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Although language deficits have often been reported in schizophrenia, the specific relevance of single linguistic levels of processing is still under debate. Moreover, little is known about language disturbances in bipolar disorder.
The aims of this study were to:
1) investigate micro-linguistic (lexicon, morphology, syntax) and macro-linguistic (discourse coherence, pragmatics) dimensions of speech production and
2) evaluate syntactic comprehension skills in both schizophrenia and, for the first time, bipolar disorder.
A story telling task and a computer-based test of syntactic comprehension were administered to 30 Italian speaking DSM-IV patients suffering from schizophrenia, 30 participants with bipolar disorder and 30 healthy controls, comparable for age and educational level (p>0.05). Analysis of variance with post-hoc correction was performed to compare linguistic performance between groups.
In comparison to healthy participants, patients with schizophrenia had significantly impaired productivity, syntactic complexity and local/global discourse coherence and bipolar disorder subjects showed deficits in mean length of utterance (p< 0.05). Also, both groups of patients collected more grammatical errors than controls (p< 0.05), but they differed in regard to the grammatical type of construction they missed (passive-affirmative and active-negative, respectively).
Our results showed the presence of both micro and macro-linguistic deficits in linguistic production in schizophrenia, but not in bipolar disorder, suggesting that these abnormalities are specific for schizophrenia. On the contrary, syntactic construction comprehension was altered in both schizophrenia and bipolar disorder, potentially representing the target of innovative rehabilitation strategies.
Several neuroimaging studies have shown impaired microstructural integrity of corpus callosum in schizophrenia, which may support inter-hemispheric misconnection. However, functional connectivity has rarely been investigated in schizophrenia.
To explore inter-hemispheric communication in a sample of patients with schizophrenia in comparison to healthy controls.
Twenty-five patients with schizophrenia and forty-one healthy controls were studied. Subjects were asked to press a key with the index-finger of their right or the left hand as quickly as possible following appearance of either a single or a double stimulus. Two measures were calculated: the difference between manual reaction times (RT) after the presentation of single stimuli to the ipsilateral (uncrossed response) or contralateral (crossed response) visual hemifield (the so-called Poffenberger Paradigm), as a measure of interhemispheric transfer time (ITT), and the difference between double and single stimuli (the Redundant Target Effect, RTE), as a measure of interhemispheric integration.
Overall, patients with schizophrenia responded faster with the left than with the right hand (Paired sample t-test p=0.019). Importantly, in schizophrenics there was no group difference in ITT but there was a significantly enhanced RTE .
The slower RT for right hand in schizophrenics possibly reflects a general delay of the left cerebral hemisphere in visuomotor RT. Moreover, the enhanced RTE suggests an impairment of interhemispheric integration in schizophrenia.
Language disturbances, such as impoverishment, disorganization and dysregulation, are a prominent feature of schizophrenia. Several neuroimaging studies have suggested the superior temporal gyrus (STG) as a likely anatomical substrate of language deficits in schizophrenia. The aim of this study was to verify a correlation between structural measures of STG and Heschl's gyrus (HG) and language dimensions.
An extensive language examination battery, which included narrative and conversational expressive tasks, and syntactic and pragmatic comprehension tests, was administered to 23 schizophrenia patients (mean age±SD= 40.30±11.60) and 21 normal controls (mean age±SD= 42.19±11.05). All subjects also underwent a 1.5T MRI session, and STG and HG were manually traced and volumes were obtained, bilaterally, using Brains2.
Specific language deficits were shown in subjects with schizophrenia compared to healthy individuals (p<0.001), particularly in verbal fluency, syntactic complexity, lexical diversity and metaphor/idiom comprehension. Interestingly, speech fluency significantly directly associated with left STG gray matter volumes in controls (r=0.46, p=0.03) but not in patients (r=-0.27, p=0.21). In contrast, complex syntax and word diversity significantly correlated, respectively, with left and right HG volumes in schizophrenia patients (r=0.45, p=0.02; r=-0.47, p=0.02), but not in controls (p>0.05).
This study confirmed a widespread impairment of language in schizophrenia. Interestingly, distinct language dimensions differently correlated with STG-HG volumes in patients with schizophrenia and controls, particularly with regard to verbal fluency and syntactic measures.
Pragmatic abilities play a crucial role in daily functioning and have been suggested to be impaired in schizophrenia. Nevertheless, patterns of such deficits at the onset of the illness still needs to be elucidated.
To outline pragmatic abilities in the first episode of psychosis (FEP).
To evaluate pragmatic verbal performance and its relationship with pre-frontal abilities in FEP subjects recruited in a large randomized multi-center controlled study (GET UP).
58 FEP (mean age±SD:34±9 years; 46% males) and 58 1:1 matched healthy controls (HC) were assessed on the metaphor and idiom comprehension subtask of the MEC Protocol and with WCST. A PAF Analysis with Promax rotation of open (=spontaneous explanations) and closed (=multiple choice) metaphors/idioms and WCST variables was conducted.
A 3-factor latent structure emerged in both groups but partially different patterns emerged. As for FEP, open metaphor/idiom explanations loaded into Factor 1 (Self-generated inferences); Factor 2 (Feedback-generated inferences) was loaded by WCST perseverative errors and by closed metaphor explanations. Finally, closed metaphors/idioms loaded into Factor 3 (Inhibition). As for HC, Factor 1 was similarly loaded but explained less variance; Factor 2 was qualitatively different (Reasoning, self+feedback-generated inferences), being loaded by the WCST number of categories and by open metaphors/idioms. Factor 3 was loaded by closed metaphors.
Findings suggest a shared underlying cognitive construct in self-generating perceptual inferences both for verbal pragmatics and pre-frontal skills in HC and patients, while a failure to integrate different sources of perceptual evidence is found only in FEP.
Vascular changes in the brain are relevant in schizophrenia [e.g. 1] and in bipolar disorder . The study of first episode psychosis (FEP) allows the analysis of brain morphology and function without confounds due to chronicity.
To characterize brain perfusion in FEP.
To see if FEP exhibit modified perfusion in respect to healthy controls (HC), and identify the most affected brain areas.
We acquired T1 and DSC images of 35 FEP patients (45 +/- 10 years old) and 35 HC (42 +/- 8), using Gadolinium (0.1 mmol/Kg). We computed cerebral blood volume (CBV), cerebral blood flow (CBF) and mean transit time (MTT)  in the whole brain and in left and right frontal, parietal, temporal and occipital lobes, insula, caudate and cerebellum
Mean values of all quantities resulted lower in patients, up to 12% for CBV in right frontal lobe, 11% for CBF in left cerebellum and 16% for MTT in right frontal lobe. We used a support vector machine (SVM) to classify subjects on the basis of the histogram of perfusion values. We found that the classification reached accuracies over 80%, especially in the frontal brain areas.
FEP show altered perfusion parameters, which allow automatic classification with good accuracy, showing that brain vascular characteristics can be considered as marker of psychosis.
 Peruzzo et al (2011). J Neural Transm, 118, 4:563-70.
 Agarwal et al (2008). J Affect Disord, 110, 1-2:106-14.
 Ostergaard et al (1996). Magn Reson Med, 36, 5:715-25.
This paper aims at providing an overview of the background, design and initial findings of Psychosis Incident Cohort Outcome Study (PICOS).
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.
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.
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.
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.
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.
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.
Our results point to dissociable processes underlying abnormal incentive decision making in BD and SZ that could potentially be mapped to different neural circuits.
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.
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.
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.
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.
Several, although not all, of the previous small diffusion-weighted imaging (DWI) studies have shown cortical white-matter disruption in schizophrenia.
To investigate cortical white-matter microstructure with DWI in a large community-based sample of people with schizophrenia.
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.
Compared with controls, the schizophrenia group had significantly greater ADCs in frontal, temporal and occipital white matter (analysis of covariance, P < 0.05).
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.
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