The document provides an overview of the neurobiology of several mental disorders including schizophrenia, mood disorders, suicide, addictive behaviors, ADHD, and anxiety disorders. It discusses the genetic, neurochemical, neural circuitry, and neuropathological factors associated with each disorder. Specifically, it describes abnormalities found in neurotransmitter systems, brain structures, and neural pathways related to each mental illness. Twin and family studies are presented showing the genetic components. The roles of dopamine, serotonin, GABA, and other neurotransmitters are summarized for different disorders.

1. NEUROBIOLOGY OF
MENTAL DISORDERS
PRESENTER : Ms LEESHMA P
CHAIR PERSON: Mr RITHVIK S KASHYAP
1

2. CONTENT
Introduction
Schizophrenia
Mood disorders
Suicide
Addictive behaviours
ADHD
Anxiety Disorders
2

3. OVERVIEW
NEUROBIOLOGY OF MENTAL DISORDERS
Neurogenetics Neurochemistry Neural circuits Neuropathology
3

4. NEUROGENETICS
Familial studies
Twin studies
Adoption studies
Gene-environment interaction
4

5. NEUROCHEMISTRY
The study of chemical inter neuronal communication
is called neurochemistry.
Neurotransmitters are chemical messengers that
transmit signals from a neuron to a target cell across
a synapse.
Chemical neurotransmission is the process involving
the release of a neurotransmitter by one neuron and
the binding of the neurotransmitter molecule to a
receptor on another neuron.
5

6. Causes of Neurotransmitter Dysfucntions
• Chronic stress
• Poor diet
• Environmental toxins
• Drugs
• Alcohol, Nicotine and Caffeine
6

7. I. Cholinergics Location/Function
ACETYL CHOLINE 1921
,Ottoloewi (German
biologist)
ANS: sympathetic and parasympathetic nerve
terminals, parasympathetic post synaptic nerve
terminals CNS: Cerebral
cortex,hippocampus,limbic structures and basal
ganglia
FUNCTIONS:
Sleep,arousal,pain,perception,movement,
memory.
II.Monoamines
NOREPINEPHRINE Is
strongly associated with
bringing our nervous
system into ―high alert‖ .
ANS: Sympathetic post synaptic nerve terminals
CNS: Thalamus,hypothalamus,limbic
system,hippocampus,cerebellum,cerebral cortex.
Functions:
Mood,cognition,perception,locomotion,cardio
vascular functioning,forming memories, sleep
and arousal
DOPAMINE generally
involved in regulatory motor
activity in mood, motivation
and attention .
Frontalcortex, limbic system, basal ganglia,
thalamus, posterior pituitary and spinal cord.
FUNCTIONS Movement and co-
ordination,emotions,voluntary judgement and
release of prolactin
7

8. SEROTONIN Hypothalamus,thalamus,limbicsystem,cerebralcortex,cerebel
lum,spinal cord FUNCTIONS Sleep and arousal, libido,
appetite, mood aggression, pain perception, coordination,
judgement
HISTAMINE FUNCTIONS: Wakefulness, pain sensation and
inflammatory response
III. Amino acids
GAMMA-
AMINOBUTYRIC
ACID (GABA)
Hypothalamus, hippocampus,cerebellum,basalganglia,spinal
cord.
FUNCTIONS: Slowdown body activity.
GLYCINE Spinal cord and brain stem.
FUNCTIONS: recurrent inhibition of motor neurons
GLUTAMATE
ASPARTATE
excitatory
neurotransmitter
in brain
Pyramid cells of the cortex, cerebellum and the primary
afferent systems: hippocampus, thalamus, hypothalamus
and spinalcord
8

9. NEUROPATHOLOGY
• Neuroimaging methodologies allow measurement
of the structure, function, and chemistry of the living
human brain.
 Computer tomography (CT)
 Magnetic Resonance Imaging (MRI)
 Functional Magnetic Resonance Imaging
(fMRI)
 Positron Emission Tomography (PET)
9

10. 10

11. GENETIC FACTORS
Population Prevalence
General population 0.5-1
First degree relatives 10
Monozygotic twins 50
Dizygotic twins 10-14
Non-twin sibling of a schizophrenia patient 8
Child with one parent with schizophrenia 12
Child of two parents with schizophrenia 40
Dizygotic twin of a schizophrenia patient 12
Monozygotic twin of a schizophrenia patient 47
11

12. Neurotransmitter Effect
Dopamine Positive symptoms,
Dopamine Hypofrontality, impaired cognition,
and negative symptoms
Serotonine +Ve & -ve symptoms
Norepinephrine Anhedonia
Decreased Acetylcholine and
nicotine receptors
Impaired cognition
Loss of GABAergic neurons in the
hippocampus.
---
NEUROCHEMISTRY
12

13. NEUROPATHOLOGY
Structural abnormalities
•Decreased brain volume
•Excessive pruning of synapses
•Lateral and third ventricular enlargement and
some reduction in cortical volume
•Decrease in the size of the region including the
amygdala, the hippocampus, and the
parahippocampal gyrus
13

14. • Anatomical and functional abnormalities in
prefontal cortex
• Reduced symmetry in several brain areas
• Volume shrinkage or neuronal loss in medial
dorsal nucleus of the thalamus
• Cell loss or the reduction of volume of the globus
pallidus and the substantia nigra
14

15. Functional abnormalities
Reduced activation of the prefrontal cortex
(hypofrontality)
Positive symptoms were associated with
increased medial temporal flow, negative
symptoms with decreased prefrontal
(dorsolateral) blood flow, and disorganization with
increased cingulate flow.
15

16. 16

17. NEURAL CIRCUITS
• The basal ganglia - cerebellum - frontal lobe
• Early developmental lesion of the dopaminergic tracts
to the prefrontal cortex results in the disturbance of
prefrontal and limbic system function, and leads to
the positive and negative symptoms and cognitive
impairments observed in patients with schizophrenia.
• Anterior cingulate- basal ganglia- thalamocortical
circuit dysfunction leads to positive symptoms
• Dysfucntion of dorsolateral prefrontal circuit leads to
negative symptoms
17

18. 18

19. NEURODEVELOPMENTAL MODEL
Genetic or environmental processes produces
damage to selected brain areas early in life.
(Temporal lobe regions such as the
hippocampus)
Alterations in limbic and prefrontal function then
produce downstream, secondary alterations in
subcortical dopamine, glutamate, and other
neurotransmitter systems.
19

20. 20

21. 21

22. GENETIC FACTORS
Population Prevalence
Monozygotic twins 70-90
Same sex Dizygotic twins 16-35
Child with one parent with mood
disorder
10-25
Child of two parents with mood
disorder
25-50
22

23. DEPRESSION
ACETYLCHOLINE
GLUTAMATE
HISTAMINE
DOPAMINE
GABA
NOREPINEPHRINE
SEROTONIN
NEUROCHEMISTRY
23

24. NOREPINEPHRINE
DOPAMINE
SEROTONIN
GLUTAMATEMANIA
24

25. 25

26. IMPAIRED NEURAL PLASTICITY
• Studies have found that antidepressants and
mood stabilizers enhance the functioning of
complex intracellular pathways which process
and modulate the signals generate by
neurotransmitters.
• Psychosocial stress often precipitates mood
episodes and is linked to impaired neuroplasticity
• Brain atrophy in mood disorders is likely
secondary to impaired neuroplasticity
26

27. NEUROPATHOLOGY
Structural abnormalities
• Volume reduction of frontal cortex
• Increased volume of amygdala in depression
• Decreased volume of hippocampus, striatum and
cerebellum in depression
• Decreased volume of amygdala in bipolar
disorder
• Increased volume of striatum in bipolar
27

28. Functional abnormalities
• Decreased and increased dorsolateral prefrontal
cortex activity.
• Increased activation of the left medial prefrontal
cortex
• Increased activation of the dorsal anterior
cingulate cortex in depression
• Increased and decreased hippocampal activation
28

29. NEURAL CIRCUITRY DISRUPTION
• Abnormalities in regions within both the ventral and
dorsal emotional control networks.
• The ventral network, which includes the ventral
prefrontal cortex, amygdala, insula, ventral striatum,
thalamus, orbitofrontal cortex, ventral anterior
cingulate cortex, and brainstem nuclei.
• The dorsal network includes the dorsolateral
prefrontal cortex, medial prefrontal cortex, dorsal
anterior cingulate cortex, and hippocampus.
29

30. 30

31. CORTICOSTRIATAL CIRCUITS
• Anterior cingulate syndrome: profound apathy, motor
and verbal inactivity, and indifference to thirst or
hunger; loss of motivation, psychomotor slowing, and
blunted affect.
• Orbitofrontal syndrome: Behavioural disinhibition and
labile emotions
• Dorsolateral prefrontal syndrome: difficulty focusing
and sustaining attention, reduced verbal fluency and
motor programming
• Striatal hyperactivation in bipolar disorder and
hypoactivation in major depressive disorder
31

32. 32
FRONTAL SUB-CORTICAL CIRCUIT

33. 33

34. 34

35. GENETICS
• Higher rate of family history
• Concordance rate more in monozygotic twins
• Higher rate of suicide in biological parents of adopted
children
• Parents of young suicide victims have higher rates of
suicidal behavior
35

36. 36

37. DIATHESIS STRESS MODEL
37

38. 38

39. NEUROCHEMISTRY
39

40. NEUROPATHOLOGY
• Damage to the ventromedial prefrontal cortex results
in defects of social behaviour, including a failure to
observe social conventions and to make poor
decisions, although learning, memory, attention,
language and many other cognitive functions are
normal
• Frontal lobe lesions - impulsive and make poor
decisions
• Defective prefrontal cortex- increased risk for suicidal
and other impulsive acts
40

41. • Increased suicide risk with decreasing cholesterol
levels, whether they occur spontaneously or whether
they are attributable to drugs or diet (Golomb, 1998)
• Elevated levels of CRH in the CSF of suicide victims
also indicate increased activity of the hypothalamic-
pituitary-adrenal (HPA) axis associated with suicidal
behaviour(arato, 1989)
41

42. 42

43. GENETIC FACTORS
• Three- to fourfold increased risk for severe alcohol
problems in close relatives of alcoholic people.
• The rate of similarity, or concordance, for severe
alcohol-related problems is significantly higher in
identical twins of alcoholic individuals than in fraternal
twins.
• The adoption-type studies revealed a significantly
enhanced risk for alcoholism in the offspring of
biological parents with alcoholism, and raised
without any knowledge of the problems within the
biological family.
43

44.  Cause its effects by interacting with the GABA receptor
 Initially anxiety is controlled, but greater amounts reduce muscle control and
delay reaction time due to impaired thinking
 Inhibits glutamate receptor - dis co-ordination, slurred speech, staggering,
memory disruption and black-out
 Opioid, catecholamine (particularly dopamine), and î³-aminobutyric acid
(GABA) systems
NEUROCHEMICAL FACTORS
44

45. NEUROPATHOLOGY
• The hindbrain - centres that control breathing and
wakefulness.
• The midbrain -motivation and learning about
important environmental stimuli, and reinforcing
behaviours that lead to pleasurable and life-
sustaining consequences, such as eating and
drinking.
• The forebrain- ability for abstract thought and
planning, and for associations of thoughts and
memories
45

46. 46

47. DOPAMINERGIC- MESOLIMBIC
PATHWAY
• Dopaminergic mesolimbic pathway is the key point of the
brain circuitry in the reinforcement of drugs of abuse (wise
2002).
• It could be activated both by the direct message of the
reinforcement that is present and by sensory stimuli that
pointed to the closeness of a reinforcer.
47

48. 48

49. PSYCHOACTIVE SUBSTANCES
49

50. 50

51. 51

52. GENETIC FACTORS
• Relatives of ADHD probands have an increased risk
for ADHD
• Twin studies: higher concordance of ADHD for
monozygotic (79 per cent) than dizygotic (32 per
cent) twins
• Adoption studies: biological parents exhibit more
ADHD or related disorders than adoptive parents
• 2-3 % high risk in siblings of children with ADHD
52

53. STRUCTURAL ABNORMALITIES
• Lower grey matter density
• White matter abnormalities
• Reduced total brain volume and volume of some
brain structures
• Cortical differences
• Delayed cortical maturation in children/adolescents
• Reduced cortical thickness in adults
53

54. 54

55. FUNCTIONAL ABNORMALITIES
• Impairments in prefrontal-striatal networks - inattention
• Impairments in frontal-limbic networks - hyperactivity.
• Over-activation (reduced suppression) of the default
mode network during task performance
• Under-activation of fronto-striatal and fronto-parietal
circuits, and other frontal brain regions
• Under-activation of systems involved in executive
function and attention
55

56. 56

57. NEUROCOGNITIVE MODEL
57

58. NEUROCHEMISTRY
Maturation of certain dopaminergic neural pathways
appears to be delayed
Levels of available dopamine receptor and
transporter molecules are typically lower in some
parts of the brain
In rats, interference with the noradrenaline system
impacts on:
• Impulsivity
• Attentional accuracy
• Response control.
58

59. 59

60. GENETIC FACTORS
• Heredity- predisposing factor
• Twin studies
• No adoption study is available
• Higher frequency of the illness in first-degree
relatives of affected patients than in the relatives
of non affected persons
60

61. NEUROCHEMISTRY
Autonomic nervous sysytem
• Increased sympathetic tone in ANS
• Stimulation of the autonomic nervous system causes
certain symptoms - cardiovascular (e.G., Tachycardia),
muscular (e.G., Headache), gastrointestinal (e.G.,
Diarrhea), and respiratory (e.G., Tachypnea
61

62. Noradrenaline
• The cell bodies of the
noradrenergic system are
primarily localized to the
locus ceruleus in the rostral
pons.
• Stimulation - fear response
in the animals
• Ablation- inhibits or
completely blocks the ability
to form a fear response.
• Panic attacks
• Insomnia
• Startle
• Autonomic hyper-arousal
62

63. Hypothalamic-Pituitary-Adrenal Axis
• Psychological stress
increase release of
cortisol.
• Alterations in
hypothalamic-pituitary-
adrenal (HPA) axis
function - PTSD.
• Panic disorder - blunted
adrenocorticoid hormone
(ACTH) responses to
corticotropin-releasing
factor (CRF).
63

64. Serotonin
• Different types of acute
stress result in increased
5-hydroxytryptamine (5-
HT) turnover in the
prefrontal cortex, nucleus
accumbens, amygdala,
and lateral hypothalamus.
GABA
• A role of GABA in anxiety
disorders is most strongly
supported by the
undisputed efficacy of
benzodiazepines, which
enhance the activity of
GABA at the GABA type A
(GABAA) receptor, in the
treatment of some types
of anxiety disorders
64

65. NEUROPATHOLOGY
• Increase in the size of cerebral ventricles
• Defect in the right temporal lobe
• Cerebral asymmetries
• Abnormalities in the frontal cortex and the occipital
area
• Caudate nucleus – OCD
• Increased activity in the amygdala - PTSD
65

66. 66
Charney, D.S. et.al, 1996

67. REFERENCES
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psychiatry, 1(1), 2.
• Grant, J. E., Brewer, J. A., & Potenza, M. N. (2006).
The neurobiology of substance and behavioral
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68. • Mann, J. J. (2003). Neurobiology of suicidal
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