The Relationship between Cognitive Impairment and Violent Behavior in People Living with Schizophrenia Spectrum Disorders: A Critical Review and Treatment Considerations.

Cognitive impairment is a core feature of schizophrenia spectrum disorders (SSD). Violent and aggressive behavior represents a complex issue in psychiatry, and people with SSD have been shown to be at risk of being both victims and perpetrators of violence. In this review, the complex relationship between cognitive impairment and violent behavior is explored, also considering the usefulness of treating cognitive impairment to improve violence-related outcomes. Several studies report that cognitive impairment is linked to violent behavior, but significant differences between domains and conflicting results are also present, leaving the identification of specific cognitive profiles predicting violent behavior in SSD as an important aim for future research. Evidence regarding the effectiveness of treating cognitive impairment to improve violent behavior, while heterogeneous, provides more consistent results: cognition-targeting interventions appear to provide significant benefits also in the prevention of aggression in people living with SSD, and preliminary evidence shows cognition-focused interventions targeting violent behavior improve both cognition- and violence-related outcomes. Implementing these interventions in clinical practice could be of great usefulness, particularly in forensic contexts. Physical exercise, which improves cognitive performance and psychosocial functioning in SSD, appears to reduce violent behavior in healthy individuals, but requires further studies in clinical samples.

Cognitive and clinical characteristics of offenders and non-offenders diagnosed with schizophrenia spectrum disorders: results of the Recoviwel observational study.

The association between schizophrenia spectrum disorders (SSD) and violent behavior is complex and requires further research. The cognitive correlates of violent behavior, in particular, remain to be further investigated. Aims of the present study were to comprehensively assess the cognitive and clinical profile of SSD violent offenders and evaluate individual predictors of violent behavior. Fifty inmates convicted for violent crimes in a forensic psychiatry setting and diagnosed with SSD were compared to fifty non-offender patients matched for age, gender, education, and diagnosis. Offender and non-offender participants were compared based on socio-demographic, clinical, and cognitive variables using non-parametric testing to select potential predictors of violent behavior. Multivariate logistic regressions were then performed to identify individual predictors of violent behavior. Offender participants showed more school failures, higher prevalence of substance use, higher Clinical Global Impression Severity Scale (CGI-S) and Positive and Negative Syndrome Scale Excited Component (PANSS-EC) scores, worse working memory and better attention performance, higher Historical Clinical and Risk Management scale 20 (HCR-20) and Hare Psychopathy Checklist (PCL-R) scores in all subdomains and factors. School failures, higher PANSS-EC scores, worse working memory and processing speed, better attention performance, higher scores in HCR-20 Management subscale and the PCL-R "Callous" factor emerged as predictors of violent behavior. Better attentional performance was correlated with higher PCL-R "Callous" factor scores, worse cognitive performance in several domains with higher PCL-R "Unstable" factor scores. In conclusion, the present study highlights the importance of carefully assessing SSD patients with violent behavior in all clinical, cognitive, and behavioral aspects.

Predictors of psychosocial functioning in people diagnosed with schizophrenia spectrum disorders that committed violent offences and in those that did not: Results of the Recoviwel study.

Psychosocial functioning represents a core treatment target of Schizophrenia Spectrum Disorders (SSD), and several clinical and cognitive factors contribute to its impairment. However, determinants of psychosocial functioning in people living with SSD that committed violent offences remain to be more thoroughly explored. This study aims to separately assess and compare predictors of psychosocial functioning in people with SSD that did and that did not commit violent offences considering several clinical, cognitive and violence-related parameters. Fifty inmates convicted for violent crimes in a forensic psychiatry setting diagnosed with SSD (OP group) and fifty participants matched for age, gender, education, and diagnosis (Non-OP group) were included in the study. A higher risk of violent relapse as measured by HCR-20 clinical subscale scores (p < 0.002) and greater global clinical severity as measured by CGI-S scores (p = 0.023) emerged as individual predictors of worse psychosocial functioning, as measured by PSP scores, in the OP group. Greater global clinical severity (p < 0.001), worse performance in the processing speed domain as measured by the BACS Symbol Coding (p = 0.002) and TMT-A tests (p = 0.016) and higher levels of non-planning impulsivity as measured by BIS-11 scores (p < 0.001) emerged as individual predictors of worse psychosocial functioning in the Non-OP group. These results confirm that clinical severity impacts psychosocial functioning in all individuals diagnosed with SSD and suggest that while cognitive impairment clearly represents a determinant of worse functional outcomes in most patients, the risk of violent relapse is a specific predictor of worse psychosocial functioning in people with SSD that committed criminal offences.

What impact can brain stimulation interventions have on borderline personality disorder?

INTRODUCTION: Borderline personality disorder (BPD) is a severe mental disorder characterized by emotion dysregulation, impulsivity, neuropsychological impairment, and interpersonal instability, presenting with multiple psychiatric comorbidities, functional disability and reduced life expectancy due suicidal behaviors. AREAS COVERED: In this perspective, the authors explore the application of noninvasive brain stimulation (NIBS) (rTMS, tDCS, and MST) in BPD individuals by considering a symptom-based approach, focusing on general BPD psychopathology, impulsivity and neuropsychological impairments, suicidality and depressive/anxious symptoms, and emotion dysregulation. EXPERT OPINION: According to a symptoms-based approach, NIBS interventions (particularly rTMS and tDCS) are promising treatment options for BPD individuals improving core symptoms such as emotional and behavioral dysregulation, neuropsychological impairments and depressive symptoms. However, the heterogeneity of stimulation protocols and of assessment tools used to detect these changes limits the possibility to provide definitive recommendations according to a symptom-based approach. To implement such armamentarium in clinical practice, future NIIBS studies should further consider a lifespan perspective due to clinical variability over time, the role of psychiatric comorbidities affecting BPD individuals and the need to combine NIBS with specialized psychotherapeutic approaches for BPD patients and with functional neuroimaging studies.

Treatment of Cognitive Impairment Associated with Schizophrenia Spectrum Disorders: New Evidence, Challenges, and Future Perspectives.

Cognitive impairment associated with schizophrenia (CIAS) represents one of the core features of the disorder and has a significant impact on functional and rehabilitation outcomes of people living with schizophrenia spectrum disorders (SSD). The aim of this critical review is to highlight the most recent evidence on effective treatments available for CIAS, to discuss the current challenges in this field, and to present future perspectives that may help to overcome them. Concerning psychopharmacological approaches, among the most indicated strategies for the management and prevention of CIAS is to favor second-generation antipsychotic medications and avoid long-term and high-dose treatments with anticholinergic medications and benzodiazepines. Moreover, non-pharmacological approaches such as cognitive remediation and physical exercise-based programs represent evidence-based interventions in the treatment of CIAS that have shown reliable evidence of effectiveness on both cognitive and functional outcomes. These treatments, however, are still delivered to people accessing mental health services with a diagnosis of CIAS in an uneven manner, even in high-income countries. Academic and clinical partnership and collaboration, as well as advocacy from service users, families, carers, and stakeholders' organizations could help to reduce the bench to bedside gap in the treatment of CIAS. Future perspectives include the development of novel pharmacological agents that could be effective in the treatment of CIAS, the implementation of novel technologies such as telemedicine and virtual reality in the delivery of evidence-based interventions to improve accessibility and engagement, and further research in the field of non-invasive brain stimulation.

The role of pharmacogenetics in the treatment of major depressive disorder: a critical review.

Pharmacological therapy represents one of the essential approaches to treatment of Major Depressive Disorder (MDD). However, currently available antidepressant medications show high rates of first-level treatment non-response, and several attempts are often required to find an effective molecule for a specific patient in clinical practice. In this context, pharmacogenetic analyses could represent a valuable tool to identify appropriate pharmacological treatment quickly and more effectively. However, the usefulness and the practical effectiveness of pharmacogenetic testing currently remains an object of scientific debate. The present narrative and critical review focuses on exploring the available evidence supporting the usefulness of pharmacogenetic testing for the treatment of MDD in clinical practice, highlighting both the points of strength and the limitations of the available studies and of currently used tests. Future research directions and suggestions to improve the quality of available evidence, as well as consideration on the potential use of pharmacogenetic tests in everyday clinical practice are also presented.

Assessment and correlates of autistic symptoms in Schizophrenia Spectrum Disorders measured with the PANSS Autism Severity Score: A systematic review.

Schizophrenia Spectrum Disorders (SSD) and Autism Spectrum Disorders (ASD) are considered separate entities, but the two spectra share important similarities, and the study of these areas of overlap represents a field of growing scientific interest. The PANSS Autism Score (PAUSS) was recently developed specifically to assess autistic symptoms in people living with SSD reliably and quickly. The aims of the present systematic review were to provide a comprehensive assessment of the use of the PAUSS scale in available literature and to systematically analyze cognitive, functional and neurobiological correlates of autistic symptoms measured with this instrument in SSD. The systematic literature search included three electronic databases (PubMed, Scopus and PsycINFO) as well as a manual search in Google Scholar and in reference lists of included papers. Screening and extraction were conducted by at least two independent reviewers. Out of 213 identified records, 22 articles referring to 15 original studies were included in the systematic review. Studies were conducted in several different countries by independent groups, showing consistent scientific interest in the use of the scale; most works focused on cognitive and functional correlates of ASD symptoms, but some also considered neurobiological features. Results of included studies showed that autistic symptoms in people with SSD are consistently associated with worse cognitive performance, especially in the social cognition domain, and with worse psychosocial functioning. However, the presence of autistic symptoms appears to also have a protective role, particularly on functioning, in subjects with more severe psychotic symptoms. Further exploring the impact of autistic symptoms could be of significant scientific and clinical interest, allowing the development of tailored interventions to improve treatment for people living with SSDs.

A Novel Mutation in the Stalk Domain of KIF5A Causes a Slowly Progressive Atypical Motor Syndrome.

KIF5A encodes the heavy chain A of kinesin; A motor protein involved in motility functions within neuron. Mutations in the KIF5A N-terminal motor domain are known to cause SPG10; An autosomal dominant hereditary spastic paraplegia (HSP), as well as rare Charcot-Marie-Tooth disease 2 (CMT2) cases. Recently C-terminal cargo-binding tail domain mutations have been associated with an amyotrophic lateral sclerosis (ALS) phenotype. Here we describe a subject presenting with an atypical slowly progressive motor syndrome evolving over a period of 4 years; Characterized by walking difficulties; Muscle hypotrophy mainly involving upper limbs and pyramidal signs confined to the lower limbs. Electromyography demonstrated chronic neurogenic damage and active denervation while electroneurography showed slowly worsening axonal damage. We identified the novel heterozygote variant c.2341A>G in the exon 21 of the KIF5A gene resulting in the amino acid change p.Lys781Glu. The residue Lys781 is located within the terminal region of the stalk domain and is highly evolutionary conserved. Our findings confirm that mutations in KIF5A cause ALS-like phenotypes. However, the stalk domain mutation described here appears to result in an "intermediate" slowly progressive phenotype having aspects resembling ALS as well as HSP and axonal neuropathy. We suggest that KIF5A gene should be considered as a candidate gene in all atypical progressive motor syndromes.