Introduction
Recognised by physicians in the early centuries AD, including figures such as Galen (ca. 129–199 A.D.), Hippocrates (ca. 460–377 B.C.), and Ishaq Ibn Imran, depression remains an enigma that totality is yet to be defined.
With their early clinical descriptions closely mirroring those of today, depressive disorders are characterized by persistent feelings of sadness, hopelessness, and a loss of interest or pleasure in daily activities. These disorders are alarmingly widespread today, estimated to be present in around 11-14% of the population and to have lasted for over a year in around 5% of the population.1
Depressive disorders can significantly impair a person's quality of life, affecting their ability to function in daily life, maintain relationships, excel academically or professionally, and even lead to severe consequences such as disability or mortality.
Signs and symptoms
While the experience and presentation may vary depending on the type of depressive disorder (see the sections below) some hallmark features are shared between them.
Symptoms of depressive disorders
The following symptoms describe what an individual with a depressive disorder may experience:
- Consistent low mood
- Lethargy (state of being exhausted, lacking motivation as well as mental and physical energy, a change in the mental state)
- Reduced appetite
- Sleep changes
- Lack of motivation and interest in daily activities/hobbies
- Inability to feel pleasure
- Poor self-esteem
- Low confidence
- Persistent feelings of guilt and worthlessness
- Impaired concentration.
Any combination of these may be present in an individual, but usually, at least 2 -3 will be present for a diagnosis of mild depression. Generally, the more severe the depression, the more symptoms with higher intensity will be present.2
Signs of a depressive episode
Signs refer to alarming evidence that another person may see as an observer. It’s worth asking the following questions if you suspect someone in your life may be experiencing a depressive disorder:
- Social isolation: is this person spending less time with friends and family?
- Low energy/fatigue: does this person seem much more tired than usual, are they sleeping for very long periods and/or throughout the day?
- Psychomotor depression: is this person speaking and moving extremely slowly, almost like they are in slow motion?
- Irritability/aggression: is this person more intolerant than usual and easier to annoy?
- Lack of interest in activities/decreased motivation: is this person spending less/no time engaging with past activities they used to spend time doing?
- Decreased work/academic performance: has there been a sudden drop in grades, performance or engagement at work?
- Cognitive dysfunction/impaired decision-making: is this person having trouble understanding and following basic tasks?
- Increased risk-taking: is this person deliberately putting themselves in dangerous situations?
- Host of unexplained medical symptoms/conditions: has this person been complaining of unexplained pains and illnesses that doctors have not been able to narrow down to causes?
Types of depressive disorders
According to the ICD-10 (International Classification of Diseases), there are multiple types of depressive disorders, depending on their characteristic symptoms, as outlined in the table below. 2
| T Type | Characteristic features |
| Major Depressive Disorder (MDD) | - The presence of a single or repetitive episode of major depression - A general and persistent low mood, lack of interest or pleasure, and a range of other symptoms affecting daily functioning - Severity levels are classified as mild, moderate, or severe |
| Recurrent Depressive Disorder | - Repetitive episodes of depression, similar to MDD - These episodes might be separated by periods of normal mood or less severe symptoms - The severity levels (mild, moderate, severe) apply as well as in MDD |
| Persistent Depressive Disorder (PDD, also known as dysthymia) | - Chronic, long-lasting form of depression (lasting for at least 2 years) - Symptoms are generally less severe than those in MDD, but they persist over a longer period - There may be periods of normal mood, but the underlying low mood persists |
| Perinatal and Postpartum D Depression | - Depressive episodes occurring during or after pregnancy - Symptoms are similar to those of MDD, but the onset is related to the perinatal period - Postpartum depression specifically refers to episodes occurring after childbirth |
| Seasonal Affective Disorder (SAD) | - Occurs during specific seasons, most commonly winter, when there is less natural sunlight - Symptoms include low mood, fatigue, and changes in sleep and appetite |
| Depression with Psychotic Symptoms | - Involves experiencing depressive symptoms along with psychotic features, such as hallucinations or delusions - Hese symptoms may be severe and can lead to more complex treatment approaches |
Causes and risk factors
Depressive disorders are complex, often resulting from an interplay of multiple causes and risk factors. These factors can broadly be categorized into the following domains:
- Genetic influence, including the factors inherited from parents
- Environmental influence, such as factors in the natural environment (air pollution, noise) or in a social environment (education, employment, crime rates, poverty, housing situation)
- Influence of coexisting disease
- Psychobiological influences, such as physical health, stress, perception and additions
However, there is a strong interplay between these factors, particularly genes and environment, which has lent to the term "gene x environment" interactions. It states that both inherited features and influences from the external environment play an important role in the development or prevention of depressive disorders, as opposed to one factor being more important than the other, as suggested by the nature vs nurture argument.
Risk factors for depression include certain life choices, habits, traits, and genes that increase the chance that you will develop depression. The risks involve the following:
- Chronic stress
- Traumatic experiences
- Family history of mental illness
- Substance abuse
- Childhood history of abuse/neglect
- Previous mental illness
- Ongoing chronic medical condition(s)
- Homelessness/unemployment
- Social isolation
- Certain personality traits
- Gender (people assigned female at birth are nearly twice as likely to be diagnosed with depression).3,4
The causes of depression are highly complex and poorly understood. You can read the sections below to learn more about what is currently known about the different factors influencing an individual to be affected with a depressive disorder.
Genetic factors
A person's genetic makeup (also known as genotype) contributes significantly to their vulnerability to depressive disorders. It is estimated nearly half of the risk for developing depression comes from genetics.5 Extensive research has identified hundreds of genetic variants (versions of genes) associated with an increased risk of developing depression. These variants often impact mechanisms related to synaptic structure (structures allowing the brain cells to communicate) and neurotransmission (sending information between the neurons - brain cells); things that appear to be impaired in depressed patients. Moreover, some of these genes have specific effects on brain regions that appear to have altered structure and function in depression, such as the prefrontal cortex, and areas responsible for feelings of reward and motivation.6
However, having one of the risk genes for depression, or even many of them, does not always directly cause depression. Instead, it appears that each of these risk genes gives a small increased risk. To complicate things, when someone with these risk genes develops depression, the role they play in depression is unclear. Moreover, it appears that many of the risk genes for depression are also considered risk ones for other psychiatric disorders, including anorexia nervosa, attention deficit hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder.7 This again highlights how little we understand about why - depression specifically - develops when these genes are present.
Environmental factors
Environmental influences, particularly early-life experiences, play a pivotal role in the development of depression. In the preteen years, the brain is in its moulding stage, particularly susceptible to outside influence due to a high level of neuroplasticity – the ability of the brain to change the way it is wired. Therefore, many of our early experiences will not only shape our view of the world but also impact the way our brain is biologically wired. Childhood trauma, chronic stress, and traumatic events have all been strongly linked to an increased risk of depressive disorders. Notably, there is a significant link between childhood trauma (especially childhood sexual and physical abuse) and depression severity. This indicates that such environmental factors may have a highly causative role in depression.8
Moreover, these adverse experiences can result in long-lasting changes in various physiological systems in the whole body. Inside the brain, various abnormalities in brain structure and function have been strongly linked to adverse childhood experiences (ACEs).14 However, it is unclear whether these brain changes are the cause of depression, occurring after an ACE, or a result of the depression.
Gene-environment interactions
The relationship between genetics and environmental factors is potent in depression's development but also highly complex. Studies have shown that multiple risk genes increase the likelihood of developing depression. However, this risk significantly intensifies when combined with early-life trauma, emphasizing the importance of gene-environment interactions.13 This is a finding associated with numerous psychiatric disorders, emphasising the need for a comprehensive understanding of the complex origins of mental health conditions in their prevention, diagnosis and treatment.
A significant part of mental health research has been focused on understanding how certain systems in the brain change in depression, the effect that genes and the environment may have on these systems, and how both of these may mediate each other’s role in causing depression. For example, research extensively focused on having genetic variation in the serotonin system in the brain, considered to be one of the major players in the development of depression. Scientists focused on the impact of ACEs on the serotonin system, its interplay with inflammation and the biological control of stress, such as through the hypothalamic-pituitary-adrenal axis. While genetic variation in these systems seemed to have an interaction with ACEs, leading to an increase in the likelihood of depression, replication of studies proves to be difficult on large-scale population studies.5 This limits our understanding of how life experiences affect biology, leading to depressive disorders in individuals.
Somatic medical illness and comorbidity
Certain somatic medical conditions, such as primary hypothyroidism and cancer, can contribute to depressive symptoms or may even cause depression by themselves.5 Individuals with these medical conditions may not respond well to traditional treatments, partly due to the highly complex nature of managing such a wide range of symptoms and the complications of medication side effects and their interactions.
Psychobiological factors
Depression is not solely determined by genetic or environmental factors; an individual's personality traits can also play a significant role in their vulnerability to this condition. These include:
- Neuroticism
- Introversion
- Impulsivity
- Perfectionism4
These personality traits may then interact with genetics and environment in the development of depression.
This multifaceted interplay of genetic, environmental, somatic, and psychobiological factors creates a complex web that influences the development of depressive disorders. While we're making strides in understanding these factors, depression is not a condition with a single, straightforward cause. Recognising these contributing elements is essential for developing holistic approaches to prevention, diagnosis, and treatment.
Impact on daily life and complications
Depression may have numerous knock-on effects, including:
- Significant emotional suffering and worsened quality of life
- Lower level of education than a person is capable of getting
- Limited career choices and income
- More frequent risk-taking behaviours
- Changes in brain structure, such as brain degeneration later on during life
- Earlier life expectancy through the condition and suicide
- Weakened immune system and increased levels of inflammation
- Other psychiatric and somatic (body) conditions.
Depression, like a shadow that extends its reach into nearly every corner of an individual’s life, casts a pall over their daily experiences. Beyond feelings of sadness, hopelessness, and lack of pleasure from daily activities, which could be overwhelming, depression makes life a complex web of challenges to navigate through.
At its core, depression influences how people perceive and engage with the world. Some of the core effects of this are persistent sadness, loss of interest, absent motivation, and an inability to concentrate. These symptoms, in turn, have numerous domino effects that can then consolidate these feelings and influence life choices, entrenching someone in the condition. For example, reduced motivation combined with an inability to concentrate impairs academic and work performance, potentially limiting career choices and income. This can then lead to feelings of inadequacy and hopelessness, further deepening the depression. It is no surprise that low income and poor educational attainment are associated with depression.5
Diagnosis
Importance of professional diagnosis
A professional diagnosis not only confirms the presence of depression but also helps determine its severity and subtype, to implement appropriate treatment strategies. In diagnosing depression, several key factors come into play. Diagnosis should be conducted by qualified healthcare professionals, such as GPs, psychiatrists, clinical psychologists, or licensed mental health practitioners. Self-diagnosis can be unreliable and may not consider the full scope of the condition. Moreover, professional diagnosis ensures that any underlying physical or mental health conditions contributing to depressive symptoms are properly evaluated and addressed.
It is essential to rule out other medical or psychiatric conditions that might mimic depressive symptoms. This step helps prevent misdiagnosis and ensures that the treatment plan is tailored to the individual's specific needs.
Diagnostic criteria
Three key factors come into play for an accurate diagnosis:
- Duration of Symptoms: To be diagnosed with a depressive disorder, a person typically must experience persistent symptoms for a specified duration. This duration can vary depending on the specific subtype of depression but often lasts at least two weeks.
- Clusters of Symptoms: The ICD-10 outlines the combination of symptoms that are characteristic of different depressive disorders.
- Severity Grading: Depressive episodes may be classified as mild, moderate, or severe based on the number and intensity of symptoms and their impact on daily functioning. The severity grading can help determine the appropriate level of care and intervention one needs.
The Mini International Neuropsychiatric Interview is a structured interview performed by a clinician to assess these 3 factors and give an accurate and specific diagnosis that then informs subsequent treatment.
Professional treatment
Recognizing the need for help is the first crucial step. This can make opening up to friends and family and reaching out to healthcare professionals much easier.
Suffering in silence is neither necessary nor beneficial to anyone. If you suspect you or someone you know may be suffering from a depressive episode, professional guidance can only help.
Therapy options
A variety of evidence-based therapies may be used by a professional to treat depression based on their qualifications, preferences and individual needs. These include but are not limited to:
- Cognitive behavioural therapy (CBT)
- Acceptance and commitment therapy (ACT)
- Psychodynamic therapy
- Interpersonal psychotherapy (IPT)
- Eye movement desensitization and reprocessing (EMDR).
Medication - antidepressants and their role
Over the years, various classes of antidepressants have been developed and approved by regulatory agencies like the FDA and its European counterpart. They are grouped based on how they work in the brain.
| Drug class | Common Examples (generic names) |
| Selective Serotonin Reuptake Inhibitors (SSRIs) | sertraline, escitalopram, fluoxetine |
| Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) | duloxetine, venlafaxine, and levomilnacipran |
| Tricyclic Antidepressants | amitriptyline, amoxapine, doxepin |
| MAO Inhibitors | Isocarboxazid, phenelzine, selegiline |
| Other Compounds | mitrazipine, agomelatine, bupropion |
Notably, while these medications have strikingly different ways of working in the brain, often working on completely different biological systems, there is no compelling evidence to suggest that any single antidepressant is superior in terms of its effects when compared to others. Furthermore, while it is evident these medications can significantly improve depression symptoms and result in remission, is unclear exactly how.
The choice of medication often depends on individual patient factors and preferences, as well as considerations of potential side effects and drug interactions. A trial-and-error approach is often used to find the best medication for a patient as it is very difficult to predict which medication is optimal for an individual patient.5
The first class of antidepressants usually prescribed are selective serotonin reuptake inhibitors (SSRIs) due to a preferable side effect profile in most patients. If these don’t work well enough at reducing symptoms, tricyclic antidepressants may be tried as the second option as they have been shown to work well in treating symptoms of severe and treatment-resistant depression, but they tend to have more side effects.9
Non-pharmacological therapies
- Electroconvulsive therapy (ECT)
- Vagus nerve stimulation (VNS)
- Transcranial magnetic stimulation (rTMS)
While more invasive than other treatments, these are all FDA-approved and have some of the highest rates of remission when used, particularly with severe treatment-resistant depression, a subtype they are generally reserved for.
Lifestyle changes
Lifestyle is often highly influential in depression maintenance or remission. Positive lifestyle changes can have a positive impact on someone’s mental health and contribute to sustained long-term recovery. These mainly include regular exercise, a balanced diet, stress management techniques, engagement in hobbies and exposure to nature. Research has pointed to a protective biological effect of these lifestyle changes, potentially through a maintenance of neuroplasticity.9 Neuroplasticity is the brain’s ability to change the connections between the neurons and whole networks of brain cells.
Combining therapies for a holistic approach
Relying solely on monotherapy, meaning using only one drug to treat this disorder, even when optimized for dosage and duration, typically results in remission for only a minority of patients.5 Research has shown combining evidence-based psychotherapy with medication has a more potent effect than either used alone.10 The same has been found for combining non-pharmacological interventions such as rTMS with antidepressant medications and lifestyle changes such as exercise regimens with antidepressants.9, 11 Clinicians may also combine multiple drugs to increase their effect.5 Treatment of depression is complex, just as the condition itself, therefore a holistic treatment approach will almost always be better than trying just one therapy.
Treatment outcomes and complications
One of the complexities in treating depression lies in the variation of treatment outcomes among individual patients. Notably, early-onset Major Depressive Disorder (MDD) often presents a more challenging clinical picture with a higher risk of suicide, decreased remission rates and increased occurrences of psychiatric comorbidities.12 Some treatments just do not work in some patients, while they are effective in others with the same condition, and it is not clear why.
Treatment-resistant depression is a term used when standard therapies like therapy and medication fail to provide adequate relief for depressive symptoms. Many treatment avenues may be explored with little success in these cases.
To improve the treatment of depression, more needs to be understood about:
- How depression manifests itself in the brain
- What causes it to take hold
- The biopsychological differences between depression subtypes
- Why and how causes and manifestations differ among individuals
- How treatments work
- How depression interacts with other diseases, personality traits, genes and environment.
Summary
Depressive disorders are prevalent worldwide, affecting millions regardless of age, gender, or background, and they have a profound impact on individuals' daily lives. These conditions encompass various forms, including Major Depressive Disorder, Recurrent Depressive Disorder, Persistent Depressive Disorder, Perinatal and Postpartum Depression, Seasonal Affective Disorder, and Depression with Psychotic Symptoms, each with its unique characteristics.
Common symptoms shared among these disorders include persistent sadness, fatigue, sleep disturbances, reduced interest in daily activities, impaired concentration, and feelings of guilt or worthlessness. Additionally, signs observed in individuals with depression encompass social withdrawal, psychomotor changes, irritability, and poor performance in work or academic settings.
Understanding the causes of depressive disorders is complex, involving genetic, environmental, somatic, and psychobiological factors, often interacting in intricate ways. Genetics contribute significantly, with hundreds of genetic variants identified. Early-life experiences, such as childhood trauma and chronic stress, play a pivotal role. These experiences can lead to long-lasting alterations in brain structure and function. Moreover, gene-environment interactions further complicate the picture.
Depression carries numerous complications, affecting emotional well-being, education, career prospects, and even life expectancy due to a heightened risk of suicide and other diseases. It can lead to changes in brain structure, weaken the immune system, and increase the likelihood of other psychiatric and somatic disorders.
Diagnosis of depressive disorders requires a professional assessment to determine severity and rule out other medical or psychiatric conditions. Treatment options include psychotherapies like cognitive-behavioral therapy (CBT) and medication, such as selective serotonin reuptake inhibitors (SSRIs). Combining therapies often yields better results, particularly for treatment-resistant cases. However, there's significant variability in individual treatment outcomes, emphasizing the need for further research to better understand the complex nature of depression and improve its prevention, diagnosis, and treatment.
References
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