Omega-3 polyunsaturated fatty acids and the psychiatric post-acute sequelae of COVID-19: A one-year retrospective cohort analysis of 33,908 patients.

BACKGROUND: Early prevention and management of psychiatric symptoms in long COVID (or post-COVID-19 conditions) are crucial for reducing long-term disability. Existing clinical guidelines recommend the use of omega-3 polyunsaturated fatty acids (PUFAs) as a promising therapeutic approach for various common psychiatric disorders due to their anti-inflammatory and neuroprotective characteristics. This study aims to investigate the potential efficacy of omega-3 PUFAs in alleviating the psychiatric sequelae following COVID-19. METHODS: This 1-year retrospective cohort study used the TriNetX electronic health records network to examine the effects of omega-3 PUFAs supplements on psychiatric sequelae in adults diagnosed with COVID-19. Using propensity-score matching, the study compared those who used omega-3 PUFAs supplements with those who did not, assessing outcomes including depression, anxiety disorders, insomnia, and other somatic conditions up to a year after COVID-19 diagnosis. RESULTS: In 16,962 patients who received omega-3 PUFAs supplements and 2,248,803 who did not, omega-3 supplementation significantly reduced the risk of developing psychiatric sequelae post-COVID-19 diagnosis (HR, 0.804; 95% CI, 0.729 to 0.888). Specifically, the risks for depression (HR, 0.828; 95% CI, 0.714 to 0.960), anxiety disorders (HR, 0.833; 95% CI, 0.743 to 0.933), and insomnia (HR, 0.679; 95% CI, 0.531 to 0.869) were reduced in the omega-3 group. This effect was consistent across sex, race, 18-59 age group, and patients with less than two doses of the COVID-19 vaccine. The omega-3 group also had a lower risk of cough and myalgia, but no significant difference was noted for other symptoms like chest pain, abnormal breathing, abdominal issues, fatigue, headache, and cognitive symptoms. CONCLUSION: Omega-3 PUFAs may require re-evaluation as a preventive strategy against adverse mental health outcomes post-COVID-19 in placebo-controlled clinical trials.

Increased risk of new-onset depression in patients with traumatic brain injury and hyperlipidemia: the important role of statin medications.

OBJECTIVE: Depression is a common complication after traumatic brain injury (TBI). This study aimed to evaluate the risk of hyperlipidemia for new-onset depression after TBI and the role of statin medications using a longitudinal population database. METHOD: A matched longitudinal cohort study of 3,792 subjects (1,264 TBI patients [ICD-9-CM code: 801-804 and 850-854] with preexisting hyperlipidemia [ICD-9-CM code: 272.0, 272.1, 272.2, 272.4] and 2,528 age- and sex-matched TBI patients without hyperlipidemia) was conducted using the Taiwan Longitudinal Health Insurance Database from January 2001 to December 2008. The incidence and hazard ratios (HRs) for the development of new-onset depression (ICD-9-CM code: 296.2X-296.3X, 300.4, and 311.X) after TBI were compared between the 2 groups. RESULTS: The incidence rate of depression in TBI with preexisting hyperlipidemia was 136.61 per 10,000 person-years. TBI patients with preexisting hyperlipidemia had a 1.72-fold increased incidence rate ratio compared with those without hyperlipidemia (P = .0056). A Cox model showed hyperlipidemia to be an independent predictor of depression (HR = 1.61; 95% CI, 1.03-2.53). TBI patients with hyperlipidemia who were not treated with statins experienced a 1.95-fold incidence risk ratio (P = .0017) and higher risk of new-onset depression (HR = 1.61; 95% CI, 1.03-2.53) compared to TBI patients without hyperlipidemia. CONCLUSIONS: Preexisting hyperlipidemia could be an independent predictor of new-onset depression in TBI patients, and TBI patients with preexisting hyperlipidemia who were not treated with statins presented a higher risk of new-onset depression than TBI patients without hyperlipidemia. Our findings may provide some insight into the important role of statin medications in the development of new-onset depression in patients with traumatic brain injury.

Pre-existing hyperlipidaemia increased the risk of new-onset anxiety disorders after traumatic brain injury: a 14-year population-based study.

OBJECTIVES: Anxiety disorders (ADs) are common after traumatic brain injury (TBI). However, the risk factors of new-onset ADs remain unclear. This study was aimed at evaluating the incidence and risk factors for new-onset ADs, including pre-existing hyperlipidaemia and three major comorbidities (diabetes mellitus, hypertension and cardiovascular disease), in patients with TBI. SETTING: A matched cohort study was conducted using the Taiwan Longitudinal Health Insurance Database between January 1997 and December 2010. PARTICIPANTS: A total of 3822 participants (1274 patients with TBI with hyperlipidaemia and 2548 age-matched and gender-matched patients with TBI without hyperlipidaemia). OUTCOME MEASURES: The incidence and HRs for the development of new-onset ADs after TBI were compared between the two groups. RESULTS: The overall incidence rate of new-onset ADs for patients with TBI with hyperlipidaemia is 142.03/10 000 person-years (PYs). Patients with TBI with hyperlipidaemia have a 1.60-fold incidence rate ratio (p<0.0001) and increased HR of ADs (1.58, 95% CI 1.24 to 2.02) compared with those without hyperlipidaemia. The incidence rates of ADs for males and females with hyperlipidaemia, respectively, were 142.12 and 292.32/10 000 PYs, which were higher than those without hyperlipidaemia (93.03 and 171.68/10 000 PYs, respectively). Stratified by age group, hyperlipidaemia is a risk factor of ADs for patients with TBI aged 65 years or younger. CONCLUSIONS: Pre-existing hyperlipidaemia is an independent predictor of new-onset ADs in patients with TBI, even when controlling for other demographic and clinical variables. Female patients with pre-existing hyperlipidaemia had significantly higher risk of new-onset ADs than males, especially between the ages of 35 and 65 years.

Longitudinal trends of the healthcare-seeking prevalence and incidence of insomnia in Taiwan: an 8-year nationally representative study.

OBJECTIVES: We used insurance claims of a nationally representative population-based cohort to assess the longitudinal healthcare-seeking prevalence and incidence of insomnia. METHODS: Participants were identified from National Health Insurance enrollees in Taiwan during 2002 to 2009. Individuals with insomnia were identified using The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic and procedure codes of 780.52, 307.41, and 307.42. RESULTS: In 2009 the prevalence of insomnia was 5.4% for women and 3.0% for men; the incidence of insomnia was 1.6% for women and 1.3% for men. Patients who were women (odds ratio [OR]), 1.82; 95% confidence interval [CI], 1.79-1.86), who were older (50-64 years: OR, 23.25; 95% CI, 21.07-25.64; ≥ 65 years: OR, 24.70; 95% CI, 22.40-27.24), and who were in the middle socioeconomic status (SES) group (OR, 1.19; 95% CI, 1.16-1.21) were more likely to have insomnia. An inverse U-shaped woman-to-man ratio trend for the insomnia prevalence was found, and this ratio reached a peak around the menopausal transitional period. CONCLUSIONS: The persistence of healthcare-seeking behaviors with insomnia was more common in women. Our findings underscore the need to initiate treatment at an early stage as opposed to waiting for the spontaneous resolution of insomnia. Future research needs to identify causes of the persistence of insomnia and to develop proper interventions to reduce its rising prevalence. More active approaches toward preventive strategies for insomnia are needed, especially for women who are at higher risk for insomnia.

Oral administration of an Enoki mushroom protein FVE activates innate and adaptive immunity and induces anti-tumor activity against murine hepatocellular carcinoma.

FVE is a documented immunomodulatory protein purified from Enoki mushroom (Flammulina velutipes) and known as an activator for human T lymphocytes. This present study was aimed to investigate the anti-tumor effect and the related mechanisms of oral administration of FVE using a murine hepatoma model. Oral administration of FVE (10mg/kg) significantly increased the life span and inhibited the tumor size of BNL 1MEA.7R.1 (BNL) hepatoma-bearing mice. Tumor-bearing mice receiving oral FVE treatment had the highest tumoricidal capacity of peritoneal macrophages and tumor-specific splenocytes against BNL hepatoma cells. In addition, in vivo neutralization of interferon-gamma (IFN-gamma) demonstrated a significant decrease of FVE-induced anti-tumor effect (P<0.05). The expression levels of major histocompatibility complex (MHC) class I and II molecules and costimulatory molecule CD80 on peripheral blood mononuclear cells obtained from the FVE-treated mice were upregulated as compared with those of the PBS-treated mice. Furthermore, immunohistochemical staining showed a strong inhibition of tumor growth and angiogenesis in hepatoma tissues after oral administration of FVE. Taken together, oral administration of FVE displayed anti-tumor activity through activating both innate and adaptive immunity of the host to prime a cytotoxic immune response and IFN-gamma played a key role in the anti-tumor efficacy of FVE.

Purification, cloning, and functional characterization of a novel immunomodulatory protein from Antrodia camphorata (bitter mushroom) that exhibits TLR2-dependent NF-κB activation and M1 polarization within murine macrophages.

A new immunomodulatory protein, designated ACA, was purified from the mycelium extract of Antrodia camphorata , a well-known folk medicine bitter mushroom in Taiwan, and N-terminally sequenced. By taking advantage of its N-terminal amino acid sequence, the full-length ACA gene was cloned using rapid amplification of cDNA ends (RACE) approach. This gene encodes a 136 amino acid protein that is homologous to the phytotoxic proteins from fungi. On the basis of the data of N-terminal sequencing and N-glycosidase F treatment, the native ACA was confirmed to be a glycoprotein. The similarity in activation of TLR4-deficient macrophages by both the native ACA and recombinant ACA (rACA) suggested that the glycosyl group(s) of the native ACA was insignificant in macrophage activation. Moreover, the failure of rACA to induce TLR2-deficient macrophages and to activate the RAW 264.7 macrophages transfected with the dominate-negative MyD88 (dnMyD88) indicated that the ACA-mediated macrophage activation was TLR2/MyD88 dependent. Microarray assay of the ACA-activated NFκB-related gene expression showed that rACA demonstrated a LPS-mimetic proinflammatory response toward RAW 264.7 macrophages. Furthermore, rACA enhanced phagocytosis activity and CD86 (B7-2) expression as well as induced TNF-α and IL-1ß production within murine peritoneal macrophages. A time-dependent induction of mRNA expression of cytokines TNF-α, IL-1ß, IL-6, and IL-12 as well as chemokines CCL3, CCL4, CCL5, and CCL10, but not IL-10, CCL17, CCL22, and CCL24, was observed after the ACA treatment of the macrophages. These results proposed that ACA exhibited M1 polarization and differentiation in macrophages. Thus, ACA is an important immunomodulatory protein of A. camphorata.