Thyroid allostasis in drug-free affective disorder patients.

AIM: To assess the thyroid allostasis in drug-free patients with affective disorder. METHODS: Patients with major depressive disorder or bipolar disorder as drug-free, defined as those without psychiatric drugs exposure for at least 4 months before admission, from a tertiary hospital were recruited in this cross-sectional study. The primary outcomes were "structure parameters of thyroid homeostasis", which include "thyroid's secretory capacity" (SPINA-GT), "sum step-up activity of deiodinases" (SPINA-GD), the ratio of total to free thyroxine and "thyroid homeostasis central set point" (TSH index and "thyroid feedback quantile-based index" [TFQI]), calculated by TSH and thyroid hormones measured at admission. A healthy population and non-affective psychiatric disorder (schizophrenia) from the same catchment area were recruited as two comparison groups. RESULTS: A total of 1263 cases of major depressive disorder, 1619 cases of bipolar disorder, 1186 cases of schizophrenia, and 162 healthy controls were included in the study. Compared to healthy control, GD and ratio of total to free thyroxine were lower in affective disorders. Bipolar with mania episode had higher GT than bipolar with depressive episode and major depressive disorder (median level at 3.70 vs. 3.04 and 3.03, respectively). Compared with healthy control, schizophrenia had higher TSH index and TFQI, but no increase in these parameters in major depressive disorder and bipolar disorder. CONCLUSION: Affective disorders have a unique profile of thyroid allostasis with impaired step-up deiodinase activity and reduced serum protein binding of thyroid hormones, but no change in thyroid homeostasis central set point. Mania episode may be associated with higher thyroid secretory capacity.

Higher central set point of thyroid homeostasis in drug-naïve patients affected by first episode schizophrenia.

AIM: To assess central set point of thyroid homeostasis in drug-naïve patients affected by first episode schizophrenia. METHODS: This cross-sectional study was conducted in Xinxiang city, Henan, China. Patients were drug-naïve patients affected by first episode schizophrenia, aged 14-50 years old and admitted to the "Second Affiliated Hospital of Xinxiang Medical University" from January 2018 to December 2018. Controls were healthy individuals who underwent annual health from Xinxiang city, a community population of the same age and time period. The parameters of "central set point of thyroid homeostasis" were measured by "thyroid-stimulating hormone (TSH) index" and "thyroid feedback quantile-based index". The parameters were compared between schizophrenia patients and controls. Linear regression models adjusted by age and sex were used to assess the association of schizophrenia with the parameters. RESULTS: A total of 235 patients and 121 controls were included in this study. Patients affected by schizophrenia had significantly higher prevalence of hyperthyroxinemia and levels of free T4, "TSH index", and "thyroid feedback quantile-based index" than controls. After adjusting age and sex, schizophrenia was independently associated with the higher level of "TSH index" (adjusted ß 0.33, 95 % confidence interval 0.17, 0.49) and "thyroid feedback quantile-based index" (adjusted ß 0.21, 95 % confidence interval 0.12, 0.30). The results with age and sex matched patients and controls were similar to those observed in the overall study population. CONCLUSION: Higher central set point may be the underlying mechanism of thyroid allostatic load in drug-naïve patients affected first episode schizophrenia.

Early onset of cardiometabolic risk factor profiles in drug naïve adolescents and young adults with first-episode schizophrenia.

OBJECTIVE AND METHOD: We performed a case-control study, which included antipsychotic-naïve first-episode schizophrenia (FES) of adolescents and young adults and general population controls, to investigate the early-onset cardiometabolic risk factors in FES. RESULTS: FES had more frequent lower HDL-C when compared to controls. However, the distribution of BMI and the frequency of hypercholesterolemia, elevated LDL-C, hypertriglyceridemia in FES were not significantly different to controls. CONCLUSIONS: The results indicated that abnormal HDL-C might be an early-onset event in drug-naïve FES of adolescents and young adults who are unlikely to have other cardiometabolic risks.

Alterations in splenic function and gene expression in mice with depressive-like behavior induced by exposure to corticosterone.

Depressed patients present with increased cortisol levels and attenuated immune responses. However, little is known about the association between depression and the spleen, as this is the largest peripheral immune organ. In this study, we examined alterations in splenic function and gene expression in mice with depressive-like behavior, well as the expression of certain proteins in related pathways. A mouse model of depression was established with the use of corticosterone. Splenic function and histopathology were assessed using Wright and H&E staining. The Agilent Whole Mouse Genome Oligo Microarray containing >41,174 transcript probes was used to measure the levels of gene-expression in the spleens from control and model mice, and the levels of certain proteins associated with depression were measured by western blot analysis in the brain and spleen separately. We found that splenic function and immunity in the mice with depressive-like behavior were markedly impaired. A total of 53 genes exhibited a differential response in the mice with depressive-like behavior, 11 of which were more notable, including collagen, type VI, α5 (Col6a5), immunoglobulin superfamily, member 11 (Igsf11), D site albumin promoter binding protein (Dbp), tachykinin 2 (Tac2) and γ-aminobutyric acid B receptor 2 (Gabbr2). Pathway analysis revealed that the amino acid biosynthesis and the clock gene pathways were more meaningful among these genes. The levels of GABBR2, DBP and substance P (SP; encoded by the Tac2 gene) related proteins in the brain were markedly downregulated, and similar results were observed in the spleen. The anti-depressant, fluoxetine, reversed the changes in the levels of these proteins. The findings of our study regarding changes occurring in the spleen during depression may indirectly elucidate and shed light into the pathogenesis of depression and depressive-like behavior.

QTc interval lengthening in first-episode schizophrenia (FES) patients in the earliest stages of antipsychotic treatment.

Antipsychotic use is reported to be associated with a higher risk of sudden cardiac death and new users are especially susceptible to that risk. In this study, we focused on the ability of antipsychotics to prolong the QTc interval at the earliest stages of antipsychotic use. We employed a retrospective cohort study design in a naturalistic setting where having three ECG measurements over time (at baseline and after drug exposure) in antipsychotic-naïve, first-episode schizophrenia (FES) inpatients. The results revealed, in this relatively homogeneous, drug naïve FES patient sample, that QTc intervals were statistically significantly prolongated after a relatively short term (2-4weeks) of antipsychotic treatments, compared with baseline. After about 2 or 4weeks of antipsychotic use, the risk of abnormal QTc prolongation was higher than at baseline. These results reinforce the importance of monitoring risk factors and assessing QTc prolongation at the beginning and throughout treatment with antipsychotics.

Cardiometabolic risk in first-episode schizophrenia (FES) patients with the earliest stages of both illness and antipsychotic treatment.

OBJECTIVE: It is well established that schizophrenia patients have high cardiovascular morbidity and mortality. However, the underlying risk factors in the earliest stages of both schizophrenia illness and antipsychotics treatment are less clear. This study aimed to characterize the metabolic features of those patients. METHODS: We performed a retrospective cohort study in a naturalistic setting, which included antipsychotic-naïve, first-episode schizophrenia (FES) inpatients with the baseline metabolic measurements and changes following a short term treatment with antipsychotic drugs. RESULTS: Although prevalence of hypertriglyceridemia, hypercholesterolemia, higher-LDL-C and hyperglycaemia in patients with FES were much lower than those of the general population (7.5% v.s. 14.9%, 9.2% v.s. 18.4%, 8.1% v.s. 14.9%, 8.6% v.s.18.3%, respectively), lower-HDL-C in patients with FES were much more prevalent than that of the general population (19.9% v.s. 6.4%). Despite significant metabolic risk profiles (as such lipid abnormalities and insulin resistance) increase, mean fasting glucose and glucosylated serum protein (GSP) were significantly decreased after the short term (median of 23days) antipsychotics exposure, compared to baseline. There is no significant difference of the metabolic profile change between monopharmacy and polypharmacy. CONCLUSION: These results indicated an early-onset nature of HDL-C abnormalities in drug-naïve FES patients. Lipids metabolism risk may develop early and quickly after antipsychotic exposure. Early monitoring is required for the purpose of early detection and hence prevention of the initial metabolic risk which may lead to diabetes mellitus and cardiovascular disease.

Anti-hepatoma activity of a novel compound glaucocalyxin H in vivo and in vitro.

Glaucocalyxin H (GLH) is a new compound isolated from a traditional Chinese medical herb Isodon japonica var. glaucocalyx which has been used for folk medicine. This study was carried out for the first time to investigate the potential role of GLH in anti-hepatoma activity and underlying mechanisms in it. GLH could inhibit the growth of tumor in mice and induce HepG2 cells to death as assessed by the tumor reduction assay, toxic assay, morphological change, and survival rate assay. Many antitumor drugs originated from plants could inhibit the growth of tumor by inducing cells to apoptosis. The morphological changes of HepG2 cells treated with different concentrations of GLH under fluorescence and electron microscope and apoptotic rates were detected to verify its effect on apoptosis. As shown in the study, GLH could induce HepG2 cells to apoptosis in a dose-dependent manner. Bcl2 and Bax proteins played important roles in apoptosis and the disequilibrium between Bcl2 and Bax might result in apoptosis. The expression of Bax protein was upregulated and Bcl2 protein was downregulated in HepG2 cells treated with GLH assessed by Western blotting, and they were in a dose-dependent manner. Taken together, GLH can inhibit the growth of hepatoma cells in vivo and in vitro by inducing cell apoptosis due to the decreased Bcl2 and increased Bax proteins suggesting that GLH could be a potential candidate as an anti-hepatoma agent for the therapeutic treatment of hepatoma.

Protocatechuic acid improves cognitive deficits and attenuates amyloid deposits, inflammatory response in aged AßPP/PS1 double transgenic mice.

Protocatechuic acid (PCA), a phenolic compound of Radix Salviae Miltiorrhizae (RSM), has been found to have a protective effect on improving cognitive deficits in STZ-induced AD rats. The present study aimed to evaluate the potential protection activity of PCA on improving cognitive deficits and attenuating Aß deposition and inflammatory responses in aged AßPP/PS1 double transgenic AD-model mice. The results of Morris water maze test showed that PCA (100mg/kg) significantly prolonged the mean latency time and the path length of AßPP/PS1 mice. PCA could significantly reduce the number of Aß positive expressions in the hippocampus and cerebral cortex of AßPP/PS1 mice by immunocytochemical assay with Congo red staining and decrease remarkably APP expression level by Western blot analysis (P<0.01). The results from ELISA and Western blot analysis showed that the levels of inflammatory cytokines including TNF-α, IL-1ß, IL-6 and IL-8 decreased remarkably by the treatment with PCA (P<0.01). Further, there was a substantial increase of brain derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex of AßPP/PS1 mice treated with PCA (P<0.01). The present study provided confirmatory evidence that PCA significantly decreased Aß deposits, APP and inflammatory response, whereas increased learning and memory ability, as well as enhanced BDNF level. Our findings indicated that PCA is an effective neuroprotective agent for AD therapy. It might be associated with the attenuation on Aß deposits and inflammation responses involved in the process.

Lactuside B decreases aquaporin-4 and caspase-3 mRNA expression in the hippocampus and striatum following cerebral ischaemia-reperfusion injury in rats.

This study aimed to investigate the effects of lactuside B (LB) on aquaporin-4 (AQP4) and caspase-3 mRNA expression in the hippocampus and the striatum following cerebral ischaemia-reperfusion (I/R) injury in rats. Cerebral I/R injury was established in Sprague-Dawley rats by occluding the middle cerebral artery for 2 h and then inducing reperfusion. Rats in the I/R + LB groups were treated with various doses of LB following reperfusion. Neurological deficit scores and brain water content were obtained to determine the pharmacodynamics of LB. Reverse transcription polymerase chain reaction was performed to determine the expression levels of AQP4 and caspase-3 mRNA in the hippocampus and the striatum. The results of the present study indicate that LB decreased the neurological deficit scores and the brain water content. In the hippocampus, AQP4 and caspase-3 mRNA expression levels were significantly downregulated in the I/R + LB groups at 24 and 72 h following drug administration, compared with those in the I/R group (P<0.05). In the striatum, LB was also shown to significantly reduce AQP4 and caspase-3 mRNA expression levels at 24 and 72 h following drug administration, compared with those in the I/R group (P<0.05). The effects became stronger as the LB dose was increased. The most significant reductions in AQP4 and caspase-3 mRNA expression were noted in the I/R + LB 25 mg/kg and I/R + LB 50 mg/kg groups at 72 h following drug administration. The results of the present study show that LB is capable of significantly downregulating AQP4 and caspase-3 mRNA expression in the hippocampus and striatum following cerebral I/R injury in rats. The mechanism by which LB improved ischaemic brain injury may be associated with changes in AQP4 and caspase-3 mRNA expression in the hippocampus and the striatum.