Pathophysiology of depression

Slides contain introduction, types, aetiology and pathophysiology of the major depressive disorder

1. Patho -physiology DEPRESSION Nem K. Jain MS (Pharm.) Pharmacology & Toxicology Asst. Professor School of Pharmacy, ITM University Gwalior, India

2. Depression: Major Depressive disorder/ Clinical Depression Depression is a mood disorder characterized by persistently low mood and a feeling of sadness and loss of interest. It is a persistent problem, not a passing one, To be diagnosed with depression, the symptoms must be present for at least two weeks It can affect person’s thoughts, behaviour , feelings and sense of wellbeing

3. Sadness vs. Depression Depression is different from the fluctuations in mood that people experience as a part of normal life. Sadness is temporary state of mind triggered by difficult, hurtful, challenging, or disappointing event, experience, or situation. Sadness is result of something! Depression is an  abnormal  emotional state, a mental illness that affects our thinking, emotions, perceptions, and behaviors in pervasive and chronic ways. In Depression, Sadness is result of everything!!

4. Types of Depression Major Depressive disorder Persistent depressive disorder ( Dysthymia ): is a depressed mood that lasts for at least two years. mild Postpartum depression:  full-blown major depression during pregnancy or after delivery. Psychotic depression:  occurs when a person has severe depression plus some form of psychosis (False beliefs or see or hear something) Seasonal affective disorder  is characterized by the onset of depression during the winter months, when there is less natural sunlight. Bipolar disorder : Episodes of depression followed by mania

5. Wide range of Symptoms.. Not all depressed / low mood reduced interest or pleasure in activities previously enjoyed, loss of sexual desire unintentional weight loss (without dieting) or low appetite or weight gain Insomnia  (difficulty sleeping) or hypersomnia (excessive sleeping) psychomotor agitation, for example, restlessness, pacing up and down delayed psychomotor skills, for example, slowed movement and speech Fatigue or loss of energy feelings of worthlessness, guilt or helplessness impaired ability to think, concentrate, or make decisions recurrent thoughts of death or suicide , or attempt at suicide

6. Symptoms

7. Causes & Risk factors Exact cause is unknown, variety of factors may be involved Genetic Factors : heritable, first degree relatives are more likely to develop depression. Biological factors: reduced level of neurotransmitters, hormonal imbalance Environmental Factors: Stress, peer pressure Psychological –social factors: Childhood trauma, Divorce, death of parents, work issues, financial problems etc., Abuse of alcohol, amphetamines, and other recreational drugs, prescription drugs like corticosteroids,

8. Pathophysiology Monoamine Hypothesis: depression is related to a deficiency in the amount or function of cortical and limbic serotonin (5-HT), norepinephrine (NE), and dopamine (DA).

9. Patho -physiology 2) Neurotrophic hypothesis: Brain Derived growth factor (BNDF) promotes the growth and development of immature neurons including mono- aminergic neurons, enhances the survival and function of adult neurons. Low BNDF level may be responsible for loss of mono- aminergic neurons and loss of function or atrophy of hippocampus and other brain areas. Hippocampus lose its ability to inhibit CRF release by hypothalamus leading to increased release of glucocorticoids .

10. Pathophysiology 3) Neuroendocrine hypothesis: Dexamethasone supression test doesn’t reduce cortisol level in 50% of depression patient; indicates imbalance in stress HPA axis (hypothalamus- pituitory - adrenal gland axis). Dysregulation in HPA axis results in increased corticotropinc releasing factor (CRF) from hypothalamus (result of hippocampus atrophy), Enlarged adrenal gland and increased secretion of cortisol ( glucocorticoids ). Dysregulation in HPT axis (hypothalamus- pituitory -thyroid) creates thyroid hormone defiency , which may be seen in depression.

11. Hypersecretion Hypertrophy Hypersecretion Impaired feedback inhibition Stress CRF level remain elevated 5-HT, NE, Dopamine levels decrease Cortisol level increase Decrease feedback inhibition from hippocampus

12. Pathophysiology .. Summary 5-HT Nor-adrenaline Dopamine CREB BNDF Monoamine Neuronal Atrophy Hippocampus atrophy Depression Glucocorticoids Cortisol - Monoamine Hypothesis HPA axis Stress - Neuroendocrine hypothesis Neurotrophic hypothesis -

13. The worst part about Depression People Who Don’t Have It They Just Don’t Get It!!