Schizophrenia Pathophysiology

Question 1

Overall, schizophrenia is:

Answer 1

Disorder of DA hyperactivity and abnormal neurodevelopment

Question 2

Schizophrenia shows disturbed:

Answer 2

content form and content of thought (intellectual function is impaired)

Question 3

**Positive symptoms are:

Answer 3

Delusion
Hallucination
Disorganized speech
Disorganized behavior

Question 4

Define Delusions

Answer 4

They have no basis in fact
•	Others are spying on your
•	Others are planning to harm you
•	Thoughts are being broadcasted
•	Thoughts are imposed on from an outside source
•	Repetitive speech

Question 5

Define Hallucinations

Answer 5

Auditory

Question 6

Positive symptoms can be treated with:

Answer 6

Antipsychotics (DA antagonists)

Question 7

**Negative Symptoms are:

Answer 7

 Speech decline
 Blunting of emotions
 Loss of sociability
 Ability to derive pleasure

Question 8

Negative symptoms can be treated with:

Answer 8

second generation antipsychotics

Question 9

***Cognitive symptoms are:

Answer 9

 Impaired ability to focus
 Poor decision making
 Impaired working memory

Question 10

Heritability for Schizophrenia

Answer 10

0.81

Question 11

Causitive factor for schizophrenia

Answer 11

DISC1

Question 12

DISC1 is:

Answer 12

scaffolding protein involved in neuronal proliferation, migration, cell signaling, spine regulation and synapse maintenance

Question 13

Other allele risk facotrs

Answer 13

COMT
CACNA1C
TCF4/ITF2
NRGN

Question 14

COMT function

Answer 14

Clearance of DA in PFC

Question 15

CACNA1C function

Answer 15

Voltage gated Ca channel

Question 16

TCF4/ITF2 function

Answer 16

Brain development

Question 17

NRGN function

Answer 17

Protein kinase
Increase Ca levels in lows by binding to calmodulin
Involved in thyroid function

Question 18

Copy Number Variants, what and importance?

Answer 18

Regions of DNA that are deleted or duplicated resulting in genes that are haploid or polyploid
Most disrupt genes involved in signaling, synaptic plasticity and neurodevelopmental processes

Question 19

NRXN1 importance:

Answer 19

Deletion of NRXN1 which encodes cell surface adhesion molecule involved in formation and maintenance of synapses

Question 20

Environmental Risk Factorks

Answer 20

Infections esp prenatal
Famine esp prenatal
Low birth weight- non-specific
Urban environment – stress
Childhood trauma esp prenatal
Paternal age
Maternal stress
Winter birth month
Obstetrical complication (gestational diabetes, emergency c-section, placental abruption)
Folate, Fe or Vit D deficiencies

Question 21

Mesolimbic/Mesocortical Anatomy

Answer 21

• VTA innervation in N. accumbens = reward and reinforcement

* NA receives inhibitory feedback from PFC but because there is less of PFC there is less inhibitory effect

Question 22

PFC Regions

Answer 22

o Dorsolateral: cognitive functions such as working memory, planning and elaboration of thoughts
o Ventral regions: conscious regulation of emotions

Question 23

Positive Symptoms are caused by:

Answer 23

Hyperactivity of DA in the ventral PFC
DA overactivity at the NA and ACC
PFC inhibition of the NA is reduced and VTA → NA is hyperactive = positive symptoms

Question 24

Negative and Cognitive Symptoms are caused by

Answer 24

Hypofunction of DA in the dorsolateral PFC

Question 25

Negative Symptoms specifically are caused by

Answer 25

frontal hypofunctionality
Serotonergic innervation of PFC inhibits its function - 5HT neurons in the Raphe are hyperactive due to stress and the hyperactivitiy reduces PFC function

Question 26

Schizophrenia patients show:

Answer 26

• Enlarged ventricles
• Reduced PFC, temporal lobe and hippocampal volume
• Reduced cerebral blood flow in frontal lobes (hypofunctionality)
• Abnormal eye movement due to frontal lobes
• Abnormal stimuli in EKG
• Default Mode Network is not easily deactivated

Question 27

Diffusion Tensor Imaging

Answer 27

used to measure connectivity between regions in a network

Shows that emotional and cognitive networks are not “wired” the same way