Elsevier

Psychiatry Research

Volume 279, September 2019, Pages 244-251
Psychiatry Research

Weight gain in Major Depressive Disorder: Linking appetite and disordered eating to leptin and ghrelin.

https://doi.org/10.1016/j.psychres.2019.03.017Get rights and content

Highlights

Abstract

Major Depressive Disorder (MDD) involves changes in appetite and weight, with a subset of individuals at an increased risk of weight gain. Pathways to weight gain may include appetite disturbances, excess eating, and dysregulation of appetite hormones. However, little research has simultaneously examined relationships between hormones, eating behaviours and MDD symptoms. Plasma ghrelin and leptin, biometrics, eating behaviours and psychopathology were compared between depressed (n = 60) and control (n = 60) participants. Depressed participants were subcategorised into those with increased or decreased appetite/weight for comparison by subtype. The Dutch Eating Behaviours Questionnaire and Yale Food Addiction Scale measured eating behaviours. Disordered eating was higher in MDD than controls, in females than males, and in depressed individuals with increased, compared to decreased, appetite/weight. Leptin levels were higher in females only. Leptin levels correlated positively, and ghrelin negatively, with disordered eating. The results provide further evidence for high levels of disordered eating in MDD, particularly in females. The correlations suggest that excessive eating in MDD is significantly linked to appetite hormones, indicating that it involves physiological, rather than purely psychological, factors. Further, longitudinal, research is needed to better understand whether hormonal factors play a causal role in excessive eating in MDD.

Introduction

Research indicates that obesity increases the risk of Major Depressive Disorder (MDD) by approximately 18–55%, and in turn, MDD increases the risk of obesity by approximately 37–58% (Luppino et al., 2010, Heiskanen et al., 2013, Mannan et al., 2015). The prevalence rates of both MDD and obesity are increasing annually, with these rises attributed to physiological and psychological stress, obesogenic environments and changes in modern lifestyles (Hidaka, 2012). Consequently, individuals with MDD are at increased risk of developing additional health complications, including cardiovascular disease and metabolic syndrome (Cassano and Fava, 2002, Penninx et al., 2013). Identifying potential mechanisms for weight gain in MDD may help improve interventions aimed at reducing the likelihood of chronic disease in these at-risk individuals.

Changes in appetite and weight are diagnostic criteria for MDD (American Psychiatric Association, 2013), with the direction of appetite/weight changes differing by MDD subtype. Melancholic MDD is characterised by decreased appetite and weight loss. In contrast, atypical MDD features hyperphagia, weight gain (American Psychiatric Association, 2013), higher BMI values, increased endocrine dysregulation and more frequent instances of cardiovascular disease and metabolic syndrome (e.g. Gecici et al., 2005, Lamers et al., 2016, Milaneschi et al., 2017). Epidemiological studies have indicated that atypical MDD is now 40% more prevalent than melancholic MDD; indicating that ‘atypical’ symptoms, including weight gain, are increasingly becoming more ‘typical’ (Blanco et al., 2012, Privitera et al., 2013). Despite clearly established risks for chronic disease (Cassano and Fava, 2002, Penninx et al., 2013), there is a lack of both specific treatment guidelines for the treatment or prevention of depressogenic weight gain, and integrated approaches that address both biological and physiological factors. The long-term success of weight loss programs in general is also limited (MacLean et al., 2015). Understanding the mechanisms underlying the pathways to weight gain in MDD may allow for better preventative strategies in individuals at risk due to MDD.

Pathways to weight gain in MDD may include appetite disturbances linked to neuroendocrine changes and associated disordered eating. Disordered eating may act as a coping mechanism for psychological distress, as foods, particularly those high in carbohydrates, can dampen physiological stress responses produced by the hypothalamic-pituitary-adrenal (HPA) axis (e.g. Dallman et al., 2003). Disordered eating includes emotional eating, increasing food intake in response to emotional distress; restrained eating, deliberately restricting food intake to prevent weight gain or encourage weight loss; and external eating, increasing food intake in response to sensory food cues (van Strien et al., 2016). Depressed mood and MDD symptom severity are associated with emotional eating (e.g. van Strien et al., 2016, Paans et al., 2018), increased consumption of food in response to external cues, and with restricting food intake (e.g. Sevincer et al., 2017).

Food addiction characterises a subset of disordered eating behaviours, defined by a preference for highly palatable foods and addiction-like behaviours such as a loss of control and withdrawal (Piccini et al., 2015). Dopaminergic reward pathways can be activated by highly palatable foods, particularly those high in carbohydrates or fat, which can result in addiction-like behaviours similar to substance use disorders (e.g. Gearhardt et al., 2009, Piccinni et al., 2015). Food addiction can be measured using the Yale Food Addiction Scale (YFAS; Gearhardt et al., 2009), with a prevalence of 5–10% in the general population, and 15–25% in obese individuals (Meule and Gearhardt, 2014, Hauck et al., 2017). In a recent pilot, we found that 25% of a sample with MDD met Yale criteria for food addiction, considerably higher than general community samples (Mills et al., 2018).

The concept of food addiction is still controversial, since food is necessary for survival whereas psychoactive substances that form the basis of other addictions are not (e.g. Ziauddeen and Fletcher, 2013, Onaolapo and Onaolapo, 2018). The composition of modern foods has been altered to increase their palatability and hedonistic qualities compared to naturally occurring foods (Leigh and Morris, 2018), to the extent that they could be argued to act similarly to addictive substances. There is increasing evidence of an overlap between activation of neural reward circuitry in response to food and drugs of addiction (e.g. Gearhardt et al., 2011, Volkow et al., 2012). Several studies have linked the concept of food addiction to MDD (e.g. Gearhardt et al., 2012, Eichen et al., 2013, Mills et al., 2018). As such, it is possible that obesogenic environments promoting the availability of highly palatable foods may be related to the increased prevalence of atypical MDD characterised by weight gain, however further research is needed.

While previous studies indicate that MDD is associated with disordered eating (e.g. Bailly et al., 2012, van Strien et al., 2016), food addiction (e.g. Eichen et al., 2013, Mills et al., 2018) and weight gain (e.g. Blanco et al., 2012), the mechanisms underlying the relationships between these factors are unclear. The hunger and satiety hormones ghrelin and leptin are related to HPA axis activity and suppression of stress responses, and therefore may be associated with MDD and associated symptomatic appetite/weight changes (Roubos et al., 2012, Spencer et al., 2014). However, little research has examined direct relationships between these hormones, disordered eating behaviours and appetite/weight changes in MDD.

Leptin is secreted by adipocyte cells in proportion to adipose tissue mass, with critical roles in regulating adipose tissue and body weight (Maffei et al., 1995). Leptin has important anorexigenic effects, acting as an appetite suppressant during times of energy excess (Elmquist et al., 1998, Trayhurn et al., 1999, Lu, 2007). Leptin resistance, or having high leptin levels but decreased leptin sensitivity (e.g. Pan et al., 2014) has been implicated in the pathogenesis of obesity (Zigman and Elmquist, 2003, Ozsoy et al., 2014). Since leptin is secreted relative to adipose tissue mass, higher levels signal the increased availability of fat and in turn lead to a reduction in food intake such that stored fat can be utilised for energy. However, in leptin resistance individuals become desensitised to endogenous satiety signals, resulting in elevated leptin levels without the usual satiety, and subsequently increased food intake and weight gain or obesity (e.g. Maffei et al., 1995).

Human research investigating leptin levels in MDD has identified inconsistent results, with either lower (e.g. Kraus et al., 2001, Atmaca et al., 2008, Westling et al., 2004) or elevated (e.g. Antonijevic et al., 1998, Jiménez et al., 2009, Morris et al., 2012) leptin levels in MDD versus control populations. In contrast, several studies, including large-scale meta-analyses, have indicated no difference between diagnostic groups (e.g. Hafner et al., 2012, Ozsoy et al., 2014, Carvalho et al., 2014). Individuals with atypical MDD have higher leptin levels compared to controls, and individuals with melancholic MDD (e.g. Gecici et al., 2005, Lamers et al., 2016, Milaneschi et al., 2017), suggesting that leptin may be involved in a subset of individuals with increased appetite/weight.

Ghrelin is secreted from the stomach and gastrointestinal tract (Kojima et al., 1999), with important orexigenic roles in promoting increased food intake (e.g. Wren et al., 2000) and increased adiposity (e.g. Tschop et al., 2001, Thompson et al., 2004). Significantly lower total ghrelin concentrations have been observed in obese humans, indicating possible downregulation of ghrelin levels associated with excessive eating (e.g. Atalayer et al., 2013).

Studies of ghrelin in MDD are also inconsistent, with elevated (e.g. Kurt et al., 2008, Atescelik et al., 2017, Ozsoy et al., 2014) lowered (e.g. Barim et al., 2009) or no difference between MDD and control participants observed (e.g. Kluge et al., 2009, Lawson et al., 2011, Matsuo et al., 2012). Whether ghrelin levels differ by melancholic/atypical subtype is currently unclear, however due to its role in stimulating appetite levels (e.g. Wren et al., 2000) ghrelin levels may possibly be higher in those experiencing appetite/weight gain, or possibly lowered due to the downregulation observed in obesity (Atalayer et al., 2013).

The inconsistent results for leptin and ghrelin levels may be accounted for by the heterogeneity in appetite/weight change symptom profiles in MDD. Previous studies have either combined symptom subtypes (e.g. Antonijevic et al., 1998, Ozsoy et al., 2014) or have classified symptoms based on broader atypical MDD criteria, differing also in the classification methods used (e.g. Gecici et al., 2005, Lamers et al., 2016, Milaneschi et al., 2017). These inconsistent classification methods may act as potential confounds in these studies. In addition, leptin levels are more strongly correlated with appetite and weight gain and not other atypical symptoms (e.g. Milaneschi et al., 2017), suggesting that comparison by appetite/weight symptom profile may provide a clearer understanding of relationships between appetite hormones and weight gain than atypical criteria more generally.

Leptin and ghrelin are noted to vary between sexes, with higher leptin and ghrelin levels reported in females than males (e.g. Antonijevic et al., 1998, Soriano-Guillen et al., 2015); which may be explained by females having different body fat compositions than males for reproductive purposes (Blaak, 2001). However, sex differences in leptin and ghrelin levels are not always observed (e.g. Kluge et al., 2009, Tschop et al., 2001). In humans, leptin and ghrelin levels have also previously been correlated with body mass index (BMI) and waist circumference (e.g. Mills et al., 2018, Akamizu et al., 2004), suggesting potential roles for both hormones as risk factors for chronic diseases. However, no studies have simultaneously examined associations between appetite hormones, disordered eating and BMI in MDD.

Our previous pilot study (Mills et al., 2018) found that a high proportion of participants with MDD reported disordered eating, including emotional and restrained eating as measured by the Dutch Eating Behaviours Questionnaire (van Strien et al., 1986), and food addiction behaviours as measured by the Yale Food Addiction Scale (Gearhardt et al., 2009). Disordered eating was higher in females with MDD than males with MDD. Further, disordered eating correlated positively with leptin levels, suggesting that leptin resistance may be involved in disordered eating in MDD. The current study expands on our previous work by investigating eating behaviours in relation to neurobiological measures in a new cohort. Leptin and ghrelin levels, biometrics and psychometric indices of mood and problematic eating behaviours were compared between individuals with MDD and healthy controls. Given the heterogeneous nature of MDD, participants with MDD were further subcategorised by appetite/weight symptom presentation to compare subtypes. It was predicted that:

  • 1

    Participants with MDD would report greater levels of disordered eating compared to controls. By symptom profile, MDD participants with increased appetite/weight would demonstrate higher instances of these behaviours than MDD participants without increased appetite/weight; with effects being greater in females.

  • 2

    Psychometric indices of problematic eating behaviours, food addiction and depression severity will correlate with leptin and ghrelin levels.

  • 3

    Leptin and ghrelin levels would not differ significantly between depressed and non-depressed participants overall. However, at the subgroup level in MDD, these values will be higher in those with increased appetite/weight compared to those with reduced or unchanged appetite/weight; with effects being greater in females.

Section snippets

Participants

One hundred and twenty (120) adults aged between 18 and 54 years (M = 25.05, SD = 6.61 years; 68 female) participated. Participants were recruited by media and university advertisements. Depressed participants were pre-screened to confirm that they currently met DSM-5 criteria prior to inclusion in the MDD group (N = 60). Control participants (N = 60) were age and gender matched to the MDD group. Depressed participants were not receiving any current or recent psychological, pharmacological or

Demographic and biometric data

Participant characteristics are shown in Table 1. There were 34 females and 26 males in both MDD (N = 60) and control (N = 60) groups. No participants had a diagnosed eating disorder, and none were current smokers. Of the 120 participants, 30 (18 MDD) had not consumed any food or drink other than water for approximately 12 h.

The groups did not differ significantly in age. Males weighed more than females (F(1, 116) = 18.159, p < .001). No further differences for Diagnosis, Sex or interaction

Discussion

The current study examined relationships between disordered eating, the hunger/satiety hormones ghrelin and leptin and symptomatic weight changes in MDD. It was found that disordered eating was higher in MDD than controls, in females than males, and in a subset of depressed individuals with appetite/weight gain compared to decreased/unchanged appetite/weight. Leptin levels correlated positively, and ghrelin negatively, with disordered eating.

Emotional and restrained eating behaviours were

Funding

This research received no specific grant from any funding agency, commercial or not-for-profit sectors. Jessica Mills’ PhD candidature is supported by an Australian Government Research Training Program Scholarship.

Authors' contributors

JM was involved in data collection, data and statistical analysis and manuscript preparation. TL, CD and ST were involved in study design, data collection, data analysis and manuscript editing.

Conflict of interest

The authors declare no potential conflicts of interest.

Ethical standards

The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

References (69)

  • B.H. Hidaka

    Depression as a disease of modernity: explanations for increasing prevalence

    J. Affect. Disord.

    (2012)
  • S.J. Leigh et al.

    The role of reward circuitry and food addiction in the obesity epidemic: an update

    Biol. Psychol.

    (2018)
  • X.Y. Lu

    The leptin hypothesis of depression: a potential link between mood disorders and obesity

    Curr. Opt. Pharmacol.

    (2007)
  • K. Matsuo et al.

    Neural correlates of plasma acylated ghrelin level in individuals with major depressive disorder

    Brain Res.

    (2012)
  • Y. Milaneschi et al.

    Leptin dysregulation is specifically associated with major depression with atypical features: evidence for a mechanism connecting obesity and depression

    Biol. Psychiatry

    (2017)
  • J.G. Mills et al.

    Problematic eating behaviours, changes in appetite and weight gain in Major Depressive Disorder: the role of leptin

    J. Affect. Disord.

    (2018)
  • N.P. Paans et al.

    Eating styles in major depressive disorder: results from a large-scale study

    J. Psychiatr. Res.

    (2018)
  • H. Pan et al.

    Advances in understanding the interrelations between leptin resistance and obesity

    Physiol. Behav.

    (2014)
  • E.W. Roubos et al.

    Leptin and the hypothalamo-pituitary-adrenal stress axis

    Gen. Comp. Endocrinol.

    (2012)
  • T. van Strien et al.

    Emotional eating as a mediator between depression and weight gain

    Appetite

    (2016)
  • S. Westling et al.

    Low CSF leptin in female suicidal attempters with major depression

    J. Affect. Disord.

    (2004)
  • T. Akamizu et al.

    Separate measurement of plasma levels of acylated and desacyl ghrelin in healthy subjects using a new direct ELISA assay

    J. Clin. Endocrinol. Metab.olism

    (2004)
  • American Psychiatric Association

    Diagnostics and Statistical Manual of Mental Disorders

    (2013)
  • M. Atescelik et al.

    The relationship between ghrelin and copeptin levels, and anxiety and depression levels in suicide attempts

    Clin. Psychopharmacol. Neurosci.

    (2017)
  • N. Bailly et al.

    The Dutch Eating Behaviours Questionnaire (DEBQ): assessment of eating behaviour in an aging French population

    Appetite

    (2012)
  • A.T. Beck et al.

    Manual for the Beck Depression Inventory-II

    (1996)
  • E. Blaak

    Gender differences in fat metabolism

    Curr. Opin. Clin. Nutr. Metab. Care

    (2001)
  • C. Blanco et al.

    Prevalence, correlates, comorbidity and treatment seeking among individuals with a lifetime major depressive episode with and without atypical features: results from the National Epidemiological Survey on Alcohol and Related Conditions

    J. Clin. Psychiatry

    (2012)
  • M.F. Dallman et al.

    Chronic stress and obesity: a new view of comfort food

    Proc. Natl Acad. Sci.

    (2003)
  • J. Elmquist et al.

    Unravelling the central nervous system pathways underlying responses to leptin

    Nat. Neurosci.

    (1998)
  • T. Ge et al.

    Leptin in depression: a potential therapeutic target

    Cell Death Dis.

    (2018)
  • A.N. Gearhardt et al.

    Neural correlates of food addiction

    Arch. Gen. Psychiatry

    (2011)
  • A.N. Gearhardt et al.

    An examination of the food addiction construct in obese patients with binge eating disorder

    Int. J. Eat. Disord.

    (2012)
  • O. Gecici et al.

    High serum leptin levels in depressive disorders with atypical features

    Psychiatry Clin. Neurosci.

    (2005)
  • Cited by (0)

    View full text