Single Episode vs Recurrent

🧠 Overview — What Are Single Episode vs Recurrent?

In the DSM-5 / DSM-5-TR, the diagnosis of Major Depressive Disorder (MDD) does not end at simply checking whether there is a Major Depressive Episode (MDE) or not. It also requires specifying what kind of course pattern the illness has — namely, “Single Episode” or “Recurrent,” which is a key specifier for understanding the long-term trajectory of the disorder.

Single Episode means the patient has had only one Major Depressive Episode in their lifetime. That episode lasted a significant period (at least 2 weeks or more) and fully met the criteria for an MDE. After that episode ended, the depressive symptoms improved or resolved completely, and no further episode has occurred since. People in this group often have a “specific trigger” such as the loss of an important person, a major life transition, or an acute, severe stressor.

In contrast, Recurrent means the patient has had 2 or more Major Depressive Episodes, and each episode is separated by a period of at least 2 months in which symptoms have clearly improved and no longer meet the full criteria for MDE (there may still be mild depressive feelings, but not at the level of a full episode). In other words, the patient has gone through at least two “deep depressive episodes” in their lifetime.

The terms “Single / Recurrent” therefore do not indicate how severe the illness is, but rather describe the course of the disorder — a course specifier that helps clinicians understand how the patient’s brain and emotions respond to stress over the long term, and how likely it is that they will have further episodes in the future.

For example, if a patient has just had their first major depressive episode, clinicians will typically use a treatment approach that includes an acute phase + continuation phase to achieve full remission and maintain it as long as possible. But if the patient has already had multiple episodes, clinicians will plan a maintenance phase or long-term preventive treatment — such as taking medication continuously for several years, or engaging in psychotherapy specifically aimed at preventing relapse (relapse prevention therapy).

Statistical data from many studies show that MDD is a disorder with a very high likelihood of recurrence —

• After the first episode, the chance of having another is about 50%
• After the second episode, the risk increases to 70%
• After the third episode, the risk is as high as 90% of all patients

This means that the more “depressive episodes” a person has had, the higher their risk of new episodes in the future, and the intervals between episodes tend to become shorter and shorter if they do not receive consistent treatment and follow-up.

Clinicians therefore use the labels “Single Episode” or “Recurrent” to estimate the future course of the disorder and to design a post-episode care plan — for example, how long to follow up symptoms, whether medication should be continued, and whether psychotherapy is needed to strengthen emotional resilience.

Another often overlooked point is that “Recurrent” does not mean the person is depressed all the time — many people have depressive episodes at certain periods, but between episodes they can function in a way that is close to normal. However, their brain circuits are more fragile, so when they face strong stress or pressure, the neurotransmitter systems that regulate mood (such as serotonin and dopamine) become imbalanced more easily than before.

In summary:

• Single Episode = “A depressive disorder that has occurred only once in a person’s life.”
• Recurrent = “A depressive disorder that has occurred more than once and is likely to recur again in the future.”

These are crucial markers for assessing recurrence risk and the need for long-term management for each patient — because with depression, “understanding the illness trajectory” is just as important as “treating the current episode until it fully remits.”

🧩 Core Symptoms — Main Symptom Profile in Terms of “Single Episode” vs “Recurrent”

Even though they differ in course (“how the illness unfolds over time”), both Single Episode and Recurrent share the same basic foundation: the Major Depressive Episode (MDE). According to DSM-5 / DSM-5-TR, this requires at least 5 out of 9 symptoms, persisting for at least 2 weeks, and these symptoms must cause significant impairment in real-life functioning — at work, in school, or in interpersonal relationships.

The 9 core symptoms are:

• Depressed mood most of the day / feeling empty / hopeless
• Markedly diminished interest or pleasure in almost all activities (Anhedonia)
• Sleep changes — insomnia or hypersomnia
• Appetite changes — poor appetite or significant weight gain
• Fatigue, low energy, or feeling tired easily
• Feelings of worthlessness or excessive/inappropriate guilt
• Diminished ability to think, concentrate, or make decisions
• Noticeable psychomotor retardation or agitation (slowed movements and speech, or, conversely, restlessness)
• Recurrent thoughts of death, suicidal ideation, or suicide attempts

🔹 Single Episode — “One Major Depressive Episode Only”

People in this group have had only one Major Depressive Episode in their life (up to the present). Before that, they may have had periods of sadness or exhaustion consistent with normal human experiences, but not severe or persistent enough to meet full MDE criteria.
Once they enter a true episode, their symptoms cover at least 5 out of the 9 points above and persist for 2 weeks or longer.

Characteristic features of this group:

• There is often a clear trigger or precipitating event, such as the loss of a loved one, being laid off, a breakup, or facing intense pressure.
• The depressive episode often arises relatively acutely, and ends after the precipitating situation passes or after receiving treatment.
• When symptoms improve, they typically return to an almost normal mood state (Full Remission).
• Some individuals may have “residual symptoms”, such as persistent fatigue or a lingering fear of “falling back into the same dark place,” but these do not reach the level of a new full episode.
• In general, the response to treatment is relatively good, especially when medication and psychotherapy are started early.
• Patients may not perceive themselves as “having a brain disorder”, because the episode occurred only once. They often view it as “normal sadness from life events” rather than “a depressive illness.”

Emotional dimension: severe sadness, feelings of loss, a sense of life being meaningless.
Physical dimension: difficulty sleeping, fatigue, poor appetite, weight loss.
Cognitive dimension: self-blame, feeling worthless, thoughts like “nothing will ever get better.”

However, if there is no ongoing follow-up after the first episode, symptoms may return within 1–2 years, at which point the diagnostic status shifts from Single Episode → Recurrent.

🔹 Recurrent — “Depression in Cycles or Repeated Episodes”

In this group, the patient has had at least 2 depressive episodes, each separated by a period of at least 2 months in which symptoms have improved or resolved (no longer meeting MDE criteria).

Characteristic features of this group:

• Each episode often has a similar emotional tone and symptom pattern — for example, every time it starts with exhaustion, insomnia, or intense self-criticism.
• New episodes tend to occur more easily than before — e.g., the first episode was triggered by a major life event, but subsequent ones can be triggered by even moderate levels of stress (consistent with the kindling effect).
• Each episode tends to last longer, recovery becomes harder, and treatment response often becomes slower over time.
• Many patients begin to recognize their own pattern of symptoms, such as “I’m starting to not sleep and feel bored by everything again — this is probably coming back.”
• Having multiple recurrences leads to lasting changes in brain structure and neurotransmitter systems, such as hippocampal atrophy and increased sensitivity to stress.

Real-life example:
Someone had a major episode at age 25 and recovered. Five years later, at age 30, another episode occurred. Three years after that, yet another one. This pattern clearly indicates Recurrent depression.

Deeper difference:

• Single Episode = like an illness that “explodes once and then goes out.”
• Recurrent = the brain’s electrical system starts to develop “memory traces of the crash” that are ready to ignite again at any time.

Clinically, distinguishing between the two is very important because treatment strategies and prevention plans are fundamentally different —

• Single Episode is often treated for a short to medium duration (6–12 months after remission).
• Recurrent requires long-term preventive treatment for 2–5 years or even indefinitely.

📋 Diagnostic Criteria — Criteria for Diagnosing Single Episode / Recurrent

All criteria are based on the DSM-5-TR and the APA Clinical Practice Guideline (2023).

🔸 1) Criteria for a Major Depressive Episode (used for both types)

• At least 5 of the 9 core symptoms (see above).
• These symptoms occur during the same 2-week period or longer, nearly every day.
• At least one of the two core symptoms must be present:
• (a) Depressed mood / feeling empty / hopeless
• (b) Markedly diminished interest or pleasure in almost all activities
• The symptoms cause clinically significant distress or impairment in social, occupational, or academic functioning.
• The symptoms cannot be better explained by:
• Effects of substances, medications, or a general medical condition (e.g., hypothyroidism),
• Or a normal psychological reaction to ordinary bereavement.
• There has never been an episode of Mania or Hypomania; if there has, the diagnosis should fall under the Bipolar spectrum instead.

🔸 2) Specific Criteria for Single Episode

Used in cases where the patient:

• Has had only one Major Depressive Episode.
• Has never had another depressive episode in the past.
• Has no history of Mania or Hypomania.
• Has no additional depressive episode for at least 2 months after recovering.

Example of chart notation in medical records:

Major Depressive Disorder, Single Episode, Moderate, with Anxious Distress

In such cases, clinicians will typically monitor the patient for at least 6–12 months after recovery to see whether symptoms recur. If no new episode occurs within 2 years, the patient is still considered to have “Single Episode” MDD.

🔸 3) Specific Criteria for Recurrent

For patients who:

• Have had at least 2 Major Depressive Episodes.
• Each episode is separated by at least ≥ 2 months during which the person does not meet the full criteria for MDE.
• Have no history of Mania / Hypomania, same as above.

Example of chart notation in medical records:

Major Depressive Disorder, Recurrent, Severe, without Psychotic Features, In Partial Remission

Additional details from DSM-5-TR:

• The symptom-free period between episodes is called inter-episode recovery.
• If symptoms persist but at a reduced level (e.g., mild fatigue, mild sadness), this is called partial remission.
• If a new cluster of symptoms emerges before two months have passed since the previous episode remitted, it is considered a relapse rather than a new episode.

Diagnostic coding (ICD-10 / ICD-11):

• F32.x = MDD, Single Episode
• F33.x = MDD, Recurrent Episode

Where x denotes severity (e.g., F33.0 Mild, F33.1 Moderate, F33.2 Severe).

🔸 Additional Clinical Notes

• A Single Episode that has fully remitted for over 2 years tends to have an excellent prognosis, with a relatively low risk of recurrence.
• Recurrent MDD tends to become chronic, especially if each episode is severe or if residual symptoms persist between episodes.

• Specifying the course helps clinicians design an accurate long-term plan, such as:

• How long to continue pharmacological treatment,
• Whether preventive psychotherapy (CBT / MBCT) is needed,
• How often follow-ups should be scheduled.

Summary overview:

Issue
Single Episode | Recurrent

Number of episodes
1 episode | ≥ 2 episodes

Interval between episodes
— | At least 2 months

Nature of episodes
Triggered by specific major events | Recur, sometimes triggered by minor stressors

Likelihood of recurrence
Low (if treatment is completed) | High (50–90%)

Treatment strategy
Short to medium term (6–12 months) | Long-term (2–5+ years)

Prognosis
Good / full recovery likely | Higher risk of chronicity / relapse, needs strong prevention

🧬 Subtypes or Specifiers — How Single / Recurrent Link with Other Specifiers

Technically, the “Single vs Recurrent” specifier can be combined with all other specifiers, for example American Psychiatric Association+1

1. Severity & Psychotic Features

• Mild / Moderate / Severe
• With / Without Psychotic Features

Both Single Episode and Recurrent can be:

• Mild / Moderate / Severe
• And may have delusions/hallucinations (psychotic features) or not.

For example:

• MDD, Single Episode, Severe, with Psychotic Features
• MDD, Recurrent, Moderate, without Psychotic Features

2. Other Course Specifiers

They can also be followed by:

• In Partial Remission / In Full Remission
• With Anxious Distress
• With Mixed Features
• With Melancholic / Atypical / Catatonia / Seasonal Pattern / Peripartum Onset, etc.

Examples seen in clinical practice:

• MDD, Recurrent, Moderate, with Seasonal Pattern
• MDD, Single Episode, Severe, with Peripartum Onset

Therefore, in terms of the structure of your website posts:

• “Single Episode / Recurrent” = a subtype category under “by course”.
• It can be cross-linked to posts on “Severity (Mild/Moderate/Severe)”, “With Psychotic Features”, “In Partial / Full Remission”, “With Anxious Distress”, etc.

🧠 Brain & Neurobiology — The Brain in Single Episode vs Recurrent

Major Depressive Disorder (MDD) is not just an “emotional problem”; it is a disorder of brain circuits and biochemical systems that regulate mood, motivation, cognition, and stress responses. This is especially true in brain regions associated with the limbic–prefrontal network, including:

• Prefrontal Cortex (PFC): center for reasoning, emotional inhibition, and decision-making
• Amygdala: center for threat detection and fear–sadness responses
• Hippocampus: memory and emotional learning center
• Anterior Cingulate Cortex (ACC): central hub integrating “emotion–thought–behavior”

Under normal conditions, these regions work together like a well-synchronized orchestra. But during a depressive episode, this balance “falls out of rhythm” — some regions (like the amygdala) are overactive, while others (like the prefrontal cortex) are underactive, leaving the person stuck in an automatic negative bias, unable to easily return to emotional equilibrium.

🔹 Single Episode — “A Brain That Temporarily Collapses but Can Recover”

In a first depressive episode, the brain reacts strongly to acute stress:

• The amygdala becomes over-activated, making the person feel more fearful, sad, and prone to interpreting neutral events as negative.
• The prefrontal cortex, especially the dorsolateral PFC (DLPFC) which governs reasoning and emotion regulation, shows decreased activity — leading to a state where “emotion overwhelms reason.”
• The main neurotransmitter systems — serotonin, norepinephrine, dopamine — fall into imbalance.
• The HPA axis (Hypothalamic–Pituitary–Adrenal), which regulates the stress hormone cortisol, becomes over-stimulated.

When the stress subsides or appropriate treatment is provided, these systems can “reset.”
Studies from Harvard and NIMH show that patients with Single Episode MDD who complete treatment properly tend to have brain volume and functional activity that return close to normal within 6–12 months after remission.

In simple terms, the brain during the first episode can be likened to an engine that overheats and shuts down, but once it is allowed to cool and is properly repaired, it can function close to its original level again.

🔹 Recurrent — “A Brain with a Memory Trace of Collapse”

When a person has gone through multiple depressive episodes, the brain starts to develop lasting structural and functional changes, explained by the Kindling Effect — the brain “learns” to switch on the depressive state more easily.

Hippocampal Atrophy:
MRI studies (Videbech & Ravnkilde, 2004; McKinnon et al., 2012) show that the hippocampus in patients with recurrent depression is on average 8–19% smaller than in healthy controls, and the more episodes they have had, the more pronounced this shrinkage becomes.

• This makes it harder to remember positive experiences, while negative memories remain vivid.
• Emotional recovery slows, because the hippocampus is central to learning that “life still has solutions.”

Hyper-amygdala Activation:
The amygdala becomes overactive even when no real threat exists — the brain interprets voices, social interactions, or ordinary situations as “danger” or “criticism,” leading to persistent sadness and anxiety.

Prefrontal Cortex Suppression:
Control from the frontal lobes (PFC), especially the ventromedial and dorsolateral regions responsible for inhibiting emotional overreaction, is progressively weakened with each episode. The patient often feels “I know exactly what I should do, but I have no energy or capacity to do it.”

HPA Axis Dysregulation:
Cortisol remains chronically elevated. The feedback loop that normally shuts down cortisol release when stress is over becomes impaired, leaving the body in a constant “fight or flight” mode, even when there is no real danger.

Neuroinflammation:
In recurrent depression, there is an increase in inflammatory cytokines (e.g., IL-6, TNF-α). This reduces neurotransmitter availability and slows neural circuit function — similar to a form of “micro-level brain inflammation.”

Deterioration of Functional Connectivity:
Connections between PFC–Amygdala–Hippocampus weaken, causing the brain to misinterpret emotional signals and making it harder to generate or maintain positive emotional states.

The consequences of these changes are:

• Patients with recurrent depression have a much lower threshold for “crashing” — even minor events, such as a colleague’s remark, can trigger a new episode.
• Response rates to antidepressants decline (overall antidepressant response rate drops by roughly 15–25%).
• The risk of cognitive decline and dementia in the long run significantly increases.

In summary:

• Single Episode is “a brain that collapses temporarily.”
• Recurrent is “a brain that has been programmed to collapse again.”

This is why clinicians often recommend “continuing treatment even after remission” — to prevent the nervous system from shifting into the recurrent, sensitized mode.

🧬 Causes & Risk Factors — What Makes It Easier to Shift from Single to Recurrent?

The first depressive episode usually arises from a combination of genetics + life experiences + environment + brain chemistry. However, recurrence typically happens because these factors remain unresolved or accumulate over the long term.

🔹 Biological Factors

Genetic Predisposition:
If there is a family history of depression / bipolar disorder / anxiety, the risk increases 2–3 times. Relevant genes such as 5-HTTLPR (serotonin transporter gene) make the brain react more intensely to stress.

Hormones and Neuroendocrine Factors:

• Dysregulation of the HPA axis causes the body to secrete excessive cortisol.
• Imbalances in thyroid hormones and sex hormones (especially estrogen/progesterone in women) make the brain more vulnerable to depressive mood.

Neuroanatomical Vulnerability:
People who naturally have a smaller hippocampus, or lower baseline connectivity between PFC and amygdala, are at higher risk of developing recurrent depression.

Neuroinflammation:
Chronic inflammation from autoimmune disorders or metabolic conditions (e.g., diabetes, obesity) increases cytokine levels, which can trigger depressive circuits in the brain.

🔹 Psychological & Personality Factors

High Neuroticism:
A personality style that tends to worry easily, ruminate over negative events, and interpret experiences pessimistically.

Self-criticism / Perfectionism:
People who set excessively high standards for themselves often blame themselves harshly when they fail, and they rarely forgive themselves. This creates a powerful internal drive toward recurrence.

Low Self-Esteem and Learned Helplessness:
Feeling worthless and believing “nothing I do will change anything” is a mental foundation that makes the brain more susceptible to learning and re-entering a state of hopelessness — and thus episodes recur more easily.

Cognitive Biases:
Recurrent MDD is frequently accompanied by negative automatic thoughts, such as “everything is going to fall apart again,” which keep the person trapped in a one-sided, negative worldview.

🔹 Environmental & Social Factors

Chronic Stressors:
Living in a continuously stressful environment — such as a highly pressured job, toxic relationships, family conflict, or chronic financial problems — means the brain never has a chance to leave “stress mode.”

Social Isolation:
People who lack friends or family support, and who have no one to listen when they go through a first episode, are more likely to relapse than those with a strong support system.

Risk Behaviors (Substance Use / Sleep Deprivation):
Alcohol, drugs, or chronic sleep deprivation destabilize serotonin and dopamine levels, gradually building risk until a new episode is easily triggered.

Early Life Trauma:
Those who have experienced childhood abuse or neglect often have an over-reactive amygdala and HPA axis, making them prone to depression even later in life.

🔹 Treatment-Related Factors

Premature Discontinuation of Medication:
Many people stop their antidepressants after only 2–3 months when they start to feel better, even though the brain has not fully rebalanced. This leads to relapse rates as high as 50–60% within 6 months.

Lack of Ongoing Psychotherapy:
Medication alone may reduce symptoms, but without changing underlying thought patterns via psychotherapy (e.g., CBT, MBCT), the recurrence risk is almost twice as high.

Residual Symptoms Not Addressed:
Even after a major episode has remitted, if “mild sadness” or “low energy” remains, these become the fuel for the next episode. Research (Prieto-Vila, 2021) shows that residual symptoms are among the strongest predictors of recurrence.

Lack of Follow-up After Recovery:
Infrequent appointments or no monitoring means early warning signs are missed — such as disrupted sleep, easy fatigue, irritability. All of these are early indicators of another descent.

🔹 Age & Course-Related Factors

Early-Onset Depression:
If depression begins during adolescence, recurrence risk is higher than in those whose depression starts in adulthood, because the brain is still developing and may be “programmed for depression” early on.

Late-Life Depression:
Often linked to medical illnesses such as cerebrovascular disease or neurodegeneration. These can trigger new episodes more easily and typically respond more slowly to treatment.

🔹 Interplay of All Factors

All the above factors do not act in isolation, but rather in a feedback loop:

• Stress → activates HPA axis → high cortisol → hippocampal shrinkage → decreased concentration → misinterpretation of situations → more stress

As episodes recur, the brain “remembers” this pattern and can slip into a depressive mode more and more easily.

Therefore, preventing Recurrent MDD requires interventions at multiple levels — biological (medication), psychological (CBT/MBCT), and environmental (relationship management, rest, exercise).

Overall summary:

Recurrent MDD is not just “the same symptoms happening again,” but a state in which the brain, thoughts, and environment join together to build a self-reinforcing depressive loop.
Treatment should not only aim to “put out the current fire,” but also to “re-wire the entire electrical system of the house” so that it doesn’t keep catching fire again.

💊 Treatment & Management — Approaches for Single vs Recurrent

In MDD, we usually talk about three key phases of treatment:

• Acute Phase — Treating to get out of the current depressive episode
• Continuation Phase — Preventing relapse within the first 6–12 months after improvement
• Maintenance Phase — Long-term prevention of recurrence (for Recurrent / Chronic cases)

1. Single Episode

Main goals:

• Pull the patient out of the depressive episode into true remission, not just “feeling halfway better.”
• Then continue treatment for at least 6–12 months after recovery from the first episode to prevent early relapse. American Psychological Association+1

Treatment usually involves a combination such as:

• Antidepressant medication (SSRIs, SNRIs, etc.)
• Psychotherapy such as CBT, IPT, behavioral activation
• Lifestyle adjustments: regular sleep, exercise, reduced alcohol use, etc.

For some cases where:

• The first episode is not very severe,
• Relapse risk factors are low,
• And the support system is strong,

clinicians may plan a carefully monitored tapering of medication after completing the continuation phase, while maintaining psychotherapy as a long-term protective factor.

2. Recurrent

Here the focus is not just “improving the current episode,” but rather “designing life and treatment to minimize the number of future episodes.”

• Long-term maintenance treatment is usually needed.
• Antidepressants may be continued for many years, or even indefinitely (similar to long-term medication for hypertension/diabetes), especially if there have been multiple episodes or prior attempts to stop medication have led to relapse.
• Psychotherapy focused on relapse prevention is emphasized.
• CBT protocols specifically designed for relapse prevention, and MBCT (mindfulness-based cognitive therapy), have strong evidence for reducing recurrence risk. Nature+1
• A plan for high-risk periods:
• Pre-agreeing that if early warning signs appear, the patient will immediately return to their doctor/therapist.
• Managing chronic factors:
• Working on relationships, boundaries, work demands, rest, and stress-management skills.

• If Recurrent depression is severe or treatment-resistant:

• ECT, rTMS, ketamine/esketamine, etc., may be considered according to guidelines and each country’s context. Mayo Clinic+1

📝 Notes — Common Misunderstandings

• Single Episode does not mean “mild” or “not serious.”
• Single Episode can still be Severe / with Psychotic Features.
• Severity is determined by the severity specifier, not by Single vs Recurrent.
• Recurrent does not mean “sick all the time.”
• Many people have recurrent episodes yet function almost normally between them.
• The key is that they have had multiple full major depressive episodes, not that they are sad 24/7.
• Do not confuse it with Persistent Depressive Disorder (PDD/Dysthymia).
• PDD is a chronic low-grade depression lasting ≥ 2 years without returning to baseline.
• Recurrent MDD is “episodic deep depression,” but between episodes the person may return close to normal.
• Some people have both at the same time (Double Depression). NCBI+1
• Someone who had Single Episode can later be reclassified as Recurrent.
• If another MDE occurs in the future,
• Their diagnosis code changes from F32.x → F33.x in ICD-10/ICD-11 systems.
• All of this information is for understanding, not for self-diagnosis.
• DSM-5-TR emphasizes that these criteria must be applied by trained professionals only. American Psychiatric Association+1

📚 References — Brain & Neurobiology / Causes & Risk Factors

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision (DSM-5-TR). Washington, DC: APA Publishing, 2022.

Videbech, P., & Ravnkilde, B. (2004). Hippocampal volume and depression: a meta-analysis of MRI studies. American Journal of Psychiatry, 161(11), 1957–1966.

McKinnon, M. C., Yucel, K., Nazarov, A., & MacQueen, G. M. (2012). A meta-analysis examining clinical predictors of hippocampal volume in major depressive disorder. Neuropsychopharmacology, 37(7), 1387–1394.

Drevets, W. C., Price, J. L., & Furey, M. L. (2008). Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Structure and Function, 213(1–2), 93–118.

Sheline, Y. I. (2003). Neuroimaging studies of mood disorder effects on the brain. Biological Psychiatry, 54(3), 338–352.

Disner, S. G., Beevers, C. G., Haigh, E. A. P., & Beck, A. T. (2011). Neural mechanisms of the cognitive model of depression. Nature Reviews Neuroscience, 12(8), 467–477.

Malhi, G. S., & Mann, J. J. (2018). Depression. The Lancet, 392(10161), 2299–2312.

Nestler, E. J., Barrot, M., DiLeone, R. J., Eisch, A. J., Gold, S. J., & Monteggia, L. M. (2002). Neurobiology of depression. Neuron, 34(1), 13–25.

Burcusa, S. L., & Iacono, W. G. (2007). Risk for recurrence in depression. Psychological Bulletin, 133(5), 779–815.

Prieto-Vila, M., et al. (2021). Risk Factors Associated with Relapse in Major Depressive Disorder. Psicothema, 33(2), 210–217.

Kendler, K. S., et al. (2006). A developmental model for major depression in women: The role of genetic and environmental factors. American Journal of Psychiatry, 163(5), 795–804.

American Psychological Association. Clinical Practice Guideline for the Treatment of Depression Across Three Age Cohorts. APA, 2023.

Hammen, C. (2005). Stress and depression. Annual Review of Clinical Psychology, 1, 293–319.

Sapolsky, R. M. (2001). Depression, antidepressants, and the shrinking hippocampus. Proceedings of the National Academy of Sciences, 98(22), 12320–12322.

Slavich, G. M., & Irwin, M. R. (2014). From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychological Bulletin, 140(3), 774–815.

National Institute of Mental Health (NIMH). Major Depression: Brain Changes and Recurrence Patterns. (Updated 2024).

World Health Organization (WHO). ICD-11: Mood Disorders Section — Depressive Disorders. Geneva, 2022.

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