Insulin-resistance as a modifiable pathway to cognitive dysfunction in schizophrenia: A systematic review.

BACKGROUND: Cognitive deficits are difficult to treat and negatively influence quality of life and functional outcomes of persons with schizophrenia. In the last twenty years, extensive literature demonstrated that persons with diabetes and insulin resistance (IR) also display cognitive deficits. Being type 2 diabetes (T2DM) and IR highly frequent in persons with schizophrenia, it is plausible to hypothesize that these conditions might play a role in determining dyscognition. If that is the case, acting on glucose dysmetabolism may eventually improve cognitive functioning. This review aims at: 1. evaluating the association between IR or T2DM and cognitive dysfunction in schizophrenia; 2. reviewing the evidence that pharmacological treatment of IR or T2DM may improve dyscognition in schizophrenia. METHODS: Two systematic searches were conducted in PubMed, PsycInfo, and Scopus. We followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. RESULTS: From the first search we included 17 studies, 8 on the effects of T2DM and 9 on the effects of IR-other prediabetes measures on cognition in persons with schizophrenia. From the second search we included 12 studies investigating the effect on cognition of glucose (4 studies), insulin (2 studies), metformin (2 studies), PPAR-γ agonists (2 studies), GLP-1 agonist (1 study), bromocriptine (1 study). CONCLUSIONS: T2DM was associated with worse cognitive function in persons with schizophrenia, while IR was less strongly associated with cognitive dysfunction. Evidence regarding the efficacy of glucose-lowering medications on cognition in schizophrenia is inconclusive, yet methodological issues likely contribute to explain conflicting results.

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.

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.

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.

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.