Major Depressive Disorder (MDD)

Definition | Aetiology | Pathophysiology | Risk factors | Signs and symptoms | Investigations | Management

Definition

Major Depressive Disorder (MDD) is a mood disorder characterised by persistent low mood, anhedonia, and associated cognitive, emotional, and physical symptoms, significantly impairing daily functioning.

Aetiology

  • Genetic factors: strong hereditary component, with polygenic risk.
  • Neurobiological factors: dysregulation of serotonin, noradrenaline, and dopamine pathways.
  • Psychosocial factors: history of trauma, adverse life events, social isolation.
  • Endocrine factors: hypothalamic-pituitary-adrenal (HPA) axis hyperactivity leading to increased cortisol levels.

Pathophysiology

  • Reduced serotonin and noradrenaline transmission in key brain regions.
  • Increased activity of the HPA axis leading to chronic stress response.
  • Structural brain changes, including hippocampal volume reduction.
  • Neuroinflammatory processes contributing to altered neurotransmission.

Risk factors

  • Family history of depression or other mood disorders.
  • Previous depressive episodes.
  • Chronic medical conditions (e.g., diabetes, cardiovascular disease).
  • Substance misuse.
  • Psychosocial stressors (e.g., bereavement, unemployment, relationship breakdown).

Signs and symptoms

  • Persistent low mood, sadness, or emptiness.
  • Anhedonia (loss of interest in previously enjoyable activities).
  • Fatigue or low energy.
  • Changes in appetite (weight loss or gain).
  • Sleep disturbances (insomnia or hypersomnia).
  • Psychomotor retardation or agitation.
  • Feelings of worthlessness, excessive guilt.
  • Difficulty concentrating, indecisiveness.
  • Recurrent thoughts of death or suicidal ideation.

Investigations

  • Clinical assessment: detailed psychiatric history and mental state examination.
  • Structured screening tools: Patient Health Questionnaire-9 (PHQ-9), Beck Depression Inventory (BDI).
  • Blood tests: FBC, U&Es, LFTs, TFTs, vitamin B12, folate to rule out medical causes.
  • Risk assessment: evaluation of suicidal ideation and self-harm risk.

Management

1. Psychological therapies:

  • Cognitive Behavioural Therapy (CBT) for mild to moderate depression.
  • Interpersonal therapy (IPT) for depression linked to relationship issues.
  • Mindfulness-based cognitive therapy for relapse prevention.

2. Pharmacological management:

  • First-line: Selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluoxetine, citalopram).
  • Second-line: Serotonin-noradrenaline reuptake inhibitors (SNRIs) (e.g., venlafaxine, duloxetine).
  • Mirtazapine if poor sleep or appetite loss is prominent.
  • Avoid tricyclic antidepressants (TCAs) in high suicide risk patients.
  • Monitor for suicidal thoughts when initiating treatment.

3. Social and lifestyle interventions:

  • Encouraging regular physical activity.
  • Social engagement and support networks.
  • Workplace or academic adjustments.
  • Sleep hygiene education.

4. Crisis management and referral:

  • Crisis team referral: if acute suicidal risk.
  • Community mental health team (CMHT): for severe or recurrent depression.
  • Psychiatrist referral: for treatment-resistant depression or complex cases.
  • Hospital admission: if high risk of self-harm or suicide.
PsychiatrymypanotesMajor Depressive Disorder (MDD)