What Remains to Be Discovered in Schizophrenia Therapeutics: Contributions by Advancing the Molecular Mechanisms of Drugs for Psychosis and Schizophrenia

Schizophrenia is a frequently debilitating and complex mental disorder affecting approximately 1% of the global population, characterized by symptoms such as hallucinations, delusions, disorganized thoughts and behaviors, cognitive dysfunction, and negative symptoms. Traditional treatment has centered on postsynaptic dopamine antagonists, commonly known as antipsychotic drugs, which aim to alleviate symptoms and improve functioning and the quality of life. Despite the availability of these medications, significant challenges remain in schizophrenia therapeutics, including incomplete symptom relief, treatment resistance, and medication side effects. This opinion article explores advancements in schizophrenia treatment, emphasizing molecular mechanisms, novel drug targets, and innovative delivery methods. One promising approach is novel strategies that target neural networks and circuits rather than single neurotransmitters, acknowledging the complexity of brain region interconnections involved in schizophrenia. Another promising approach is the development of biased agonists, which selectively activate specific signaling pathways downstream of receptors, offering potential for more precise pharmacological interventions with fewer side effects. The concept of molecular polypharmacy, where a single drug targets multiple molecular pathways, is exemplified by KarXT, a novel drug combining xanomeline and trospium to address both psychosis and cognitive dysfunction. This approach represents a comprehensive strategy for schizophrenia treatment, potentially improving outcomes for patients. In conclusion, advancing the molecular understanding of schizophrenia and exploring innovative therapeutic strategies hold promise for addressing the unmet needs in schizophrenia treatment, aiming for more effective and tailored interventions. Future research should focus on these novel approaches to achieve better clinical outcomes and improve the functional level and quality of life for individuals with schizophrenia

Editorial: Reviews in Psychiatry 2022: Schizophrenia

The reviews aim to collect and analyze in an all-encompassing light article separately published in the literature to provide a higher-order view that allows a broader assessment of the topic described, all in a thorough and unbiased manner (1). The previous view based only on certain pathology aspects can no longer be considered sufficient to achieve an optimal outcome. Integrating microscopic and macrobiological aspects, identifying biomarkers, and the need for integrated care that includes all aspects currently considered in the scientific literature becomes essential in the understanding of psychiatric disorder

Longitudinal assessment of brain-derived neurotrophic factor in Sardinian psychotic patients (LABSP): a protocol for a prospective observational study

Brain-derived neurotrophic factor (BDNF) plays a crucial role in neurodevelopment, synaptic plasticity and neuronal function and survival. Serum and plasma BDNF levels are moderately, but consistently, decreased in patients with schizophrenia (SCZ) compared with healthy controls. There is a lack of knowledge, however, on the temporal manifestation of this decline. Clinical, illness course and treatment factors might influence the variation of BDNF serum levels in patients with psychosis. In this context, we propose a longitudinal study of a cohort of SCZ and schizophrenic and schizoaffective disorder (SAD) Sardinian patients with the aim of disentangling the relationship between peripheral BDNF serum levels and changes of psychopathology, cognition and drug treatments

Perception of University Nursing Students and Faculty Members Regarding Simulated Practices: A Mixed Methods Study

Introduction: Clinical simulation has been used as a teaching strategy for students in health programmes, fostering greater preparedness and confidence in performing procedures. Objective: This study aimed to analyse the perception of fourth-semester nursing students and teachers regarding the simulated practice methodology implemented in a private university in Cali, Colombia. Method: A robust mixed-methods approach was used, incorporating quantitative surveys and qualitative interviews with 41 students and 5 teaching nursing faculty members. Data triangulation was applied to ensure the robustness of the results. Results: Both students and teachers reported a positive perception of simulated practice, which contributes to knowledge acquisition and contextual learning. Students emphasised that simulation improved their prior knowledge and motivated them to explore new topics. Lecturers emphasised the importance of well-trained instructors in simulation environments. However, participants identified challenges affecting performance, including simulation duration, group size, realism, and resource constraints. Conclusions: Students and teachers recommend strategic changes to the curriculum to optimise simulation practices

The Impact on Anxiety Symptoms of an Immersive Virtual Reality Remediation Program in Bipolar Disorders: A Randomized Clinical Trial

: Background: The objective of this work is to investigate the effectiveness of a cognitive remediation intervention on anxiety symptoms in people with bipolar disorder and the therapeutic effect on people whose anxiety symptoms were above the threshold for a screener and whose comorbidity could be identified as an anxiety disorder. Methods: The experimental intervention included 24 sessions (around 45 min each), two for each week over three months. The entire program was inspired by user-centered rehabilitation principles in a recovery-oriented perspective and an approach to bipolar disorder in an evolutionary and non-discriminating vision. The primary outcomes measure the score of the Zung Self-Rating Anxiety Scale (SAS), hypothesizing a higher decrease in the experimental group than in the control group. The survey has been conducted per the CONSORT guidelines for feasibility studies. Results: We evaluate a decrease in the overall SAS score from T0 to T1 to be higher in the experimental group compared to the control group, indicating an improvement in anxiety symptoms (p < 0.0001). Conclusions: The study suggests that virtual reality could have a role in treating anxiety symptoms and disorders in young adults with bipolar disorders or anxiety symptoms in people with hyperactivity and novelty-seeking behaviorsunder stress and high risk for bipolar disorder

Prevalence and Risk by Age and Sex of Sleep Dysregulation and Depressive Episodes in Bipolar and Depressive Disorders in a Community Survey in Sardinia, Italy

Background/Objectives: Sleep disturbances often accompany mood disorders and persistent insomnia after mood symptoms have resolved may be a marker of poor outcome. The association between sleep symptoms and mood disorders seems to change with age and sex. This study aims to assess the frequency of depressive episodes and sleep disorders in the general population through an agile screening questionnaire and to evaluate the association of depressive episodes and sleep symptoms by sex and age categories. Methods: 774 women and 728 men from Sardinia aged > 16 years old were enrolled. The Patient Health Questionnaire (PHQ-9) was administered through a computer-assisted telephonic interview. Results: The frequency of depressive episodes was double in women (10.6% vs. 4.4%; p < 0.0001), with the highest values in women > 75 yo (17.4%). The frequency of sleep dysregulation was double in women (18.7% vs. 9.6%; p < 0.0001), with the highest values in women > 75 yo (35.9%) and the lowest in the group of men > 75 yo. The group of young males showed the lowest frequency of depressive episodes (1.4%) and a frequency of sleep dysregulation (9.1%) similar to that of the other groups of age and sex. Sleep dysregulation without depressive episodes presented a higher distribution in the elderly, both in males (20.7%) and in females (18.5%). No significative differences were found across sex and age groups in the distribution of depressive episodes without sleep dysregulation. Conclusions: The use of an agile screener such as PHQ9 in the general population and/or in populations at risk can be a valuable tool in finding those individuals in whom sleep dysregulation may represent an early warning signal, one that may be thoroughly evaluated to identify and treat possible sleep disorders early

A Virtual Reality Cognitive Stimulation Program as an Effective Tool Against Residual/Prodromal Depressive Symptoms in Bipolar Disorders

Background: Bipolar disorder (BD) is a severe psychiatric illness characterized by a chronic course and recurrent episodes, including residual depressive symptoms even during euthymic phases. These symptoms, although not meeting criteria for a depressive episode, are linked to relapse risk and impaired social functioning. This study aims to assess whether Virtual Reality Cognitive Remediation Training reduces depressive symptoms below the clinical threshold in individuals with BD. Methods: This post hoc analysis focuses on the secondary outcome (PHQ9) of a randomized–controlled trial. Participants were recruited from the Center of Liaison Psychiatry and Psychosomatics in Italy. The experimental group received Virtual Reality Cognitive Remediation, while the control group received standard treatment Results: Data from 39 individuals in the experimental group and 25 in the control group were analyzed. A greater reduction in PHQ-9 scores (>9) was observed in the experimental group (71.8% to 48.7%) compared to the control group. Significant improvements in total PHQ-9 scores and specific symptoms were noted in the experimental group compared to the control group. Conclusions: The study highlights the significant impact of virtual reality intervention on reducing depressive symptoms in bipolar disorder. This promising outcome underscores the potential preventive role of cognitive stimulation in relapse prevention. The intervention could offer valuable benefits for both treatment and prevention strategies in bipolar disorder

Prior Engagement in Physical Activity Correlates with Enhanced Quality of Life Perceptions among Older Adults during COVID-19 Lockdown

Background: This longitudinal study aimed to evaluate whether prior engagement in a physical exercise program correlated with enhanced perceptions of quality-of-life components among older adults during the COVID-19 lockdown period. Methods: The cohort comprised elderly individuals (aged ≥ 65 years) who had previously partaken in a 12-week randomized controlled trial investigating the effects of a mixed aerobic-anaerobic, moderate-intensity exercise program. Participants' health-related quality of life was assessed using the Short Form Health Survey-12 item (SF-12) at the beginning of the initial trial and, again, one year later during the COVID-19 lockdown. In the exercise group, 44 participants were included, while the control group consisted of 49 participants, with computer-based, double-blind randomization conducted in Cagliari, Italy. The differences in scores for each SF-12 item between the two groups from T0 to T1 were compared using one-way ANOVA with Bonferroni corrections. Data were analyzed using the Statistical Package for Social Sciences (SPSS) version 27. Results: No statistically significant differences were observed on average by age (exercise group vs. control group 72.20 ± 4.78 vs. 72.91 ± 4.77; F = 0.513, p = 0.476). A decrease from T0 to T1 towards a better score on the SF-12 was observed in the exercise group compared to the control group in item 1 (F = 67.463, p < 0.0001); in item 5 (F = 4.319, p = 0.041); item 8 (F = 4.269, p = 0.041); item 9 (F = 10.761, p = 0.001); item 10 (F = 170.433, p < 0.001); and item 11 (F = 4.075, p = 0.046). Conclusions: The results suggest that participation in a moderate physical exercise program one year prior may have equipped older adults with better coping mechanisms to navigate the stress and isolation imposed by the COVID-19 lockdown, as reflected by their enhanced scores on quality-of-life components pertaining to mental well-being. Exercise may confer a protective effect against the adverse psychological impacts of stressful events like the pandemic, even among older adults with chronic conditions. This study underscores the potential benefits of exercise interventions for promoting quality of life and preventing mood disorders in the elderly population

Hyperactivity and Risk for Dysregulation of Mood, Energy, and Social Rhythms Syndrome (DYMERS): Standardization of a Simple One-Item Screener versus the Mood Disorder Questionnaire (MDQ)

Background: This study aims to verify the accuracy of item 10 on the energy level of the Short-Form Health Survey (SF-12) in an item screening according to Mood Disorder Questionnaire (MDQ) results, providing a measure of hyper-energy. Methods: Regression techniques were employed in a dataset comprising 4093 records of respondents to test both linear and nonlinear relationships between predictor and outcome variables (energy level and symptoms considered in the MDQ). We examined the relationship of energy level with cases identified using MDQ with a cut-off of 7. Results: Levels of energy, as rated on item 10 of the SF-12, were related to the MDQ score with sensitivity = 0.72 and specificity = 0.70. In linear regression, the associations were stronger with MDQ items on excessive energy or activity, showing a medium effect size and an explained variance of 10% or higher. A greater association was observed for items on excessive energy and activity, as expected, as well as for items concerning self-confidence, sociability, and talkativeness. Conclusions: This result may have implications for the research on risk factors and the pathogenesis of the dysregulation of mood, energy, and social rhythms syndrome (DYMERS), a syndrome that is hypothesized to occur in stressful conditions like those shown under the COVID-19 pandemic

Symptomatic remission and recovery in major psychosis: Is there a role for BDNF? A secondary analysis of the LABSP cohort data

Remission, relapse prevention, and clinical recovery are crucial areas of interest in schizophrenia (SCZ) research. Although SCZ is a chronic disorder with poor overall outcomes, years of research demonstrated that recovery is possible. There are considerable data linking brain-derived neurotrophic factor (BDNF) to SCZ, however, evidence on the role of BDNF in remission in SCZ is scarce. This secondary analysis of the Longitudinal Assessment of BDNF in Sardinian patients (LABSP) data aimed to investigate the relationship between serum BDNF levels and symptomatic remission, simultaneous clinical and functional remission, and recovery in patients with SCZ. A total of 105 patients with SCZ or schizoaffective disorder were recruited for a longitudinal assessment of BDNF levels over 24 months. Longitudinal data were analyzed using mixed-effects linear regression models. The study found significant associations between use of long acting injectables (chi 2 = 7.075, df = 1, p = 0.008), baseline serum BDNF levels (U = 701, z = -2.543, p = 0.011), and "childhood" (U = 475, z = -2.124, p = 0.034) and "general" (U = 55, z = -2.014, p = 0.044) subscales of the Premorbid Adjustment Scale (PAS) with patients maintaining remission and recovery. The diagnosis of SCZ was significantly associated with lower BDNF levels for patients with simultaneous clinical and functional remission (Z = 2.035, p = 0.0419) and recovery (Z = 2.009, p = 0.0445) compared to those without. There were no significant associations between remission in the entire sample and longitudinal serum BDNF levels or genetic variants within the BDNF gene. These findings provide further insight into the complex relationship between BDNF and SCZ