It is estimated that depression will be the second leading cause of disability in Australia by 2020 , and in 2015 two thirds of Australian adults were overweight or obese.

Depression and obesity are ever increasing health risks that have a bidirectional relationship with common pathophysiological mechanisms. Being overweight or obese is associated with increased risk of depression and being depressed increases the risk of weight gain and obesity.

INFLAMMATION: CORNERSTONE OF THE RELATIONSHIP BETWEEN OBESITY AND DEPRESSION

Inflammation drives different factors that appear to link obesity and depressive disorders. These include inflammatory processes and the related alterations to neuroendocrine and neurotransmitter pathways.

The occurrence of depression in obesity is about 30% which is a much higher rate when compared to the general population. These people also have a high risk of being non-responders to anti-depressant medications with a higher recurrence of relapse after treatment.

Obesity is now considered to be a condition of inflammation that affects the immune system. Adipose tissue accumulates macrophages and T cells which stimulate the release of inflammatory cytokines such as interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-a) and C-Reactive Protein (CRP).Inflammation occurs systemically and can also affect the liver and muscles.

The gut microbiota are also involved in the pathogenesis of obesity with their influence on energy metabolism, modulation of inflammation and body weight balance. Alterations in the ratio of the major phyla Bacteroides/Firmicutes lead to local, systemic and brain inflammation which is corrected after weight loss.

Recent research has shown increased inflammatory processes in the brains of obese individuals, particularly the hypothalamus, hippocampus and cortex. Animal studies indicated that blocking this inflammation prevents high-fat diet-induced obesity and its associated metabolic imbalance.

Inflammatory cytokines activate the hypothalamic-pituitary-adrenal (HPA) axis, alter brain plasticity, affect brain circuitry and impair neurotransmitter metabolism. These changes can then lead to mood and behavioural changes.

Cancer and hepatitis patients being treated with interferon (cytokine) therapy had a high chance (45%) of developing major depression unless receiving a prophylactic anti-depressant. Cytokine-induced depression impairs serotonin, dopamine and glutamate. This is due to the activation of several enzymes that may affect the activity of tetrahydrobiopterin (BH4) which is a cofactor essential to the production of neurotransmitters such as serotonin and dopamine. Low levels of BH4 have been found in those with psychiatric disorders.

Another enzyme activated by cytokines is indoleamine2.3 dioxygenase (IDO). IDO degrades tryptophan via the kynurenine pathway and prevents it being used to produce serotonin. The activation of the kynurenine pathway can also lead to production of glutamatergic neuroactive compounds which promote neuronal cell death and oxidative stress, impair neurogenesis and promote the development of neuropsychiatric symptoms. These findings support the theory that inflammation can induce impairment of brain neurotransmission and promote neurotoxicity that can contribute to mood disorders.

CLINICAL RESEARCH SUPPORTING THE LINK BETWEEN OBESITY AND DEPRESSIVE STATES

Clinical research has found that obesity-related inflammation plays a significant role in the development of depressive comorbidities with a strong correlation between elevated levels of CRP, IL-6 and leptin in depressed patients. Reduction in inflammatory markers after weight loss or bariatric surgery significantly improved emotional status and depression in obese patients.

Obese patients have lower levels of circulating tryptophan and higher levels of kynurenine in comparison to those within the normal weight range. This was found to contribute to hippocampal atrophy.

HPA axis activation in response to immune stimulation is heightened in those with obesity and may act together to alter mood states. Glucocorticoids and cytokines impair hippocampal neurogenesis and neuronal function in obese mice. The behavioural changes in these mice were linked to the increased inflammation and reduced levels of brain derived neurotrophic factor (BDNF) in the cortex and hippocampus. It was found that normalising BDNF levels prevented cognitive impairment.

Insulin signalling pathways and circulating levels of insulin are altered in obesity and causes an interaction with inflammatory mediators to act within the brain to control energy expenditure, glucose balance and feeding behaviour. TNF can impair signalling of insulin receptors within the brain. Dysfunction of the insulin signalling pathway is involved in neurological and neuropsychiatric disorders. Insulin resistance is associated with emotional alterations; compounds that enhance insulin transmission in the brain show an antidepressant effect in those with depression. Several antidiabetic drugs have been observed to have a positive impact on inflammation and neuronal activity.

NON-PHARMACOLOGICAL INTERVENTIONS:

• Weight loss induced by low-calorie diets can potentially regulate inflammation and improve depressive symptoms in obese individuals.
• Exercise promotes the stimulation of cytokines within the muscle with anti-inflammatory properties with research showing this had a similar effect to anti-depressant medication.
• Omega-3 polyunsaturated fatty acids have been found to have an anti-depressant effect by preventing interferon-induced depression in those with hepatitis C. Recent research has found that depressed patients with high levels of inflammation responded positively to omega-3 EPA supplementation in comparison to depressed patients with low inflammation.
• Pre- and Probiotics beneficially alter the microbiome and exert immune-modulatory properties that have a positive effect on mood and behaviour.
• Antioxidant therapy –oxidative stress is correlated with low levels of BDNF and supports BH4 activity.

The research indicates that there is a link between the increasing incidence of obesity and depression and the common factor is inflammation. Weight loss, management of insulin resistance, oxidative stress and inflammation may support those with these comorbid conditions.

INNER-ALCHEMY APPROACH

Our Metabolic Alchemy course firstly address the microbiome and investigate pathways of inflammation and insulin resistance. Addressing these in the first weeks of the course create an optimal environment for weight loss and improved mental health. 

Without the ground work, all efforts to lose weight and keep it off along with a reduction in anxiety and depression markers, ultimately fail.

This is why working with a Naturopath with expertise in metabolic health always works better than DIY courses. 

“The Body Does not Quick Fix, It Fixes Right” – Carly Gallagher

Contact me for your suitability to these courses.