Major Depressive Disorder

 Major Depressive Disorder - MDD :

Certainly. Major Depressive Disorder (MDD), also known as clinical depression, is a mental health condition characterized by a persistent and pervasive low mood, loss of interest or pleasure in most activities, and a variety of other cognitive, emotional, and physical symptoms that significantly impair daily functioning.

Diagnostic Criteria (DSM-5) :

To diagnose MDD, at least five of the following symptoms must be present for a minimum of two weeks, and they must represent a change from previous functioning. At least one of the symptoms must be either depressed mood or anhedonia (loss of interest or pleasure).
  • Depressed mood : Most of the day nearly every day.

  • Anhedonia : Markedly diminished interest or pleasure in all, or almost all, activities.
  • Significant weight change : Either weight loss when not dieting or weight gain.
  • Sleep disturbances : Insomnia or hypersomnia.¨
  • Psychomotor changes : Observable psychomotor agitation or retardation.
  • Fatigue : Loss of energy nearly every day.
  • Feelings of worthlessness or guilt : Excessive or inappropriate guilt.
  • Cognitive impairments : Diminished ability to think, concentrate, or make decisions.
  • Recurrent thoughts of death : Suicidal ideation, with or without a specific plan.
These symptoms must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning and must not be attributable to the physiological effects of a substance or another medical condition.

Etiology :

MDD is multifactorial in origin :
  • Genetic predisposition : Family history increases risk.
  • Neurochemical dysregulation : Abnormal levels of neurotransmitters, such as serotonin, norepinephrine, and dopamine.
  • Neuroanatomical changes : Altered function in brain regions like the prefrontal cortex and hippocampus.
  • Psychosocial : stressors : Chronic stress, trauma, or significant life changes.
  • Medical comorbidities : Conditions like hypothyroidism, chronic pain, or diabetes.

Pathophysiology :

MDD involves disruptions in :
  • Monoamine neurotransmitter systems : Reduced serotonin, norepinephrine, and dopamine activity.
  • Hypothalamic-pituitary-adrenal (HPA) axis : Hyperactivity leading to elevated cortisol levels.
  • Neuroplasticity : Impaired and neurogenesis, particularly in the hippocampus.
  • Inflammatory markers : Elevated levels of pro-inflammatory cytokines have been implicated.

Management :

Pharmacological Treatment :

Antidepressants :
  • Selective serotonin reuptake inhibitors (SSRIs) : First-line agents (e.g: fluoxetine, sertraline).
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs) : Venlafaxine, duloxetine.
  • Tricyclic antidepressants (TCSs) : Amitriptyline (used less frequently due to side

    effects).
  • Atypical antidepressants : Bupropion, mirtazapine.
  • Monoamine oxidase inhibitors (MAOIs) : Rarely used due to dietary restriction.
Adjunctive therapies :
  •  Atypical antipsychotics or mood stabilizers in treatment-resistant cases.

Psychotherapy :
  • Cognitive-behavioral therapy (CBT) : Effective for modifying negative thought patterns.
  • Interpersonal therapy (IPT) : Focuses on improving relationships and social functioning.
  • Psychodynamic processes influencing behavior.
Other Interventions :
  • Electroconvulsive Therapy (ECT) : For severe or refractory depression.
  • Transcranial Magnetic Stimulation (TMS) : Non-invasive neuromodulation technique.
  • Lifestyle modifications : Regular exercise, sleep hygiene, and nutritional improvements.
  • Mindfulness-based therapies : Meditation and stress management techniques.
Prognosis :
  • Course : MDD is episodic in nature, with variable duration and recurrence.
  • Risk of recurrence : Higher in those with multiple prior episodes, ongoing psychosocial stressors, or incomplete recovery from prior episodes.
  • Complications : Suicidal behavior, substance abuse, and significant functional impairment if untreated.
Preventive Strategies :
  • Early identification and management or risk factors.
  • Ongoing support systems and adherence to treatment.
  • Regular follow-ups to monitor symptoms and adjust therapy as needed.

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