Integrating Clinical Neuropsychology and Psychotic Spectrum Disorders: A Systematic Analysis of Cognitive Dynamics, Interventions, and Underlying Mechanisms.

Background and Objectives: The study aims to provide a comprehensive neuropsychological analysis of psychotic spectrum disorders, including schizophrenia, bipolar disorder, and depression. It focuses on the critical aspects of cognitive impairments, diagnostic tools, intervention efficacy, and the roles of genetic and environmental factors in these disorders. The paper emphasizes the diagnostic significance of neuropsychological tests in identifying cognitive deficiencies and their predictive value in the early management of psychosis. Materials and Methods: The study involved a systematic literature review following the PRISMA guidelines. The search was conducted in significant databases like Scopus, PsycINFO, PubMed, and Web of Science using keywords relevant to clinical neuropsychology and psychotic spectrum disorders. The inclusion criteria required articles to be in English, published between 2018 and 2023, and pertinent to clinical neuropsychology's application in these disorders. A total of 153 articles were identified, with 44 ultimately included for detailed analysis based on relevance and publication status after screening. Results: The review highlights several key findings, including the diagnostic and prognostic significance of mismatch negativity, neuroprogressive trajectories, cortical thinning in familial high-risk individuals, and distinct illness trajectories within psychosis subgroups. The studies evaluated underline the role of neuropsychological tests in diagnosing psychiatric disorders and emphasize early detection and the effectiveness of intervention strategies based on cognitive and neurobiological markers. Conclusions: The systematic review underscores the importance of investigating the neuropsychological components of psychotic spectrum disorders. It identifies significant cognitive impairments in attention, memory, and executive function, correlating with structural and functional brain abnormalities. The paper stresses the need for precise diagnoses and personalized treatment modalities, highlighting the complex interplay between genetic, environmental, and psychosocial factors. It calls for a deeper understanding of these neuropsychological processes to enhance diagnostic accuracy and therapeutic outcomes.

Clinical implementation of preemptive pharmacogenomics in psychiatry.

BACKGROUND: Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology, demonstrating a beneficial effect of PGx-guided treatment in reducing adverse drug reactions, there are very few such studies in psychiatry, none of which spans across all main psychiatric indications, namely schizophrenia, major depressive disorder and bipolar disorder. In this study we aim to investigate the clinical effectiveness of PGx-guided treatment (occurrence of adverse drug reactions, hospitalisations and re-admissions, polypharmacy) and perform a cost analysis of the intervention. METHODS: We report our findings from a multicenter, large-scale, prospective study of pre-emptive genome-guided treatment named as PREemptive Pharmacogenomic testing for preventing Adverse drug REactions (PREPARE) in a large cohort of psychiatric patients (n = 1076) suffering from schizophrenia, major depressive disorder and bipolar disorder. FINDINGS: We show that patients with an actionable phenotype belonging to the PGx-guided arm (n = 25) present with 34.1% less adverse drug reactions compared to patients belonging to the control arm (n = 36), 41.2% less hospitalisations (n = 110 in the PGx-guided arm versus n = 187 in the control arm) and 40.5% less re-admissions (n = 19 in the PGx-guided arm versus n = 32 in the control arm), less duration of initial hospitalisations (n = 3305 total days of hospitalisation in the PGx-guided arm from 110 patients, versus n = 6517 in the control arm from 187 patients) and duration of hospitalisation upon readmission (n = 579 total days of hospitalisation upon readmission in the PGx-guided arm, derived from 19 patients, versus n = 928 in the control arm, from 32 patients respectively). It was also shown that in the vast majority of the cases, there was less drug dose administrated per drug in the PGx-guided arm compared to the control arm and less polypharmacy (n = 124 patients prescribed with at least 4 psychiatric drugs in the PGx-guided arm versus n = 143 in the control arm) and smaller average number of co-administered psychiatric drugs (2.19 in the PGx-guided arm versus 2.48 in the control arm. Furthermore, less deaths were reported in the PGx-guided arm (n = 1) compared with the control arm (n = 9). Most importantly, we observed a 48.5% reduction of treatment costs in the PGx-guided arm with a reciprocal slight increase of the quality of life of patients suffering from major depressive disorder (0.935 versus 0.925 QALYs in the PGx-guided and control arm, respectively). INTERPRETATION: While only a small proportion (∼25%) of the entire study sample had an actionable genotype, PGx-guided treatment can have a beneficial effect in psychiatric patients with a reciprocal reduction of treatment costs. Although some of these findings did not remain significant when all patients were considered, our data indicate that genome-guided psychiatric treatment may be successfully integrated in mainstream healthcare. FUNDING: European Union Horizon 2020.

Sintomatología de las fases activa y prodrómica de la esquizofrenia paranoide de inicio en el joven y de inicio tardío / Active and prodromal phase symptomatology of young-onset and late-onset paranoid schizophrenia

Introducción: Se comparó a pacientes con esquizofrenia paranoide de inicio en el joven y de inicio tardío en lo relativo a la fase prodrómica y la fase activa del trastorno, con objeto de examinar la influencia que tenía la edad de inicio en la sintomatología de ambas fases de la enfermedad. Material y métodos: Examinamos a 88 pacientes consecutivos hospitalizados por esquizofrenia paranoide. Los valores de corte de la edad se establecieron en <30 años para el grupo de inicio en el joven y >=35 años en el grupo de inicio tardío. Los diagnósticos se hicieron de forma prospectiva, con el empleo de la entrevista clínica estructurada Structured Clinical Interview for DSM-IV-Patient Edition para los trastornos del Eje I (SCID-P). Se evaluó el tipo y la gravedad de la psicopatología en la fase activa mediante la aplicación de la entrevista clínica estructurada para la escala Positive and Negative Syndrome Scale (PANSS). Se efectuó un examen retrospectivo de los pacientes respecto a los síntomas prodrómicos iniciales, mediante la aplicación de la Structured Clinical Interview for DSM-III-R Patient Edition y una entrevista clínica respecto a otros síntomas adicionales. Se realizaron comparaciones con el empleo de las pruebas estadísticas de ji2 y de suma de rangos de Wilcoxon bilaterales. Resultados: El grupo de inicio en el joven se caracterizaba por la presencia significativamente mayor de síntomas prodrómicos negativos, y por una sintomatología negativa más intensa en la fase activa, en comparación con el grupo de inicio tardío. Las diferencias observadas fueron más prominentes en los pacientes varones. Conclusiones: La edad de inicio más avanzada de la esquizofrenia paranoide parece estar relacionada con una forma menos grave de la enfermedad, que se caracteriza por una menor intensidad de la sintomatología negativa, que se aprecia ya en la fase prodrómica del trastorno(AU)

Introduction: Young and late onset patients with paranoid schizophrenia were compared, regarding the initial prodromal and active phases of the disorder, in order to examine the influence of age of onset on the prodromal and active phase symptomatology of the disease. Materials and methods: We examined 88 consecutively hospitalized patients with paranoid schizophrenia. Age cutoff points were set at <30 years of age for the young, and >=35 years of age for the late onset group. Diagnoses were made prospectively, using the Structured Clinical Interview for DSM-IV-Patient Edition for Axis I disorders (SCID-P). Type and severity of psychopathology in the active phase were assessed by applying the Structured Clinical Interview for Positive and Negative Syndrome Scale (PANSS). Patients were retrospectively examined regarding their initial prodromal symptoms by applying the Structured Clinical Interview for DSM-III-R Patient Edition and clinical interviewing for additional symptoms. Comparisons were performed by applying the two-tailed Wilcoxon rank-sum and the chi-square statistical tests. Results: The young onset group was characterized by significantly more negative prodromal symptoms, and heavier negative symptomatology in the active phase, than the late onset group. Differences were more prominently shown in male patients. Conclusions: Older age of onset of paranoid schizophrenia appears to be related to a less severe form of the disease, characterized by less severity of negative symptomatology, already demonstrated in the prodromal phase of the disorder(AU)