This document discusses schizophrenia genes and periodic catatonia. Over 100 genes have been identified that contribute to schizophrenia risk, which has around 80% heritability. Periodic catatonia involves recurring catatonic episodes separated by remission periods, and may be caused by schizophrenia, mood disorders, medical issues, or drugs. Treatment for periodic catatonia involves benzodiazepines or ECT for acute episodes, and medications like amantadine, lithium, or mood stabilizers for maintenance.

1. Schizophrenia Genes
and
Periodic Catatonia
Dr. Ahsan Aziz
MD and FCPS Part 2 Trainee

2.  A polygenic disorder causes abnormality in
neurotransmission, plasticity and synapse
development.
 80% heritability.
 Over 100 genes have been identified.

3. SNPs explains 30% genetic risk.
CNVs explains 5-10% risk.
Other risks
Gene- gene interaction (epistasis)
Gene environment interaction
Missing genes

4. Biology of SCZ genes or how they
affect
 NMDA receptor
 Dopamine hyperactivity
 Expression of recessive genes

5. Schizophrenia Genes
Velocardiofacial Syndrome/ Di George Syndrome
22q11.21 deletion.
COMT activity decreases.
COMT is responsible for Dopamine metabolism in
synapses.

6. Schizophrenia Genes
Neuregulin (NRG 1)
It is a growth factor involved in neuron growth
and synaptic plasticity.
Increase Neuregulin signaling suppress NMDA
receptor leading to lowered glutamate level.

7. Schizophrenia Genes
Dysbindin (DTNBP1)
Biogenesis of lysosome related organelles.
Expression is decreased in schizophrenia.
Decrease Dysbindin leads to decrease
glutamate.

8. Schizophrenia Genes
DISC1/Disrupted in Schizophrenia 1
Interacts with PDE4B which decreases cyclic
AMP level
cAMP is important for learning, memory and
mood.

9. Schizophrenia Genes
miR-137: A microRNA which regulates other
genes
ZNF804A: Zinc Finger Protein 804A is a
transcription factor.
MHC region: Immune hypothesis of
schizophrenia

10. Schizophrenia Genes
C4: Increase activation of Complement
component 4 in schizophrenia leads to
abnormality in synaptic pruning.
VIPR2 duplication: Decrease VIP concentration
in lymphocyte of schizophrenia.
Neorexin (NRXN1) deletion: Synapse formation.

11. Schizophrenia Genes
Gene Name of Gene/Product Note
CACNA1C L type calcium channel @
subunit
Important in neuronal
function
Brugada Syndrome
DAO D Amino Acid Oxidase Enzyme which degrades
the NMDA receptor co-
agonist D-serine.
Expression and activity
increased in schizophrenia
DRD2 Dopamine D2 receptor Key target of antipsychotic
drugs
ERBB4 Receptor Tyrosine Kinase
erbb4
Receptor for neuregulin 1
GRIN2A NMDA Receptor subunit 2 Influences properties of
the NMDAR, including
synaptic localization and
channel conductance.

12. Crow’s lateralization hypothesis
Handedness, language function, anatomic
asymmetry.
Decrease lateralization in schizophrenia.
Mediated by Protocadherin X/Y gene.

13. Implication in treatment
Genetic counseling
CACNA1C (Calcium Voltage-Gated Channel
Subunit Alpha1 C) associated with sudden
cardiac death
Comorbidity: Epilepsy (15q11) ASD,
Microcephaly (16p11)

14. Implication in treatment
Nonsteroidal anti-inflammatory drugs,
omega-3 fatty acids, and statins.
Available anticytokine atlizumab, monoclonal
antibody(infliximab, etanercept, and
alimumab) are currently in use.

15. Periodic catatonia
Frequently recurring catatonic episodes with
intervening phases of remission.
2/3rd are female
Age before 20
Family history of psychotic illness present

16. Etiology
 Schizophrenia
 Mood disorder
 Medical causes
 Metabolic
 Neurological
 Drug induced

17. Consequence of catatonia
 Rhabdomyolysis
 Kidney failure
 Dehydration
 Thromboembolic events

18. Pathophysiology
Blockade of postsynaptic D1 and D2 receptor
Glutametergic dysfunction
Decrease GABA-A binding
Thyroid Dysfunction causing abnormality in
BMR
WKL1 (Leu309met) and KCNA1 genes are
associated with it.

19. Difference with systematic catatonia
 Rapid onset
 Lasts for 4-10 days
 Recurs within weeks to year
 Seasonality
 Better prognosis than catatonia

20. Treatment
Acute stage
Benzodiazepine Lorazepam, Diazepam
ECT
Maintenance
Amantadine
Lithium
Mood stabilizers

21. Thank You