01 – Major depressive disorder

MAJOR DEPRESSIVE DISORDER IS A MENTAL DISORDER WHICH AFFECTS MILLIONS OF PEOPLE WORLDWIDE.

It is characterized by a state of profound sadness and hopelessness, as well as a decrease in the ability to enjoy activities that were once considered pleasant.

Symptoms of major depressive disorder may include changes in appetite, sleep, energy, and concentration, as well as feelings of worthlessness and guilt.

Episodes of major depressive disorder can last for weeks or even months if not properly treated.

IN THIS MODULE, WE WILL ADDRESS THE MOST RELEVANT ASPECTS OF MAJOR DEPRESSIVE DISORDER FROM A MEDICAL POINT OF VIEW, INCLUDING ITS PATHOGENESIS, DIAGNOSIS AND TREATMENT.

STRESS AND DEPRESSION

Stress plays a central role in the onset and course of depression. However, only a subset of individuals who experience stressful life events develop a depressive episode. One of the most consistent conclusions about depression is that stressful life events precipitate the onset and prolong the duration of depressive episodes. [1].

The past few years of research on stress and depression have occurred in the context of numerous major world events that significantly increased exposure to stress in the general population. For example, the coronavirus disease (COVID-19) pandemic disrupted work, education, health, finances, relationships, and recreation [2]. Given the link between stressful life events and depression, it is not surprising that rates of depression have increased following these events [3], especially given that symptoms of post-traumatic stress disorder (PTSD) mediate the association between early stress exposure and depressive symptoms [4].

A growing body of evidence documents that the connection between stress exposure and depression is influenced by affective, social, cognitive, and biological factors, and their inter-association [5].

To learn more about this topic, please read the following article. > Advances in stress and depression research/a>

1. Joelle LeMoult, Ashley M. Battaglini, Bronwen Grocott, Ellen Jopling, Katerina Rnic and Lisa Yang, Stress and depression LeMoult et al. 2022 Wolters Kluwer Health, Inc.
2. Douglas M, Katikireddi SV, Taulbut M, et al. Mitigating the wider health effects of covid-19 pandemic response. BMJ 2020; 369:m1557.
3. Bueno-Notivol J, Gracia-Garcı ́a P, Olaya B, et al. Prevalence of depression during the COVID-19 outbreak: a meta-analysis of community-based studies. Int J Clin Health Psychol 2021; 21:100196.
4. Fung HW, Chien WT, Ling HW, et al. The mediating role of posttraumatic stress disorder symptoms in the relationship between childhood adversities and depressive symptoms in two samples. Child Abuse Neglect 2022; 131:105707.
5. LeMoult J. From stress to depression: bringing together cognitive and biological science. Curr Dir Psychol Sci 2020; 29:592–598.

SLEEP AND DEPRESSION

Major depression, characterized mainly by a depressed mood and/or loss of interest or pleasure in daily activities for 2 weeks or more, is a common and often debilitating mental disorder [1]. Sleep disturbance is common in depression; insomnia symptoms (i.e. difficulty initiating or maintaining sleep) exceed 80% in those who are concurrently depressed [2].

Sleep disturbance is a diagnostic feature of depression. According to the DSM-5, insomnia or hypersomnia are clinical symptoms of a major depressive episode [1]. In addition to sleep disorders such as insomnia or hypersomnia, there has been increasing recognition of the importance of circadian rhythm characteristics in depression. Specifically, depressed patients with a nocturnal circadian preference (i.e. a daytime preference for activity and alertness in the late afternoon/evening) experience more severe depressive symptoms, greater functional impairment, and higher rates of suicidal ideation compared to patients without a nocturnal preference [3,4].

Sleep disturbance is an important factor in the development and maintenance of major depression. Treating specific sleep disturbances in the context of existing depression has the potential to improve outcomes for both conditions, although evidence is mixed. Accumulating evidence suggests that treating sleep disturbance reduces the likelihood of an incident and recurrent MDD episode for years following treatment, suggesting that sleep treatment may be an important tool in preventing depression and reducing the overall disease burden [5].

1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-51). USA: American Psychiatric Publication; 2013.
2. Stewart R, Besset A, Bebbington P, et al. Insomnia comorbidity and impact and hypnotic use by age group in a national survey population aged 16 to 74 years. Sleep 2006; 29:1391–1397.
3. Chan JWY, Lam SP, Li SX, et al. Eveningness and insomnia: independent risk factors of nonremission in major depressive disorder. Sleep 2014; 37:911–917.
4. Gaspar-Barba E, Calati R, Cruz-Fuentes CS, et al. Depressive symptomatology is influenced by chronotypes. J Affect Disord 2009; 119:100–106.
5. Pulantara IW, Parmanto B, Germain A. Clinical feasibility of a just-in-time adaptive intervention app (iREST) as a behavioral sleep treatment in a military population: feasibility comparative effectiveness study. J Med Internet Res 2018; 20:e10124.

DEPRESSION IN PEOPLE WITH CANCER

Depression is a common comorbidity in cancer patients throughout the course of the disease, requiring treatment due to the psychological burden it imposes as well as its association with numerous negative cancer outcomes. There is limited but growing research evidence to guide the treatment of depression in cancer. Expanding research on the inflammatory hypothesis of depression [1] may uncover pathways for developing much-needed treatments for cancer-related depression. The wide range of current pharmacological and psychological treatments for depression should be tailored to the individual and the patient's cancer-related needs.

Depression rates in cancer vary across studies, depending on demographic and disease factors (e.g., tumor site, stage, age, sex) and study methodology (e.g., clinical interview versus self-assessment scale, diagnostic cutoff scores, timing of assessment), but are two to three times higher than in the general population [2,3]. Meta-analytic estimates suggest the prevalence of major depressive disorder in cancer is 14.9% [4]. However, subthreshold presentations, categorized as minor depression, adjustment disorder, or persistent depressive disorder, are even more common. Estimates based on self-report tools capturing subclinical symptoms found pooled prevalence estimates of up to 24% [5].

The development and maintenance of depression in cancer is multifactorial, resulting from the interaction of multiple psychosocial, iatrogenic, and biological factors [6,7,8]. Risk factors for primary depression, such as female gender, family or individual history of depression, social isolation, and maladaptive coping strategies, are also observed in cancer-related depression. Cancer-specific risk factors include poor communication with healthcare providers, specific cancer types (e.g., pancreatic and head and neck cancers [3,9]), severity of pain and physical symptoms, and proximity to death [6,10]. Unlike primary depression, research has found an absence of gender differences in the prevalence of depression in advanced cancer [11], suggesting that medical factors may overwhelm gender effects in cancer. Due to these differences with primary depression, it is postulated that cancer-related depression has an inflammatory basis, mediated by immune system activation [12,13].

1. Beurel E, Toups M, Nemeroff CB. The bidirectional relationship of depression and inflammation: double trouble. Neuron 2020; 107:234–256.
2. Caruso R, Nanni MG, Riba M, et al. Depressive spectrum disorders in cancer: prevalence, risk factors and screening for depression: a critical review. Acta Oncol 2017; 56:146–155.
3. Linden W, Vodermaier A, Mackenzie R, Greig D. Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord 2012; 141:343–351.
4. Mitchell AJ, Chan M, Bhatti H, et al. Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies. Lancet Oncol 2011; 12:160–174.
5. Krebber AM, Buffart LM, Kleijn G, et al. Prevalence of depression in cancer patients: a meta-analysis of diagnostic interviews and self-report instruments. Psychooncology 2014; 23:121–130.
6. Smith HR. Depression in cancer patients: pathogenesis, implications and treatment (review). Oncol Lett 2015; 9:1509–1514.
7. Schulz-Quach C, Li M, Miller K, Rodin G. Depressive disorders in cancer. In: William Breitbart PB, Paul Jacobsen, Wendy Lam, Mark Lazenby, Matthew Loscalzo, editors. Psycho-oncology, 4 ed. Oxford: Oxford University Press; 2021. pp. 320–328.
8. Rosenblat JD, Kurdyak P,Cosci F, et al. Depression in the medically ill. Aust N Z J Psychiatry 2020; 54:346–366.
9. Zabora J, BrintzenhofeSzoc K, Curbow B, et al. The prevalence of psychological distress by cancer site. Psychooncology 2001; 10:19–28.
10. Li M, Fitzgerald P, Rodin G. Evidence-based treatment of depression in patients with cancer. J Clin Oncol 2012; 30:1187–1196.
11. Shapiro GK, Mah K, de Vries F, et al. A cross-sectional gender-sensitive analysis of depressive symptoms in patients with advanced cancer. Palliat Med 2020; 34:1436–1446.
12. McFarland DC, Walsh L, Miller AH. Depression, inflammation and cancer. In: William Breitbart PB, Paul Jacobsen, Wendy Lam, Mark Lazenby, Matthew Loscalzo, editors. Psycho-oncology, 4th ed. Oxford: Oxford University Press; 2021. pp. 644–653. This chapter provides the most up-to-date review of the associaton between inflammatory markers and depression in cancer.
13. Santos JC, Pyter LM. Neuroimmunology of behavioral comorbidities associated with cancer and cancer treatments. Front Immunol 2018; 9:1195.

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