Genetics of Major Depression

Introduction

A prevalent mental illness called major depressive disorder (MDD) is inherited in 30 to 50% of instances. It is a psychiatric disorder. MDD has a higher prevalence, moderate heritability, and strong polygenicity (a disorder influenced by more than one gene), which has posed major challenges in determining genes' role in MDD. Psychiatric Genomics Consortium confirms that MDD is highly polygenic, meaning more than one gene can cause MDD. Genetic factors are promising for improving clinical care and determining the exact cause of MDD. This article will discuss the causes of MDD and the role of genes in MDD. MDD is a common, debilitating, disorder. Its heritability ranges between 30 % and 50 %. MDD with early onset, recurrence, comorbid anxiety, greater severity, and postpartum depression may be more heritable subtypes. Compared to other psychiatric disorders, its high prevalence, moderate heritability, and strong polygenicity have posed major challenges for gene mapping. This article explains the genetic cause of depression.

What Is Major Depressive Disorder (MDD)?

MDD is a heterogeneous disorder that affects clinical practice. A prevalent mood condition that has a negative impact on lifestyle and life expectancy is a major depressive disorder. AMD (age-related macular degeneration) is the leading cause of disability worldwide. The exact cause of MDD is not known, but it is proven that genes play an important role in the underlying depression. The 12-month prevalence of MDD is estimated to be approximately six percent and the lifetime prevalence is around 20 %. The term depression refers to a depressed mood.

The risk factors for MDD include age, female sex, separated/divorced marital status, physical health problems, and childhood trauma. The peak onset of MDD is in the early 40s, with the median in the mid-20s (early adolescence). Men have a two times greater likelihood of having an MDD diagnosis. MDD is at risk due to sex hormones and environmental variables. MDD is associated with chronic physical health problems, including cardiovascular diseases, chronic pain disorders, and cancers.

The following feeling characterizes MDD:

• The feeling of sadness.

• The feeling of irritability or emptiness.

• Decreased ability to feel pleasure (anhedonia).

• Decreased ability to experience interest in the usual activity.

• Decrease concentration.

• The feeling of emotional low.

• The feeling of worthlessness or hopelessness.

The following are the symptoms of MDD:

• Loss of appetite.

• Weight changes.

• Insomnia (a state of not sleeping).

• Hypersomnia (a state of sleeping more).

What Causes Major Depression?

The exact cause of major depression is not fully comprehended, however research indicates that it likely influenced by a combination of biological, genetic, environmental, and psychological factors. The risk factors for MDD include age, female sex, separated/divorced marital status, physical health problems, and childhood trauma.

The following elements are some of those thought to be involved:

• Biological Factors: Serotonin, norepinephrine, and dopamine abnormalities are some of the neurotransmitters hypothesized to have a role in the emergence of serious depression. Additionally, changes in the structure and function of certain brain regions involved in mood regulation, such as the amygdala, hippocampus, and prefrontal cortex, have been observed in individuals with depression.

• Genetic Factors: There is evidence that genetics can predispose some individuals to major depression. a family history of mood disorders or depression increases the risk of developing the condition. However, specific genes or genetic mutations linked to major depression have not been definitively identified.

• Environmental Factors: Various environmental factors can contribute to the development of major depression. Depressive episodes can be triggered or made worse by stressful life events, such as trauma, the loss of a loved one, issues in relationships, or financial troubles. Chronic stress, social isolation, childhood adversity, and Additionally, certain medical problems can raise the danger of depression.

• Psychological Factors: Psychological factors can influence the onset and course of major depression. Negative thinking patterns, low self-esteem, a pessimistic outlook on life, and difficulties in coping with stress or emotions can contribute to the development of depressive symptoms. Depression may be more prevalent among those who have specific personality features, such as high levels of neuroticism.

• Medical Conditions and Medications: Some medical conditions, such as chronic pain, hormonal imbalances, thyroid disorders, and certain neurological conditions, have been associated with an increased risk of developing depression. Additionally, certain medications, including some antidepressants, can potentially trigger or worsen depressive symptoms in susceptible individuals.

What Are the Genetics of Major Depression?

The 12-month prevalence of MDD is estimated to be around six percent and the lifetime prevalence around 20 %, although these figures vary considerably across countries. Historical linkage studies in families with MDD failed to identify causal variants but implicated regions on chromosomes 2, 3, 11, and 15 in disorder risk. Familial aggregation of MDD was early evidenced by family-based studies, with first-degree relatives of MDD patients having a higher risk. Genetic epidemiology research has strongly emphasized assessing the proportional contributions of environmental and genetic factors to the risk of MDD in families. Phenotypic variance is divided into hereditary and environmental components in traditional quantitative genetic models. The percentage of phenotypic variance attributed to additive genetic factors is then used to estimate the pedigree heritability. These models are frequently used in twin or adoption research.

MDD is consistently shown to be moderately heritable in twin studies comparing monozygotic and dizygotic twins, with an early meta-analysis placing the heritability at 37 %. The estimates from subsequent twin investigations ranged between 29 % and 49 %, with higher estimates among study samples. Historical linkage studies in families with MDD failed to identify causal variants but implicated regions on chromosomes 2, 3, 11, and 15 in disorder risk. Thus, gene is also responsible for causing MDD.

Conclusion

In conclusion, MDD is a widespread, crippling, and phenotypically diverse illness. Its heredity ranges from 30 to 50 percent. Postpartum depression and severity may be more heritable subtypes. For gene mapping, schizophrenia's high prevalence, moderate heritability, and great polygenicity have presented significant difficulties when compared to other psychiatric illnesses. Rare CNVs (Copy Number Variants) have recently been linked to an increased risk of MDD. Large worldwide collaborations like the propelled studies of common variation in MDD, which validated the condition's highly polygenic origin and implicated over 100 loci in disorder risk. These studies discovered genes related to neuronal growth, synapse function, and inflammation in the condition's pathophysiology.