Felice N. Jacka

So depression is an inflammatory disease, but where does the inflammation come from?

BackgroundWe now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to neuroprogression in the disorder. The obvious question this poses is ‘what is the source of this chronic low-grade inflammation?’DiscussionThis review explores the role of inflammation and oxidative and nitrosative stress as possible mediators of known environmental risk factors in depression, and discusses potential implications of these findings. A range of factors appear to increase the risk for the development of depression, and seem to be associated with systemic inflammation; these include psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental cares, sleep and vitamin D deficiency.SummaryThe identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. Critically, most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Most, but not all, of the above mentioned sources of inflammation may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism and post-traumatic stress disorder.

Association of high-sensitivity C-reactive protein with de novo major depression

BACKGROUND Although there is cross-sectional evidence that changes in the immune system contribute to the pathophysiology of depression, longitudinal data capable of elucidating cause and effect relationships are lacking. AIMS We aimed to determine whether subclinical systemic inflammation, as measured by serum high-sensitivity C-reactive protein (hsCRP) concentration, is associated with an increased risk of de novo major depressive disorder. METHOD Major depressive disorder was diagnosed using a clinical interview (SCID-I/NP). This is a retrospective cohort study; from a population-based sample of 1494 randomly selected women recruited at baseline during the period 1994-7, 822 were followed for a decade and provided measures of both exposure and outcome. Of these women, 644 (aged 20-84 years) had no prior history of depression at baseline and were eligible for analysis. RESULTS During 5827 person-years of follow-up, 48 cases of de novo major depressive disorder were identified. The hazard ratio (HR) for depression increased by 44% for each standard deviation increase in log-transformed hsCRP (ln-hsCRP) (HR = 1.44, 95% CI 1.04-1.99), after adjusting for weight, smoking and use of non-steroidal anti-inflammatory drugs. Further adjustment for other lifestyle factors, medications and comorbidity failed to explain the observed increased risk for depression. CONCLUSIONS Serum hsCRP is an independent risk marker for de novo major depressive disorder in women. This supports an aetiological role for inflammatory activity in the pathophysiology of depression.

A Prospective Study of Diet Quality and Mental Health in Adolescents

Objectives A number of cross-sectional and prospective studies have now been published demonstrating inverse relationships between diet quality and the common mental disorders in adults. However, there are no existing prospective studies of this association in adolescents, the onset period of most disorders, limiting inferences regarding possible causal relationships. Methods In this study, 3040 Australian adolescents, aged 11–18 years at baseline, were measured in 2005–6 and 2007–8. Information on diet and mental health was collected by self-report and anthropometric data by trained researchers. Results There were cross-sectional, dose response relationships identified between measures of both healthy (positive) and unhealthy (inverse) diets and scores on the emotional subscale of the Pediatric Quality of Life Inventory (PedsQL), where higher scores mean better mental health, before and after adjustments for age, gender, socio-economic status, dieting behaviours, body mass index and physical activity. Higher healthy diet scores at baseline also predicted higher PedsQL scores at follow-up, while higher unhealthy diet scores at baseline predicted lower PedsQL scores at follow-up. Improvements in diet quality were mirrored by improvements in mental health over the follow-up period, while deteriorating diet quality was associated with poorer psychological functioning. Finally, results did not support the reverse causality hypothesis. Conclusion This study highlights the importance of diet in adolescence and its potential role in modifying mental health over the life course. Given that the majority of common mental health problems first manifest in adolescence, intervention studies are now required to test the effectiveness of preventing the common mental disorders through dietary modification.

Tobacco smoking as a risk factor for major depressive disorder: Population-based study

BACKGROUND Smoking is disproportionately prevalent among people with psychiatric illness. AIMS To investigate smoking as a risk factor for major depressive disorder. METHOD A population-based sample of women was studied using case-control and retrospective cohort study designs. Exposure to smoking was self-reported, and major depressive disorder diagnosed using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP). RESULTS Among 165 people with major depressive disorder and 806 controls, smoking was associated with increased odds for major depressive disorder (age-adjusted odds ratio (OR)=1.46, 95% CI 1.03-2.07). Compared with non-smokers, odds for major depressive disorder more than doubled for heavy smokers (>20 cigarettes/day). Among 671 women with no history of major depressive disorder at baseline, 13 of 87 smokers and 38 of 584 non-smokers developed de novo major depressive disorder during a decade of follow-up. Smoking increased major depressive disorder risk by 93% (hazard ratio (HR)=1.93, 95% CI 1.02-3.69); this was not explained by physical activity or alcohol consumption. CONCLUSIONS Evidence from cross-sectional and longitudinal data suggests that smoking increases the risk of major depressive disorder in women.

Oxidative & nitrosative stress in depression: Why so much stress?

Many studies support a crucial role for oxidative & nitrosative stress (O&NS) in the pathophysiology of unipolar and bipolar depression. These disorders are characterized inter alia by lowered antioxidant defenses, including: lower levels of zinc, coenzyme Q10, vitamin E and glutathione; increased lipid peroxidation; damage to proteins, DNA and mitochondria; secondary autoimmune responses directed against redox modified nitrosylated proteins and oxidative specific epitopes. This review examines and details a model through which a complex series of environmental factors and biological pathways contribute to increased redox signaling and consequently increased O&NS in mood disorders. This multi-step process highlights the potential for future interventions that encompass a diverse range of environmental and molecular targets in the treatment of depression.

The association between habitual diet quality and the common mental disorders in community-dwelling adults : The Hordaland health study

Objective: Recent evidence suggests a role for diet quality in the common mental disorders depression and anxiety. We aimed to investigate the association between diet quality, dietary patterns, and the common mental disorders in Norwegian adults. Methods: This cross-sectional study included 5731 population-based men and women aged 46 to 49 and 70 to 74 years. Habitual diet was assessed using a validated food frequency questionnaire, and mental health was measured using the Hospital Anxiety and Depression Scale. Results: After adjustments for variables including age, education, income, physical activity, smoking, and alcohol consumption, an a priori healthy diet quality score was inversely related to depression (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.59-0.84) and anxiety (OR = 0.77, 95% CI = 0.68-0.87) in women and to depression (OR = 0.83, 95% CI = 0.70-0.99) in men. Women scoring higher on a healthy dietary pattern were less likely to be depressed (OR = 0.68, 95% CI = 0.57-0.82) or anxious (OR = 0.87, 95% CI = 0.77-0.98), whereas men were more likely to be anxious (OR = 1.19, 95% CI = 1.03-1.38). A traditional Norwegian dietary pattern was also associated with reduced depression in women (OR = 0.77, 95% CI = 0.64-0.92) and anxiety in men (OR = 0.77, 95% CI = 0.61-0.96). A western-type diet was associated with increased anxiety in men (OR = 1.27, 95% CI = 1.14-1.42) and women (OR = 1.29, 95% CI = 1.17-1.43) before final adjustment for energy intake. Conclusions: In this study, those with better quality diets were less likely to be depressed, whereas a higher intake of processed and unhealthy foods was associated with increased anxiety.FFQ = food frequency questionnaire; HADS = Hospital Anxiety and Depression Scale; OR = odds ratio; CI = confidence interval; SD = standard deviation; Kj = kilojoule; PA = physical activity; SES = socioeconomic status; MI = myocardial infarction.

Associations between diet quality and depressed mood in adolescents : results from the Australian healthy neighbourhoods study

Objective: Adolescence frequently coincides with the onset of psychiatric illness and depression is commonly observed in adolescents. Recent data suggest a role for diet quality in adult depression. Given the importance of adequate nutrition for brain development, it is of interest to examine whether diet quality is also related to depression in adolescents. Methods: The study examined 7114 adolescents, aged 10–14 years, who participated in the Australian Healthy Neighbourhoods Study. Healthy and unhealthy diet quality scores were derived from a dietary questionnaire. The Short Mood and Feelings Questionnaire for adolescents measured depression. Adjustments were made for age, gender, socioeconomic status, parental education, parental work status, family conflict, poor family management, dieting behaviours, body mass index, physical activity, and smoking. Results: Compared to the lowest category of the healthy diet score, the adjusted odds ratios (95% confidence interval) for symptomatic depression across categories (C) was: C2 = 0.61 (0.45–0.84); C3 = 0.58 (0.43–0.79); C4 = 0.47 (0.35–0.64); and C5 = 0.55 (0.40–0.77). Compared to the lowest quintile, the adjusted odds ratios (95% confidence interval) for symptomatic depression across increasing quintiles of the unhealthy diet score were: Q2 = 1.03 (0.87–1.22); Q3 = 1.22 (1.03–1.44); Q4 = 1.29 (1.12–1.50); and Q5 = 1.79 (1.52–2.11). Conclusions: Our results demonstrate an association between diet quality and adolescent depression that exists over and above the influence of socioeconomic, family, and other potential confounding factors.

Nutritional medicine as mainstream in psychiatry

Psychiatry is at an important juncture, with the current pharmacologically focused model having achieved modest benefits in addressing the burden of poor mental health worldwide. Although the determinants of mental health are complex, the emerging and compelling evidence for nutrition as a crucial factor in the high prevalence and incidence of mental disorders suggests that diet is as important to psychiatry as it is to cardiology, endocrinology, and gastroenterology. Evidence is steadily growing for the relation between dietary quality (and potential nutritional deficiencies) and mental health, and for the select use of nutrient-based supplements to address deficiencies, or as monotherapies or augmentation therapies. We present a viewpoint from an international collaboration of academics (members of the International Society for Nutritional Psychiatry Research), in which we provide a context and overview of the current evidence in this emerging field of research, and discuss the future direction. We advocate recognition of diet and nutrition as central determinants of both physical and mental health.

Relationship between diet and mental health in children and adolescents: a systematic review.

We systematically reviewed 12 epidemiological studies to determine whether an association exists between diet quality and patterns and mental health in children and adolescents; 9 explored the relationship using diet as the exposure, and 3 used mental health as the exposure. We found evidence of a significant, cross-sectional relationship between unhealthy dietary patterns and poorer mental health in children and adolescents. We observed a consistent trend for the relationship between good-quality diet and better mental health and some evidence for the reverse. When including only the 7 studies deemed to be of high methodological quality, all but 1 of these trends remained. Findings highlight the potential importance of the relationship between dietary patterns or quality and mental health early in the life span.

The association between diet quality, dietary patterns and depression in adults: a systematic review

BackgroundRecent evidence suggests that diet modifies key biological factors associated with the development of depression; however, associations between diet quality and depression are not fully understood. We performed a systematic review to evaluate existing evidence regarding the association between diet quality and depression.MethodA computer-aided literature search was conducted using Medline, CINAHL, and PsycINFO, January 1965 to October 2011, and a best-evidence analysis performed.ResultsTwenty-five studies from nine countries met eligibility criteria. Our best-evidence analyses found limited evidence to support an association between traditional diets (Mediterranean or Norwegian diets) and depression. We also observed a conflicting level of evidence for associations between (i) a traditional Japanese diet and depression, (ii) a “healthy” diet and depression, (iii) a Western diet and depression, and (iv) individuals with depression and the likelihood of eating a less healthy diet.ConclusionTo our knowledge, this is the first review to synthesize and critically analyze evidence regarding diet quality, dietary patterns and depression. Further studies are urgently required to elucidate whether a true causal association exists.