Concept: Sickness behavior
The possible therapeutic impact of dietary changes on existing mental illness is largely unknown. Using a randomised controlled trial design, we aimed to investigate the efficacy of a dietary improvement program for the treatment of major depressive episodes.
When we contract an infection, we typically feel sick and behave accordingly. Symptoms of sickness behavior (SB) include anorexia, hypersomnia, depression, and reduced social interactions. SB affects species spanning from arthropods to vertebrates, is triggered nonspecifically by viruses, bacteria, and parasites, and is orchestrated by a complex network of cytokines and neuroendocrine pathways; clearly, it has been naturally selected. Nonetheless, SB seems evolutionarily costly: it promotes starvation and predation and reduces reproductive opportunities. How could SB persist? Former explanations focused on individual fitness, invoking improved resistance to pathogens. Could prevention of disease transmission, propagating in populations through kin selection, also contribute to SB?
Family caregivers of individuals with serious illness are at risk for depressive symptoms and depression. Hospice includes the provision of support services for family caregivers, yet evidence is limited regarding the effect of hospice use on depressive symptoms among surviving caregivers.
Sickness behavior is characterized by lethargy, reduced appetite, anhedonia and anxiety. It can be induced in experimental animals by bacterial endotoxin, lipopolysaccharide (LPS). We investigated the impact of intracerebroventricular agmatine injections (5 - 20 μg/rat, icv) on sickness behavior induced by LPS (100 μg/rat, ip) in rats. Rats challenged with LPS demonstrated hyperthermia, anorexia, anxiety, depression like phenomenon and reduction in body weights. Additionally, mediators of sickness behaviors, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) level in LPS treated rat serum were also increased. The present study revealed that these LPS induced symptoms of sickness behavior including anorexia were normalized by pretreatment with agmatine. The IL-6 and TNF-α serum levels were also normalized in agmatine pretreated rats. It is anticipated that agmatine may suppress LPS induced sickness behavior by inhibiting proinflammatory pathway and/or activity circuitry in brain. This study suggests that agmatine may be important therapeutic target in the treatment of anorexia and other neurological abnormalities associated with bacterial infection.
Cognitive dysfunction is a prevalent and disabling symptom of Major Depressive Disorder (MDD), and is often retained in the remitted stage of illness. Emerging evidence suggests that cognitive impairment may be associated with dysfunction in a number of psychosocial domains (e.g., workplace productivity, social relationships). The current study explored the relationship between cognition and psychosocial functioning in remitted MDD and in healthy controls.
This article investigates various reasons for sickness presenteeism (SP), that is, going to work despite illness. The research questions asked is: What are the main reported reasons for SP in Norway and Sweden?
In mice a 50% calorie restriction (CR) for 28 days attenuates sickness behavior after lipopolysaccharide (LPS) and these mice demonstrate a central anti-inflammatory bias. This study examined the dose-dependent effect of CR on sickness behavior (fever, anorexia, cachexia) and peripheral immune markers post-LPS. Male Sprague-Dawley rats fed ad libitum or CR by 50% for 14, 21, or 28 days were injected on day 15, 22, or 29 with 50μg/kg of LPS or saline (1mL/500g). Changes in body temperature (Tb), locomotor activity, body weight, and food intake were determined. A separate cohort of rats was fed ad libitum or CR by 50% for 28 days and serum levels of corticosterone (CORT), interleukin 6 (IL-6), and IL-10 were determined at 0, 2, and 4 hours post-LPS. The rats CR for 28 days demonstrated the largest attenuation of sickness behavior: no fever, limited reduction in locomotor activity, no anorexia, and reduced cachexia following LPS. Rats CR for 14 and 21 days demonstrated a partial attenuation of sickness behavior. Rats CR for 14 days demonstrated a larger increase in Tb, larger reduction in locomotor activity, and larger weight loss compared to rats CR for 21 days. Serum CORT was increased at 2 hours post-LPS in ad libitum and CR groups; however it was two times larger in the CR animals. Levels of IL-6 were significantly attenuated at 2 hours post-LPS in the CR animals. IL-10 levels were similar post-LPS. CR results in an enhanced anti-inflammatory response in the form of increased CORT and diminished pro-inflammatory signals.
It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers.
The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD.
Marijuana (MJ) use is common. Research shows risks for psychiatric illnesses, including major depressive disorder (MDD) and cognitive deficits with MJ use, particularly early-onset use. We investigated cognitive function, functional connectivity, and genetic risk with MDD alone and combined with MJ use, and differences between early-vs. late-onset/non-MJ use in youth.