Pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in bipolar disorder: A systematic review.

BACKGROUND: The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD. METHODS: PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected. RESULTS: Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1ß, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients. CONCLUSION: Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.

Suicidal behavior in persons attended in out-of-hospital emergency services in Spain.

Background: The aims of this study were to describe the use of health services by patients attended for suicidal behavior by out-of-hospital emergency services and to identify the variables associated with the repetition of this behavior in Spain. Methods: An analytical, observational, retrospective study was carried out. A total of 554 patients attended by the mobile teams of the Primary Care Emergency (mt-PCES) of the Malaga Health District (Spain), after being coordinated by the 061 Emergency Coordination Center (ECC) were analyzed. Results: Of the total, 61.9% of the patients were women and the mean age was 43.5 years. Ninety-six percent (N = 532) of the patients attended by mt-PCES were transferred to hospital emergency services. Regarding clinical decision, of those transferred 436 persons (82%) were discharged home. Of the total sample 25.5% (N = 141) were referred to primary care, while 69% (N = 382) were referred to outpatient mental health care. Regarding follow up in the 6 months after being seen by emergency services, among those referred to a mental health facility, 64.4% (N = 246) attended the follow-up appointment while out of the total sample only 50.5% (N = 280) attended a follow-up appointment with an outpatient mental health service. Finally, it should be noted that 23.3% presented a relapse of suicidal behavior in the 6 months following index episode. The variables associated with repetition of suicidal behavior were older age, greater number of previous suicide attempts and having any contact with mental health services in the following 6 months. Conclusion: We believe that selective suicide prevention initiatives should be designed to target the population at risk of suicide, especially those receiving both out-of-hospital and in-hospital emergency services.

The Inflammatory Signals Associated with Psychosis: Impact of Comorbid Drug Abuse.

Psychosis and substance use disorders are two diagnostic categories whose association has been studied for decades. In addition, both psychosis spectrum disorders and drug abuse have recently been linked to multiple pro-inflammatory changes in the central nervous system. We have carried out a narrative review of the literature through a holistic approach. We used PubMed as our search engine. We included in the review all relevant studies looking at pro-inflammatory changes in psychotic disorders and substance use disorders. We found that there are multiple studies that relate various pro-inflammatory lipids and proteins with psychosis and substance use disorders, with an overlap between the two. The main findings involve inflammatory mediators such as cytokines, chemokines, endocannabinoids, eicosanoids, lysophospholipds and/or bacterial products. Many of these findings are present in different phases of psychosis and in substance use disorders such as cannabis, cocaine, methamphetamines, alcohol and nicotine. Psychosis and substance use disorders may have a common origin in an abnormal neurodevelopment caused, among other factors, by a neuroinflammatory process. A possible convergent pathway is that which interrelates the transcriptional factors NFκB and PPARγ. This may have future clinical implications.

Clinical Value of Inflammatory and Neurotrophic Biomarkers in Bipolar Disorder: A Systematic Review and Meta-Analysis.

Bipolar disorder (BD) is a multifactorial chronic psychiatric disease highly defined by genetic, clinical, environmental and social risk factors. The present systematic review and meta-analysis aimed to examine the relationship between inflammatory and neurotrophic factors and clinical, social and environmental factors involved in the development and the characterization of BD. Web of Science, PubMed, PsycINFO, Scopus and Science Direct were searched by two independent reviewers. The systematic review was registered in PROSPERO (CRD42020180626). A total of 51 studies with 4547 patients with a diagnosis of BD were selected for systematic review. Among them, 18 articles were included for meta-analysis. The study found some evidence of associations between BDNF and/or inflammatory factors and different stressors and functional and cognitive impairment, but limitations prevented firm conclusions. The main finding of the meta-analysis was a negative correlation between circulating levels of BDNF and depression severity score (standardized mean difference = -0.22, Confidence Interval 95% = -0.38, -0.05, p = 0.01). Evidence indicates that BDNF has a role in the depressive component of BD. However, the poor consistency found for other inflammatory mediators clearly indicates that highly controlled studies are needed to identity precise biomarkers of this disorder.

Trends in Psychiatric Hospitalizations of Patients With Dual Diagnosis in Spain.

OBJECTIVE: Substance use disorders are highly prevalent in people living with a mental health disorder. Co-occurring substance use disorders have been associated with a worse prognosis and poorer adherence to treatment. The aim of this study was to analyze the temporal trends in the prevalence of substance use disorders in patients admitted to a psychiatric inpatient unit between 1998 and 2020. METHODS: This is a retrospective study based on the registry of 18,367 hospitalizations and 7,124 patients with a mental health disorder admitted during the period 1998 to 2020 in Malaga, Spain. Time trend analysis by gender and substance used was calculated using a segmented regression model. The permutation test was used to determine inflection points. A sensitivity analysis was performed based on the assumptions of autocorrelation and homoscedasticity. RESULTS: A total of 22.2% of admissions had a diagnosis of mental health disorder and co-occurring substance use disorders. Prevalence was higher among males (30.0%) than females (9.4%; p < .001). Patients with both disorders had a shorter length of stay by 2 days (p < .001) and a younger age at first admission (by 6.5 years; p < .001) compared to patients without substance use disorders. There was no difference in the total number of hospitalizations between the two groups. Psychotic disorders and multiple drug use disorders were the most prevalent diagnoses in men compared to women, whereas personality disorders and alcohol use were the most common diagnoses in women. We observed an increase in the prevalence of dual diagnosis between 2005 and 2020. There was a 3.0% increase in cannabis-related admissions per year during the whole study period (p < .001). Cannabis and cocaine use disorders have become the most prevalent in the last 10 years, while opioid and alcohol use disorders have decreased. CONCLUSIONS: Co-occurring substance use disorders are highly prevalent among hospitalized patients. In recent years, the pattern of substance use has shifted, with cannabis being the most prevalent, while opiates and alcohol substance use have decreased. We need to devise a specialized approach and integrative treatment for patients with co-occurring disorders.

The Impact of COVID-19 Confinement on Cognition and Mental Health and Technology Use Among Socially Vulnerable Older People: Retrospective Cohort Study.

BACKGROUND: COVID-19 forced the implementation of restrictive measures in Spain, such as lockdown, home confinement, social distancing, and isolation. It is necessary to study whether limited access to basic services and decreased family and social support could have deleterious effects on cognition, quality of life, and mental health in vulnerable older people. OBJECTIVE: This study aims to explore the impact of the COVID-19 outbreak on cognition in older adults with mild cognitive impairment or dementia as the main outcome and the quality of life, perceived health status, and depression as secondary outcomes and to analyze the association of living alone and a change in living arrangements with those outcomes and other variables related with the use of technology and health services. Likewise, this study aims to analyze the association of high and low technophilia with those variables, to explore the access and use of health care and social support services, and, finally, to explore the informative-, cognitive-, entertainment-, and socialization-related uses of information and communications technologies (ICTs) during the COVID-19 outbreak. METHODS: This cohort study was conducted in Málaga (Spain). In total, 151 participants with mild cognitive impairment or mild dementia, from the SMART4MD (n=75, 49.7%) and TV-AssistDem (n=76, 50.3%) randomized clinical trials, were interviewed by telephone between May 11 and June 26, 2020. All participants had undergone 1-3 assessments (in 6-month intervals) on cognition, quality of life, and mood prior to the COVID-19 breakout. RESULTS: The outbreak did not significantly impact the cognition, quality of life, and mood of our study population when making comparisons with baseline assessments prior to the outbreak. Perceived stress was reported as moderate during the outbreak. After correction for multiple comparisons, living alone, a change in living arrangements, and technophilia were not associated with negative mental health outcomes. However, being alone was nominally associated with self-perceived fear and depression, and higher technophilia with better quality of life, less boredom, perceived stress and depression, and also less calmness. Overall, health care and social support service access and utilization were high. The most used ICTs during the COVID-19 outbreak were the television for informative, cognitive, and entertainment-related uses and the smartphone for socialization. CONCLUSIONS: Our findings show that the first months of the outbreak did not significantly impact the cognition, quality of life, perceived health status, and depression of our study population when making comparisons with baseline assessments prior to the outbreak. Living alone and low technophilia require further research to establish whether they are risk factors of mental health problems during lockdowns in vulnerable populations. Moreover, although ICTs have proven to be useful for informative-, cognitive-, entertainment-, and socialization-related uses during the pandemic, more evidence is needed to support these interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04385797; https://clinicaltrials.gov/ct2/show/NCT04385797. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/26431.

Migration of Medical Professionals: The Case of Psychiatric Trainees in Spain.

The social and economic situation in Europe seems to play a role in the migratory flow of doctors and other health professionals within the continent. However, little is known about the particular reality of workforce migration in Spain. The objective of this study was to explore the factors that motivate migration among junior doctors training in psychiatry in Spain. A semistructured questionnaire of 61 items was circulated to psychiatric trainees in Spain to explore the extent and the factors that influence the decisions regarding workforce migration. A total of 95 psychiatric trainees participated in the survey. More than two-thirds (n = 71, 74.7%) had "ever" considered migrating to another country, and more than one-fourth (n = 21, 29.5%) had already taken "practical steps" to go abroad. The main reasons to consider leaving the country were financial (n = 82, 86%) and the opportunity to progress professionally (n = 82, 84%). However, nearly half of the trainees (n = 47, 49%) were satisfied with their current income. While the majority of the psychiatric trainees in this survey had considered migrating abroad, these potential future migrations could lead to a loss of human capital with an important sociosanitary impact.

Met and Unmet Needs in an Inpatient Psychiatry Setting in Spain.

PURPOSE: Patients with severe mental disorder have health and social needs that require care. The aim of the study was to determine the main areas of perceived needs among inpatients with severe mental disorders and to identify risk factors of the group of patients with the greatest unmet needs. PATIENTS AND METHODS: A total of 150 patients with severe mental illness were assessed during admission prior to discharge from the hospital. Camberwell Assessment of Needs was used as evaluation measure, in addition to clinical status (The Brief Psychiatric Rating Scale), social functioning (Personal and Social Performance) and sociodemographic variables. A descriptive and a multivariate logistic regression analysis were used to analyse variables related to the group of patients with the highest number of unmet needs (≥3). RESULTS: Mean number of needs was 7.93, being 4.61 the mean number of needs met and 3.32 the needs unmet. The highest proportion of unmet needs were intimate relationships (44.0%), company (40.7%) and daytime activities (38.7%). A relationship was also found between the presence of three or more unmet needs and the following variables: Brief Psychiatric Rating Scale score (p=0.004), Personal and Social Performance score (p = 0.013), marital status (p=0.018), employment status (p=0.009) and voluntary admission (p=0.032). The multivariate model explained 29.5% of the variance (Nagelkerke's R2: 0.295). CONCLUSION: Treatments aimed at improving social relationships and daytime activities could be a good option for inpatients with many unmet needs.

SERP: una Sociedad en crecimiento y con horizonte europeo / SERP: a growing society and with an European horizon

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