Mental depression: Relation to different disease status, newer treatments and its association with COVID-19 pandemic (Review)

Abstract

The present study aimed to review major depression, including its types, epidemiology, association with different diseases status and treatments, as well as its correlation with the current COVID-19 pandemic. Mental depression is a common disorder that affects most individuals at one time or another. During depression, there are changes in mood and behavior, accompanied by feelings of defeat, hopelessness, or even suicidal thoughts. Depression has a direct or indirect relation with a number of other diseases including Alzheimer's disease, stroke, epilepsy, diabetes, cardiovascular disease and cancer. In addition, antidepressant drugs have several side effects including sedation, increased weight, indigestion, sexual dysfunction, or a decrease in blood pressure. Stopping medication may cause a relapse of the symptoms of depression and pose a risk of attempted suicide. The pandemic of COVID-19 has affected the mental health of individuals, including patients, individuals contacting patients and medical staff with a number of mental disorders that may adversely affect the immune ability of their bodies. Some of the drugs currently included in the protocols for treating COVID-19 may negatively affect the mental health of patients. Evidence accumulated over the years indicates that serotonin (5HT) deficiencies and norepinephrine (NE) in the brain can lead to mental depression. Drugs that increase levels of NE and 5HT are commonly used in the treatment of depression. The common reason for mood disorders, including mania and bipolar disease are not clearly understood. It is assumed that hyperactivity in specific parts of the brain and excessive activity of neurotransmitters may be involved. Early diagnosis and developing new treatment strategies are essential for the prevention of the severe consequences of depression. In addition, extensive research should be directed towards the investigation of the mental health disturbances occurring during and/or after COVID-19 infection. This may lead to the incorporation of a suitable antidepressant into the current treatment protocols.

Keywords: COVID-19; latest treatments; major depression; mental health; molecular mechanism; neurotransmitters.

Figure 1.

Areas affected in the brain during depression. The areas affected in the brain include the temporal and frontal lobes and the cingulate gyrus of the limbic system.

Figure 2.

Common types of depression. Types of depression include unipolar (unipolar I, II and cyclothymia) and bipolar (major, dysthymia, postpartum, seasonal, atypical and psychotic).

Figure 3.

Fold increase in the risk of diseases resulting from depression. Depression can cause several medical diseases, including Alzheimer's (by 2.0-fold), CVS (1.5–2.0-fold), stroke (1.8-fold), epilepsy (4.0–6.0-fold), diabetes (1.6-fold) and cancer (1.3–1.8-fold) compared with control non-depressed individuals. CVS, cardiovascular disease.

Figure 4.

Depression and metabolic disorders. Depression is accompanied by metabolic syndrome, obesity, T2DM and T1DM (,,, respectively). By contrast, depression may increase the risk of diabetes. Gastrointestinal hormones, such as ghrelin, leptin and the lipid endocannabinoid, may regulate mood in the case of depression. Improving depression symptoms has been accompanied by inhibition of cholecystokinin receptors and the hyperactivity of the HPA axis. Hippocampal neurogenesis is induced by IGF and the disturbance of neuronal IGF results in depression. Regulation of synaptic plasticity and improving depressive behavior results from releasing gastrin-releasing peptide in the hippocampus. HPA, hypothalamic-pituitary-adrenal; IGF, insulin-like growth factor; GRP, gastrin-releasing peptide; 5-HT, 5-hydroxytryptamine; NE, norepinephrine.

Figure 5.

Depression and endocrine disorders. Cushing's syndrome and hypothyroidism are accompanied by a high rate of psychiatric morbidity. The raised concentration of thyrotrophin releasing hormone in cerebrospinal fluid in patients with depression is noted in a previous study. Secondary hypothyroidism is characterized by decreased blood level thyroid-stimulating hormone, which is concomitant with an increased risk of depressive episodes. It is found that 40% of patients with hypothyroidism suffer from clinical depression. Hyperthyroidism patients have a high risk of depression by 28% compared with normal individuals, whereas it occurs in 50% of all cases of patients with hypothyroidism. Blood and cerebrospinal levels of T4 are relatively increased during the depression. T4, thyroxin; TSH, thyroid stimulating hormone.

Figure 6.

Depression and inflammatory disorders. Depression increases cytokines, including IL-6, TNF-α and IL-1. Furthermore, stress regulates prostaglandin-E2, lipid peroxidation IL-1β, cyclooxygenase-2 and Toll-like receptor-4. NK-1, neurokinin-1 receptor.

Figure 7.

Depression and daylight. Deficiency of light has been shown to suppress neurogenesis and increase symptoms of depression. Nocturnal melatonin, vitamin D and platelet 5-HT values are induced by environmental light and improve depression symptoms. Melatonin has anti-oxidative effects, increases sleep propensity and has been known to decrease alertness and attenuate weight gain. 5-HT, 5-hydroxytryptamine.

Figure 8.

Depression and deficiency. Intake of omega-3 fatty acids, fish, vitamin B6, vegetables, fruits, folate, olive oil, vitamin B12, nuts and legumes improves depressive symptoms, although the exact mechanism remains to be elucidated. A previous study demonstrates that unipolar depression can be effectively controlled by folic acid. A study conducted on >70 patients showed that major depressive disorder in non-responders to selective serotonin reuptake inhibitors could be improved by s-adenosyl methionine if taken concurrently with serotonin reuptake inhibitor.

Figure 9.

Depression and neurodegenerative cases. Long-time stress may negatively affect the process of neurogenesis and cause neuronal loss in the hippocampus. In depressive behaviors, synaptic plasticity has been revealed to be controlled by BDNF. The blood level of BDNF is decreased in patients with depression and its level is increased by antidepressant drugs. In patients with depression, a decreased level of VGF has been shown and an antidepressant effect is produced by treatment with recombinant VGF in an experimental animal model. NT-3 and NGF may contribute to the antidepressant responses by improving plasticity and neurogenesis in the hippocampus. Other factors, such as GDNF and FGF-2, are modulated in depression. BDNF, brain-derived neurotrophic factor; VGF, vascular growth factor; NT-3, neurotrophin-3; NGF, nerve growth factor; GDNF, glial cell line-derived neurotrophic factor; FGF-2, fibroblast growth factor-2.