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Background: Major depressive disorder (MDD) is a highly heterogeneous disease, with differences in clinical manifestations among depression patients based on onset ages and genders. The neural mechanisms underlying these differences remain unclear. In this study, we utilized resting state functional imaging data from a large sample database and adopted the ReHo method to investigate gender differences in local brain function in MDD patients across different onset age groups. Methods: The study included 364 MDD patients and 695 healthy participants who were part of the REST-meta-MDD project. Regional homogeneity (ReHo) assessed gender disparities in MDD and healthy individuals within groups delineated by gender and onset age (young group: 18–29 years; middle-aged group: 30–45 years). Results: Among the young MDD groups, there were significant gender differences in the right superior frontal gyrus, right inferior frontal gyrus, left superior temporal gyrus, and right superior parietal lobule, with male MDD patients having higher ReHo values compared to females. When compared to healthy males, male MDD patients exhibited elevated ReHo values in the right superior parietal lobule. In the middle-aged groups, a marked ReHo difference was observed in the bilateral cerebellum posterior lobe, with female MDD patients showing higher ReHo values. Conclusions: The functional mechanisms of MDD differ between genders and show distinct variations across different onset age groups. These findings underscore the importance of developing personalized interventions that address the unique needs of MDD patients, tailored to their gender and age, and necessitate the development of antidepressant medications targeted at each gender-age subgroup. [ABSTRACT FROM AUTHOR]

Background: X chromosome inactivation (XCI) is the mechanism by which the X-linked gene dosage is adjusted between the sexes. Evidence shows that many sex-specific diseases have their basis in X chromosome biology. While female schizophrenia patients often have a delayed age of disease onset and clinical phenotypes that are different from those of males, it is unknown whether the sex differences in schizophrenia are associated with X-linked gene dosage and the choice of X chromosome silencing in female cells. Previous studies demonstrated that sex chromosome aneuploidies may be related to the pathogeneses of some psychiatric diseases. Here, we examined the changes in skewed XCI in patients with schizophrenia. Methods: A total of 109 female schizophrenia (SCZ) patients and 80 age- and sex-matched healthy controls (CNTLs) were included in this study. We evaluated clinical features including disease onset age, disease duration, clinical symptoms by the Positive and Negative Syndrome Scale (PANSS) and antipsychotic treatment dosages. The XCI skewing patterns were analyzed by the methylation profile of the HUMARA gene found in DNA isolated from SCZ patient and CNTL leukocytes in the three age groups. Results: First, we found that the frequency of skewed XCI in SCZ patients was 4 times more than that in the age- and sex-matched CNTLs (p < 0.01). Second, we found an earlier onset of severe XCI skewing in the SCZ patients than in CNTLs. Third, we demonstrated a close relationship between the severity of skewed XCI and schizophrenic symptoms (PANSS score ≥ 90) as well as the age of disease onset. Fourth, we demonstrated that the skewed XCI in SCZ patients was not transmitted from the patients' mothers. Limitations: The XCI skewing pattern might differ depending on tissues or organs. Although this is the first study to explore skewed XCI in SCZ, in the future, samples from different tissues or cells in SCZ patients might be important for understanding the impact of skewed XCI in this disease. Conclusion: Our study, for the first time, investigated skewed XCI in female SCZ patients and presented a potential mechanism for the sex differences in SCZ. Our data also suggested that XCI might be a potential target for the development of female-specific interventions for SCZ. [ABSTRACT FROM AUTHOR]

Background: We have previously reported using two-step cluster analysis to classify myasthenia gravis (MG) patients into the following five subtypes: ocular MG; thymoma-associated MG; MG with thymic hyperplasia; anti-acetylcholine receptor antibody (AChR-Ab)-negative MG; and AChR-Ab-positive MG without thymic abnormalities. The objectives of the present study were to examine the reproducibility of this five-subtype classification using a new data set of MG patients and to identify additional characteristics of these subtypes, particularly in regard to response to treatment. Methods: A total of 923 consecutive MG patients underwent two-step cluster analysis for the classification of subtypes. The variables used for classification were sex, age of onset, disease duration, presence of thymoma or thymic hyperplasia, positivity for AChR-Ab or anti-muscle-specific tyrosine kinase antibody, positivity for other concurrent autoantibodies, and disease condition at worst and current. The period from the start of treatment until the achievement of minimal manifestation status (early-stage response) was determined and then compared between subtypes using Kaplan-Meier analysis and the log-rank test. In addition, between subtypes, the rate of the number of patients who maintained minimal manifestations during the study period/that of patients who only achieved the status once (stability of improved status) was compared. Results: As a result of two-step cluster analysis, 923 MG patients were classified into five subtypes as follows: ocular MG (AChR-Ab-positivity, 77%; histogram of onset age, skewed to older age); thymoma-associated MG (100%; normal distribution); MG with thymic hyperplasia (89%; skewed to younger age); AChR-Ab-negative MG (0%; normal distribution); and AChR-Ab-positive MG without thymic abnormalities (100%, skewed to older age). Furthermore, patients classified as ocular MG showed the best early-stage response to treatment and stability of improved status, followed by those classified as thymoma-associated MG and AChR-Ab-positive MG without thymic abnormalities; by contrast, those classified as AChR-Ab-negative MG showed the worst early-stage response to treatment and stability of improved status. Conclusions: Differences were seen between the five subtypes in demographic characteristics, clinical severity, and therapeutic response. Our five-subtype classification approach would be beneficial not only to elucidate disease subtypes, but also to plan treatment strategies for individual MG patients. [ABSTRACT FROM AUTHOR]

Background: We have previously reported using two-step cluster analysis to classify myasthenia gravis (MG) patients into the following five subtypes: ocular MG; thymoma-associated MG; MG with thymic hyperplasia; anti-acetylcholine receptor antibody (AChR-Ab)-negative MG; and AChR-Ab-positive MG without thymic abnormalities. The objectives of the present study were to examine the reproducibility of this five-subtype classification using a new data set of MG patients and to identify additional characteristics of these subtypes, particularly in regard to response to treatment., Methods: A total of 923 consecutive MG patients underwent two-step cluster analysis for the classification of subtypes. The variables used for classification were sex, age of onset, disease duration, presence of thymoma or thymic hyperplasia, positivity for AChR-Ab or anti-muscle-specific tyrosine kinase antibody, positivity for other concurrent autoantibodies, and disease condition at worst and current. The period from the start of treatment until the achievement of minimal manifestation status (early-stage response) was determined and then compared between subtypes using Kaplan-Meier analysis and the log-rank test. In addition, between subtypes, the rate of the number of patients who maintained minimal manifestations during the study period/that of patients who only achieved the status once (stability of improved status) was compared., Results: As a result of two-step cluster analysis, 923 MG patients were classified into five subtypes as follows: ocular MG (AChR-Ab-positivity, 77%; histogram of onset age, skewed to older age); thymoma-associated MG (100%; normal distribution); MG with thymic hyperplasia (89%; skewed to younger age); AChR-Ab-negative MG (0%; normal distribution); and AChR-Ab-positive MG without thymic abnormalities (100%, skewed to older age). Furthermore, patients classified as ocular MG showed the best early-stage response to treatment and stability of improved status, followed by those classified as thymoma-associated MG and AChR-Ab-positive MG without thymic abnormalities; by contrast, those classified as AChR-Ab-negative MG showed the worst early-stage response to treatment and stability of improved status., Conclusions: Differences were seen between the five subtypes in demographic characteristics, clinical severity, and therapeutic response. Our five-subtype classification approach would be beneficial not only to elucidate disease subtypes, but also to plan treatment strategies for individual MG patients.