Depression: What It Is, How It Is Diagnosed and Treatment Options

Depression is one of the major psychiatric disorders affecting individuals worldwide. It is estimated that more than 300 million people suffer from the condition, according to the World Health Organization (WHO) (1).

Depression can be caused by complex interactions between social, psychological, and biological factors. Certain life events, such as childhood adversities or high-stress situations, can contribute to or trigger the development of depression.

The most common symptoms of depression include (2, 3):

• Persistent sadness, irritability, or emptiness;
• Lack of interest or pleasure in previously rewarding or enjoyable activities (anhedonia);
• Changes in sleep and appetite;
• Fatigue;
• Difficulty concentrating and indecision;
• Feelings of worthlessness and hopelessness.

There are psychological and pharmacological treatments available for moderate to severe depression. However, in low- and middle-income countries, treatment and support services for depression are often non-existent or underdeveloped. It is estimated that 76–85% of people suffering from mental disorders in these countries do not have access to the necessary treatment.

Types of Depressive Disorders

Depressive disorders can be classified based on the number and severity of episodes, ranging from mild to moderate to severe (4). It is also assessed whether the patient has a history of manic episodes.

Depression usually presents chronically, with relapses, especially when the disorder is untreated or inadequately treated. In addition to being often disabling, depression can lead to suicide. It is estimated that about 800,000 people die by suicide each year, making it the second leading cause of death among people aged 15 to 29 (5).

Major Depressive Disorder

Major depression is characterized by the presence of at least five of the nine common symptoms. The most common symptom is a sense of sadness or loss of interest and pleasure in most usual activities.

Other symptoms associated with major depression include changes in appetite, changes in sleep, agitation or psychomotor retardation, constant fatigue, feelings of worthlessness or excessive and inappropriate guilt, recurring thoughts of death and suicidal ideation with or without specific plans for suicide, and cognitive difficulties, such as decreased ability to think, concentrate, and make decisions.

Persistent Depressive Disorder (Dysthymia)

This is essentially characterized by a mood disorder, with a persistently low, dark, or sad mood present for most of the day and most days for at least 2 years (children and adolescents may experience primarily irritability, and the mood persists for at least 1 year).

For an individual to receive a diagnosis of persistent depressive disorder, they must also have two of the diagnostic symptoms, which include changes in appetite, changes in sleep, low energy or fatigue, low self-esteem, poor concentration, difficulty making decisions, or feelings of hopelessness.

During this period, symptom-free intervals do not last longer than two months. The symptoms are less severe than in major depression. Major depression can precede persistent depressive disorder, and major depressive episodes can also occur during persistent depressive disorder.

Premenstrual Dysphoric Disorder (PMDD)

PMDD is characterized by a severe and sometimes disabling extension of premenstrual syndrome (PMS). Mood changes in PMDD are more severe and can impact social, occupational, and other areas. Both PMS and PMDD symptoms occur seven to 10 days before the start of the menstrual period and persist into the first days of the menstrual cycle.

Symptoms may include breast tenderness, abdominal bloating, fatigue, and changes in sleep and appetite. PMDD is characterized by more severe emotional and behavioral symptoms, such as sadness, anxiety, tension, extreme mood swings, irritability, or anger.

Adjustment Disorder with Depressed Mood

This is diagnosed when depressive symptoms are triggered within three months of a stressful event. The stressful event typically involves some type of life change for the individual, even if it is a positive but stressful event.

Symptoms generally subside within six months as the person begins to adjust to the stressor or when the stressful event is removed.

Many individuals suffering from depression have a history of anxiety disorders early in life (4). However, there is no evidence that one disorder causes the other, but there is clear evidence that many people suffer from both disorders. Read more in our article on Pharmacogenetics for Anxiety.

The severity of symptoms and the number of episodes are related to the individual’s ability to maintain their normal activities. An individual with a mild depressive episode will have some difficulty maintaining normal work and social activities but will be able to carry them out.

However, during a severe depressive episode, it is unlikely that the individual will be able to continue social, work, or household activities.

Bipolar Disorder

Bipolar consists of alternating manic and depressive episodes, separated by periods of normal mood. During manic episodes, the individual experiences elevated or irritable mood, excessive activity, high self-esteem, and decreased need for sleep.

Treatment for Depressive Disorders

Treatment for depressive disorders includes psychological therapies such as behavioral activation, cognitive-behavioral therapy (CBT), and interpersonal psychotherapy (IPT), as well as antidepressant medications like selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs).

Antidepressant medications can be an effective treatment for moderate to severe depression. However, according to the WHO, they are not the first choice for mild depression cases, which include psychotherapy, physical activity, and psychosocial interventions.

Role of Genetics in Depressive Disorders

Genetic variants play a significant role in depression, influencing both the predisposition to the disorder and the response to treatment.

A common question about depressive disorders is whether they are hereditary. It is estimated that the heritability of depression ranges between 30% and 50% (6), indicating that a significant part of the risk of developing depression is related to genetic factors.

Genome-wide association studies (GWAS) have identified more than 100 genomic regions (loci) associated with the risk of depression. Some of these genes are linked to the functioning of neurotransmitters such as serotonin, dopamine, and norepinephrine, which are crucial for mood regulation, as well as to neuronal growth, synaptic function, and inflammatory processes related to the disorder (7).

However, genetics is not an isolated factor; it interacts with the environment. People with a genetic predisposition may be more vulnerable to depression when exposed to significant stressors, such as childhood trauma or adversity (8).

Genetics also affects the response to antidepressant treatments. Variants in the genes CYP2D6 and CYP2C19 influence the metabolism of many antidepressants, impacting their efficacy and risk of side effects.

These insights into the genetic basis of depression have multiple potential applications, such as developing new treatments, guiding discussions about the risk of the disorder, and personalizing therapeutic approaches (9).

How Genetic Testing Can Aid in Depression Treatment

Genetic tests are examinations that assess DNA. Genetic variants can alter the body’s normal response by modulating protein transcription and disease development. Genetic testing aims to provide important information for diagnosing, treating, and preventing diseases.

Pharmacogenetics is a field of genomics that analyzes variants in genes responsible for drug metabolism, allowing for more precise treatment and dosing, and aiding in selecting the medication with the best therapeutic effect and lowest risk of adverse events. One way to achieve this is through the FG Neuro Depression test.

What the FG Neuro Depression Test from SYNLAB Analyzes

The FG Neuro Depression pharmacogenetic panel offered by SYNLAB assesses variants in genes responsible for the expression of key enzymes involved in the metabolism of the most commonly used antidepressant medications:

• Amitriptyline;
• Bupropion;
• Citalopram;
• Clomipramine;
• Desipramine;
• Doxepin;
• Duloxetine;
• Escitalopram;
• Fluoxetine;
• Fluvoxamine;
• Imipramine;
• Mirtazapine;
• Moclobemide;
• Nortriptyline;
• Paroxetine;
• Reboxetine;
• Sertraline;
• Trimipramine;
• Venlafaxine;
• Vortioxetine.

How to Interpret the Results

Through the analysis of the FG Neuro Depression pharmacogenetic panel offered by SYNLAB, it is possible to classify the patient according to the metabolism and toxicity risk of each medication:

• Standard metabolism and standard toxicity risk;
• Rapid metabolism and reduced toxicity risk;
• Ultra-rapid metabolism and reduced toxicity risk, but also reduced therapeutic response;
• Intermediate metabolism and increased toxicity risk;
• Slow metabolism and high toxicity risk.

These results can assist the prescribing physician in selecting the best medication and dosage for the patient, promoting a safer and more effective treatment.

How Physicians Should Request the Test

Healthcare professionals should consider the potential adverse effects associated with antidepressant medications and individual preferences.

The FG Neuro Depression pharmacogenetic panel enables a more effective choice of medication for better treatment response, with reduced risk of toxic side effects.

For whom is it indicated?

The FG Neuro Depression test offered by SYNLAB is recommended for:

• Patients undergoing treatment with antidepressants who want to personalize their treatment based on their genetic profile;
• Patients experiencing side effects from medications;
• Patients whose antidepressant treatment is not yielding the expected results.

How Is the Test Performed?

The test is conducted with a sample obtained from a single blood draw via venipuncture. The test analyzes variants in the CYP2C19 and CYP2D6 genes, involved in the expression of respective cytochrome P450 enzymes, using Next-Generation Sequencing (NGS) technology. This approach provides greater accuracy and speed, high yield, and increased sensitivity of the analysis (99%).

Get to Know the SYNLAB Group, a Leader in Medical Diagnostic Services!

Conducting accurate and up-to-date tests is essential for more precise diagnoses and better treatment guidance. SYNLAB is here to help.

We offer diagnostic solutions with stringent quality control to the companies, patients, and doctors we serve. We have been in Brazil for over 10 years, operate in 36 countries across three continents, and are a leader in diagnostic services in Europe.

Contact the SYNLAB team to learn more about the available tests.

References

1. Depressão. [s.d.]. Disponível em: https://www.paho.org/pt/topicos/depressao.
2. Malhi, G. S., & Mann, J. J. Depression. The Lancet. 2018;392, 2299–2312.
3. [s.d.]. Disponível em: https://www.who.int/news-room/fact-sheets/detail/depression.
4. What is Depression? [s.d.]. Disponível em: https://adaa.org/understanding-anxiety/depression.
5. [s.d.]. Disponível em: https://www.who.int/news-room/fact-sheets/detail/suicide.
6. Kendall KM, Van Assche E, Andlauer TFM, Choi KW, Luykx JJ, Schulte EC, Lu Y. The genetic basis of major depression. Psychol Med. 2021 Oct;51(13):2217-2230.
7. Howard, D. M, Adams, M. J, Clarke, T. K, Hafferty, J. D, Gibson J, et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nature Neuroscience. 2019;22(3), 343–352.
8. Coleman, J. R., Gaspar, H. A., Bryois, J., Byrne, E. M., Forstner, A. J., et al. The genetics of the mood disorder spectrum: Genome-wide association analyses of more than 185000 cases and 439000 controls. Biological Psychiatry. 2020;88(2), 169–184.
9. Lewis, C. M., & Vassos, E. Polygenic risk scores: From research tools to clinical instruments. Genome Medicine. 2020;12, 1–11.