Anna Comparelli

Emotion recognition impairment is present early and is stable throughout the course of schizophrenia

Individuals with schizophrenia experience problems in the perception of emotion throughout the course of the disorder. Few studies have addressed the progression of the deficit over time. The present investigation explores face emotion recognition (FER) performance throughout the course of schizophrenia. The aim of the study was to test the hypotheses that: 1) FER impairment was present in ultra high-risk (putatively prodromal) individuals, and that 2) impairment was stable across the course of the illness. Forty-three individuals with a putative prodromal syndrome, 50 patients with first episode of schizophrenia, 44 patients with multi-episode schizophrenia and 86 unaffected healthy control subjects were assessed to examine emotion recognition ability. ANCOVA analysis adjusted for possible confounder factors and subsequent planned contrasts with healthy controls was undertaken. The results revealed deficits in recognition of sadness and disgust in prodromal individuals, and of all negative emotions in both first-episode and multi-episode patients. Furthermore, there were no significant differences between clinical groups. Within the framework of the neurodevelopmental model of schizophrenia, our results suggest the presence of emotional recognition impairment before the onset of full-blown psychosis. Moreover, the deficit remains stable over the course of illness, fitting the pattern of a vulnerability indicator in contrast to an indicator of chronicity or severity.

Xanthurenic Acid Activates mGlu2/3 Metabotropic Glutamate Receptors and is a Potential Trait Marker for Schizophrenia

The kynurenine pathway of tryptophan metabolism has been implicated in the pathophysiology of psychiatric disorders, including schizophrenia. We report here that the kynurenine metabolite, xanturenic acid (XA), interacts with, and activates mGlu2 and mGlu3 metabotropic glutamate receptors in heterologous expression systems. However, the molecular nature of this interaction is unknown, and our data cannot exclude that XA acts primarily on other targets, such as the vesicular glutamate transporter, in the CNS. Systemic administration of XA in mice produced antipsychotic-like effects in the MK-801-induced model of hyperactivity. This effect required the presence of mGlu2 receptors and was abrogated by the preferential mGlu2/3 receptor antagonist, LY341495. Because the mGlu2 receptor is a potential drug target in the treatment of schizophrenia, we decided to measure serum levels of XA and other kynurenine metabolites in patients affected by schizophrenia. Serum XA levels were largely reduced in a large cohort of patients affected by schizophrenia, and, in patients with first-episode schizophrenia, levels remained low after 12 months of antipsychotic medication. As opposed to other kynurenine metabolites, XA levels were also significantly reduced in first-degree relatives of patients affected by schizophrenia. We suggest that lowered serum XA levels might represent a novel trait marker for schizophrenia.

Neurocognition in schizophrenia: From prodrome to multi-episode illness

Individuals with schizophrenia present a neuropsychological deficit throughout the course of the disorder. Few studies have addressed the progression of the deficit since the prodromal phase of the disorder. This investigation explored neurocognition in accordance with the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus recommendations. The aim of the study was to explore the presence of neurocognitive impairment in ultra-high-risk individuals and the stage of this impairment in samples at different phases of illness. Thirty-six individuals with a prodromal syndrome, 53 first-episode and 44 multi-episode schizophrenia patients were assessed to examine neuropsychological performance. ANCOVA analysis adjusted for possible confounder factors and planned contrasts with healthy controls were undertaken. The results revealed deficits in speed-of-processing, visual-learning and social-cognition in prodromal individuals, and of all other neuropsychological domains in both first-episode and multi-episode patients. Furthermore impairment was found in the first-episode and in the multi-episode group, respectively on working-memory and attention. Within the framework of the neurodevelopmental model of schizophrenia, our results suggest the presence of neuropsychological impairment before the onset of full-blown psychosis. Moreover, the deficits are larger in the more chronic groups, according to the theory of an ongoing neurodevelopmental alteration.

Structural brain alterations in bipolar disorder II: a combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) study.

BACKGROUND Brain structural changes have been described in bipolar disorder (BP), but usually studies focused on both I and II subtypes indiscriminately and investigated changes in either brain volume or white matter (WM) integrity. We used combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis to track changes in the grey matter (GM) and WM in the brains of patients affected by BPII, as compared to healthy controls. METHODS Using VBM and DTI, we scanned 20 DSM-IV-TR BPII patients in their euthymic phase and 21 healthy, age- and gender-matched volunteers with no psychiatric history. RESULTS VBM showed decreases in GM of BPII patients, compared to controls, which were diffuse in nature and most prominent in the right middle frontal gyrus and in the right superior temporal gurus. DTI showed significant and widespread FA reduction in BPII patients in all major WM tracts, including cortico-cortical association tracts. LIMITATIONS The small sample size limits the generalisability of our findings. CONCLUSIONS Reduced GM volumes and WM integrity changes in BPII patients are not prominent like those previously reported in bipolar disorder type-I and involve cortical structures and their related association tracts.

Symptom Correlates of Facial Emotion Recognition Impairment in Schizophrenia

Background: The ability to facial emotion recognition (FER), a key component of socioemotional competence, is often impaired in schizophrenic disorders. The purpose of the present study was to examine the relationship between emotion recognition performance and symptoms in a group of patients with schizophrenia spectrum disorders. Sampling and Methods: Seventy-nine patients meeting DSM-IV-TR criteria for schizophrenia, schizophreniform disorder and schizoaffective disorder were assessed by the Positive and Negative Syndrome Scale and a FER task. In schizophrenia patients and healthy control subjects, FER performance was compared. In order to avoid a possible confounding role of cognitive impairment, we carried out partial correlations corrected for an index of global cognition. Results: Patients performed worse than a healthy control group on all negative emotions. Partial correlations showed that cognitive/disorganized symptoms correlated with a worse performance in the FER task, whereas no correlations were found with positive, negative, excitement and depressive symptoms. Conclusions: Our findings support that in schizophrenia FER impairment is specific for negative emotions and that there is a relationship between this deficit and cognitive/disorganized symptoms, regardless of the general cognitive level.

Neurological soft signs discriminate schizophrenia from bipolar disorder

Background. Although neurological soft signs have been consistently described in patients with schizophrenia, their diagnostic specificity is not well clarified. Methods. To test the hypothesis that neurological soft signs are specifically related to schizophrenia, we examined 305 subjects (patients with schizophrenia-spectrum disorder, n=167; patients with bipolar I disorder, n=88; controls, n=50). Neurological soft signs were assessed using the Neurological Evaluation Scale (NES). Multiple logistic regression analysis was used to compute the diagnostic predictive power of neurological soft signs. Results. Patients in the schizophrenia-spectrum disorder group were found to have significantly greater neurological impairment (NES total score=23.9, standard deviation [SD] 11.2) than those in the bipolar disorder group (NES total score=18.2, SD 7.6; p<0.001). Neurological functioning was closely associated with psychopathology (all p<0.001). The NES total score reliably distinguished patients with schizophrenia spectrum disorders from those with bipolar disorder in 68.7% of the cases (p<0.001). Moreover, a particular set of neurological soft signs showed specificity for the schizophrenia-spectrum disorder diagnostic group. Conclusions. Our findings suggest that schizophrenia and bipolar disorder can be distinguished in terms of neurological impairment. Furthermore, we recommend the utility of neurological soft signs as a useful, quantifiable, sensitive, and inexpensive tool for the diagnostic work-up of schizophrenia. (Journal of Psychiatric Practice 2014;20:147–153)

Relationships between psychopathological variables and insight in psychosis risk syndrome and first-episode and multiepisode schizophrenia

Abstract Insight may vary across psychosis risk syndrome (PRS), first-episode schizophrenia (FES), or multiepisode schizophrenia (MES). We aimed to compare insight domains (awareness, relabeling, and compliance) in PRS, FES, and MES groups and to correlate scores with psychopathological measures. Insight was assessed in 48 (14 PRS, 16 FES, and 18 MES) patients using the Schedule for the Assessment of Insight–Expanded Version. We conducted psychopathological assessment through the Brief Psychiatric Rating Scale (BPRS). In the whole group, the BPRS psychosis factor correlated with all insight domains. In the MES group, the more severe the anxiety/depression, the higher the insight score in the symptom relabeling domain. Insight did not differ significantly between the PRS, FES, and MES groups. Our results suggest that, across different phases of the illness, lack of insight behaves like a trait and is modulated by positive symptom severity. Anxiety and depression may be associated with increased insight in patients with chronic schizophrenia.

Anatomical substrates of cognitive and clinical dimensions in first episode schizophrenia

To explore gray (GM) and white matter (WM) abnormalities and the relationships with neuropsychopathology in first‐episode schizophrenia (FES).

Pathways to functional outcome in subjects with schizophrenia living in the community and their unaffected first-degree relatives

RATIONALE Variables influencing real-life functioning have repeatedly been modeled in schizophrenia subjects but not systematically investigated in their unaffected first-degree relatives (SRs), in whom milder forms of deficits reported in schizophrenia have been observed, but confounders of clinical cohorts are not in play. Demonstrating that pathways to functional outcome are similar between patients and SRs would validate structural models developed in schizophrenia subjects. The present multicenter study aimed to explore whether variables associated with real-life functioning are similar in schizophrenia patients and their unaffected relatives. METHODS The study sample included 921 schizophrenia patients, 379 SRs and 780 healthy controls. Structural Equation Models (SEMs) were used in patients and SRs to test associations of psychopathological dimensions, neurocognition, social cognition, resilience, perceived stigma and functional capacity with real-life functioning domains, impaired in both patients and SRs. RESULTS Interpersonal Relationships and Work Skills were the only functional domains impaired in both patients and SRs. For both domains, functional impairment in patients was found to predict impairment in unaffected relatives, suggesting the involvement of similar illness-related vulnerability factors. In both groups variables significantly associated with Interpersonal Relationships included Social Cognition, Neurocognition, Avolition, Resilience, Disorganization, Perceived Stigma and Gender, and those significantly associated with Work Skills included Social Cognition, Neurocognition and Disorganization. CONCLUSIONS Pathways to functional outcome for Interpersonal relationships and Work skills are similar between schizophrenia patients and their unaffected first-degree relatives. These findings validate, in the absence of confounders of clinical cohorts, structural models of determinants of functional outcome in people with schizophrenia.

White matter microstructure in ultra-high risk and first episode schizophrenia: A prospective study

There is increasing evidence of white matter (WM) pathology in schizophrenia, but its role at the very early stage of the disorder remains unclear. In an exploration of WM microstructure in ultra-high risk (UHR) subjects and first episode schizophrenia (FES), 34 FES, 27 UHR and 26 healthy control (HC) subjects underwent a magnetic resonance imaging (MRI) tract based spatial statistics (TBSS) investigation. Whole brain fractional anisotropy (FA), mean diffusivity (MD), radial (RD) and axial diffusivity (AD) values were extracted. UHR subjects who later developed psychosis showed lower FA compared with HC in the corpus callosum (CC), the left superior and inferior longitudinal fasciculus, the left inferior fronto-occipital fasciculs (IFO), and the forceps; RD was significantly higher in the CC, the forceps, the anterior thalamic radiation bilaterally, and the cingulum bundle. FES, compared to HC, showed a significant FA reduction of the CC, the superior and inferior longitudinal fasciculi bilaterally, the IFO bilaterally, the corona radiate bilaterally, and the forceps; while RD was found to be significantly increased in the left superior longitudinal fasciculus. UHR who later developed psychosis had WM abnormalities affecting brain pathways that are crucial for intra- and inter-hemispheric connections.