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Over the past 50 years, the application of structural neuroimaging techniques to schizophrenia research has added relevant information about the pathophysiology of the disorder. Several lines of investigation gave strong evidence that schizophrenia is associated with multiple subtle brain abnormalities that involve both cerebral grey and white matter volumes and structure. The time of onset and longitudinal course of brain morphological abnormalities support the notion that brain pathology of schizophrenia has a neurodevelopmental component and a progressive course, although several confounders of brain changes should be carefully taken into account. Brain anomalies detected before and close to the onset of schizophrenia are likely to be unrelated to confounders of brain changes such as antipsychotic drug treatment, duration of illness or illicit substance abuse, i.e. they related to the pathological process of the disorder per se. Nonetheless, clinically useful diagnostic or prognostic biomarkers have not derived from neuroimaging studies and this is likely related to the neurobiological heterogeneity of the disorder. Thus, there is the compelling need to set new methodological standards for developing innovative hypothesis-driven studies to overcome what we have missed to date in neuroimaging research in schizophrenia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cannabis use is considered an important risk factor for the development of psychotic illness and is associated with worse outcomes of the disorder. This study aimed to determine through a meta-analytic approach whether patients at the onset of schizophrenia with comorbid cannabis use (SCH CU+) show a different pattern of brain abnormalities as compared to patients with no comorbid cannabis use (SCH CU-). Ten Magnetic Resonance Imaging (MRI) studies were identified as suitable for analysis leading to the inclusion of n= 465 patients with schizophrenia (n= 227 SCH CU+ and n= 238 SCH CU-) and n= 366 healthy controls. Compared to healthy controls, both SCH CU+ and SCH CU- patients showed reduction of whole brain, total grey matter and hippocampal volumes. The direct comparison of SCH CU+ and SCH CU- patients, including up to 5 independent studies, did not demonstrate significant differences of brain volumes between the two groups even though total and regional grey matter volume deficits were more prominent in SCH CU+ patients. The available literature data indicate that, essentially, there is an overlap of brain abnormalities in SCH CU+ and SCH CU- patients at the onset of schizophrenia. The common vs specific trajectories of brain pathomorphology in SCH CU+ and SCH CU- patients are discussed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Recently, Kuo and Pogue-Geile (2019) quantitatively reviewed Magnetic Resonance Imaging (MRI) findings in patients with schizophrenia demonstrating, besides altered volume of several brain structures significantly greater structural variability in patients relative to controls as for intracranial, lateral and third ventricles volumes. We believe that additional points could be usefully included in the discussion of the conceptual meaning of these findings. In this commentary, first we highlight the role of potential confounding factors such as antipsychotic medication intake and duration of illness when interpreting MRI data in schizophrenia. Second, we discuss the finding of greater variability of cerebral structure volumes in the broader context of the pathophysiology and time course of brain abnormalities in the disease., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Cognitive remediation therapy (CRT) has been reported to positively affect neurocognitive processes among patients with schizophrenia; however, the degree to which changes in cognition is linked to improved clinical symptoms, remains poorly understood. The current study aimed to investigate whether cognitive gains were associated to improvements in negative symptoms' severity in patients with schizophrenia living in two Italian psychiatric facilities., Methods: Patients with a diagnosis of schizophrenia were consecutively assigned to CRT (n = 33) and compared with an historical control group (n = 28). Assessments were performed at baseline and post-treatment using a neuropsychological battery (Trail Making Test A and B, Self-Ordered Pointing Task, California Verbal Learning Test), along with clinical and functioning measures., Results: Visual attention (TMT-A score change) was found as the only significant predictor of improvement in negative symptoms subscale of the Positive and Negative Syndrome Scale. Furthermore, a mediation path analysis confirmed that better performance in visual attention acts as mediator of the positive association between CRT intervention and lower post-treatment negative symptoms score., Conclusions: CRT can have a positive impact on a measure of visual attention in patients with schizophrenia and on negative symptoms reduction that is mediated by this significant intervention effect.

Background: Deficits in cortical gray matter (GM) have been found in patients with schizophrenia, with evidence of progression over time. The aim of this study was to determine the role of potential moderators of such changes, in particular of the amount and type of antipsychotic medication intake., Methods: Longitudinal magnetic resonance imaging studies comparing changes in the volume of cortical GM over time between patients with schizophrenia and healthy control subjects published between January 1, 1983, and March 31, 2014, were analyzed. Hedges' g was calculated for each study and volume changes from baseline to follow-up were analyzed. Meta-regression statistics were applied to investigate the role of potential moderators of the effect sizes., Results: Eighteen studies involving 1155 patients with schizophrenia and 911 healthy control subjects were included. Over time, patients with schizophrenia showed a significantly higher loss of total cortical GM volume. This was related to cumulative antipsychotic intake during the interval between scans in the whole study sample. Subgroup meta-analyses of studies on patients treated with second-generation antipsychotics and first-generation antipsychotics revealed a different and contrasting moderating role of medication intake on cortical GM changes: more progressive GM loss correlated with higher mean daily antipsychotic intake in patients treated with at least one first-generation antipsychotic and less progressive GM loss with higher mean daily antipsychotic intake in patients treated only with second-generation antipsychotics., Conclusions: These findings add useful information to the controversial debate on the brain structural effects of antipsychotic medication and may have both clinical relevance and theoretical implications., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Although the efficacy of cognitive remediation interventions has been demonstrated in several experimental studies on schizophrenia, few studies have investigated the predictors of response to such interventions. We were interested in determining what factors contribute to a positive outcome after cognitive rehabilitation and whether different factors are associated with different degrees of improvement in cognitive and real-world functioning in individual patients after cognitive remediation., Methods: The study sample consisted of 56 patients with schizophrenia who had completed a 6-month cognitive remediation intervention and showed different cognitive and functional outcomes. Measures of cognitive and functional amelioration after cognitive remediation were analyzed in relation to patients' clinical, neuropsychological and functional variables at baseline using logistic regression analysis., Results: Lower antipsychotic intake at baseline predicted cognitive improvement, whereas lower antipsychotic intake, severity of specific symptoms, and higher neurocognitive functioning (particularly executive functions and verbal memory) at baseline were associated with cognitive normalization after remediation treatment. Functional improvement was predicted by lower patient age and type of cognitive remediation intervention, whereas functional normalization was related to lower baseline antipsychotic intake and, at a trend level, to higher executive functioning and type of cognitive remediation intervention., Conclusion: Cognitive remediation could be more effective in younger, less disorganized, and cognitively less impaired patients, who take a smaller amount of antipsychotics. The predictive role of lower antipsychotic dosage on cognitive and functional outcome after remediation suggests either that patients with less severe illness could gain better advantage from cognitive remediation interventions or that high dose or complex antipsychotic therapy may limit the effectiveness of such interventions., (© 2013 Elsevier B.V. All rights reserved.)

Introduction: The Schizophrenia Cognition Rating Scale (SCoRS), an interview-based assessment of cognition, has proved to be a valid measure of cognitive performance in patients with schizophrenia., Objective: The aims of this study were to analyze the validity of this scale in a naturalistic setting representative of the Italian system of psychiatric care, and to test whether the SCoRS could be appropriately used in different phases of illness and contexts of care., Methods: Eighty-six patients with schizophrenia (DSM-IV-TR criteria) (N = 59 clinically stabilized patients; N = 27 recently hospitalized patients) were administered the SCoRS. The reliability of SCoRS was assessed and global ratings were correlated with neurocognitive, clinical, and psychosocial functioning measures., Results: SCoRS inter-rater and test-retest reliability were high. In clinically stabilized patients, SCoRS global ratings were significantly correlated with composite scores of cognitive performance (global cognitive index: r = -0.570, P<0.001), symptoms (Positive and Negative Syndrome Scale (PANSS) total score: r = 0.602, P < 0.001), and psychosocial functioning (Global Assessment of Functioning (GAF): r = -0.532, P<0.001; Health of the Nation Outcome Scale (HoNOS): r = 0.433, P < 0.001). On the other hand, no such correlations were found in recently hospitalized patients. Correlations with neuropsychological and functional measures were less significant as the severity of the patients' symptoms, especially positive symptoms, increased., Conclusion: The SCoRS is a valid measure of cognitive performance and is related to psychosocial functioning, especially in clinically stable patients with schizophrenia. The usefulness of the SCoRS in patients recently admitted to hospital for an acute phase of illness is uncertain., (Copyright © 2013 Elsevier B.V. All rights reserved.)

In recent years, measurement of the effectiveness of antipsychotic therapy in schizophrenia has received increasing attention from clinicians and researchers. Several studies have used time to antipsychotic discontinuation for any reason as a global index of antipsychotic effectiveness because it reflects both the physician's and patient's judgment of drug efficacy and tolerability. In this study, we extend this approach by analyzing the rate of discontinuation for different reasons of antipsychotics administered to patients with schizophrenia in a naturalistic setting of care, and explore the determinants of such discontinuation. Ninety-nine patients with schizophrenia who received a first or second generation antipsychotic were followed for 18 months in the Italian outpatient community psychiatric system. We found discontinuation rates for different reasons to be variable and to be influenced by several factors not involving the type of pharmacologic therapy. Some of these factors, such as the frequency of visits to the care unit, underline the need to take into account the role of the care delivery system as potentially influencing the effectiveness of antipsychotics in the "real world"., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Cortical gray matter deficits have been found in patients with schizophrenia, with evidence of progression over time. The aim of this study was to determine the extent of progressive cortical gray matter volume changes over time in schizophrenia, their site and time of occurrence, and the role of potential moderators of brain changes. English language articles published between 1 January 1983 and 31 March 2012 in the MEDLINE and EMBASE databases were searched. Longitudinal magnetic resonance imaging studies comparing changes in cortical gray matter volume over time between patients with schizophrenia and healthy controls were included. Hedges g was calculated for each study. Analyses were performed using fixed- and random-effects models. A subgroup analysis was run to explore the pattern of brain changes in patients with first-episode schizophrenia. A meta-regression statistic was adopted to investigate the role of potential moderators of the effect sizes (ESs). A total of 19 studies, analyzing 813 patients with schizophrenia and 718 healthy controls, were included. Over time, patients with schizophrenia showed a significantly higher volume loss of total cortical gray matter, left superior temporal gyrus (STG), left anterior STG, left Heschl gyrus, left planum temporale and posterior STG bilaterally. Meta-analysis of first-episode schizophrenic patients showed a more significant pattern of progressive loss of whole cerebral gray matter volume involving the frontal, temporal and parietal lobes, and left Heschl gyrus compared with healthy controls. Clinical, pharmacologic and neuroradiological variables were found to be significant moderators of brain volume changes in patients with schizophrenia. The meta-analysis demonstrates that progressive cortical gray matter changes in schizophrenia occur with regional and temporal specificity. The underlying pathological process appears to be especially active in the first stages of the disease, affects the left hemisphere and the superior temporal structures more and is at least partly moderated by the type of pharmacological treatment received.

Background: The aim of cognitive remediation is to target the cognitive impairments of patients with psychosis, including attentional deficits, memory problems, and limitations in planning and problem solving. It is hoped that by addressing these deficits, patients will be more able to take advantage of other interventions and will be more able to function in social and other domains. Many results in controlled trials of cognitive remediation in adult patients affected by schizophrenia have demonstrated its effectiveness on different cognitive domains and on patient's functioning. Some researchers speculate that deficits in cognition are more amenable to remediation during earlier phases of illness than when chronicity has developed. For these reasons cognitive rehabilitation should be a key component of early intervention programs, seeking to produce durable functional changes in the early course of schizophrenia. Although there is strong evidence that cognitive remediation is effective in adult schizophrenia, there is little evidence about its efficacy and long-term generalized effectiveness in the early course of the disease, and its possible application in the prodromal phase of the disease., Purpose of Review: The aim of this paper is to review the available literature on cognitive remediation in the prodromal phase and in the early course of schizophrenia. This review summarizes especially findings of cognitive changes induced in the early course or in the prodromal phases of schizophrenia by different remediation methods. Controlled studies of cognitive training are discussed in more detail., Conclusion: Few studies on the effects of cognitive training programs have been conducted in first episode or in early schizophrenia and only one study has been conducted in the prodromal phase of the disease. Although preliminary positive results have been achieved, more empirical research is needed to confirm the efficacy of cognitive remediation in the early course of schizophrenia, and future studies should address the issue of the usefulness of cognitive remediation in the prodromes of psychosis.

A number of structural brain imaging studies and meta-analytic reviews have shown that multiple subtle brain abnormalities are consistently found in schizophrenia and bipolar disorder. Several studies suggest that schizophrenia and affective psychoses share a largely common pattern of brain abnormalities. Aim of the present study was to compare, by means of a meta-analytic approach, brain structural abnormalities, as detected by Magnetic Resonance Imaging (MRI), found at the onset of schizophrenia and bipolar disorder in order to address the question of the specificity of brain abnormalities across diagnostic groups. Forty-five studies were identified as suitable for analysis. In both schizophrenic and bipolar patients significant overall effect sizes were demonstrated for intracranial, whole brain, total grey and white matter volume reduction as well as for an increase of lateral ventricular volume at disease onset. Thus, the available literature data strongly indicate that some brain abnormalities are already present in first-episode schizophrenia or bipolar disorder and that there is a significant overlap of brain abnormalities in affective and non-affective psychotic disorders at the onset of the disease. However, whole grey matter volume deficits and lateral ventricular enlargement appear to be more prominent in first-episode schizophrenia whereas white matter volume reduction seems more prominent in bipolar disorder. The common vs specific trajectories of brain pathomorphology in schizophrenia and bipolar disorder are discussed.

Objectives: The efficacy of cognitive remediation interventions in schizophrenia has been demonstrated in several experimental studies. However, the effectiveness of such treatments in the usual setting of care of schizophrenia and a direct comparison of different modalities of interventions have not been systematically analyzed. The aim of the study was to assess the effectiveness of the cognitive subprograms of Integrated Psychological Therapy (IPT-cog) and of a computer-assisted cognitive remediation (CACR) method on symptomatological, neuropsychological and functional outcome measures in schizophrenia., Methods: Ninety patients with schizophrenia were assigned to IPT-cog, CACR or usual rehabilitative interventions (REHAB) in a naturalistic setting of care. Clinical, neuropsychological, and functional outcome variables were assessed at baseline and after 24 weeks of treatment., Results: Both the IPT-cog and CACR groups improved more than the comparison group with respect to all outcome variables. The more responsive cognitive domains were speed of processing and working memory. The effectiveness of the 2 remediation methods on the outcome dimensions considered was comparable. However, IPT-cog, but not CACR, was more effective than REHAB on speed of processing, and the CACR group had better outcome than both the REHAB and the IPT-cog groups when the Health of the Nation Outcome Scale was considered. Few correlations between neurocognitive and functional outcome changes were found., Conclusions: The study demonstrates the effectiveness, although nongeneralized, of IPT-cog and CACR in schizophrenia when applied within a psychiatric and psychosocial treatment regimen representative of the usual setting and modality of care, with no evident superiority of any of the methods, and indicates that the changes in functional outcome during treatment are modestly mediated by improvement in specific cognitive domains., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Cognitive dysfunction has been demonstrated in patients with schizophrenia, and this may affect patients' functional outcome. The improvement of such dysfunction by means of cognitive remediation interventions has become a relevant target in the care of schizophrenia., Objective: To assess the effectiveness of the cognitive subprograms of Integrated Psychological Therapy (IPT) on symptomatological, neuropsychological and functional outcome variables and to analyze the relationships between cognitive and functional outcome changes in schizophrenia., Methods: Thirty-two patients with schizophrenia were assigned to cognitive remediation (IPT-cog) or usual rehabilitative interventions in a naturalistic setting of care. Clinical, neuropsychological and functional outcome variables were assessed at baseline and after 24 weeks of treatment., Results: The IPT-cog group improved significantly more than the comparison group with respect to psychopathological and functional outcome variables. Moreover, only the IPT-cog group improved significantly in the neuropsychological domains of verbal and working memory, with specific significant correlations between neurocognitive performance and functional outcome changes., Conclusions: The results of the study confirm the effectiveness of the cognitive remediation component of IPT in schizophrenia, and indicate that some of the changes in functional outcome may be mediated by improvement in specific cognitive domains., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Negative symptoms of schizophrenia have generally been found in association with ventricular enlargement and prefrontal abnormalities. These relationships, however, have not been observed consistently, most probably because negative symptoms are heterogeneous and result from different pathophysiological mechanisms. The concept of deficit schizophrenia (DS) was introduced by Carpenter et al to identify a clinically homogeneous subgroup of patients characterized by the presence of primary and enduring negative symptoms. Findings of brain structural abnormalities reported by magnetic resonance imaging (MRI) studies focusing on DS have been mixed. The present study included 34 patients with DS, 32 with nondeficit schizophrenia (NDS), and 31 healthy comparison subjects, providing the largest set of MRI findings in DS published so far. The Schedule for the Deficit Syndrome was used to categorize patients as DS or NDS patients. The 2 patient groups were matched on age and gender and did not differ on clinical variables, except for higher scores on the negative dimension and more impaired interpersonal relationships in DS than in NDS subjects. Lateral ventricles were larger in NDS than in control subjects but were not enlarged in patients with DS. The cingulate gyri volume was smaller in NDS but not in DS patients as compared with healthy subjects. Both groups had smaller dorsolateral prefrontal cortex and temporal lobes than healthy subjects, but DS patients had significantly less right temporal lobe volume as compared with NDS patients. These findings do not support the hypothesis that DS is the extreme end of a severity continuum within schizophrenia.

This paper analyses the effects of antipsychotic drug treatment on cerebral structure and function in schizophrenia reviewing qualitatively some of the relevant literature on the issue. Magnetic resonance imaging (MRI) studies of brain morphology in patients at different stages of illness and after varying times of neuroleptic exposure and longitudinal studies show possible different effects of first and second generation antipsychotics. This is true also for functional parameters, such as regional cerebral blood flow and metabolism, analysed, both in resting condition and after specific activation paradigms, with such diverse techniques as positron emission tomography (PET), single photon emission computed tomography (SPECT), functional MRI and MR spectroscopy. The possible molecular mechanisms underlying such differences and whether they represent direct drug effects or indirect consequences of their different and specific interactions with the 'natural' pathophysiological trajectory of brain abnormalities in schizophrenia are matter of present research and debate.

Background: A number of meta-analytic reviews of structural brain imaging studies have shown that multiple subtle brain abnormalities are consistently found in schizophrenia. However, quantitative reviews till now published have included mainly studies performed on chronic schizophrenic patients but have failed to provide clear information on specific, possibly different, findings in first-episode schizophrenia., Methods: We performed a systematic search for MRI studies that reported quantitative measurements of volumes of brain regions in first-episode schizophrenic patients and in healthy controls. Twelve meta-analyses were performed for 6 cerebral regions., Results: Twenty-one studies were identified as suitable for analysis. Significant overall effect sizes were demonstrated for lateral and third ventricular volume increase, and for volume reduction of whole brain and hippocampus, but not for temporal lobe, amygdala and total intracranial volumes., Conclusions: The available literature data strongly indicate that some brain abnormalities are already present in first-episode schizophrenic patients. However, unlike the results of published meta-analyses conducted primarily on samples of chronic schizophrenic patients, the present study did not confirm a significant reduction of temporal lobe or amygdala volumes in first-episode schizophrenia. These findings support the hypothesis of different patterns of involvement of various cerebral areas over the time course of schizophrenia.

Cognitive deficits are a core feature of schizophrenia and the need for a simple and reliable method for assessment of cognitive functions in schizophrenia is well recognized. The Schizophrenia Cognition Rating Scale (SCoRS) has proved to be a valid measure of neurocognitive performance and to correlate with the psychosocial functioning of schizophrenic patients. Aim of the present study was to investigate the correlations among global ratings of the Italian version of the SCoRS and measures of cognitive performance, symptoms severity and psychosocial functioning in schizophrenic subjects. We intended also to test the SCoRS sensitiviity to change over time, in relation also to changes of the above mentioned clinical, neurocognitive and outcome parameters. Forty-eight patients with schizophrenia (29 males, 19 female; mean age 39.1 years) were assessed at baseline and after three months of usual outpatient treatment according to the Italian community assertive treatment program, with the following instruments: 1)SCoRS; 2)comprehensive neuropsychological battery; 3)the Positive And Negative Syndrome Scale and the Clinical Global Impression; 4)the Global Assessment of Functioning, the Health of the Nation Outcome Scale, the Camberwell Assessment of Needs scale. At baseline, SCoRS global ratings significantly correlated with the composite scores of cognitive performance, with positive, negative and total PANSS scores and with all measures of psychosocial functioning. Conversely, SCoRS global ratings did not change significantly over the 3-month follow up and the changes from baseline did not significantly correlate with the changes of neurocognitive, clinical and functional assessments over the same time period. [ABSTRACT FROM AUTHOR]