Optimizing
Wellness
(OWL) Lab
Biological Psychiatry
Our research program focuses on investigating biological psychiatry-related scar and vulnerability theories. Specifically, we study the bidirectional relationships between immune and endocrine markers and common mental disorders (CMDs). We are particularly interested in vulnerability models, like the cytokine and social signal transduction theories of depression, which suggest that increased inflammatory activity may be a distant risk factor for major depressive disorder, particularly in socially vulnerable populations. We use longitudinal designs to explore these less-studied ideas to uncover potential causal relations beyond the commonly observed cross-sectional links among psychopathology, executive functioning (EF), and inflammation/endocrine markers. These studies could inform the development and improvement of evidence-based therapies for inflammation-related neuropsychiatric disorders, considering their significant global impact on public health and the economy.
Consistent with these ideas, we have observed that higher plasma levels of C-reactive protein, fibrinogen, and interleukin-6 are more predictive of changes in the diagnostic status of major depressive disorder over 9 years in younger individuals, women, individuals with lower income, and those who experienced more childhood trauma and chronic illnesses (Zainal & Newman, 2021b). In a different longitudinal network analysis, elevated C-reactive protein and high-density lipoprotein levels within individuals were linked to future occurrences of depressive mood, somatic symptoms, and interpersonal problems (Zainal & Newman, 2023e). Moreover, higher low-density lipoprotein levels predicted heightened depressive mood and interpersonal problems, and increased triglyceride levels were associated with greater somatic symptoms. In line with scar theories, greater interpersonal issues preceded elevated fibrinogen and low-density lipoprotein levels. At the same time, more pronounced somatic symptoms were connected to increased fibrinogen levels in the future. These results underscore the complex and bidirectional connections between immune/endocrine markers and symptoms of common mental disorders (CMDs) influenced by various biopsychosocial determinants of health.
Moreover, we examined scar theories focused on executive functioning (EF) and found that increased inflammation acts as a mediator between depression, anxiety, and future EF decline. Understanding the link between inflammation-related common mental disorders (CMDs) and EF decline is valuable for therapy development, especially given societal immune and mental health (MH) challenges. Through longitudinal structural equation modeling (SEM) analysis, it was evident that elevated levels of worry and depression, but not panic, predicted lower EF scores after 20 months due to increased inflammation (Zainal & Newman, 2021a). This pattern was consistent in another adult sample followed for 18 years (Zainal & Newman, 2022b). Notably, plasma inflammation mediated the impact of worry and depression on future EF deficits in these studies, even after accounting for potential confounds such as age, gender, medication use, exercise, and medical conditions.
These findings carry significant clinical implications. Lowering interleukin-6, C-reactive protein, and fibrinogen levels could help prevent future cardiovascular and metabolic disorders through lifestyle modifications like diet, exercise, nutrition, and yoga. Additionally, customizing treatment based on inflammation profiles may enhance psychopharmacological treatment outcomes, especially when dealing with increased proinflammatory markers.
