Relationship between Lifestyle and Mental Health: A Population-Based Survey in Nagasaki Prefecture, Japan Bcl11b Heterozygous Mice are Susceptible to N-methyl-N-nitrosourea-induced Thymic Lymphomas

Objective: Mental health disorders among community dwelling Japanese people has not been well documented. The objective of the present study was to gain insights into the relationships between lifestyle factors and mental health in a community population. Methods: Associations between lifestyle factors and mental health were investigated in Nagasaki prefecture with a selfadministrated questionnaire including socio-demographic (age and sex), lifestyle (diet, exercise, sleep, smoking, alcohol drinking), and mental health factors. Results: A total of 2,146 people (1,052 men and 1,094 women) responded fully to the 12-item version of the General Health Questionnaire (GHQ-12). High GHQ-12 scores (defined as a score of 4, to indicate poor mental health) were more prevalent in women (18.9%) than in men (15.6%) (P=0.041). Moreover, the proportion of high GHQ-12 score was higher in the younger age group (20 to 39 years), comparing to other age groups. As the result of multiple logistic regression analysis, four variables were selected as factors associated with a high GHQ-12 score: women (odds ratio (OR): 1.3, 95% confidence interval (95% CI): 1.0-1.6); 20 to 39 years (OR: 2.5, 95% CI: 1.7-3.6) and 40 to 64 years (OR: 1.4, 95% CI: 1.0-1.9), both with 65 years as reference; not eating meals regularly (OR: 1.7, 95% CI: 1.2-2.4); and not getting enough sleep (OR: 2.8, 95% CI: 2.1-3.6). Conclusion: The findings indicate that the young and women are more likely to have poor mental health, and that lifestyle factors such as diet behavior and sleep are associated with mental health.

N-methyl-N-nitrosourea (MNU) is an alkylating agent that can modify the guanine base in DNA.The mode of mutation induction differs from that of radiation, which generates large mutations such as chromosomal deletion and translocation. Our previous studies showed that Bcl11b is a tumor suppressor gene and that Bcl11b+/- heterozygous mice are susceptible to γ-ray induced thymic lymphomas. This study investigates whether or not the Bcl11b+/- genotype also provides susceptibility to MNU-induced thymic lymphomas. The results showed that loss of one copy of the Bcl11b gene contributed to lymphomagenesis, indicating that Bcl11b can suppress MNUinduction of thymic lymphomas. Interestingly, loss of the wild-type Bcl11b allele was not detected in those lymphomas, contrasting with the finding ofa high frequency of the loss in the γ-ray induced Bcl11b+/- thymic lymphomas. On the other hand, epigenetic inactivation of Bcl11b was observed in 74% (14/19) of the Bcl11b+/- lymphomas. This may be the main contributor to the loss of Bcl11b function and probably affects the elevation of lymphoma incidence and the shortening of the latency in Bcl11b+/- mice when MNU is administrated.