Treatment Of Severe Mental Disorders Research Articles

Maternal treatment with a selective delta-opioid receptor agonist during gestation has a sex-specific pro-cognitive action in offspring: mechanisms involved.

Background: There is growing evidence that the treatment of several mental disorders can potentially benefit from activation of delta-opioid receptors. In the future, delta-agonists with a safe pharmacological profile can be used for the treatment of mood disorders in pregnant women. However, the data on prenatal exposure to delta-opioid agonists are missing. The present study is aimed to test the hypothesis that the activation of delta-opioid receptors during gravidity has positive effects on the behaviour accompanied by changes in glutamate and monoamine neurotransmission. Methods: Gestating Wistar rats were chronically treated with a selective delta-agonist SNC80 or vehicle. Adult male and female offspring underwent novel object recognition (for the assessment of cognition) and open field (for the assessment of anxiety and habituation) tests, followed by in vivo electrophysiological examination of the activity of hippocampal glutamate and midbrain serotonin (5-HT) and dopamine neurons. Results: We found that the maternal treatment with SNC80 did not affect the offspring's anxiety, habituation, and 5-HT neuronal firing activity. Female offspring of SNC80-treated dams exhibited improved novelty recognition associated with decreased firing rate and burst activity of glutamate and dopamine neurons. Conclusion: Maternal treatment with delta-opioid agonists during gestation may have a pro-cognitive effect on offspring without any negative effects on anxiety and habituation. The putative pro-cognitive effect might be mediated via mechanism(s) involving the firing activity of hippocampal glutamate and mesolimbic dopamine neurons.

Happy Birthday "One Flew Over the Cuckoo's Nest": A Momentous Tale in the Quest for an Effective and Ethical Approach to Psychosurgery.

The anniversary of the publication of 'One Flew Over the Cuckoo's Nest' by Ken Kesey offers an opportunity for reflection on the use of neurosurgery in psychiatry. We used a narrative, historical and dialectical method to deliver an account of the controversial subject. A balanced representation of the negative and positive aspects, acknowledging some of the questionable ethical practices while describing well-reasoned applications is provided. It includes neurosurgeons, psychiatrists who have embraced these procedures with unwarranted enthusiasm and those who have opposed. Neurosurgical techniques for the treatment of severe mental disorders have evolved from rudimentary procedures which were used to 'correct' unwanted behaviours associated with a wide range of severe mental disorders to more refined and selective approaches used as a last resort to treat specific mental health conditions. In the absence of specific aetiological models to guide ablative surgical targets, non-ablative, stimulatory techniques have more recently been developed to allow reversibility when surgical treatment fails to obtain a sizeable improvement in quality of life. The subject is concretely illustrated by two eloquent clinical images: one on a series of brain computed tomography scans carried out on a Canadian population of subjects, who underwent leukotomy decades ago, and the other more contemporary on an implantation surgery to epidural stimulation. Alongside technical advances in psychosurgery, a regulatory framework has gradually developed to ensure vigilance in the appropriateness of patients' selection. Nevertheless, harmonisation of protocols around the world is necessary to ensure consistency in obtaining and maintaining the highest possible ethical standards for the benefit of patients. If the neurosciences promise today, in their new, better framed, and reversible applications, to provide answers to unmet therapeutic needs, we still must remain attentive to drifts linked the introduction of intrusive technologies for purposes of domination or behaviour modification that would impede our individual freedom.

Analysis of the role of CAPS in the treatment of severe mental disorders:an integrative review

Analysis of the role of CAPS in the treatment of severe mental disorders:an integrative review

An Investigation of Suicidal Ideation from Social Media Using Machine Learning Approach

Despite improvements in the detection and treatment of severe mental disorders, suicide remains a significant public health concern. Suicide prevention and control initiatives can benefit greatly from a thorough comprehension and foreseeability of suicide patterns. Understanding suicide patterns, especially through social media data analysis, can help in suicide prevention and control efforts. The objective of this study is to evaluate predictors of suicidal behavior in humans using machine learning. It is crucial to create a machine learning model for detection of suicide thoughts by monitoring a user's social media posts to identify warning signs of mental health issues. Through the analysis of social media posts, our research intends to develop a machine learning model for identifying suicide ideation and probable mental health problems. This study will help immensely to comprehend the environmental risk factors that influence suicidal thoughts and conduct across time. In this research the use of machine learning on social media data is an exciting new direction for understanding the environmental risk factors that impact an individual's susceptibility to suicide ideation and conduct over time. The machine learning algorithms showed high accuracy, precision, recall, and F1-score in detecting suicide patterns on social media data whereas SVM has the highest performance with an accuracy of 0.886.

Cannabidiol attenuates the expression of conditioned place aversion induced by naloxone-precipitated morphine withdrawal through the activation of 5-HT1A receptors

The misuse of and addiction to opioids are serious public health problems in some countries, such as the USA. Drug addiction is a chronic and relapsing medical condition that involves motivational and memory-related processes due to the strong associations between drugs and consuming-related stimuli. These stimuli usually trigger continuous and compulsive use and are associated with relapses after periods of withdrawal. Several factors contribute to relapse, including withdrawal-induced mood changes. Therefore, drugs attenuating withdrawal-induced affective alterations could be useful alternative treatments for relapse prevention. Cannabidiol (CBD), a non-psychotomimetic component from the Cannabis sativa plant, has anti-anxiety and anti-stress properties and has been investigated as an alternative for the treatment of several mental disorders, including drug addiction. Here, we evaluated if CBD administered 30 min prior to test for a conditioned place aversion (CPA) would attenuate the aversion induced by morphine withdrawal precipitated by the opioid receptor antagonist naloxone in male C57BL/6 mice. We also investigated if this effect involves the activation of 5-HT1A receptors, a mechanism previously associated with CBD anti-aversive effects. As expected, morphine-treated mice spent less time exploring the compartment paired with the naloxone-induced withdrawal, indicating a CPA induced by naloxone-precipitated morphine withdrawal. This effect was not observed in animals treated with CBD, at 30 and 60 mg/kg, prior to the CPA test, indicating that CBD attenuated the expression of CPA induced by naloxone-precipitated morphine withdrawal. Pretreatment with the 5-HT1A receptor antagonist WAY100635 (0.3 mg/kg) blocked CBD effects. Our findings suggest that CBD may reduce the expression of a previously established conditioned aversion induced by morphine withdrawal by a mechanism involving the activation of 5-HT1A receptors. Thus, CBD may be a therapeutic alternative for preventing relapse to opioid addiction by decreasing withdrawal-induced negative affective changes.

Executive Functions and mental health

This research seeks to clarify the role that executive functions play in the treatment and prevention of psychiatric disorders. Mental health is a cornerstone for the development of societies, and it is affected to the problem of availability of an effective, lasting, and no-side effects treatment that help in mental disorder recovering which has been known to rise in terms of their forms and the number of sufferers around the world, especially in low to middle-income societies. This study, with an analytical descriptive approach, aims at shedding light on a recent trend in the treatment and prevention of mental disorders, especially in their early stages. The originality of this study lies in touching on functions that are rarely tackled in our societies, as a kind of prevention and treatment, by integrating them within the children’s school track, and developing training programs on them that take into account the local culture, intending to achieve a balanced psychological immunity in societies. This study has concluded the importance of the role of executive functions in the treatment of several mental disorders, in addition to the preventive role played by these abilities in limiting the emergence of some diseases despite the availability of genetic factors behind their emergence. Keywords: Executive Functions, Mental Health, Psychiatric Disorders, Cognitive Neuropsychology, Training programs

Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review

Introduction:Small-scale clinical studies with psychedelic drugs have shown promising results for the treatment of several mental disorders. Before psychedelics become registered medicines, it is important to know the full range of adverse events (AEs) for making balanced treatment decisions.Objective:To systematically review the presence of AEs during and after administration of serotonergic psychedelics and 3,4-methyenedioxymethamphetamine (MDMA) in clinical studies.Methods:We systematically searched PubMed, PsycINFO, Embase, and ClinicalTrials.gov for clinical trials with psychedelics since 2000 describing the results of quantitative and qualitative studies.Results:We included 44 articles (34 quantitative + 10 qualitative), describing treatments with MDMA and serotonergic psychedelics (psilocybin, lysergic acid diethylamide, and ayahuasca) in 598 unique patients. In many studies, AEs were not systematically assessed. Despite this limitation, treatments seemed to be overall well tolerated. Nausea, headaches, and anxiety were commonly reported acute AEs across diagnoses and compounds. Late AEs included headaches (psilocybin, MDMA), fatigue, low mood, and anxiety (MDMA). One serious AE occurred during MDMA administration (increase in premature ventricular contractions requiring brief hospitalization); no other AEs required medical intervention. Qualitative studies suggested that psychologically challenging experiences may also be therapeutically beneficial. Except for ayahuasca, a large proportion of patients had prior experience with psychedelic drugs before entering studies.Conclusions:AEs are poorly defined in the context of psychedelic treatments and are probably underreported in the literature due to study design (lack of systematic assessment of AEs) and sample selection. Acute challenging experiences may be therapeutically meaningful, but a better understanding of AEs in the context of psychedelic treatments requires systematic and detailed reporting.

Trends and Geographic Variabilities in Benzodiazepines Prescription in Primary Care to Older Adults: A 3-Year Population-Based Ecological Study in Portugal.

(1) Background: According to the World Health Organization (WHO), benzodiazepines (BZD) are considered essential medicines for the treatment of several mental disorders in older adults over 65 years old. However, the long-term use of BZD could present a harmful impact on this population, leading to cognitive deficits, drug dependence, falls, and fractures. This study aims to analyze trends of BZD prescription to Portuguese older adults in the primary care setting, and to analyze the change in the prescription rate of BZD over time, assessing the geographical variability in mainland Portugal. (2) Methods: A nationwide, retrospective ecological study was performed between January 2019 and December 2021 for BZD prescribing data reported in a national public database for all persons aged 65 and older in mainland Portugal (about 2.4 million). Trends of BZD by defined daily doses (DDD) and per 1000 older adults’ inhabitants per day (DID) were analyzed. (3) Results: A total of 19 BZD were included in this study and more than 1 million BZD prescriptions were recorded in each year of this study period. BZD prescriptions were three times higher in females than in males. Alprazolam, lorazepam, diazepam, ethyl loflazepate, and bromazepam were the most prescribed BZD over the years, presenting the higher DDD and DID values. (4) Conclusions: Despite the DID value growth of several BZD, Portugal is now showing stable BZD prescriptions in older adults, between the years 2019 to 2021. More studies are needed to access if these results are a consequence of successful health programs or just a consequence of the pandemic context that we are facing, which limited older adults’ clinical appointments.

Revisiting Drug Compliance: The Need for a Holistic Approach in the Treatment of Severe Mental Disorders

INTRODUCTION: The limited practice of depot antipsychotics and psychoeducation use, recommended for overcoming the noncompliance of patients with severe mental disorders, is linked to a high incidence of treatment violation. Therefore, the development of personalized mental healthcare approaches is a crucial healthcare task.
 AIM: To describe and differentiate the role of clinical, social and psychological factors that lead to different level of treatment engagement of psychiatric inpatients.
 METHODS: Secondary analysis of findings from 91 inpatients, based on the Treatment Motivation Assessment Questionnaire and Medication Compliance Scale, as well as the Scale of Internalized Stigma of Mental Illness and Perceived Discrimination and Devaluation Scale. Factorial analysis, cluster analysis and analysis of variance with p-level=0.05 and the calculation of the effect size (ES) according to Cohens d and Cramers V were used.
 RESULTS: The nature of therapy compliance in various categories of patients is mediated differentially, including: the severity of negative symptoms (ES=0.29), the global level of functioning and work maladjustment (ES=0.230.26), various motivational and behavioral styles (ES0.74) and the intensity of psychiatric stigmatization (ES0.88).
 CONCLUSIONS: Consideration of the clinical, social and psychological factors should empirically determine the strategies for the personalized use of prolonged antipsychotics and socio-psychotherapeutic interventions when developing an individual treatment plan for psychiatric in-patients.

Closed-loop enhancement and neural decoding of cognitive control in humans.

Deficits in cognitive control-that is, in the ability to withhold a default pre-potent response in favour of a more adaptive choice-are common in depression, anxiety, addiction and other mental disorders. Here we report proof-of-concept evidence that, in participants undergoing intracranial epilepsy monitoring, closed-loop direct stimulation of the internal capsule or striatum, especially the dorsal sites, enhances the participants' cognitive control during a conflict task. We also show that closed-loop stimulation upon the detection of lapses in cognitive control produced larger behavioural changes than open-loop stimulation, and that task performance for single trials can be directly decoded from the activity of a small number of electrodes via neural features that are compatible with existing closed-loop brain implants. Closed-loop enhancement of cognitive control might remediate underlying cognitive deficits and aid the treatment of severe mental disorders.

Association of Low-Dose Quetiapine and Diabetes

Quetiapine has been associated with increased risk of type 2 diabetes when used in medium or high doses for the treatment of severe mental disorders. It is not known whether low doses, commonly used off-label for sedative-hypnotic purposes, are also associated with increased risk of type 2 diabetes. To investigate whether there is an association between prescription of low-dose quetiapine and the risk of type 2 diabetes. This cohort study examined nationwide Danish health registers for data regarding new users of quetiapine (n = 185 938) or selective serotonin reuptake inhibitors (SSRIs) (n = 1 031 920) who were aged 18 years or older between January 1, 1998, and December 31, 2018. Individuals with schizophrenia or bipolar disorder were excluded. Quetiapine-initiators were matched 1:1 with initiators of SSRIs, using a high-dimensional propensity score (hdPS). Maximum follow-up was 5 years. Association with cumulative dose was investigated, using a case-control approach nested among quetiapine users. Data analysis was performed from May to September 2020. Dispensing of quetiapine or SSRIs. Quetiapine prescriptions were limited to tablet strengths of 25 mg and 50 mg to focus on low-dose use. Incident type 2 diabetes was defined as first filling of an antidiabetic medication, first register diagnosis of type 2 diabetes or first hemoglobin A1C measurement greater than or equal to 6.4% (≥48 mmol/mol). Incidence rates (IRs), incidence rate ratios (IRRs), and number-needed-to-harm (NNH) were calculated for full and matched cohorts using as-treated and intention-to-treat approaches. Odds ratios (ORs) were calculated for the association with cumulative quetiapine dose. Altogether, 896 285 patients were included in the full cohort; 538 164 (60%) were female and the median (interquartile range) age was 47 (33-67) years. There were 57 701 low-dose quetiapine initiators and 838 584 SSRI initiators. The matched cohort consisted of 54 616 pairs. In as-treated analyses, the incidence of type 2 diabetes during treatment with low-dose quetiapine (425 cases) was 9.59 cases/1000 person-years (PY) (95% CI, 8.72-10.5/1000 PY), which was slightly higher than for SSRI users (8462 cases; IR, 8.13/1000 PY; 95% CI, 7.96-8.30/1000 PY), resulting in a significant IRR of 1.18 (95% CI, 1.07-1.30) and NNH of 684 (95% CI, 418-1873). However, the between-group difference was nonsignificant in the hdPS-matched cohort (IR, 9.49 vs IR, 9.58; IRR, 0.99; 95% CI, 0.87-1.13). The case-control analysis found no dose-response association of low-dose quetiapine with diabetes (OR for doubling of the cumulative dose: 1.02; 95% CI, 0.95-1.09; P = .54), but in sensitivity analyses higher daily doses were associated with diabetes (all tablet strengths: OR, 1.08; 95% CI, 1.03-1.13). In this cohort study, use of low-dose quetiapine was not associated with excess risk of type 2 diabetes in comparison with SSRIs.

运用大麻制品(THC和CBD)治疗多种精神障碍的研究进展

运用大麻制品(THC和CBD)治疗多种精神障碍的研究进展

Antidepressant effect of Gentiana olivieri Griseb. in male rats exposed to chronic mild stress

ABSTRACT Background: The flowering parts of Gentiana olivieri, known as ‘Afat’ in the southeastern Anatolia region of Turkey, are used as a tonic, an appetizer, and for the treatment of several mental disorders, including depression. The purpose of this study is to investigate the antidepressant effect of G. olivieri ethanol extract (GOEE) in a chronic mild stress-induced rat model, which was used to mimic a depressive state in humans, and to compare the effect with that of imipramine. Methods: Male Sprague-Dawley rats were randomly divided into six groups: control, stress, treated with imipramine (positive control) and treated with GOEE at three different (200, 500, 1000 mg/kg) doses groups. The rats in all groups, except the control group, were exposed to chronic mild stress. At the end of the 3-week experimental period, biochemical and behavioral parameters were examined. Results: The results showed that treatment with GOEE or imipramine significantly improved rats’ sucrose consumption which was diminished by chronic mild stress, restored serum levels of corticosterone and proinflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)), prevented the increase of liver index of rats. Moreover, in the hippocampus tissue, decreased serotonin and noradrenaline levels were significantly increased by treatment with GOEE or imipramine, and antioxidant parameters (thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH)) were significantly improved by treatment with GOEE though not with imipramine. Conclusion: The data demonstrate that G. olivieri may exert its antidepressant activity by improving monoaminergic system disorders, and by favorably affecting the antioxidant, inflammatory and the endocrine mechanisms.

Integrated Programs for Early Recognition of Severe Mental Disorders: Recommendations From an Italian Multicenter Project.

The onset of mental disorders often occurs in adolescence or young adulthood, but the process of early diagnosis and access to timely effective and appropriate services can still be a challenge. The goal of this paper is to describe a pilot case of implementation of the ultra-high-risk (UHR) paradigm in six Italian departments of mental health employing an integrated approach to address clinical practice and service organization for youth in a broader preventive perspective. This approach entailed the integration of the UHR paradigm with a service provision model which prioritizes prevention and the promotion of local community coalitions to improve youth service accessibility. The multicenter Italian project “Integrated programs for recognition and early treatment of severe mental disorders in youths” funded by the National Centre for Disease Prevention and Control (CCM2013 Project) implemented in three Italian regions will be described. As a result of synergic actions targeting accessibility of young individuals to innovative youth mental health teams, a total of 376 subjects aged 15–24 years were recruited by integrated youth services within 12 months. Subjects have been screened by integrated multidisciplinary mental health youth teams employing standardized procedure and evidence-based clinical assessment instruments for at-risk mental states in young subjects [e.g., Comprehensive Assessment of At-Risk Mental States (CAARMS)]. Considering the three UHR categories included in CAARMS, the percentage of UHR subjects was 35% (n = 127) of the sample. In conclusion, future strategies to improve the organization of youth mental health services from a wider preventive perspective will be proposed.

Perspective On Excellence in Forensic Mental Health Services: What We Can Learn From Oncology and Other Medical Services.

We propose that excellence in forensic and other mental health services can be recognized by the abilities necessary to conduct randomized controlled trials (RCTs) and equivalent forms of rigorous quantitative research to continuously improve the outcomes of treatment as usual (TAU). Forensic mental health services (FMHSs) are growing, are high cost, and increasingly provide the main access route to more intensive, organized, and sustained pathways through care and treatment. A patient newly diagnosed with a cancer can expect to be enrolled in RCTs comparing innovations with the current best TAU. The same should be provided for patients newly diagnosed with severe mental illnesses and particularly those detained and at risk of prolonged periods in a secure hospital. We describe FMHSs in four levels 1 to 4, basic to excellent, according to seven domains: values or qualities, clinical organization, consistency, timescale, specialization, routine outcome measures, and research. Excellence is not elitism. Not all centers need to achieve excellence, though all should be of high quality. Services can provide each population with a network of centers with access to one center of excellence. Excellence is the standard needed to drive the virtuous circle of research and development that is necessary for teaching, training, and the pursuit of new knowledge and better outcomes. Substantial advances in treatment of severe mental disorders require a drive at a national and international level to create services that meet these standards of excellence and are focused, active, and productive to drive better functional outcomes for service users.

Cognitive functioning in patients treated with electroconvulsive therapy.

BackgroundElectroconvulsive therapy (ECT) is an effective treatment method for severe mental illnesses. ECT has gone through significant modernization. Side effects of ECT have largely decreased. Temporary disturbance of cognitive performance can be still present as a side effect of electroconvulsive treatment.MethodsCognitive functioning in the sample of patients with severe and acute mental illness treated with electroconvulsive therapy (ECT) was assessed. Basic assessment of cognitive functions was applied in the beginning, in the middle, and at the end of ECT course treatment with the Montreal Cognitive Assessment (MoCA). Complex and detailed testing of cognitive functions using the MATRICS Consensus Cognitive Battery (MCCB) was done at two points in time – within the first week of and then 6 weeks after the end of ECT.ResultsParticipants had cognitive deficits at baseline, which were most likely influenced markedly by the psychopathology of the illness itself. The improvement in cognition came together with the reduction in psychopathology; psychopathology scores were significantly reduced during ECT treatment. Compared to the baseline, all scores for cognitive testing were significantly improved but remained low in comparison with the controls. After 6 weeks, there was further significant improvement.ConclusionOur results confirm the safety and efficacy of ECT in the treatment of severe mental disorders.

Exploring the Wnt signaling pathway in schizophrenia and bipolar disorder

The Wnt signaling pathway plays a crucial role in neurodevelopment and in regulating the function and structure of the adult nervous system. Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders with evidence of subtle neurodevelopmental, structural and functional neuronal abnormalities. We aimed to elucidate the role of aberrant regulation of the Wnt system in these disorders by evaluating plasma levels of secreted Wnt modulators in patients (SCZ = 551 and BD = 246) and healthy controls (HCs = 639) using enzyme immune-assay. We also investigated the expression of 141 Wnt-related genes in whole blood in a subsample (SCZ = 338, BD = 241, and HCs = 263) using microarray analysis. Both SCZ and BD had dysregulated mRNA expression of Wnt-related genes favoring attenuated canonical (beta-catenin-dependent) signaling, and there were also indices of enhanced non-canonical Wnt signaling. In particular, FZD7, which may activate all Wnt pathways, but favors non-canonical signaling, and NFATc3, a downstream transcription factor and readout of the non-canonical Wnt/Ca2+ pathway, were significantly increased in SCZ and BD (p < 3 × 10−4). Furthermore, patients had lower plasma levels of soluble dickkopf 1 and sclerostin (p < 0.01) compared with HC. Our findings suggest that SCZ and BD are characterized by abnormal Wnt gene expression and plasma protein levels, and we propose that drugs targeting the Wnt pathway may have a role in the treatment of severe mental disorders.

The incidence, psychiatric co-morbidity and pharmacological treatment of severe mental disorders in children and adolescents

BackgroundAntipsychotic drug use among children and adolescents is increasing, and there is growing concern about off-label use and adverse effects. The present study aims to investigate the incidence, psychiatric co-morbidity and pharmacological treatment of severe mental disorder in Norwegian children and adolescents. MethodsWe obtained data on mental disorders from the Norwegian Patient Registry on 0–18 year olds who during 2009–2011 were diagnosed for the first time with schizophrenia-like disorder (International Classification of Diseases, 10th revision codes F20-F29), bipolar disorder (F30-F31), or severe depressive episode with psychotic symptoms (F32.3 or F33.3). Data on filled prescriptions for psychotropic drugs were obtained from the Norwegian Prescription Database. ResultsA total of 884 children and adolescents (25.1 per 100 000 person years) were first time diagnosed with schizophrenia-like disorder (12.6 per 100 000 person years), bipolar disorder (9.2 per 100 000 person years), or severe depressive episode with psychotic symptoms (3.3 per 100 000 person years) during 2009–2011. The most common co-morbid mental disorders were depressive (38.1%) and anxiety disorders (31.2%). Antipsychotic drugs were prescribed to 62.4% of the patients, 72.0% of the schizophrenia-like disorder patients, 51.7% of the bipolar disorder patients, and 55.4% of the patients with psychotic depression. The most commonly prescribed drugs were quetiapine (29.5%), aripiprazole (19.6%), olanzapine (17.3%), and risperidone (16.6%). ConclusionsWhen a severe mental disorder was diagnosed in children and adolescents, the patient was usually also prescribed antipsychotic medication. Clinicians must be aware of the high prevalence of depressive and anxiety disorders among early psychosis patients.

Sirukumab: A Potential Treatment for Mood Disorders?

Convergent evidence indicates that abnormalities in the innate immune system may be pertinent to the pathogenesis, phenomenology, and possible treatment of several mental disorders. In keeping with this view, the targeting of interleukin-6 with the human monoclonal antibody sirukumab may represent a possible treatment and disease modification approach, for adults with brain-based disorders (e.g., major depressive disorder). A PubMed/Medline database search was performed using the following search terms: sirukumab; anti-IL-6; IL-6; major depressive disorder; inflammation. A systematic review was conducted of both preclinical and clinical trials reporting on the pharmacology of sirukumab or investigating the efficacy of targeting IL-6 signaling. Overall, sirukumab has been reported to be a safe and well-tolerated agent, capable of modulating the immune response in healthy populations as well as in subjects with inflammatory disorders (e.g., rheumatoid arthritis). Sirukumab’s effects on cytokine networks as part of the innate immune system provide a coherent rationale for possible application in neuropsychiatric disorders with possible benefits across several domains of the biobehavioral Research Domain Criteria matrix (e.g., general cognitive processes, positive valence systems). Amongst individuals with complex brain-based disorders (e.g., mood disorders), the dimensions/domains most likely to benefit with sirukumab are negative valence disturbances (e.g., anxiety, depression, rumination), positive valence disturbances (e.g., anhedonia) as well as general cognitive processes. We suggest that sirukumab represents a prototype and possibly a proof-of-concept that agents that engage IL-6 targets have salutary effects in psychiatry.

Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data.

A new application for omega-3 fatty acids has recently emerged, concerning the treatment of several mental disorders. This indication is supported by data of neurobiological research, as highly unsaturated fatty acids (HUFAs) are highly concentrated in neural phospholipids and are important components of the neuronal cell membrane. They modulate the mechanisms of brain cell signaling, including the dopaminergic and serotonergic pathways. The aim of this review is to provide a complete and updated account of the empirical evidence of the efficacy and safety that are currently available for omega-3 fatty acids in the treatment of psychiatric disorders. The main evidence for the effectiveness of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been obtained in mood disorders, in particular in the treatment of depressive symptoms in unipolar and bipolar depression. There is some evidence to support the use of omega-3 fatty acids in the treatment of conditions characterized by a high level of impulsivity and aggression and borderline personality disorders. In patients with attention deficit hyperactivity disorder, small-to-modest effects of omega-3 HUFAs have been found. The most promising results have been reported by studies using high doses of EPA or the association of omega-3 and omega-6 fatty acids. In schizophrenia, current data are not conclusive and do not allow us either to refuse or support the indication of omega-3 fatty acids. For the remaining psychiatric disturbances, including autism spectrum disorders, anxiety disorders, obsessive-compulsive disorder, eating disorders and substance use disorder, the data are too scarce to draw any conclusion. Concerning tolerability, several studies concluded that omega-3 can be considered safe and well tolerated at doses up to 5 g/day.