Advancements in Cortisol Detection: From Conventional Methods to Next-Generation Technologies for Enhanced Hormone Monitoring.

The hormone cortisol, released as the end-product of the hypothalamic-pituitary-adrenal (HPA) axis, has a well-characterized circadian rhythm that enables an allostatic response to external stressors. When the pattern of secretion is disrupted, cortisol levels are chronically elevated, contributing to diseases such as heart attacks, strokes, mental health disorders, and diabetes. The diagnosis of chronic stress and stress related disorders depends upon accurate measurement of cortisol levels; currently, it is quantified using mass spectroscopy or immunoassay, in specialized laboratories with trained personnel. However, these methods are time-consuming, expensive and are unable to capture the dynamic biorhythm of the hormone. This critical review traces the path of cortisol detection from traditional laboratory-based methods to decentralised cortisol monitoring biosensors. A complete picture of cortisol biology and pathophysiology is provided, and the importance of precision medicine style monitoring of cortisol is highlighted. Antibody-based immunoassays still dominate the pipeline of development of point-of-care biosensors; new capture molecules such as aptamers and molecularly imprinted polymers (MIPs) combined with technologies such as microfluidics, wearable electronics, and quantum dots offer improvements to limit of detection (LoD), specificity, and a shift toward rapid or continuous measurements. While a variety of different sensors and devices have been proposed, there still exists a need to produce quantitative tests for cortisol ─ using either rapid or continuous monitoring devices that can enable a personalized medicine approach to stress management. This can be addressed by synergistic combinations of technologies that can leverage low sample volumes, relevant limit of detection and rapid testing time, to better account for cortisol's shifting biorhythm. Trends in cortisol diagnostics toward rapid and continuous monitoring of hormones are highlighted, along with insights into choice of sample matrix.

Effects of chronotype on antidepressant treatment and symptoms in patients with depression: a multicenter, parallel, controlled study.

AIM: To analyze the changes of chronotypes in patients with depression before and after treatment, and explore the effects of different chronotypes on antidepressant treatment and the dimensions of common symptoms in patients with depression. METHODS: 180 patients with depression were selected from 10 tertiary psychiatric hospitals in Zhejiang province, according to the scores of morningness-eveningness questionnaire (MEQ), the patients were divided into three groups: early-type group, middle-type group and late-type group. The 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale anxiety Scale (HAMA), Snaith Hamilton Pleasure Scale (SHAPS), multidimensional fatigue inventory-20(MFI-20) and Pittsburgh sleep quality index (PSQI) were measured at baseline and at the end of the 2nd, 4th, 8th and 12th weeks, the variance analysis of repeated measures was used to analyze the change of each index in the study. The remission rate of depression at each time point was statistically analyzed. RESULTS: Of the 180 patients included in the study, 26 were lost to follow-up, and 154 were finally included in the analysis. At baseline, 14.93%, 56.5% and 28.57% of the subjects were diagnosed as middle-late type, middle-late type and early-late type respectively, the total scores of Shaps and MFI-20 in the early-type group were higher than those in the late-type group and the middle-type group (p < 0.05). During the 12-week antidepressant treatment period, the time effect of PSQI, Shaps, MFI-20 and MEQ had interaction with different time groups (p < 0.05). During the treatment, the multiple symptom dimensions of depression were improved to different degrees, but the changing trend was not the same, and the recovery of the anhedonia was obviously delayed, in early-type patients, there are many symptoms such as loss of pleasure and sleep disorders. There was no significant effect on the remission rate of depression in different time type (p > 0.05) . CONCLUSION: The disorder of chronotypes is common in patients with depression. The time effect of different time type on different symptom dimension of depression was affected, but the effect on remission rate of depression was not significant. To strengthen the management of biological chronotype rhythm in patients with depression may be of great significance in the treatment of depression.

Perceived stress and depressive symptoms among Chinese college students: A moderated mediation model of biorhythm and ego resilience.

Objective: To explore whether biological rhythm disturbance mediates the association between perceived stress and depressive symptoms and to investigate whether ego resilience moderates the mediation model. Methods: A cross-sectional study was carried out using an online self-report questionnaire distributed to college students from September 2021 to October 2021. Patient Health Questionnaire-9 (PHQ-9), Perceived Stress Severity (PSS-10), the Biological Rhythms Assessment in Neuropsychiatry (BRIAN), and Ego Resilience (ER-96) were used for investigation. SPSS 23 was used for data analyses. The significance of mediation was determined by the PROCESS macro using a bootstrap approach. Results: Among the participants, 9.2% (N = 1,282) exhibited significant symptoms of depression. Perceived stress was positively associated with depressive symptoms, and biorhythm partially mediated this relationship. The direct and indirect effects were both moderated by ego resilience. Perceived stress had a greater impact on depressive symptoms and biorhythm for college students with lower ego resilience, and the impact of biorhythm on depressive symptoms was also stronger for those with lower ego resilience. Perceived stress had an impact on depressive symptoms directly and indirectly via the mediation of biorhythm. Conclusion: Schools and educators should guide college students to identify stress correctly and provide effective suggestions to deal with it. Meanwhile, maintaining a stable biorhythm can protect college students from developing depressive symptoms. Students with low resilience should be given more attention and assistance.

Brainwaves beyond diagnosis: Wider applications of electroencephalography in idiopathic generalized epilepsy.

Electroencephalography (EEG) has long been used as a versatile and noninvasive diagnostic tool in epilepsy. With the advent of digital EEG, more advanced applications of EEG have emerged. Compared with technologically advanced practice in focal epilepsies, the utilization of EEG in idiopathic generalized epilepsy (IGE) has been lagging, often restricted to a simple diagnostic tool. In this narrative review, we provide an overview of broader applications of EEG beyond this narrow scope, discussing how the current clinical and research applications of EEG may potentially be extended to IGE. The current literature, although limited, suggests that EEG can be used in syndromic classification, guiding antiseizure medication therapy, predicting prognosis, unraveling biorhythms, and investigating functional brain connectivity of IGE. We emphasize the need for longer recordings, particularly 24-h ambulatory EEG, to capture discharges reflecting circadian and sleep-wake cycle-associated variations for wider EEG applications in IGE. Finally, we highlight the challenges and limitations of the current body of literature and suggest future directions to encourage and enhance more extensive applications of this potent tool.

Application of chronopharmacology in the hypertension treatment / 中国临床药理学与治疗学

The human biorhythm is closely related to the blood pressure level and the effect of the antihypertensive treatment of hypertension. The human circadian biorhythm changes the therapeutic effect of antihypertensive drugs by affecting the pharmacokinetics and pharmacodynamics; at the same time, following the human blood pressure rhythm in the treatment of hypertension can reduce the risk of target organ damage and cardiovascular and cerebrovascular events. Therefore, in the treatment of hypertension, the administration time and drug dosage should be adjusted according to the pharmacochronology to obtain the best curative effect and minimal side effects, and reduce the occurrence of adverse reactions and complications.

INTERRELATION OF BIOLOGICAL RHYTHMS AND CIRCADIAN HORMONES PRODUCEMENT AND THEIR IMPACT ON MEDICINE USAGE.

OBJECTIVE: The aim of the article is to establish the interrelation of human biological rhythms and circadian hormones producement as well as to determine their impact on the medicine usage. PATIENTS AND METHODS: Materials and methods: The review and latest data analysis of scientific and medical literature were performed. CONCLUSION: Conclusions: Proceeding from the literature sources there is a firm interrelation between human biological rhythms and circadian hormones producement. Following chronotherapy principles will allow to increase effectiveness of diseases treatment, including dental ones. It will also allow to reduce dosage of prescribed medicines as well as their side effects. Prospects for a further research are to identify a clear relationship between circadian biorhythms in patients with chronic generalized periodontitis in order to increase the effectiveness of therapeutic measures.

Effects of high-pressure treatment on the structure and function of myofibrils.

The effects of high pressure (40-70 MPa) on the structure and function of myofibrils were investigated by high pressure microscopy. When this pressure was applied to myofibrils immersed in relaxing solution, the sarcomere length remained almost unchanged, and the A band became shorter and wider. The higher the applied pressure, the faster the change. However, shortening and widening of the A band were not observed when pressure was applied to myofibrils immersed in a solution obtained by omitting ATP from the relaxing solution. However, even under these conditions, structural loss, such as loss of the Z-line structure, occurred. In order to evaluate the consequences of this pressure-treated myofibril, the oscillatory movement of sarcomere (sarcomeric oscillation) was evoked and observed. It was possible to induce sarcomeric oscillation even in pressure-treated myofibrils whose structure was destroyed. The pressurization reduced the total power of the sarcomeric oscillation, but did not change the average frequency. The average frequency did not change even when a pressure of about 40 MPa was applied during sarcomeric oscillation. The average frequency returned to the original when the pressure was returned to the original value after applying stronger pressure to prevent the sarcomere oscillation from being observed. This result suggests that the decrease in the number of myosin molecules forming the crossbridge does not affect the average frequency of sarcomeric oscillation. This fact will help build a mechanical hypothesis for sarcomeric oscillation. The pressurization treatment is a unique method for controlling the structure of myofibrils as described above.

IDH1 gene mutation activates Smad signaling molecules to regulate the expression levels of cell cycle and biological rhythm genes in human glioma U87­MG cells.

Isocitrate dehydrogenase1 (IDH1) mutation is the most important genetic change in glioma. The most common IDH1 mutation results in the amino acid substitution of arginine 132 (Arg/R132), which is located at the active site of the enzyme. IDH1 Arg132His (R132H) mutation can reduce the proliferative rate of glioma cells. Numerous diseases follow circadian rhythms, and there is growing evidence that circadian disruption may be a risk factor for cancer in humans. Dysregulation of the circadian clock serves an important role in the development of malignant tumors, including glioma. Brain­Muscle Arnt­Like protein 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK) are the main biological rhythm genes. The present study aimed to further study whether there is an association between IDH1 R132H mutation and biological rhythm in glioma, and whether this affects the occurrence of glioma. The Cancer Genome Atlas (TCGA) database was used to detect the expression levels of the biological rhythm genes BMAL1 and CLOCK in various types of tumor. Additionally, U87­MG cells were infected with wild­type and mutant IDH1 lentiviruses. Colony formation experiments were used to detect cell proliferation in each group, cell cycle distribution was detected by flow cytometry and western blotting was used to detect the expression levels of wild­type and mutant IDH1, cyclins, biological rhythm genes and Smad signaling pathway­associated genes in U87­MG cells. TCGA database results suggested that BMAL1 and CLOCK were abnormally expressed in glioma. Cells were successfully infected with wild­type and mutant IDH1 lentiviruses. Colony formation assay revealed decreased cell proliferation in the IDH1 R132H mutant group. The cell cycle distribution detected by flow cytometry indicated that IDH1 gene mutation increased the G1 phase ratio and decreased the S phase ratio in U87­MG cells. The western blotting results demonstrated that IDH1 R132H mutation decreased the expression levels of the S phase­associated proteins Cyclin A and CDK2, and increased the expression levels of the G1 phase­associated proteins Cyclin D3 and CDK4, but did not significantly change the expression levels of the G2/M phase­associated protein Cyclin B1. The expression levels of the positive and negative rhythm regulation genes BMAL1, CLOCK, period (PER s (PER1, 2 and 3) and cryptochrom (CRY)s (CRY1 and 2) were significantly decreased, those of the Smad signaling pathway­associated genes Smad2, Smad3 and Smad2­3 were decreased, and those of phosphorylated (p)­Smad2, p­Smad3 and Smad4 were increased. Therefore, the present results suggested that the IDH1 R132H mutation may alter the cell cycle and biological rhythm genes in U87­MG cells through the TGF­ß/Smad signaling pathway.

Slowly seeing the light: an integrative review on ecological light pollution as a potential threat for mollusks.

Seasonal changes in the natural light condition play a pivotal role in the regulation of many biological processes in organisms. Disruption of this natural condition via the growing loss of darkness as a result of anthropogenic light pollution has been linked to species-wide shifts in behavioral and physiological traits. This review starts with a brief overview of the definition of light pollution and the most recent insights into the perception of light. We then go on to review the evidence for some adverse effects of ecological light pollution on different groups of animals and will focus on mollusks. Taken together, the available evidence suggests a critical role for light pollution as a recent, growing threat to the regulation of various biological processes in these animals, with the potential to disrupt ecosystem stability. The latter indicates that ecological light pollution is an environmental threat that needs to be taken seriously and requires further research attention.

Expert Consensus on Clinical Management of Digestive System Diseases Associated With Biorhythm Disorders / 胃肠病学

Biorhythm such as sleep-wake, resting-activity, dietary intake, hormone secretion, temperature and blood pressure fluctuation affect the pathophysiological process of digestive system. Disturbances of biorhythm, especially circadian rhythm, are associated with the development, progress and outcome of digestive system diseases. Reconstructing normal biorhythm is of great significance for the maintaining of health of digestive system. However, there is lack of consensus on the management of clinical issues related to digestive system diseases and biorhythm disorders. The Chinese Digestive Psychosomatic Union organized experts to form a consensus on clinical management of digestive system diseases associated with biorhythm disorders on the basis of systemic review of research progress and clinical experience. The consensus opinion contains 21 statements. Each statement with evidence-based medicine grade and interpretations were reported.

Research progress of chronic diseases in hyperandrogenized animal models / 中国药理学通报

Chronic disease is defined as a persistent, recurrent illness with long course. Common symptoms include insulin resistance, dyslipidemia, chronic inflammation, and so on. It is well known that chronic dehydroepiandrosterone (DHEA) or dihydrotestosterone (D H T) exposure induces symptoms in rats or mice. These animals possess characteristics of obesity, ovarian dysfunction, vascular endothelial dysfunction, inflammation, and so on. In addition, DHT-treated animals have been used to explore insulin resistance, dyslipidemia, and biorhythm disorder. DHEA-treated animals were fit to detect ovarian stress. Although DHEA-treated animals does not apply to studies of metabolic diseases such as hyperlipidemia, DHEA-treated animals under high fat diet represent the related phenotypes. Based on the previous research, it can be predicted that new achievements will be made in endometrial development, ovarian cell function, inflammation modulation, atherosclerotic, and biorhythm disorder by using these hyperandrogenic animal models.

Polymorphic Appetite Effects on Waist Circumference Depend on rs3749474 CLOCK Gene Variant.

Chronobiological aspects controlled by CLOCK genes may influence obesity incidence. Although there are studies that show an association between the expression of these genes and energy intake, waist circumference or abdominal obesity phenotypes, interactions with appetite have been insufficiently investigated in relation to chrononutrition. The objective was to identify interactions between CLOCK genetic variants involved in appetite status. A total of 442 subjects (329 women, 113 men; aged 18 to 65 years) were recruited. Anthropometric, dietary and lifestyle data were collected by trained nutritionists. Participants were classified according to their appetite feelings with a Likert scale. Multiple linear regression models were used to examine associations of the type genotype x appetite status on adiposity-related variables. p values were corrected by the Bonferroni method. A significant influence was found concerning the effects of appetite on waist circumference with respect to rs3749474 CLOCK polymorphism (p < 0.001). An additive model analysis (adjusted by age, gender, exercise and energy intake) showed that risk allele carriers, increased the waist circumference around 14 cm (ß = 14.1, CI = 6.3-22.0) by each increment in the level of appetite. The effects of appetite on waist circumference may be partly modulated by the rs3749474 CLOCK polymorphism.

Lack of M4 muscarinic receptors in the striatum, thalamus and intergeniculate leaflet alters the biological rhythm of locomotor activity in mice.

The deletion of M4 muscarinic receptors (MRs) changes biological rhythm parameters in females. Here, we searched for the mechanisms responsible for these changes. We performed biological rhythm analysis in two experiments: in experiment 1, the mice [C57Bl/6NTac (WT) and M4 MR -/- mice (KO)] were first exposed to a standard LD regime (12/12-h light/dark cycle) for 8 days and then subsequently exposed to constant darkness (for 24 h/day, DD regime) for another 16 days. In experiment 2, the mice (after the standard LD regime) were exposed to the DD regime and to one light pulse (zeitgeber time 14) on day 9. We also detected M1 MRs in brain areas implicated in locomotor biological rhythm regulation. In experiment 1, the biological rhythm activity curves differed: the period (τ, duration of diurnal cycle) was shorter in the DD regime. Moreover, the day mean, mesor (midline value), night mean and their difference were higher in KO animals. The time in which the maximal slope occurred was lower in the DD regime than in the LD regime in both WT and KO but was lower in KO than in WT mice. In experiment 2, there were no differences in biological rhythm parameters between WT and KO mice. The densities of M1 MRs in the majority of areas implicated in locomotor biological rhythm were low. A significant amount of M1 MR was found in the striatum. These results suggest that although core clock output is changed by M4 MR deletion, the structures involved in biological rhythm regulation in WT and KO animals are likely the same, and the most important areas are the striatum, thalamus and intergeniculate leaflet.

Daylight saving time and the incidence of thrombolysis to treat acute ischemic stroke.

BACKGROUND: Twenty-five percent of the global population lives in one of the more than 70 countries that observe daylight saving time (DST). These people are exposed to 1hour of time transition twice a year, influencing the circulatory system. We aimed to analyze the incidence of thrombolysis to treat acute ischemic stroke in relation to clock changes in Hungary over a 10-year period. METHODS: The number of thrombolytic treatments performed within the period between 2006 and 2015 was analyzed. Anonymized nationwide data on the dates and exact daily numbers of thrombolysis interventions were provided by the National Health Insurance Fund. We compared the mean number of thrombolytic treatments on the day before with that on the day after each transition, and also between the preceding and following one week and month. RESULTS: Our data including the last days of each month suggested a significant increase in thrombolysis numbers both in spring and in autumn on the day and the week after the clock change. However, when the last days of each month were excluded from analysis (as this in itself was associated with a 7-fold increase in stroke incidence in our earlier study), no significant difference in the number of thrombolysis treatments between the days and weeks before and after the clock change was detectable. The long-term, monthly analysis also did not reveal a significant difference. CONCLUSIONS: Our findings reflect that psychosocial factors, such as the approach of the last day of the month override the intrinsic effect of disturbances of the circadian rhythm on stroke incidence.

Variability in the Drug Response of M4 Muscarinic Receptor Knockout Mice During Day and Night Time.

Mice are nocturnal animals. Surprisingly, the majority of physiological/pharmacological studies are performed in the morning, i.e., in the non-active phase of their diurnal cycle. We have shown recently that female (not male) mice lacking the M4 muscarinic receptors (MR, M4KO) did not differ substantially in locomotor activity from their wild-type counterparts (C57Bl/6Tac) during the inactive period. Increased locomotion has been shown in the active phase of their diurnal cycle. We compared the effects of scopolamine, oxotremorine, and cocaine on locomotor response, hypothermia and spontaneous behavior in the open field arena in the morning (9:00 AM) and in the evening (9:00 PM) in WT and in C57Bl/6NTac mice lacking the M4 MR. Furthermore, we also studied morning vs. evening densities of muscarinic, GABAA, D1-like, D2-like, NMDA and kainate receptors using autoradiography in the motor, somatosensory and visual cortex and in the striatum, thalamus, hippocampus, pons, and medulla oblongata. At 9:00 AM, scopolamine induced an increase in motor activity in WT and in M4KO, yet no significant increase was observed at 9:00 PM. Oxotremorine induced hypothermic effects in both WT and M4KO. Hypothermic effects were more evident in WT than in M4KO. Hypothermia in both cases was more pronounced at 9:00 AM than at 9:00 PM. Cocaine increased motor activity when compared to saline. There was no difference in behavior in the open field between WT and M4KO when tested at 9:00 AM; however, at 9:00 PM, activity of M4KO was doubled in comparison to that of WT. Both WT and KO animals spent less time climbing in their active phase. Autoradiography revealed no significant morning vs. evening difference. Altogether, our results indicate the necessity of comparing morning vs. evening drug effects.

Microscopic markers of an infradian biorhythm in human juvenile ribs.

Recent studies have indicated that there may be an infradian systemic biorhythm that coordinates aspects of human hard tissue growth and influences adult body size. Here we investigate if evidence of this biorhythm retained in human teeth as the periodicity of Retzius lines (RP) corresponds with the microstructural growth of a non-weight bearing bone, the rib, in a sample of 50 human juvenile skeletons. Using static histomorphometric methods, the RP of one permanent tooth from each skeleton was calculated and combined with measures of bone remodeling in a rib from the same individual. Results provide the first evidence that the infradian biorhythm is linked to bone remodeling in children. Retzius periodicity was negatively correlated with relative osteon area (r = -0.563, p = 0.008) and positively related to Haversian canal area (r = 0.635, p = 0.002) and diameter (r = 0.671, p = 0.001) in children between the age of 8 to 12 years. There was also a negative correlation between RP and the relative cortical area of ribs (r = -0.500, p = 0.048). Relationships between bone remodeling and the biorhythm were much more variable in younger children. Results imply that as the biorhythm speeds up there is increased bone deposition during remodeling of the rib, leading to the larger osteonal lamellar bone areas and smaller Haversian canals in children between 8 and 12 years of age. Our results support the idea that there is an infradian biorhythm that coordinates aspects of human hard tissue growth.

The deletion of M4 muscarinic receptors increases motor activity in females in the dark phase.

OBJECTIVES: M4 muscarinic receptors (MR) presumably play a role in motor coordination. Previous studies have shown different results depending on genetic background and number of backcrosses. However, no attention has been given to biorhythms. MATERIAL AND METHODS: We therefore analyzed biorhythms under a light/dark cycle obtained telemetrically in intact animals (activity, body temperature) in M4 KO mice growth on the C57Bl6 background using ChronosFit software. Studying pure effects of gene knockout in daily rhythms is especially important knowledge for pharmacological/behavioral studies in which drugs are usually tested in the morning. RESULTS: We show that M4 KO mice motor activity does not differ substantially from wild-type mice during light period while in the dark phase (mice active part of the day), the M4 KO mice reveal biorhythm changes in many parameters. Moreover, these differences are sex-dependent and are evident in females only. Mesor, night-day difference, and night value were doubled or tripled when comparing female KO versus male KO. Our in vitro autoradiography demonstrates that M4 MR proportion represents 24% in the motor cortex (MOCx), 30% in the somatosensory cortex, 50% in the striatum, 69% in the thalamus, and 48% in the intergeniculate leaflet (IGL). The M4 MR densities were negligible in the subparaventricular zone, the posterior hypothalamic area, and in the suprachiasmatic nuclei. CONCLUSIONS: We conclude that cholinergic signaling at M4 MR in brain structures such as striatum, MOCx, and probably with the important participation of IGL significantly control motor activity biorhythm. Animal activity differs in the light and dark phases, which should be taken into consideration when interpreting the results.

Effect of circadian intracranial pressure changes on prognosis of patients with traumatic brain injury / 中华创伤杂志

Objective To investigate the effect of intracranial pressure fluctuation on the prognosis of patients with traumatic brain injury (TBI).Methods A retrospective case series study was conducted on the clinical data of 30 patients with TBI hospitalized between June 2012 and June 2014.There were 21 males and 9 females,aged (43.0 ± 19.8) years.After the intracranial pressure probe was implanted,the intracranial pressure of TBI patients was monitored continuously and the data were recorded per minute.A single cosine method was used in analyzing the circadian rhythm of intracranial pressure data.Furthermore,the ratio of the amplitude of the circadian parameter (A) to the median (M) value (A/M) was selected to evaluate the biologic rhythm of patients.The correlations of circadian rhythm parameter A/M with Glasgow Outcome Scale (GCS) and with extended Glasgow Outcome Scale (GOS-E) were analyzed using linear regression.Results The circadian rhythm was observed in all patients regardless of injury severity (P ＜ 0.01).The circadian rhythm parameter A/M of intracranial pressure was positively correlated with the GCS of patients at discharge (R2 =0.346,F =14.797,P ＜0.01) and with the GOS-E (R2 =0.356,F =15.502,P ＜ 0.01).Conclusion The intracranial pressure fluctuation of TBI patients follows circadian rhythm,which might be correlated with the prognosis of TBI patients.

Do some anxiety disorders belong to the prodrome of bipolar disorder? A clinical study combining retrospective and prospective methods to analyse the relationship between anxiety disorder and bipolar disorder from the perspective of biorhythms.

BACKGROUND: In clinical practice, some patients diagnosed with anxiety disorder (AD) may develop bipolar disorder (BD) many years later, and some cases of AD may be cured by the use of mood stabilizers. However, the relationship between AD and BD should be explored further. METHOD: To track how many cases of AD turned to BD and to discover the differences between them, we recruited 48 patients diagnosed with BD, who were assigned to the BD group for the retrospective analysis, and we also recruited 186 patients diagnosed with AD at enrolment; this latter group was asked to complete follow-up surveys conducted 3 months, 6 months, 12 months and 18 months after the primary stage of the study. We defined another two groups according to the usage of mood stabilizers, the rates of reduction in scores on the Hamilton Anxiety Scale and Yale-Brown Obsessive Compulsive Scale, and the changes in Clinical Global Impression scores at different follow-up times: the anxiety group and the atypical BD group (who used mood stabilizers to treat AD). All subjects also completed the NEO Five-Factor Inventory and supplied blood samples to be tested for several endocrine indices (TSH, T3, FT3, T4, FT4, ACTH,PTC) and inflammatory cytokines (IL-6, IL-8, IL-10, TNF-α, CRP) at enrolment. RESULTS: In total, 14 subjects developed BD by the end of the study. One hundred eleven subjects were included in the anxiety group. Sixty-three subjects were assigned to the atypical BD group, and they had similar features to the 48 subjects in the BD group in terms of personality traits, abnormality rates of endocrine indices and levels of inflammatory cytokines. From the anxiety group to the atypical BD group and then the BD group, the age of first onset gradually decreased, while the frequency of onset and the score of suicidal ideation gradually increased. Furthermore, the atypical BD group showed markedly higher levels of TSH, IL-6, TNF-α and CRP than the other two groups. CONCLUSIONS: Some ADs with unique features might belong to the prodromal stage or the atypical presentation of BD, and recognizing these ADs early will economize many medical resources.