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.

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.

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.

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.

Dorsolateral prefrontal cortex and hippocampus sustain impulsivity and aggressiveness in borderline personality disorder.

BACKGROUND: Borderline Personality Disorder (BPD) patients are characterized by increased levels of aggressivity and reduction of impulse control, which are behavioural dimensions mainly sustained by hippocampus and dorsolateral prefrontal cortex (DLPFC). In this study we aimed at investigating whether hippocampus and DLPFC anatomy may sustain impulsive and aggressive behaviours in BPD. METHODS: Fifteen DSM-IV BPD patients (11 females, 4 males) and fifteen 1:1 matched healthy controls (11 females, 4 males) were studied with a 1.5T magnetic resonance imaging (MRI) and underwent a psychopathological assessment in order to measure the severity of aggressive and impulsive traits. RESULTS: Right hippocampal volumes were significantly reduced in BPD patients compared to healthy subjects (p=0.027), particularly in those with a history of childhood abuse (p=0.01). Moreover, in patients but not in controls, right hippocampal volumes significantly inversely correlated with aggressiveness and DLPFC grey matter volumes significantly inversely associated with impulsiveness (p<0.05). CONCLUSIONS: Our results provide evidence that hippocampus and DLPFC play a separate and unique role in sustaining the control of impulse and aggressive behaviours in BPD patients.

Altered microstructure integrity of the amygdala in schizophrenia: a bimodal MRI and DWI study.

BACKGROUND: The amygdala plays a central role in the fronto-limbic network involved in the processing of emotions. Structural and functional abnormalities of the amygdala have recently been found in schizophrenia, although there are still contradictory results about its reduced or preserved volumes. METHOD: In order to address these contradictory findings and to further elucidate the possibly underlying pathophysiological process of the amygdala, we employed structural magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI), exploring amygdalar volume and microstructural changes in 69 patients with schizophrenia and 72 matched healthy subjects, relating these indices to psychopathological measures. RESULTS: Measuring water diffusivity, the apparent diffusion coefficients (ADCs) for the right amygdala were found to be significantly greater in patients with schizophrenia compared with healthy controls, with a trend for abnormally reduced volumes. Also, significant correlations between mood symptoms and amygdalar volumes were found in schizophrenia. CONCLUSIONS: We therefore provide evidence that schizophrenia is associated with disrupted tissue organization of the right amygdala, despite partially preserved size, which may ultimately lead to abnormal emotional processing in schizophrenia. This result confirms the major role of the amygdala in the pathophysiology of schizophrenia and is discussed with respect to amygdalar structural and functional abnormalities found in patients suffering from this illness.

Brain morphometry by probabilistic latent semantic analysis.

The paper propses a new shape morphometry approach that combines advanced classification techniques with geometric features to identify morphological abnormalities on the brain surface. Our aim is to improve the classification accuracy in distinguishing between normal subjects and schizophrenic patients. The approach is inspired by natural language processing. Local brain surface geometric patterns are quantized to visual words, and their co-occurrences are encoded as visual topic. To do this, a generative model, the probabilistic. Latent Semantic Analysis is learned from quantized shape descriptors (visual words). Finally, we extract from the learned models a generative score, that is used as input of a Support Vector Machine (SVM), defining an hybrid generative/discriminative classification algorithm. An exhaustive experimental section is proposed on a dataset consisting of MRI scans from 64 patients and 60 control subjects. Promising results are reporting by observing accuracies up to 86.13%.

Increased fronto-temporal perfusion in bipolar disorder.

OBJECTIVES: Previous imaging reports showed over-activation of fronto-limbic structures in bipolar patients, particularly in response to emotional stimuli. In this study, for the first time, we used perfusion weighted imaging (PWI) to analyze lobar cerebral blood volume (CBV) in bipolar disorder to further explore the vascular component to its pathophysiology. METHODS: Fourteen patients with DSM-IV bipolar disorder (mean age+/-SD=49.00+/-12.30 years; 6 males, 8 females) and 29 normal controls (mean age+/-SD=45.07+/-10.30 years; 13 males, 16 females) were studied. PWI images were obtained following intravenous injection of paramagnetic contrast agent (Gadolinium-DTPA), with a 1.5 T Siemens magnet using an echo-planar sequence. The contrast of enhancement (CE), was calculated pixel by pixel as the ratio of the maximum signal intensity drop during the passage of contrast agent (Sm) by the baseline pre-bolus signal intensity (So) (CE=Sm/So*100) for frontal, temporal, parietal, and occipital lobes, bilaterally, on two axial images. Higher CE values correspond to lower CBV and viceversa. RESULTS: Bipolar patients had significantly lower CE values in left frontal and temporal lobes (p=0.01 and p=0.03, respectively) and significantly inverse laterality index for frontal lobe (p=0.017) compared to normal controls. No significant correlations between CE measure and age or clinical variables were found (p>0.05). CONCLUSION: This study found increased left frontal and temporal CBV in bipolar disorder. Fronto-temporal hyper-perfusion may sustain over-activation of these structures during emotion modulation, which have been observed in patients with bipolar illness.

Cortical white-matter microstructure in schizophrenia. Diffusion imaging study.

BACKGROUND: Several, although not all, of the previous small diffusion-weighted imaging (DWI) studies have shown cortical white-matter disruption in schizophrenia. AIMS: To investigate cortical white-matter microstructure with DWI in a large community-based sample of people with schizophrenia. METHOD: Sixty-eight people with schizophrenia and 64 healthy controls underwent a session of DWI to obtain the apparent diffusion coefficient (ADC) of white-matter water molecules. Regions of interest were placed in cortical lobes. RESULTS: Compared with controls, the schizophrenia group had significantly greater ADCs in frontal, temporal and occipital white matter (analysis of covariance, P < 0.05). CONCLUSIONS: Our findings confirm the presence of cortical white-matter microstructure disruption in frontal and temporo-occipital lobes in the largest sample of people with schizophrenia thus for studied with this technique. Future brain imaging studies, together with genetic investigations, should further explore white-matter integrity and genes encoding myelin-related protein expression in people with first-episode schizophrenia and those at high risk of developing the disorder.