Background: This study aimed to determine the major neurological and psychological elements affecting depression, anxiety (DEPXITY), and the overall quality of life. Methods: This analytical descriptive study was carried out on 141 respondents with formal mood disorder diagnosis, with mental illness identity, with current depression and anxiety symptoms of at least moderate severity and people with mild symptoms. Data were analyzed using descriptive statistics, correlation test, reliability test, and separate regression models. Statistical significant level was set as 0.05. Results: The findings showed that external control by others on one's own life (EC) is the most significant factor (0.45) related to depression and the social conflict (SC) was found to be the most influential factor (0.28) for the anxiety. Internal control over own personal life (IC) is the most significant factor to cure or regulate some of the negative symptoms of the anxiety (-0.66). Good performance in personal life (PP) is a common positive factor to regulate both depression (DEP) and anxiety (XITY). This study shows that DEPXITY is associated with negative life quality. Conclusions: The lack of internal control and the control by others on one's own personal life are associated with impaired cognitive, affective, and behavioral functioning. The results of this study can also be a good indicator and confirmation that the medial prefrontal cortex is able with the support of IC and PP to coordinate self-appraisal processes by regulating activity in the posterior cingulate cortex area of the brain.