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.

Dysregulation of Plasma Growth Factors and Chemokines in Cocaine Use Disorder: Implications for Dual Diagnosis with Schizophrenia and Antisocial Personality Disorder in an Exploratory Study.

INTRODUCTION: Dual diagnosis in individuals with cocaine use disorders (CUDs) presents a mental health challenge marked by an increased susceptibility to disabling morbidities and premature mortality. Despite extensive research on depression and anxiety, other prevalent comorbidities, such as psychotic and personality disorders, have received less attention. This study explores inflammation-related mediators as potential biomarkers for CUD and dual diagnosis with schizophrenia (SCZ) or antisocial personality disorder (APD). METHODS: This exploratory study included 95 participants, comprising 40 healthy subjects and 55 abstinent patients with CUD. Lifetime CUD was diagnosed either as single diagnosis (CUD group, N = 25) or as a dual diagnosis (DD group. N = 30) with SCZ (CUD+SCZ subgroup) or APD (CUD+APD subgroup). Participants were clinically assessed, and the plasma concentrations of growth factors (i.e., G-CSF, BDNF, and VEGF-A) and chemokines (i.e., CCL11/eotaxin-1, CCL2/MCP-1, and CXCL12/SDF-1) were determined and log(10)-transformed for analysis. RESULTS: Growth factors and chemokines were dysregulated by CUD and psychiatric diagnoses. Specifically, patients in the CUD group exhibited significantly lower concentrations of G-CSF and CCL11/eotaxin-1 than the control group. In contrast, the DD group showed significantly higher concentrations of all analytes than both the CUD and control groups. Additionally, no differences in these analytes were observed between the CUD+SCZ and CUD+APD subgroups within the DD group. Regarding cocaine-related variables, significant associations were identified in the CUD group: an inverse correlation between the age at first cocaine use and the concentrations of BDNF and CCL2/MCP-1; and a positive correlation between the duration of the cocaine abstinence and the concentrations of BDNF and CCL11/eotaxin-1. Lastly, a logistic regression model incorporating all these analytes demonstrated high discriminatory power in distinguishing patients with CUD alone from those with dual diagnosis. CONCLUSIONS: Individuals with dual diagnosis of CUD exhibit elevated concentrations of growth factors and chemokines, distinguishing them from those with CUD alone. It is unclear whether the differences in these inflammatory mediators are specific to the presence of SCZ and APD. The study highlights potential biomarkers and associations, providing valuable insights into the intricate interplay of CUD and psychiatric disorders to enhance clinical diagnosis and therapeutics.

Gender differences and risk of readmission in hospitalizations with a diagnosis of psychotic spectrum disorders.

BACKGROUND: Gender differences in psychosis are a topic that has been studied considering different aspects. Although some available evidence would point to a possible better prognosis in women, this claim is far from conclusively established. METHODS: We propose an analysis of gender differences in the risk of readmission to an acute hospitalization unit, an indicator related to prognosis. RESULTS AND CONCLUSIONS: We found that although the risk of readmission at 1 year is lower in women, this seems to be explained by other confounding factors.

Antidepressant Medication Does Not Contribute to the Elevated Circulating Concentrations of Acylethanolamides Found in Substance Use Disorder Patients.

Circulating acylethanolamides (NAEs) are bioactive signaling molecules that modulate multiple homeostatic functions including mood and hedonic responses. Variations in their plasma concentrations are associated with substance use disorders (SUD) and recent studies suggest that psychotropic medication might influence its circulating levels, limiting its use as a clinical biomarker of addiction. In addition, they might have a role as mediators of the pharmacological effects of psychotropic drugs. Thus, in mild depression, the response to selective serotonin reuptake inhibitor-type antidepressants (SSRI) is associated with a marked increase in circulating NAEs. To further investigate if antidepressants are able to modify the plasma concentration of NAEs in SUD patients, we analyzed the circulating levels of NAEs in 333 abstinent and 175 healthy controls on the basis of the treatment with SSRI antidepressants. As described previously, SUD patients display higher concentrations of NAEs than those measured in a control population. This increase was not further modified by antidepressant therapy. Only marginal increases in palmitoylethanolamide (PEA), oleoylethanolamide (OEA), or docosatetraenoyl-ethanolamide (DEA) were found, and the net effect was very small. Thus, our study shows that treatment with SSRI-type antidepressants does not modify the clinical utility of monitoring enhanced NAE production as biomarkers of SUD. In addition, the possibility that a blunted NAE response to antidepressant therapy might be related to the loss of efficacy of SSRIs in dual depression emerges as an attractive hypothesis that needs to be addressed in future studies.

Psychometric validation of the 15-item Questionnaire about the Process of Recovery in Spain (QPR-15-SP).

Introduction: Reliable and valid instruments are needed to measure the impact of mental health services and programs on the journeys of recovery of service users. The aim of this study was to explore the psychometric properties of the cross-culturally adapted 15-item Questionnaire about the Process of Recovery in Spain (QPR-15-SP). Methods: One hundred and ten participants from three locations in Spain (Málaga, Barcelona and Madrid), who were users of primary and specialized mental health services, were interviewed from October 2021 to June 2022. Results: The internal consistency obtained was excellent: ω =.93 and α =.92. Temporal reliability using intraclass correlation coefficients was moderate (ICC=.684, p <.000). Regarding convergent validity, the QPR-15-SP had a moderate correlation with the Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) (ρ =-.500, p <.000), a Visual Numeric Recovery Scale (VNRS) (ρ =.591, p <.000), and the Stages of Recovery Instrument (STORI) (r =.566, p <.000). Correlations between advanced stages of recovery and higher QPR-15-SP scores were found (Moratorium: ρ =-.579, p <.000; Awareness: ρ =-.130, p =.189; Preparation: r =-.043, P=.665; Rebuilding: r =.460, p <.000; Growth: ρ =.697, p <.000). In terms of divergent validity, the QPR-15-SP had low correlation with the DUKE-UNC Functional Social Support Scale (ρ =.273, p <.005). The confirmatory factor analysis of the 1-factor structure obtained reasonable goodness of fit indexes. Discussion: The QPR-15-SP has acceptable psychometric properties, providing support for measuring recovery in Spain and allowing international comparison research.

Antipsychotic Medication Influences the Discriminative Value of Acylethanolamides as Biomarkers of Substance Use Disorder.

Plasma acylethanolamides (NAEs), including the endocannabinoid anandamide (AEA), have been proposed as circulating biomarkers of substance use disorders. However, the concentration of these lipid transmitters might be influenced by the use of drugs prescribed for either the treatment of addiction or the associated psychiatric co-morbidities such as psychosis. As an example, neuroleptics, used for attenuation of psychotic symptoms and sedation, might theoretically interfere with the monoamine-mediated production of NAEs, obstructing the interpretation of plasma NAEs as clinical biomarkers. To solve the lack of information on the impact of neuroleptics on the concentration of NAEs, we evaluated the concentrations of NAEs in a control group and compared them to those present in (a) substance use disorders (SUD) patients that are not prescribed with neuroleptics, and (b) SUD patients (both alcohol use disorder and cocaine use disorder patients) using neuroleptics. The results demonstrate that SUD patients exhibited greater concentrations of NAEs than the control population, affecting all species with the exception of stearoylethanolamide (SEA) and palmitoleoylethanolamide (POEA). Neuroleptic treatment enhanced the concentrations of NAEs, especially those of AEA, linoleoylethanolamide (LEA), and oleoylethanolamide (OEA). This effect of neuroleptic treatment was observed independently of the drug addiction that motivated the demand for treatment (either alcohol or cocaine). This study remarks the need to control the current use of psychotropic medication as a potential confounding variable when considering the use of NAEs as biomarkers in SUD.

Changing the paradigm in treatment-resistant depression: A review of long-term efficacy and tolerability of esketamine nasal spray.

Treatment-resistant depression (TRD) is a major public health problem worldwide. There are currently five strategies for its treatment: optimization, change, combination, augmentation, and somatic therapies. However, many of these therapies are not fully effective, are not accessible, or have a significant number of side effects. Esketamine nasal spray has recently been approved, in combination with another oral antidepressant, for TRD, with excellent results in short-term studies. We consider in this review whether this therapy is also safe and effective in the long-term treatment of patients. A narrative review, using a comprehensive Pubmed search, and other search strategies, of long-term studies evaluating the safety and efficacy of esketamine nasal spray for the treatment of TRD has been conducted. Five studies have been included in the review. Esketamine nasal spray has demonstrated long-term efficacy and safety in both placebo-controlled and open-label studies evaluating maintenance of antidepressant response. In addition, one study has reported a high level of patient satisfaction with treatment. As limitations, a systematic search for studies has not been carried out and these are still scarce, given the short time that has elapsed since the discovery of the molecule. Esketamine nasal spray is the greatest pharmacological novelty in the treatment of major depression in the last 50 years. It constitutes a new paradigm in the treatment of TRD, which should make us rethink the care protocols that we currently follow. However, more studies are still needed to consolidate the data found so far. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Risk of psychiatric readmission in the homeless population: A 10-year follow-up study.

Homelessness continues to be a major social and clinical problem. The homeless population has a higher burden of disease that includes psychiatric disorders. In addition, they have a lower use of ambulatory health services and a higher use of acute care. Few investigations analyze the use of services of this population group in the long term. We analyzed the risk of psychiatric readmission of homeless individuals through survival analysis. All admissions to a mental health hospitalization unit in the city of Malaga, Spain, from 1999 to 2005, have been analyzed. Three analyses were carried out: two intermediate analyses at 30 days and 1 year after starting follow-up; and one final analysis at 10 years. In all cases, the event was readmission to the hospitalization unit. The adjusted Hazard Ratio at 30 days, 1-year, and 10-year follow-ups were 1.387 (p = 0.027), 1.015 (p = 0.890), and 0.826 (p = 0.043), respectively. We have found an increased risk of readmission for the homeless population at 30 days and a decreased risk of readmission at 10 years. We hypothesize that this lower risk of long-term readmission may be due to the high mobility of the homeless population, its low degree of adherence to long-term mental health services, and its high mortality rate. We suggest that time-critical intervention programs in the short term could decrease the high rate of early readmission of the homeless population, and long-term interventions could link them with services and avoid its dispersion and abandonment.

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.