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.