The personality trait of Persistence is highly valued by conscientious overachievers, but it has both psychological costs and benefits. The interactions among multiple personality factors influencing the development of mood and anxiety disorders have been confounded in prior clinical samples, but can be disentangled in terms of their underlying brain circuitry and influence on perception of emotional stimuli. 285 individuals who represented the full range of personality variation in a large sample of adult volunteers from the general community of Israel were selected for follow-up by psychiatric interviews, cognitive testing, and medical examinations. The Temperament and Character Inventory (TCI) measured profiles of traits that distinguished individuals with diagnoses of mood and/or anxiety disorders using linear discriminant analysis and non-linear profile analysis. High Harm Avoidance and low Self-directedness strongly distinguished people with mood and/or anxiety disorders from those with neither. High Persistence distinguished people with only anxiety disorders from those with mood disorders. High Persistence was associated with greater health and happiness overall, but also led to more negative emotions than in people with low Persistence unless they were both unusually tolerant of frustration (i.e., low in Harm Avoidance) and self-accepting of personal limitations (i.e. high in Self-directedness). Subjects were volunteers over 40 years of age at assessment. People who are highly persistent (i.e., persevering, ambitious, perfectionistic) are more likely to have anxiety disorders than mood disorders, even when they have other traits increasing risk for both (i.e., high Harm Avoidance and low Self-directedness). High Persistence increases both positive and negative emotions in most people. However, high Persistence reduces negative emotions and increases positive emotions if a person is easy-going (i.e., "happy-go-lucky" when low in both Harm Avoidance and Self-directedness).