2. Diet and Depression

The typical diets of western societies have high amounts of saturated fats and refined sugars, as well as high amounts of red and processed meats, with concurrent low levels of fruit, vegetable and fiber intake. This results in a diet that is energy-dense and nutrient-poor with profound consequences for both our physical and mental health. The relationship between diet and obesity is clear; individuals consuming more calories than the recommended daily allowance, combined with consuming high amounts of foods high in fat and sugar content, are more likely to develop obesity. More recently, the impact of diet on mental health has also been revealed to be significant; for example, a recent meta-analysis found that adults following a healthy dietary pattern have fewer depressive symptoms and lower risk of developing depressive symptoms [11].

The precise etiology of depression is unknown, but many psychological, social, and biological underpinnings are thought to contribute to its development [12]. The latter includes genetic, hormonal, immunological, biochemical, and neurodegenerative factors. Concurrently, research has shown that these physiological aspects can be modulated by diet and nutrition. For example, in the case of genes, vitamin E has been shown to modulate several genes involved in neural signal transduction, inflammation and cell proliferation among others, while omega-3 polyunsaturated fatty acids (n-3 PUFAs) [13] have been shown to interact with genes that code for cytokines, cholesterol metabolizing enzymes, and growth factors [14].

3. Depression and Obesity

Many authors posit that depression is a heterogenous assortment of symptoms that can be divided into subtypes based on the accompanying presenting symptoms beyond low mood. Most recently, it has been subdivided into two main subtypes: type 1, which is characterized by loss of appetite and body weight, insomnia, and suicidal ideation, and type 2, also known as atypical depression, which presents with increased appetite and weight gain, leaden paralysis, hypersomnia, and a persistently poor metabolic profile [15]. Several factors are thought to moderate the relationship between obesity and depression. Stunkard et al. have reviewed the literature pertaining to what those moderators and mediators could be, and they have identified several including the severity of obesity, the severity of depression, and stress [16].

Correlations between both disorders involve disturbance of appetite regulation, changes in metabolic, hormonal and immunological parameters, and behavioral problems such as reduced physical activity [9,10,17,18,19,20]. More specifically, obesity has been shown to induce important physical, psychological, and behavioral changes in vulnerable patients, such as changes in the hormone and cytokine systems [18,21], changes in thought processes such as rumination [9], and behavioral changes such as reduced physical activity [20]. These changes are known risk factors of depression [17,20]. Thus, in obese patients, depression can be seen as a health consequence of obesity. If obesity contributes to the development and maintenance of depression, we can hypothesize that weight loss might help those depressed patients who are obese. Indeed, recent studies indicate that weight loss due to caloric restriction or gastric bypass surgery improves depressive symptoms among obese patients with depression [22,23,24,25]. Therefore, we sought to review and collate the existing research literature on the effects of diet modifications on depressive symptoms in overweight or obese individuals enrolled in dietary weight loss programs. The underlying idea was that in people with obesity and depression, depression occurs as a consequence of obesity, and therefore weight loss could not only help with regard to obesity but could also reduce depressive symptoms.

4.1. Physiological Mechanisms

Research has exposed metabolic and inflammatory dysregulation as a common denominator in depression and obesity [70,71]. Additionally, both depressed and obese patients exhibit dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis [72,73] and consequently chronic elevations in cortisol [74,75]. Increases in cortisol levels have been reported as having a causal role in depression, as well as leading to weight gain, specifically in abdominal adiposity. Recently, white adipose tissue (WAT) has been conceptualized as an endocrine organ, as opposed to how it was previously thought of—as an inert storage tissue—due to its ability to produce cytokines and other related molecules. Among these are interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α [76,77,78], which are known proinflammatory cytokines, as well as chemokines, including monocyte chemoattractant protein (MCP)-1 [79,80]. The ensuing signaling cascade leads to immune activation and white blood cell accumulation, and an overall increased inflammatory response. This immune activation has various downstream effects. For example, IL-2 reduces tryptophan plasma levels [81], possibly by activating tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO). Tryptophan is an essential amino acid necessary for 5-HT synthesis. Low levels of tryptophan could lead to lower levels of serotonin and thus affect mood. Another example is the accumulation of peripheral monocytes in the brain as a result of systemic inflammation [82], and specifically the increased production of MCP-1 in hypothalamic neurons. This monocyte migration has been associated with increased anxiety and depression [83]. Minimization of accumulated adipose tissue through weight loss could attenuate this inflammatory process, leading to improved mood.

Another molecule implicated in both obesity and depression is leptin. Leptin is a peptide hormone released by adipocytes and crosses the blood–brain barrier via a saturable transport mechanism. Low plasma levels of leptin have been observed in depressed patients [84,85]. In the case of obesity however, plasma leptin levels have been found to be elevated [86,87]. This contradictory finding can be explained by leptin resistance (as in the case of type 2 diabetic patients being resistant to insulin) and could be a result of impaired transport across the blood–brain barrier, of reduced function of the leptin receptor, or errors in signal transduction [88,89]. Similar to cortisol and inflammatory molecules described previously, leptin modulates HPA axis function [90,91]. Leptin also interacts with monoamines and although its effect on monoamine neurotransmission remains unclear, there is evidence for leptin’s involvement in the 5-HT system [92] and in the activation of STAT3 in dopamine neurons of the ventral tegmental area (VTA) [93]. Reducing the amount of adipose tissue through diet and subsequent weight loss could ameliorate leptin resistance, reinstate leptin function, and relieve low mood.

4.2. Psychosocial Mechanisms

It should be borne in mind that psychosocial attributes may affect physiology, and the distinction between the two mechanisms here is for ease of discussion. A good example of this environment x biology interaction is the finding that weight discrimination, often experienced by obese individuals, increases cortisol levels [94]. Additionally, repeated discrimination can lead to lower self-esteem and increased negative affect [95]. Many studies have reported on the negative attitudes of employers, peers, and even clinicians towards obese persons [96,97]. Continued maltreatment can impact obese persons’ mood and self-concept, both of which can contribute to depression.

Even if obese individuals do not experience weight discrimination or stigma by others, their self-esteem could be impacted by their own body image dissatisfaction (BID). Some research has found correlations between BID and depressive symptoms and suggested that obesity confers risk for developing depression through increased BID [98,99]. Therefore, it is possible that losing weight improves body image satisfaction and low mood. For a more thorough discussion see Markowitz et al. [100].

(References would be added automatically after the entry is online)