Long-term ambient ozone, omega-3 fatty acid, genetic susceptibility, and risk of mental disorders among middle-aged and older adults in UK biobank.

BACKGROUND: Evidence linking ozone to depression and anxiety disorders remains sparse and results are heterogeneous. It remains unknown whether omega-3 fatty acid, or genetic susceptibility of mental disorders modify the impacts of ozone. The aim is to assess the associations of ambient ozone with depression and anxiety, and further explore the potential modification effects of omega-3 fatty acid and genetic susceptibility. METHODS: In total of 257,534 participants were enrolled from 2006 to 2010 and followed up to 2016. Depression and anxiety were assessed using mental health questionnaires, primary care records and hospital admission records. The annual average concentrations of ozone were calculated and linked to individuals by home address. Dietary intake and plasma concentration were selected to reflect levels of omega-3 fatty acid. Polygenetic risk scores were selected to reflect genetic susceptibility. We examined the associations of ozone and incident mental disorders, and potential modification of omega-3 fatty acid and genetic susceptibility. RESULTS: Incidences of depression (N = 6957) and anxiety (N = 6944) was associated with increase of ozone. Higher levels of omega-3 fatty acid might attenuate the ozone related depression risk. However, the modification effects of genetic susceptibility were not found. CONCLUSIONS: Long-term exposure to ambient ozone increase the risk of mental disorders among the middle aged and older adults, and omega-3 fatty acid could reduce the adverse effects of ozone on mental health. Higher intake of omega-3 fatty acid is a potential strategy to prevent the risks caused by ozone on public mental health.

Asiatic acid attenuates aluminium chloride-induced behavioral changes, neuronal loss and astrocyte activation in rats.

Aluminium (Al) is a potent neurotoxic metal known to cause neurodegeneration. Al exposure causes oxidative stress by accumulation of reactive oxygen species, followed by the activation of neuronal cell death in the brain. Asiatic acid (AA), the major bioactive compound of Centella asiatica (a medicinal plant), act as multifunctional drug as well as an antioxidant. Thus, the present study aimed to investigate the potential neuroprotective effect of AA against Al neurotoxicity. Rats were orally administered aluminium chloride (AlCl3; 100 mg/kg b. wt.) dissolved in distilled water for 8 weeks or AA (75 mg/kg b. wt.) in combination with AlCl3. The results showed that AlCl3-intoxication causes significant impairment of memory, enhances anxiety-like behavior, acetyl cholinesterase (AChE) activity, malondialdehydes (MDA) level, and concomitant decrease in the activities of superoxide dismutase (SOD) and catalase (CAT) in the cortex and hippocampus regions of rat brain. In addition, AlCl3-intoxication enhanced neuronal loss and reactive astrogliosis in both regions. However, co-administration of AA with AlCl3 significantly attenuated the behavioral alterations, restored SOD and CAT activities, while reduced AChE activity and MDA content. Further, the study demonstrated that AA attenuates neuronal loss and reactive astrogliosis in rat brain. In conclusion, the study suggests that AA protects rat brain from Al neurotoxicity by inhibiting oxidative stress, neuronal loss and reactive astrogliosis.

Psilocybin Therapy of Psychiatric Disorders Is Not Hampered by hERG Potassium Channel-Mediated Cardiotoxicity.

Psilocybin, a hallucinogen contained in "magic" mushrooms, holds great promise for the treatment of various psychiatric disorders, and early clinical trials are encouraging. Adverse cardiac events after intake of high doses of psilocybin and a trial reporting QT interval prolongation in the electrocardiogram attributed to the drug's main metabolite, psilocin, gave rise to safety concerns. Here we show that clinical concentrations of psilocin do not cause significant human ether-a-go-go-related gene (hERG) potassium channel inhibition, a major risk factor for adverse cardiac events. We conclude that hERG channel blockage by psilocin is not liable for psilocybin- associated cardiotoxic effects.

Does vitamin B12 deficiency explain psychiatric symptoms in recreational nitrous oxide users? A narrative review.

Background Recreational use of nitrous oxide (N2O) is associated with many side effects, of which neurological complications are most common. Nitrous oxide abuse is also associated with psychiatric symptoms, but these have received less attention so far. Vitamin B12 deficiency may play a role in the development of these psychiatric symptoms.Aims To explore the relationship among the occurrence of recreational nitrous oxide-induced psychiatric symptoms, accompanying neurological symptoms, vitamin B12 status and choice of treatment.Methods A retrospective search for case reports was conducted across multiple databases (Pubmed, Embase, Web of Science, PsycINFO and CINAHL). Keywords included variants of "nitrous oxide", "case report" and "abuse". No restrictions to language or publication date were applied.Results The search retrieved 372 articles. A total of 25 case reports were included, representing 31 patients with psychiatric complications following nitrous oxide abuse. The most often reported symptoms were: hallucinations (n = 16), delusions (n = 11), and paranoia (n = 11). When neurological symptoms were present, patients were treated more frequently with vitamin B12 supplementation.Conclusions This review highlights the need to recognize that psychiatric symptoms may appear in association with nitrous oxide use. Approximately half of the cases that presented with nitrous oxide-induced psychiatric complaints did not show neurological symptoms, and their vitamin B12 concentration was often within the hospital's reference range. Psychiatrists and emergency physicians should be aware of isolated psychiatric symptoms caused by recreational nitrous oxide abuse. We suggest asking all patients with new psychiatric symptoms about nitrous oxide use and protocolizing the management of nitrous oxide-induced psychiatric symptoms.

Neuroprotective effect of hesperidin against emamectin benzoate-induced neurobehavioral toxicity in rats.

Emamectin Benzoate (EMB) is an avermectin insecticide widely used in agriculture and veterinary medicine. Hesperidin (HSP) is a flavanone glycoside predominantly found in citrus fruits and has various beneficial health effects. The current research was conducted to study the neurobehavioral toxic effects of EMB in rats and also to evaluate the protective effect of HSP against these toxic effects. Sixty Sprague-Dawley rats were randomly divided into 4 equal groups: control group, EMB group, HSP group, and EMB + HSP group. EMB (8.8. mg/kg) and/or HSP (100 mg/kg) were administered daily by gavage for 8 weeks. The behavioral assessment demonstrated the adverse effects of EMB on the behavioral, motor, and cognitive brain functions. Exposure to EMB also decreased the activity of antioxidants (catalase and reduced glutathione) and increased the malondialdehyde level in nervous tissue. Moreover, EMB increased the level of inflammatory cytokines (tumor necrosis factor-α and interleukin-1ß) and decreased brain-derived neurotrophic factor (BDNF) levels in rats' brains. On the other hand, concurrent administration of HSP ameliorated the toxic effects of EMB as indicated by improvements in neural functions and reduction of oxidative stress and inflammation. The study concluded that exposure to EMB induces toxic effects in the brain of rats and that HSP has a protective effect against these toxic effects.

Acute Psychological Adverse Reactions in First-Time Ritual Ayahuasca Users: A Prospective Case Series.

BACKGROUND: In recent decades, ritualistic use of ayahuasca has spread throughout the world. Retrospective studies have suggested a good psychological safety profile, but prospective studies involving ceremony ayahuasca-naive participants are lacking. METHODS: We conducted the study using a subsample from a previous study, for which first-time ceremony ayahuasca participants were recruited. The subsample consisted of 7 subjects who experienced acute and challenging psychological reactions. The semistructured Mini-International Neuropsychiatric Interview and psychometric questionnaires were administered before participants attended the ayahuasca ceremony and at 1 and 6 months after exposure. Subjective experiences were also recorded. RESULTS: Seven subjects from a sample of 40 reported having experienced intense challenging psychological effects during the ayahuasca ceremony. Four of those 7 subjects met the diagnostic criteria for 1 or more psychiatric disorder before the ayahuasca ceremony. One month after the ceremony, 2 of those subjects no longer showed psychiatric symptoms, whereas the symptoms of the other 2 were reduced considerably. Those results persisted at the 6-month follow-up. Inappropriate setting/context (poor guiding skills and screening) contributed to some of the challenging reactions. Most of the participants (6 of 7) did not take ayahuasca again during the study period. CONCLUSIONS: Based on the cases reported here, we suggest that although it is possible that participating in ayahuasca ceremonies may entail acute psychological negative reactions, those challenging experiences can also have positive long-term effects. Prospective research on the safety profile of ayahuasca and how it is affected by the context of different practices and safety strategies is therefore necessary.

Effects of ayahuasca on mental health and quality of life in naïve users: A longitudinal and cross-sectional study combination.

Ayahuasca is a hallucinogenic decoction used as a traditional medicine in several Amazonian regions. The ritualistic use of ayahuasca has spread throughout many countries, making it necessary to study its risks and benefits. Two sub-studies were designed for this investigation. In sub-study 1, a psychiatric interview and a battery of questionnaires were administered to subjects (n = 40) before their first ayahuasca use. Two follow-ups were conducted at 1 and 6 months. In sub-study 2, the same interview and battery of questionnaires were administered to long-term ayahuasca users (n = 23) and their scores were compared with those of the ayahuasca-naïve group. In the first assessment, nearly half (45%) of the naïve users were found to meet the diagnostic criteria for a psychiatric disorder. After the ayahuasca use, more than 80% of those subjects showed clinical improvements that persisted at 6 months. The questionnaires showed significant reductions in depression and psychopathology. Regarding sub-study 2, long-term users showed lower depression scores, and higher scores for self-transcendence and quality of life, as compared to their peers in sub-study 1. Further controlled and observational naturalistic studies assessing the eventual risks and potential benefits of ayahuasca are warranted.

Pyridoxine supplementation for levetiracetam-related neuropsychiatric adverse events: A systematic review.

OBJECTIVE: Among people with epilepsy, levetiracetam (LEV) can cause neuropsychiatric adverse events (NPAEs) that impact negatively on quality of life. It has been suggested that pyridoxine can ameliorate LEV-related NPAEs. We conducted a systematic review of studies on the use of pyridoxine supplementation to relieve NPAEs associated with LEV therapy. METHODS: The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, EMBASE, Scholar, Cochrane-CENTRAL (2000-2019), and EThOS platform were searched for studies on the use of pyridoxine in patients with LEV-related NPAEs. Proportions of patients reported to benefit from pyridoxine supplementation were tabulated, and a random-effect model meta-analysis was conducted. RESULTS: Eleven retrospective studies/case reports and one randomized prospective study, mostly including pediatric populations, were identified. Retrospective studies, which were rated as low quality due to failure to control for bias, reported an overall improvement of NPAEs after pyridoxine supplementation in 72.5% (108/149) of patients. The proportion of patients showing improvement in a pooled analysis of the four largest retrospective studies (n = 134) was 72.1% (95% confidence interval (CI) 47.1-88.3), although there was high heterogeneity across studies (I2 = 82%, pheterogeneity < 0.01). In the only prospective trial, patients randomized to pyridoxine supplementation were more likely to show relief from NPAEs than patients not receiving supplementation (p < 0.01), but outcomes might have been affected by assessment bias. CONCLUSION: This systematic review suggests that pyridoxine might be of benefit in relieving LEV-related NPAEs. However, the quality of the evidence is poor, and better-designed prospective studies that include quantitative as well as qualitative data are needed to define the role of pyridoxine in the management of LEV-related NPAEs.

Potassium supplementation mitigates corticosteroid-induced neuropsychiatric effects in pediatric oncology patients.

Corticosteroids play an essential role in the treatment of pediatric malignancies, but have many untoward side effects including behavioral and mood disturbances which can be quite burdensome to families. Potassium chloride has been used anecdotally to decrease these neuropsychiatric effects but this experience has not been studied systematically. We therefore retrospectively reviewed our experience utilizing KCl supplementation to reduce corticosteroid-induced neuropsychiatric effects among children with acute lymphoblastic leukemia. Thirteen of 16 patients (81%) had a objective benefit with KCl at a median dose of 0.5 mEq/kg/day, with no reported adverse effects. Further prospective study is required to confirm these data.

Attenuation of Aluminum Chloride-Induced Neuroinflammation and Caspase Activation Through the AKT/GSK-3ß Pathway by Hesperidin in Wistar Rats.

Hesperidin, a flavanoglycone abundantly present in citrus fruits, is reported to have antioxidant, anti-inflammatory, and neuroprotective properties. Previous reports from our laboratory indicated the neuroprotective effect of hesperidin against aluminum chloride (AlCl3)-induced memory loss, acetylcholine esterase hyperactivity, oxidative stress, and enhanced expression of amyloid ß protein biosynthesis-related markers. However, their role on AlCl3-induced inflammation, caspase activation, Tau pathology, altered Akt/GSK 3ß signaling pathway, and Aß clearance marker has not yet been fully elucidated. Intraperitonial injection of AlCl3 (100 mg/kg body weight) for 60 days significantly elevated the expressions of insulin-degrading enzyme (IDE), cyclin-dependent kinase 5 (CDK 5), and phosphoTau (pTau); inflammatory markers such as glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), NF-kB, cyclooxygenase-2 (COX-2), interleukin (IL)-1ß, IL-4, IL-6, tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS); and apoptotic markers including cytosolic cytochrome c (cyto c), caspase-3, caspase-8, and caspase-9, and lowered expressions of mitochondrial cyto c, phospho-Akt (pAkt) and phospho-glycogen synthase kinase-3ß (pGSK-3ß) in the hippocampus and cortex. Co-administration of hesperidin to AlCl3 rats for 60 days significantly ameliorated the aluminum-induced pathological changes. The behavioral studies also supported the above findings. Our results imply that treatment with hesperidin might be a potent option for treating the symptoms of cognitive impairment in Alzheimer's disease by targeting its most prominent hallmarks.

Psychiatric disorders, acne and systemic retinoids: comparison of risks.

BACKGROUND: The link between isotretinoin, treatment of a severe form of acne, and psychiatric disorders remains controversial, as acne itself could explain the occurrence of psychiatric disorders. This study aims at assessing the disproportionality of psychiatric adverse events reported with isotretinoin in the French National PharmacoVigilance Database, compared with other systemic acne treatments and systemic retinoids. MATERIALS AND METHODS: Data were extracted from the French National PharmacoVigilance Database for systemic acne treatments, systemic retinoids and drugs used as comparators. Each report was subjected to double-blind analysis by two psychiatric experts. A disproportionality analysis was performed, calculating the number of psychiatric ADRs divided by the total number of notifications for each drug of interest. RESULTS: Concerning acne systemic treatments: all 71 reports of severe psychiatric disorders involved isotretinoin, the highest proportion of mild/moderate psychiatric adverse events was reported with isotretinoin (14.1%). Among systemic retinoids, the highest proportion of severe and mild/moderate psychiatric events occurred with isotretinoin and alitretinoin. CONCLUSION: Our study raises the hypothesis that psychiatric disorders associated with isotretinoin are related to a class effect of retinoids, as a signal emerges for alitretinoin. Complementary studies are necessary to estimate the risk and further determine at-risk populations.

Serious and reversible levetiracetam-induced psychiatric symptoms after resection of frontal low-grade glioma: two case histories.

Levetiracetam may induce serious behavioral disturbances, especially after surgical resection of frontal lobe low-grade glioma. Two patients, treated with levetiracetam, developed serious psychiatric complications postoperatively which completely resolved after switching to valproate. We aim to create awareness for this serious but reversible adverse effect of levetiracetam in this specific patient category.

Adverse Psychiatric Effects Associated with Herbal Weight-Loss Products.

Obesity and overeating are among the most prevalent health concerns worldwide and individuals are increasingly using performance and image-enhancing drugs (PIEDs) as an easy and fast way to control their weight. Among these, herbal weight-loss products (HWLPs) often attract users due to their health claims, assumed safety, easy availability, affordable price, extensive marketing, and the perceived lack of need for professional oversight. Reports suggest that certain HWLPs may lead to onset or exacerbation of psychiatric disturbances. Here we review the available evidence on psychiatric adverse effects of HWLPs due to their intrinsic toxicity and potential for interaction with psychiatric medications.

[Delayed neurological syndrome following carbon monoxide poisoning]. / Síndrome neurológico tardío tras intoxicación por monóxido de carbon.

INTRODUCTION: Poisoning by carbon monoxide is the most frequent form of intoxication in our milieu as a result of exposure to poisonous gases. The effects of carbon monoxide poisoning are not limited to acute exposure, since, following apparent recovery from the acute intoxication, neurological or behavioural disorders may appear. PATIENTS AND METHODS: A study was conducted to examine the cases of carbon monoxide poisoning that had occurred in a healthcare area of 80,000 inhabitants over a 10-year period. These patients were then submitted to a follow-up to appraise the appearance of delayed neurological syndrome (DNS) and its relationship with different variables in the initial exposure to the carbon monoxide, in the treatment that was administered or in the severity of the intoxication. RESULTS AND CONCLUSIONS: It was observed that around 9.1% of those intoxicated by carbon dioxide detected within the healthcare district of Salnés went on to develop DNS, which is more frequent in patients with severe analytical criteria and very unlikely in those who do not have them. Patients with DNS did not express any clinical or analytical manifestations that differed from those who did not have the syndrome; no differences were observed in relation to the oxygen therapy that was administered. The rate of DNS within the healthcare district of Salnés between 2002 and 2012 is 0.84 cases per 100,000 inhabitants per year.

TITLE: Sindrome neurologico tardio tras intoxicacion por monoxido de carbono.Introduccion. La intoxicacion por monoxido de carbono es la mas frecuente en nuestro medio a consecuencia de la exposicion a gases toxicos. Los efectos de la intoxicacion por monoxido de carbono no se limitan a la exposicion aguda porque, tras la aparente recuperacion de la intoxicacion, pueden aparecer alteraciones neurologicas o del comportamiento. Pacientes y metodos. Se realizo un estudio de las intoxicaciones por monoxido de carbono en un area sanitaria de 80.000 habitantes durante un periodo de 10 años. Posteriormente se hizo un seguimiento de estos pacientes y se valoro la aparicion de sindrome neurologico tardio (SNT) y su relacion con diferentes variables en la exposicion inicial al monoxido de carbono, en el tratamiento administrado o en la gravedad de la intoxicacion. Resultados y conclusiones. Se observo que el 9,1% de los intoxicados por monoxido de carbono detectados en el area sanitaria de Salnes desarrollan el SNT, que es mas frecuente en los pacientes con criterios analiticos de gravedad y muy poco probable en los que no los tienen. Los pacientes con SNT no expresaron manifestaciones clinicas ni analiticas diferentes a los que no presentaron el sindrome; tampoco se observaron diferencias en relacion con la terapia con oxigeno administrada. La tasa de SNT en el area sanitaria de Salnes entre 2002 y 2012 es de 0,84 casos por 100.000 habitantes y año.

[Delayed neurological syndrome after CO intoxication of elderly female]. / Laattijdige neuropsychologisch syndroom na CO-intoxicatie bij een bejaarde vrouw.

This article discusses the case history of an 87-year old woman with loss of consciousness following accidental CO intoxication. A few weeks later, the patient's cognitive abilities progressively deteriorated. This is hence a case of Delayed Neurological Symptoms after CO intoxication. This condition occurs in 40% of patients with CO intoxication and manifests itself 3-240 days after apparent recovery. Symptoms can linger for a long time and are in some cases even permanent. Treatment of CO intoxication usually consists of administering normobaric oxygen and in certain cases hyperbaric oxygen. The role of treatment with hyberbaric oxygen in delayed neurological symptoms after CO intoxication remains controversial, however.

[Monitoring and Care of Expectant Mothers with Epilepsy].

Women with epilepsy are exposed to social stigma, and they have anxiety and lose self-confidence in their social role as a woman. Psychiatrists, especially female psychiatrists, are able to support them. Important considerations are: 1) Pre-pregnant counseling; Physicians give appropriate advice and guidance. We need to provide the latest information on the teratogenicity of AEDs, and replace them with a safer combination of AEDs BEFORE pregnancy. Folate supplementation is also recommended. 2) Management during pregnancy: Patients are advised to adhere to taking AEDs as instructed, which prevents not only seizures during pregnancy but also reduces the risk of miscarriage and premature delivery. Doses of AED are to be increased after the second trimester. 3) Collaborating with obstetricians at delivery: Obstetricians are also nervous when faced with women with epilepsy. Basically, patients can deliver spontaneously, and the correct way to deal with unexpected seizures during labor should be fully understood. 4) Parental care: women with epilepsy can breastfeed. Physicians advise other family members on how to bottle feed at night to help mothers avoid a lack of sleep due to breastfeeding. Childcare is one of the most precious experiences in life. Patients with epilepsy, especially women, have a lower self-esteem; however, once they experience delivery, they act positively and become even-tempered. Physicians should be aware that childcare fosters a profound insight into their lives, allowing them to mature as a person.

Delayed leukoencephalopathy after acute carbon monoxide intoxication.

Delayed leukoencephalopathy is an uncommon complication of hypoxic-ischemic events of different etiologies, including carbon monoxide intoxication. We present a case of a 40-year-old male patient who was admitted with rapidly progressive neurocognitive and behavioral deficits. There was a history of accidental carbon monoxide intoxication one month before, presenting with loss of consciousness and short hospitalization, followed by a complete clinical recovery. The imaging studies in the delayed phase depicted confluent, symmetric supra-tentorial white matter lesions in keeping with diffuse demyelinization. Restricted diffusion and metabolite abnormalities in magnetic resonance proton spectroscopy were also seen. The diagnosis of CO-mediated delayed post-hypoxic leukoencephalopathy was assumed after exclusion of other mimickers. Hyperbaric oxygen therapy was tentatively performed and the patient had a favorable clinical and radiological evolution.

[Clinical and hygienic substantiation of individual biocorrection for ecologically dependent conditions in the critical groups of the population of Ukrainian industrial areas].

In the article there is considered the problem of pollution of the environment and human body with heavy metals, the effectiveness of individual biocorrection in critical groups of the population--pregnant women and children residing in technologically contaminated areas. In spite of the correspondence of the content of abiotic heavy metals to their MACs in the environment, the concentration of lead and cadmium in the internal environment of the organism in 1,6-15,4 times was found to exceed physiological norms that accompanied by a significant deficiency of essential trace elements. Similar situation has been proved to lead to a reduction in mental health and ability to learn in children, as well as to the various complications in pregnancy. The obtained results served as the scientific substantiation of the feasibility of biocorrection of the trace element imbalance ecological dependent states in the population of the industrial region. The proved high clinical effectiveness of this hygienic biocorrection is a scientific justification for widespread introduction of pectin preparations for health promotion, prevention of ecologically dependent states and increasing the adaptive capacity of the organism.

[Clinical hygienic substantiation for the individual biocorrection of ecologically dependent conditions in the critical population groups industrial areas of Ukraine].

In the article there is considered the problem of environmental and human body pollution with heavy metals, the effectiveness of individual biocorrection in critical population groups--pregnant females and children residing in technologically contaminated areas. It was established that, in spite of the correspondence of the content of abiotic heavy metals to their MACs in the environment, the concentration of lead and cadmium in the internal environment of the organism is 1,6-15,4 times larger than physiological norms and accompanied by substantial deficiency of essential trace elements. The similar situation in children was proved to cause the fall in mental capacity and learning ability, in pregnant females--to various complications. The obtained results were the scientific substantiation for the feasibility of performing of biocorrection for trace elements imbalance and ecologically dependent conditions in the population of the industrial region, proved its high clinical and hygienic efficiency, which is the basis for the wide introduction of pectin containing preparations with the aim to enforce the health, prevent ecologically dependent conditions and increasing the adaptive capacity of the organism.