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The prediction and prevention of aggression in individuals with schizophrenia remains a top priority within forensic psychiatric settings. While risk assessment methods are well rooted in forensic psychiatry, there are no available tools to predict longitudinal physical aggression in patients with schizophrenia within forensic settings at an individual level. In the present study, we used evidence-based risk and protective factors, as well as variables related to course of treatment assessed at baseline, to predict prospective incidents of physical aggression (4-month, 12-month, and 18-month follow-up) among 151 patients with schizophrenia within the forensic mental healthcare system. Across our HARM models, the balanced accuracy (sensitivity + specificity/2) of predicting physical aggressive incidents in patients with schizophrenia ranged from 59.73 to 87.33% at 4-month follow-up, 68.31-80.10% at 12-month follow-up, and 46.22-81.63% at 18-month follow-up, respectively. Additionally, we developed separate models, using clinician rated clinical judgement of short term and immediate violent risk, as a measure of comparison. Several modifiable evidence-based predictors of prospective physical aggression in schizophrenia were identified, including impulse control, substance abuse, impulsivity, treatment non-adherence, mood and psychotic symptoms, substance abuse, and poor family support. To the best of our knowledge, our HARM models are the first to predict longitudinal physical aggression at an individual level in patients with schizophrenia in forensic settings. However, it is important to caution that since these machine learning models were developed in the context of forensic settings, they may not be generalisable to individuals with schizophrenia more broadly. Moreover, a low base rate of physical aggression was observed in the testing set (6.0-11.6% across timepoints). As such, larger cohorts will be required to determine the replicability of these findings., Competing Interests: Declaration of competing interest Devon Watts reports a CIHR Doctoral Scholarship, outside of the submitted work. Taiane de Azevedo Cardoso reports a CIHR Postdoctoral Scholarship, outside of the submitted work. Heather Moulden, Mini Mamak, Casey Upfold, and Gary Chaimowitz report no biomedical financial interests or potential conflicts of interest. Flávio Kapczinski reports personal fees from Daiichi sankyo, and Janssen-Cilag; grants from Stanley Medical Research Institute 07TGF/1148, grants from INCT - CNPq 465458/2014-9, and from the Canadian Foundation for Innovation - CFI, outside the submitted work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The objective of this study was to compare the expression of genes involved in the reelin pathway, in the post-mortem brain of individuals with schizophrenia (SZ) and mood disorders (MD) with a healthy control (HC) group; and to investigate the role f body mass index (BMI) as a potential mediator. The "Gene Expression in Postmortem dlPFC and Hippocampus from Schizophrenia and Mood Disorders" study holds microarray data on individuals with SZ, MD and HCs (from whom 849 specimens are from the dlPFC and 579 from the hippocampus). mRNA data was obtained using HumanHT-12 v4 BeadChip arrays (Illumina). Multivariate analysis of covariance were used to investigate the main effects of group and relevant covariates on RELNm, NOTCH1, GRIN1m, GRIN3A, CAMK2Gm, CAMK2A, CAMK2Bm, CAMK2N2, GRIN2Bm, GRIN2A, CREBBPm, APOE, LDLR and DAB1 gene expression. In the dlPFC, individuals with SZ had higher expression, relative to HCs, of APOE. Individuals with MD had higher expression, relative to HCs, of CAMK2A, CAMK2N2, and GRIN2Bm. Moreover, individuals with MD had higher expression, relative to SZ patients, of CAMK2N2. There were significant group by BMI effects for expression of RELN, CAMK2A, CAMK2N2, and GRIN2A. In the hippocampus, individuals with MD had lower expression, relative to HCs, of APOE. The results of this study suggest that the expression of genes related to the reelin pathway could be different between individuals with SZ and MD and healthy controls, with a greater vulnerability associated with greater BMI., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Schizophrenia (SZ) is a debilitating neurodevelopmental disorder that strikes at a critical period of a young person's life. Its pathophysiology could be the result of deregulation of synaptic plasticity, with downstream alterations of inflammatory immune processes regulate by cytokines, impaired antioxidant defense and increased lipid peroxidation. The aim of this study was to examine serum oxidative stress markers and inflammatory cytokines in early and late phases of chronic SZ. Twenty-two patients at early stage (within first 10 years of a psychotic episode), 39 at late stage (minimum 10 years after diagnosis of SZ) and their respective matched controls were included. Each subject had 5 ml blood samples collected by venipuncture to examined thiobarbituric acid-reactive substances (TBARS), total reactive antioxidant potential (TRAP), protein carbonyl content (PCC), Interleukins 6 and 10 (IL-6, IL-10) and tumor necrosis factor alpha (TNF-alpha). TBARS, IL-6 and PCC levels were significantly higher in patients with SZ at early and late stages than in controls. There were no differences for TRAP and TNF-alpha levels in patients with SZ at early and late stages than in controls. IL-10 levels were decreased in patients at late stage and a decrease trend in early stage was found. Results provided evidence consistent with comparable biological markers across chronic SZ. The concept of biochemical staging proposed by others for bipolar disorder is not seen in this cohort of patients with SZ, at least for cytokines and oxidative stress markers. Our findings reinforce the need of assessment of individuals in ultra high risk to develop psychosis and first-episode population., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: About two-thirds of patients with bipolar disorder (BD) have a lifetime history of at least one psychotic symptom., Objective: To compare the neurocognitive performance of four groups: BD patients with and without a history of psychotic symptoms (BD HPS+ and BD HPS-, respectively); patients with schizophrenia (SZ); and healthy control (HC) subjects., Method: In this cross-sectional study, 35 stabilized patients with SZ, 79 euthymic (44 HPS+ and 35 HPS-) patients with BD, and 50 HC were administered a comprehensive battery of neuropsychological tests., Results: There was worse neurocognitive functioning in both BD and SZ patients compared to HC. Overall, data from both groups of BD patients did not differ on sociodemographic, clinical, or neurocognitive variables. However, BD HPS+ patients had significantly more negative symptoms, as measured by the Positive and Negative Syndrome Scale (PANSS), and showed a trend toward worse performance on executive functions compared to BD HPS- patients. Moreover, both BD groups had better performance on all neurocognitive tests compared to SZ group., Conclusions: Neurocognitive dysfunction may be more marked in SZ than in BD, yet qualitatively similar. A history of past psychotic symptoms in BD was not associated with more severe cognitive impairment during euthymia. Therefore, BD with psychotic symptoms does not appear to be a distinct neurocognitive phenotype.

Objective: Previous reports suggest that cytokines act as potential mediators of the interaction between the immune and neuroendocrine systems, and that a proinflammatory state may be associated with bipolar disorder and schizophrenia. The aim is to compare cytokine levels in both disorders., Method: Twenty euthymic bipolar disorder patients, 53 chronic stabilized schizophrenia patients and 80 healthy controls were recruited. Subjects were all non-smokers and non-obese. Cytokines TNF-α, IL-6, and IL-10 were examined by sandwich ELISA., Results: IL-6 levels were increased in schizophrenia patients when compared to controls (p < 0.0001) and euthymic bipolar disorder patients (p < 0.0001). IL-6 levels were no different in controls compared to euthymic bipolar disorder patients (p = 0.357). IL-10 was lower in controls compared to schizophrenia patients (p = 0.001) or to bipolar disorder patients (p = 0.004). There was no significant difference in TNF-α serum levels among the groups (p = 0.284). Gender-based classification did not significantly alter these findings, and no correlation was found between the antipsychotic dose administered and cytokine levels in patients with schizophrenia., Discussion: These findings evidence a chronic immune activation in schizophrenia. Bipolar disorder seems to present an episode-related inflammatory syndrome. Increased anti-inflammatory factor IL-10 in bipolar disorder and schizophrenia suggests different patterns of inflammatory balance between these two disorders. Results further support the need to investigate cytokines as possible biomarkers of disease activity or treatment response.

Brain-derived neurotrophic factor (BDNF) plays a critical role in neurodevelopment and neuroplasticity. Altered BDNF signaling is thought to contribute to the pathogenesis of schizophrenia (SZ) especially in relation to cognitive deficits. Clozapine (CLZ) has been shown a beneficial effect on cognition in SZ in some studies and a detrimental effect in others. To examine serum BDNF, two groups of chronically medicated DSM-IV SZ patients (n=44), on treatment with clozapine (n=31) and typical antipsychotics (n=13) had 5ml blood samples collected by venipuncture. Serum BDNF levels were significantly correlated with CLZ daily dose (r=0.394, p=0.028), but not with typical antipsychotic daily dose (r=0.208, p=0.496). This study suggests that serum BDNF levels are correlated with CLZ daily dose, and this may lead to the cognitive enhancement as seen in patients with SZ under CLZ. Despite the strong evidence that chronic administration of CLZ is effective for patients with SZ, it is still unknown whether atypical antipsychotic drugs regulate BDNF expression. Serum BDNF levels concentration in SZ merits further investigations with regard to the role of neurotrophins in the cognitive response to treatment with CLZ and other atypical antipsychotics., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: There is an increasing body of evidence suggesting that oxidative stress may play a role in the pathophysiology of both schizophrenia (SZ) and bipolar disorder (BD)., Methods: We compared the antioxidant enzyme, serum superoxide dismutase (SOD) and the lipid peroxidation product, thiobarbituric acid reactive substances (TBARS) as assessed in depressed (N=21), manic (N=32) and euthymic (N=31) bipolar patients, and in chronically medicated patients with schizophrenia (N=97), all fulfilling DSM-IV diagnostic criteria, and a group of healthy controls (N=32)., Results: Serum SOD (U/mg protein) activity was significantly increased (p<0.001) in manic (7.44+/-3.88) and depressed (6.12+/-4.64) BD patients and SZ (9.48+/-4.51) when compared to either controls (1.81+/-0.63) or euthymic (2.75+/-1.09) BD patients. TBARS (mol/L) levels were significantly higher in the SZ group (4.95+/-1.56, p=0.016), bipolar euthymic (6.36+/-1.46, p<0.001), bipolar manic (7.54+/-1.74, p<0.001), and bipolar depressed patients (5.28+/-1.54, p=0.028) compared to controls (3.96+/-1.51)., Discussion: Our findings show increased SOD activity in SZ, as well as in depressed and manic bipolar patients, but not in euthymic BD subjects. This suggests a dysregulation in oxidative defenses in both disorders. It is likely that such changes reflect state changes in bipolar disorder. It is possible that this is a compensatory response to the oxidative stress that occurs in the acute phase of bipolar episodes. TBARS results show increases in lipid peroxidation in mania. TBARS levels in SZ and in euthymic as well as depressed individuals with BD were higher than in controls. This suggests persistent increases in SZ, which may reflect ongoing symptomatology or treatment, and a state dependent gradient in BD, with greatest oxidative stress in mania. These data support oxidative biology as both a key component of the pathophysiology of both BD and SZ, and the use of agents that modulate oxidative biology as a promising avenue for intervention in both disorders.

There is evidence that major psychiatric disorders such as schizophrenia (SZ) are associated with deregulation of synaptic plasticity with downstream alterations of neurotrophins. NT3 is an important neurotrophin in the central nervous system, and performs key biological functions, such as promoting the survival, differentiation, and plasticity of neurons. NT3 has a central role in the early neuronal development; enhancing the survival of dopaminergic neurons, suggesting possible involvement in the physiopathology of dopamine related neuropsychiatric disorders such as SZ. Variations in the NT3 gene increase the risk of SZ. Three groups of chronically medicated DSM-IV patients with SZ, on treatment with clozapine (n=12), haloperidol (n=12), risperidone (n=12) and 10 healthy controls had 5 ml blood samples collected by venipuncture. NT3 serum levels were assessed using sandwich-ELISA and were significantly lower in SZ patients (p<0.005) when compared to either controls. These findings suggest that the NT3 signaling system may play a role in the pathophysiology of SZ and might be related to the course of illness or to treatment variables. Longitudinal studies are warranted.

Impaired antioxidant defenses are suggested to participate in the pathophysiology of schizophrenia. Altered superoxide dismutase (SOD) and increased lipid peroxidation, measured by the thiobarbituric acid reactive substances (TBARS), are increased in schizophrenia. The aim of this study was to determine the effects of clinical course and subtype on oxidative stress parameters. In this study, 68 male patients, classified according to DSM-IV schizophrenia subtypes and clinical course (partial remission, marked symptoms, and deteriorated), were studied, and TBARS and SOD measured. Mean serum SOD and mean serum TBARS concentrations were similarly not significantly different among different subtypes (paranoid, disorganized and undifferentiated). However, marked symptoms status was associated with higher TBARS levels compared to the deteriorated group. This suggests a possible relationship between symptom acuity and oxidative stress in males.

There is evidence that major psychiatric discords such as schizophrenia (SZ) and bipolar disorder (BD) are associated with dysregulation of synaptic plasticity with downstream alterations of neurotrophins. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system (CNS), and performs many biological functions such as promoting the survival, differentiation, and plasticity of neurons. Variants in the BDNF gene increase the risk of SZ and bipolar disorder. Chronic administration of drugs used to treat SZ and BD, such as lithium, valproate, quetiapine, clozapine, and olanzapine, increases BDNF expression in rat brain. To examine serum BDNF, three groups of chronically medicated DSM-IV SZ patients, on treatment with clozapine (n=27), typical (n=14), and other atypical antipsychotics (n=19), 30 euthymic BD patients, and 26 healthy control had 5 ml blood samples collected by venipuncture. Serum BDNF levels were significantly higher in SZ patients (p<0.001) when compared to either controls or euthymic BD patients. Increased BDNF in SZ patients might be related to the course of illness or to treatment variables. Prospective studies are warranted.

There is strong evidence that oxygen free radicals may play an important role in the pathophysiology of schizophrenia. Impaired antioxidant defense and increased lipid peroxidation have been previously reported in drug-naïve, first episode and chronically medicated schizophrenic patients using typical neuroleptics. We measured serum SOD and TBARS in two groups of chronic medicated DSM-IV schizophrenic patients, under haloperidol (n = 10) or clozapine (n = 7) and a group of healthy controls (n = 15). Serum SOD and TBARS were significantly higher (p = 0.001) in schizophrenic patients (7.1 +/- 3.0 and 3.8 +/- 0.8) than in controls (4.0 +/- 1.6 and 2.5 +/- 0.7). Among patients, serum TBARS was significantly higher (p = 0.008) in those under clozapine (4.4 +/- 0.7) than in those under haloperidol treatment (3.4 +/- 0.7). For SOD levels the difference between groups was not found. It is reasonable to argue that the difference found in TBARS levels might be due to the course of the disease, instead of medication. Further investigation on the role of oxidative tonus and lipid peroxidation in different schizophrenia subtypes and different outcome patterns in this disorder is warranted. Additionally it could also address questions concerning a possible oxidant/antioxidant imbalance in schizophrenia.

Initial descriptions of bipolar disorder (BD) emphasized that patients returned to a baseline condition after acute episodes. Such definitions were operational in teasing bipolar disorder apart from schizophrenia, where patients were described to be permanently impaired after the initial episodes. However, this view of BD as a disorder where cognition and overall functioning was spared has been changing after the scrutiny of new research. Currently, the cognitive impairment and neuroanatomical changes related to cumulative mood episodes, particularly manic episodes, are well described. In terms of neuropathological findings~ recent data suggest that changes in neuronal plasticity, particularly in cell resilience and connectivity, are the main findings in BD. Data from differential lines of research converge to BDNF as an important contributor to the pathophysiology of BD. Serum BDNF levels have been shown to be decreased in depressive and manic episodes, returning to normal levels in euthymia. Moreover, factors that negatively influence the course of BD, such as life stress and trauma, have been shown to be associated with a decrease in serum BDNF levels among bipolar patients. These findings suggest that BDNF plays a central role in the transduction of psychosocial stress and recurrent episodes into the neurobiology of bipolar disorder. The present review discusses the role of BDNF as a mediator of the neuroplastic changes that occur in portion with mood episodes and the potential use of serum BDNF as a biomarker in BD. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the expression of genes involved in the reelin pathway, in the post-mortem brain of individuals with schizophrenia (SZ) and mood disorders (MD) with a healthy control (HC) group; and to investigate the role f body mass index (BMI) as a potential mediator. The “Gene Expression in Postmortem dlPFC and Hippocampus from Schizophrenia and Mood Disorders” study holds microarray data on individuals with SZ, MD and HCs (from whom 849 specimens are from the dlPFC and 579 from the hippocampus). mRNA data was obtained using HumanHT-12 v4 BeadChip arrays (Illumina). Multivariate analysis of covariance were used to investigate the main effects of group and relevant covariates on RELNm, NOTCH1, GRIN1m, GRIN3A, CAMK2Gm, CAMK2A, CAMK2Bm, CAMK2N2, GRIN2Bm, GRIN2A, CREBBPm, APOE, LDLR and DAB1 gene expression. In the dlPFC, individuals with SZ had higher expression, relative to HCs, of APOE. Individuals with MD had higher expression, relative to HCs, of CAMK2A, CAMK2N2, and GRIN2Bm. Moreover, individuals with MD had higher expression, relative to SZ patients, of CAMK2N2. There were significant group by BMI effects for expression of RELN, CAMK2A, CAMK2N2, and GRIN2A. In the hippocampus, individuals with MD had lower expression, relative to HCs, of APOE. The results of this study suggest that the expression of genes related to the reelin pathway could be different between individuals with SZ and MD and healthy controls, with a greater vulnerability associated with greater BMI. [ABSTRACT FROM AUTHOR]

Impairment on episodic memory (EM) has been strongly correlated with psychiatric disorders, including schizophrenia (SZ) and bipolar disorder (BD). Morevover, the effects of course and progression of the illness on cognitive functioning have not been well established. The aim of the present study is to assess performance of episodic memory in BD and SZ according to their clinical stages. Subjects who met DSM-IV criteria for bipolar disorder ( n =43) and schizophrenia (31), on euthymia or clinical remission, were recruited from the outpatients facilities at Hospital de Clínicas de Porto Alegre (Brazil). They were classified into two clinical stages (early or late for BD, and recent onset or chronic for SZ) and compared to 54 healthy controls. Episodic memory performance was assessed by means the Hopkins Verbal Learning Test-Revised (HVLT-R) that measures verbal learning and episodic memory in both disorders. Our results showed that patients in early stage of BD (EBD) performed better performance on the total immediate free recall ( p <0.0001, F =12.060) as well as in delayed free recall ( p <0.0001, F =13.914) compared to late stage (LBD) and SZ groups. In the ability to retain words learned, LBD and chronic (CSZ) were more impaired than other groups. Furthermore, the variation of learning (i.e, learning effects) along the 3 trials of immediate free recall was similar between groups. In conclusion, we found a cognitive decline alongside with the progression of BD whereas such impairment was evident in the early of SZ. Despite this, both groups (BD and SZ) seem to maintain the ability to learn. It emphasizes the relevance of studying new therapeutic strategies, in particular, cognitive rehabilitation/remediation techniques as promissory treatment for psychiatric patients, even in those with moderate disabilities. [ABSTRACT FROM AUTHOR]

Objective: Previous reports suggest that cytokines act as potential mediators of the interaction between the immune and neuroendocrine systems, and that a proinflammatory state may be associated with bipolar disorder and schizophrenia. The aim is to compare cytokine levels in both disorders. Method: Twenty euthymic bipolar disorder patients, 53 chronic stabilized schizophrenia patients and 80 healthy controls were recruited. Subjects were all non-smokers and non-obese. Cytokines TNF-α, IL-6, and IL-10 were examined by sandwich ELISA. Results: IL-6 levels were increased in schizophrenia patients when compared to controls (p < 0.0001) and euthymic bipolar disorder patients (p < 0.0001). IL-6 levels were no different in controls compared to euthymic bipolar disorder patients (p = 0.357). IL-10 was lower in controls compared to schizophrenia patients (p = 0.001) or to bipolar disorder patients (p = 0.004). There was no significant difference in TNF-&PROP; serum levels among the groups (p = 0.284). Gender-based classification did not significantly alter these findings, and no correlation was found between the antipsychotic dose administered and cytokine levels in patients with schizophrenia. Discussion: These findings evidence a chronic immune activation in schizophrenia. Bipolar disorder seems to present an episode-related inflammatory syndrome. Increased anti-inflammatory factor IL-10 in bipolar disorder and schizophrenia suggests different patterns of inflammatory balance between these two disorders. Results further support the need to investigate cytokines as possible biomarkers of disease activity or treatment response. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which compared the increased serum levels of C3 and C4 in patients with schizophrenia with eutymic patients with bipolar disorder and healthy.