According to the Centers for Disease Control and Prevention (CDC), the prevalence of diagnosed diabetes has increased from 0.93% of the U.S. population in 1958 to 8.7% in 2019 [8]. It is important to note that 8.5 million people have diabetes but remain undiagnosed [8,9]. By 2025, it is predicted that 15% to 20% of all Americans will have a diagnosis of diabetes or impaired glucose tolerance [10].

The most common types of diabetes are type 1 and type 2. However, gestational diabetes is also relatively common and is a source of significant morbidity and mortality. Gestational diabetes complicates approximately 10% of all pregnancies [13,14]. It is first recognized in pregnancy, usually after 24 weeks of gestation, and typically resolves after the birth of the child [13]. Other less common types of diabetes include [10,15]:

American Diabetes Association (ADA) criteria for screening for diabetes or prediabetes in asymptomatic adults include [13]:

Although much research has been conducted on the neurobiologic causes of depression, the exact underlying pathophysiology of depression (specifically major depression) remains unknown [18]. One consistent observation is that stress or emotional trauma, especially when experienced earlier in life, is associated with increased risk of developing depression [19]. It is believed that 40% to 50% of the risk for developing depression is due to genetic factors and that the interactions between genetic and environmental factors across the lifespan underlie depressive vulnerability in most patients [20]. Early-life stress can result in persistent neuroendocrine, physiologic, behavioral, and psychologic changes that negatively affect the development of brain systems involved in learning, motivation, and stress response, and that may also reflect a biologic priming for the development of depression, especially with additional stress exposure [18,21].

However, depression is now realized to be a heterogeneous disorder in which different biologic abnormalities contribute to the disruptions in sleeping, eating, energy, and emotional reactions [23]. The four domains of cognitive function that are disturbed in persons with depression are executive control, memory, affective processing, and feedback sensitivity [24]. Although enormous gaps remain in understanding depression and its treatment, there is an increasing focus on dysregulated neural circuitry as the underlying pathophysiology of depression, with a corresponding de-emphasis on specific neurotransmitter system dysfunction [22].

Chronic depression can be mild to severe in its debilitation of the patient and may persist for years if untreated [5,25]. It is defined as a chronically depressed mood that is present more than half the time for a minimum of two years in adults or one year in children and adolescents [26,27].

Major depression is a mood disorder characterized by feelings of sadness, loss, anger, and/or frustration that interfere with everyday life and last for weeks or longer [25]. The essential feature of major depression is depressed mood or anhedonia (loss of interest in usual activities) experienced most of the day and nearly every day for a period of at least two weeks [2,27].

Seasonal affective disorder (also referred to as major depression with seasonal pattern) is a cyclic type of depression defined by depressive episodes experienced only during certain times of the year, most commonly the fall and winter [5,27]. It is more frequently noted in women than men and in younger individuals than older adults [26]. Seasonal affective disorder is often considered to be related to a lack of exposure to sunlight and may be treated with bright visible-spectrum light therapy [25].

Postpartum depression (diagnosed as major depression with peripartum onset) occurs in approximately 10% of new mothers [27,28,29,30]. A study of low-income mothers found that the presence of diabetes during pregnancy was associated with an almost twofold increase in the incidence of postpartum depression compared to women without diabetes [31]. The study did not specify if the diabetes diagnoses were present prior to the pregnancy. One study examined the association between gestational diabetes and depression incidence during both the pre- and postnatal periods. Of 58,400 mothers, women with gestational diabetes had a nearly twofold greater risk of being diagnosed with depression compared with those without gestational diabetes during the prenatal period [32].

As stated, it is common for individuals with diabetes to experience emotional distress as a result of living with the disease, its complications, and treatment and self-monitoring [2]. The most common factor affecting psychologic well-being, reported in about one-third of individuals with diabetes, is worrying about the future and the possibility of diabetes complications. Other areas endorsed as "serious" by patients with diabetes include [2]:

The PAID-1 scale is a 20-item evaluation covering a range of emotional problems frequently reported in patients with diabetes [5]. Each item is scored based on the severity of the problem, with 100 total points possible. A higher score is indicative of greater emotional distress. Studies using this questionnaire have demonstrated the greatest worries for these patients to be related to an undefined future, the possibility of serious complications, and guilt due to treatment noncompliance [36]. Greater emotional distress according to PAID-1 scale results is correlated to poor glycemic control [37].

The PAID-1 scale is a 20-item evaluation covering a range of emotional problems frequently reported in patients with diabetes [5]. Each item is scored based on the severity of the problem, with 100 total points possible. A higher score is indicative of greater emotional distress. Studies using this questionnaire have demonstrated the greatest worries for these patients to be related to an undefined future, the possibility of serious complications, and guilt due to treatment noncompliance [36]. Greater emotional distress according to PAID-1 scale results is correlated to poor glycemic control [37].

Approximately 16% of Americans will suffer a major depressive disorder at some point in their lives, although the rate is greater when other forms of depression (e.g., persistent depressive disorder) are included. A great number of Americans also have diabetes, and these two diseases can interact in harmful ways. Depression is associated with poor health behaviors, such as smoking, physical inactivity, and excessive caloric intake, that increase the risk of type 2 diabetes. Furthermore, depression is related to central adiposity, obesity, and impaired glucose tolerance [7,52]. Likewise, psychologic stress and depression have significant effects on metabolism by increasing counter-regulatory hormones, resulting in elevated blood glucose levels even in patients without diabetes [2]. Depression is linked with worse clinical outcomes. A study of more than 900,000 U.S. veterans found that comorbid depression in patients with diabetes is associated with increased risk of developing chronic kidney disease and poor cardiovascular outcomes [53]. Depression is also associated with physiologic abnormalities, including activation of the hypothalamic-pituitary-adrenal axis, sympathoadrenal system, and proinflammatory cytokines, which can induce insulin resistance and contribute to an increased risk for diabetes [7,54].

Depression and insulin resistance are both associated with atrophy of the limbic system of the brain as well as with difficulties with memory and attention. A reciprocal interaction between proper insulin function and cognitive abilities is strongly suggested by the persistence of insulin resistance and memory and attention problems in individuals with depression. Experts believe insulin function to be central to proper mood regulation and maintenance of memory and attention, and understanding and treatment of depression should account for this underlying metabolic dysregulation [55]. Although it has been shown that depression and diabetes may independently increase the risk for dementia, no studies have examined whether the risk for dementia is increased in people who have both diabetes and depression. Danish researchers examined health data for more than 2.4 million individuals 50 years of age or older, including 477,133 with depression, 223,174 with diabetes, and 95,691 with both diabetes and depression [56]. When compared with adults who did not have diabetes or depression, the risk for dementia was 20% higher in adults with diabetes alone, 83% higher in adults with depression alone, and 117% higher in adults with both diabetes and depression [56]. This again underscores the need for better understanding and treatment of depression in individuals with diabetes.

After possible physical causes are ruled out or addressed, referral to a psychiatrist, psychologist, psychiatric nurse, licensed social worker, and/or professional counselor is warranted. Psychotherapy or counseling should be the first-line therapy, with pharmacotherapy and other approaches used for patients with severe depression or depression that does not respond to counseling [4]. Depression-specific psychologic treatment is more effective than general supportive counseling, and the level of glycemic control and the presence or absence of diabetes complications is predictive of the response to depression treatment [1]. A review of available evidence indicates that psychosocial interventions, particularly cognitive-behavioral therapy, can effectively treat depressive symptoms in patients with diabetes [57]. However, it is unclear whether these interventions are also effective in improving self-care and physical health outcomes. Studies of individuals with diabetes and major depressive disorder demonstrate improvement in symptoms of depression as well as blood glucose levels with active treatment with an effective antidepressant [57]. In studies of comorbid diabetes and depression, nortriptyline (a tricyclic antidepressant) has led to worsening glucose control, whereas bupropion, fluoxetine, and sertraline were correlated with reductions in glucose levels [57].

After possible physical causes are ruled out or addressed, referral to a psychiatrist, psychologist, psychiatric nurse, licensed social worker, and/or professional counselor is warranted. Psychotherapy or counseling should be the first-line therapy, with pharmacotherapy and other approaches used for patients with severe depression or depression that does not respond to counseling [4]. Depression-specific psychologic treatment is more effective than general supportive counseling, and the level of glycemic control and the presence or absence of diabetes complications is predictive of the response to depression treatment [1]. A review of available evidence indicates that psychosocial interventions, particularly cognitive-behavioral therapy, can effectively treat depressive symptoms in patients with diabetes [57]. However, it is unclear whether these interventions are also effective in improving self-care and physical health outcomes. Studies of individuals with diabetes and major depressive disorder demonstrate improvement in symptoms of depression as well as blood glucose levels with active treatment with an effective antidepressant [57]. In studies of comorbid diabetes and depression, nortriptyline (a tricyclic antidepressant) has led to worsening glucose control, whereas bupropion, fluoxetine, and sertraline were correlated with reductions in glucose levels [57].

Education for any individuals diagnosed with or at risk for depression should include recognition of signs and symptoms of depression, discussing fears related to the stigma of depression, and treatment options available [1]. When psychologic counseling is recommended, it is essential the individual understands the importance of [60]:

When an individual with diabetes is being treated for depressive symptoms, it is crucial to convey the need for self-care regardless of the severity of the depression. Steps to ensure proper self-care include [4]:

The patient and family or support system should be advised to be aware of signs and symptoms of worsening depression that necessitate notifying their healthcare provider or contacting emergency services. This includes [4,35,61]:

It is imperative to inform individuals that changes to the treatment plan may be necessary in order to effectively manage depression [60]. Antidepressants begin to work gradually, so therapy must be adhered to for several weeks before determining effect. Patients should continue antidepressant therapy even if they feel better or symptoms improve; discontinuing these medications abruptly can be dangerous. Patients should be aware that the goal of treatment is complete remission, though it may require trials of different therapies to identify the best combination [60].