Neurobiology of Depression

1. NEUROBIOLOGY OF DEPRESSION
• Dr.Tapendra Kumar Satpathy
PGT,PSYCHIATRY
MHI, SCB Medical College

2. Introduction and Epidemiology
• DEPRESSION word comes from Latin word Deprimere(to press down) which origin
from Sanskrit word “VISADA”.
• Prevalence:5-17% (mean 12%),as per NHMS (National Mental Health Survey) every 1
in 20 people encounter.
• Female > Male (Middle aged)
• Socioeconomic Status LOW = HIGH.
• Genetics - Hereditary 30-40% cases
- Family members are in 10 – 25 times more risk .
- Monozygotic twins (90% ) > Dizygotic (10-35 % ) risk.

3. Age wise prevalence in Female

4. Agewise Prevalence in Male

5. Diagnostic Criteria (DSM 5)
A.
1. Sadness of Mood.
2. Anhedonia (decresed interst in previously pleasurable activities)
3. Guilt feeling/Pessimistic views
4. Energy Lack
5. Lack of concentration (Memory)
6. Decreased Appetite (wt loss) /increased (wt gain)
7. Psychomotor Activity (increased/decreased)
8. Sleep (decreased/increased)
9. Suicidal thoughts/Death wishes,gestures,attempts,ideation.
5 out of 9 for 2 weeks

6. • B.Socioocupational Impairment.
• C.Must not be explainable by substance or medical condition.
• D.Not Explainable by Schizophrenia or Schizophreniform or
Schizoaffective disorders.
• E.Never Hypomania or Mania

7. With Specifier
• 1.With Anxious Distress
a.Feeling keyed up or tensed.
b.Feeling usually restless.
c.Difficulty concentrating because of excessive worry.
d.Feeling that something awful might happen.
e. Feeling that indivisual might loose control of himself or
herself.
2-mild High suicidal risk
3-moderate Longer Duration of illness
4-5-Severe Greater likelihood of treatment nonresponsiveness

8. 2.With Melancholic features
• A.One of the following a. lack of pleasure in activities
b.lack of reactivity to usually pleasurable stimulus.
• B.3 or more of following.
a.Distinct quality of depressed mood characterised by profound loss of courage.
b.Depression more in morning.
c.Early morning awakening.
d.Marked Psychomotor Retardation.
e.Significant Anorexia or wt loss.
f.Excessive or inappropriate GUILT.

9. 4.With Psychotic Features
A.Mood congruent (delusion of guilt,nihilism,suicide).
B.Mood incongruent(other diagnosis must be ruled out first)
5.With Seasonal Pattern (worse in winter)
6.With Mixed features(elevated mood)
7.With Catatonic Symptoms.

10. 3.With Atypical Symptoms
• A.Mood Reactivity
• B. >2 of following
a.significant wt gain or increased appetite.
b.Hypersomnia.
c.Leyden Paralysis or Body Heaviness.
d.Interpersonal Rejection sensitivity.

11. Other Psychiatric Disorders as Differential
• Uncomplicated Bereavement Reaction.
• Adjustment Disorder.
• Anxiety Disorder.
• Substance use disorder.
• Schizophrenia.
• Other mood disorders.

12. Diseases and Drugs
ENDOCRINAL DRUGS INFECTIONS OTHERS
1.Hypo/Hyper
Thyroidism
1.Cycloserine 1.Infectitious
Mononucleosis
1.COLLAGEN (RA,SLE)
2.Cushing Disease 2.Steroidal
contraceptives
2.AIDS 2.NUTRITIVE (Pellagra,Pernicious
anemia)
3.Diabetes Mellitus 3.Reserpine,Methyl
dopa
3.Viral Hepatitis 3.Neurologic
Parkinson dis
Multiple Sclerosis
4.Addisons’s Disease 4.Amphetamine and
Cocaine withdrawal
4.Viral Pneumonia 4.Obstructive Sleep Apnea
5.Anticholine esterase
insecicide
5.
Toxoplasmosis,Tertiar
y Syphillis
5.Cerebral Space occupying lesions also

13. Symptoms and Signs (Summary)

14. As per functional areas of Brain

15. Functions
1. Prefrontal Cortex = Creativity,Problem solving,Comprehension,impulse
control.
2. Basal Forebrain=Wakefullness and REM sleep
3. Striatum=Goal directed movement and Decision making
4. Nucleus Accumbens=Motivation,Reward
5. Amygdala=Emotional Learning,Reward,Memory Modulation
6. Hippocampus=Spatial Memory,Approach – Avoidance conflict processing

17. Hippocampal volume reduction in Major Depressive Disorder

18. Neuroimaging in Depression
• Apart from decrease in size of Hippocampus other structural changes
of Brain can be seen
1. Ventricular Enlargement
2. Cortical Atrophy
3. Sulcal widening
4. Decrease size of Hippocampus
5. Decrease size of Amygdala
6. Increase size of Pituitary

19. Loss of Positive and Gain of Negative

20. 1.Monoamine Hypothesis of Depression

21. Receptors Upregulation

22. Site of Release
1. Dopamine = Ventral Tegmental Area
(Substantia Nigra)
2. Norepinephrine = Locus Coeruleus
3. Serotonin = Raphe Nucleus

23. Monoamine synthesis pathway

24. Major Dopamine
Projections(Vetral Tegmental area)
Ascending
Movement
Pleasure
Reward
Cognition
Psychosis
Other Functions

25. Major Norepinephrine
Projections(Locus coeruleus)
Ascending
Mood
Arousal
Cognition
Descending
Extenddown
spinalcord
Regulatepain
pathway

26. Major Serotonin Projections(Raphe
nucleus)
Ascending
Mood
Anxiety
Sleep
Other functions
Descending
Extend down Brain
stem and Spinal cord
May regulate pain
path way

27. Drawback of Monoamone Hypothesis
1. On Antidepressant medication increase in monoamine levels in
brain occurs within minutes.
2. But therapeutic effects takes weeks of time.

28. Recent Study

29. Study Goals
• Six areas were identified, addressing the following questions
1.Serotonin and the serotonin metabolite 5-HIAA–whether there are lower
levels of serotonin and 5-HIAA inbody fluids in depression.
2.Receptors - whether serotonin receptor levels are altered in people with
depression.
3. The serotonin transporter (SERT) - whether there are higher levels ofthe
serotonin transporter in people with depression (which would lower synaptic
levels of serotonin).
4.Depletion studies – whether tryptophan depletion (which lowers available
serotonin) can induce depression.
5.SERT gene – whether there are higher levels of the serotonin transporter
gene in people with depression.
6.Whether there is an interaction between the SERT gene and stress in
depression.

31. Study result
• Not Significant (<50% in all the parameters)

32. 2.BDNF Hypothesis
BDNF = Brain Derived Neurotropic Factor
• Stress and Glucocorticoid reduce expression of BDNF mRNA
• BDNF expression is decresed in the serum of Major Depressive
Disorder patients.
• Decrease not seen in patient treated with Antidepressant.
• Administration of several classes of Antidepressant increase BDNF
mRNA in Hippocampus and frontal cortex
• Direct infusion of BDNF protein into the Hippocampus, midbrain
,HIP,intracerebrovascular region exerts Antidepressant effects in
rodents.

33. BDNF Supression

34. • BDNF Summarised

35. 3.Stress –Diathesis Model (HPA Axis)

36. Hypothalamus – Pituitary – Adrenal Axis hyperactivity in
Depression

37. Dexamethasone suppression Test
• Dexamethasone 1 mg at 11pm
• Serum cortisol at next day 8 am
• Unable to supress cortisol level.
• Not diagnostic not specific.
• Also positive in Eaing disorder,Alzheimers dementis,Bipolar disorder.
• Only prognostic value nonsupressor having increased severity.

38. 1.Stress Resilience (normal)

39. 2.Stress sensitisation development

40. 3.Stress sensitisation to Depression

41. Summarised

42. But Why Childhood Psychological Trauma is so
significant ?

43. Jean Piaget (Cognitive Devlopment Theory)

44. Cont..

45. 4.Inflammatory theory of depression
• Increase in proinflammatory(IL 6,IL 1,TNF alpha,CRP) cytokines.
• Increase Depression in Inflammatory Medical disorders.
• Antiinflammatory drugs like CELECOXIB(COX 2
inhibitor),ETANERCEPT(TNF alpha antagonist) acts as antidepressant.

46. Other Theories of Depression
1. Opoid System and Depression
2. Glutaminergic(Excitotoxicity) system
3. Nitric oxide signalling system
4. Neuropeptide Y and depression
5. Melatonergic (related to circadian rhythm) system

47. 5.Melatonergic system (Normal)

48. In Depression(Dysruption of circardian Rhythm)

49. Are Biological Rhythm related to Depression ?

50. Melatonin And Depression

51. Recent Study
• Nile grass rats
• (Arvicanthis niloticus), a diurnal
rodent, exposed to
• Short photoperiod (5 h light/19 h
dark) for 6 weeks.
• presented reduced saccharin
preference, higher immobility time
in the forced swim test, and no
changes on time spent in the light
side of thedark/light box in
comparison to controls .

52. Melatonin Synthesis Pathway

53. After giving Melatonin Receptor Agonist

54. 6.Cognitive Theory
Cognitive Triad
• Self Worthlessness
• Environment Helplessness
• Future hopelessnes
• Cognitive Distortion
1.Overgeneralisation(Applying lessons
learned from negative experiences more
broadly)
2.Dichotomous Thinking (Absolutist)(
all good or all bad)
3.Magnification/minification
4.Selective Abstraction(focussing on
negative )
5.Arbitary Inference (Drawing negative
conclusion without evidence)

55. Psychotherapeutic Modalities
• 1.CBT(Cognitive Behavioural Therapy)
Maldaptive assumption
Cognitive Restructuring (To modify
behaviour)
• 2.Metacognitive Therapy
activating events can be a cognition
rather than some external occurrence.
Means people can be depressed,anxious or
otherwise psychologically unwell because
reaction to their own thought rather than
their reactions to the things that happen to
them.
So cause of unhappiness is thoughts about
thoughts .

56. References
• Kaplan and Saddock’s Textbook of Psychiatry.
• Stahl’s Psychopharmacology.
• Neurobiology of Depression.
• Natures’s Journal.
• Frontiers’s Journal.
• Dr.Rasmita Didi’s Note.

57. THANK YOU