General introduction 19 2.2. Depression Major depressive disorder (MDD), commonly called depression, is one of the most prevalent mental disorders worldwide, with a high impact on quality of life. Although presence of key symptoms (e.g. depressed mood or anhedonia) is required for a clinical diagnosis of depression, the symptoms that depressed people report vary widely: one can experience increases or decreases in appetite, increased propensity to sleep or total inability to sleep, and physical restlessness or a total slowing down of physical activity (American Psychiatric Association, 2013). This diversity in depression symptoms is also called heterogeneity, which refers to the idea that depression is not a single condition, but it is a set of symptoms which can manifest differently in different individuals. To gain further insight into heterogeneity in depression, clinicians and researchers have also studied subtypes of depression, such as melancholic or atypical depression, or specific clusters of symptoms. In many people, depression can show a recurrent or chronic course: longitudinal data show that in the 9 years after a depressive episode, an estimated 68% of patients reported at least one recurrent depressive episode (Solis et al., 2021). Sex differences in depression Depression is more common in women compared to men across cultures and countries (Hopcroft & Bradley, 2007). In the Netherlands, the lifetime prevalence of depression in women is 24%, whereas it is 13% in men (de Graaf et al., 2010). As the sex differences are evident, almost all researchers studying depression correct for sex. Most studies do not yet conduct sexstratified analyses, meaning they do not examine whether their research results are generalizable to both sexes (Rechlin et al., 2022). Sex differences are also found show in the type of depressive symptoms and in comorbidity: atypical depression, which is characterized by the absence of anhedonia and the presence of hypersomnia, excessive eating, leaden paralysis and sensitivity to rejection, is up to four times more prevalent in depressed women than in depressed men (Lamers et al., 2010; Łojko & Rybakowski, 2017). Depressed women are also more likely to report somatic and cognitive-affective symptoms than men and they are more likely to present with comorbid anxiety (Altemus et al., 2014). However, studies find
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