses. No effects of age, gender, antipsychotic treatment and chronicity were shown on DLPFC volumes. This integrated innovative ROI-SVM approach allows to reliably detect subjects with schizophrenia, based on a structural brain marker for the disease such as the DLPFC. Such classification should be performed in first-episode patients in future studies, by considering males and females separately.