GENETICS AND EARLY ENVIRONMENT.

Jesse Gill
Funto Olonade
20XX PSYC 4500 – Schizophrenia 1
OBJECTIVES
Background: From research, genes have a
stronger part to play as a risk factor for
schizophrenia nevertheless it is likely that the
disorder is the result of interaction with non-
genetic factors.

Approach- Consider and understand GXE

interaction, examine and estimate the
magnitude of environmental exposures, review
prevalence studies and potential directions for
future.

Areas of concentration- sequentially across

development, prior to conception, prenatal,
and postnatal, (divided into perinatal and later
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life period)
 Do you think the DSM-V should
include biological factors?
OBJECTIVES OF GENETICS.
Overview
-Punnet squares.
-The statistics of the disorder
-Heritability
-What gens are responsible for the disorder
-Shared genetic traits
-Epigenetics
-Evolutionary cause

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 APPROACH

S t r e ng t h o f a s s o c i a t i o n S p e c i f i c i t y o f c a us e & o f P r e d i c t i v e p e r f o r m a nc e S t a t i s t i c a l c o h e r e nc e
effec t

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PUNNETT SQUARE
WHY THIS DOESN’T WORK
LIKELIHOOD OF
DEVELOPING THE
DISORDER.
INTRODUCTION Who will
develop
Schizophrenia?
Etiology: Gene,
environment, GXE
interaction

Critically to note the importance to

quantify the contribution that
genes make relative to that made
by environmental factor. In the
search of the cause, the overall
impression many evidence have
suggested is that theoretically the
disorder is highly hereditary,
suggests environmental factors
also can act independently. Are
they mainly an additive or a more
PSYC 4500 – PSYC 4500 – Schizophrenia
Schizophrenia
interactive level of analysis?
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PSYC 4500 – Schizophrenia
 GENE-ENVIRONMENT (GXE) INTERACTIONS

TORCH INFECTION Cannabis Use PSCA

Toxoplasma Cannabis use -COMT COMT Met allele
gondii (Toxo) –deletion carriers – stress, and
in glutathione s- PRS scores cannabis
childhood adversity,
transferase theta 1 use and schizophrenia
(GSTT1). Cannabis in BDNF, CACNA1C, NRG1
adolescence - as a and FKBP5 –stress and
Toxoplasma childhood adversity
gondii (Toxo) - C4 gene form of self-
copy number and medication? SZ PSR scores and
haplotype groups may not be as straight childhood bullying,
forward . sexual abuse,
Herpes simplex viruses emotional abuse and
– HLA on chromosome neglect.
6p, GM gentypes (γ
marker) allotype .
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ENVIRONMENTAL EXPOSURES
CAN BE

-BIOLOGICAL
-PSYCHOLOGICAL
-SOCIAL
Cannabis Migration

Obstetrical Infectious
complications agents

Socio-
Seasonality of
demographic
birth
factors

Childhood
traumas

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PSYC 4500 – Schizophrenia
HERITABILITY

If you are a monozygotic twin, you'll

have a 33% of also having the disorder
genetically
If you are a dizygotic twin, you’ll have a
7% of also having the disorder
genetically.
The heritability of the schizophrenia is
79%
The heritability of schizophrenia
spectrum disorder is 73%

-bipolar disorder heritability of 80%-

RISK AND VULNERABILITY: AT KEY POINT
THROUGHOUT LIFESPAN
Preconceptual risk factors Prenatal risk factors

E p id e m ic / p a nd e m ic , c linic a l
re c ord , se rolog ic a l e vid e nc e ,
p roinf la m m a tory m a rke rs
De m og ra p hic ,
p a re nta l f e a ture s PSYC 4500 – Schizophrenia
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2023
PRENATAL RISK FACTORS
.This hypothesis was first demonstrated in the 19 th century. Cases of
schizophrenia was being carried out using indirect measures.
.Kraepelin proposed that infection in the years of development may be
significance in high risk factor for schizophrenia.

Brain development due to nutritional deficiencies

can lead to increased risk to the disorder. A relationship between schizophrenic
births and the occurrences of known
viral infection in the community-
The Dutch Hunger Winter of 1944-1945
The Chinese famine in the late 1950s increases the risk of the disorder.

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 Maternal infection during pregnancy and the risk for
schizophrenia.

Exposure ​ Effects Population(s) Association/time References

Pregnant during Significant/second

Polio, poliomyelitis Finland 1957 Suvisaari, J et al. 1999
epidemic/pandemic trimester

Respiratory infection
Infection during
G/R Infection – pelvic US 1960-1967 Increased risk of
pregnancy clinical Brown et al. 2000
inflammatory Denmark 1973-1983 SZ/second trimester
records
Influenza
Infection during
Toxoplasma gondii Denmark 1981 Mortensen et al.2006
pregnancy serological Significant/utero
Urinary tract infection Finland 1947-1990 Clarke et al. 2009
evidence
Circulating
TNFα, IL-1β, and IL-6 US 1960-1967 Allswede et al. 2020
proinflammatory Higher risk /(7-20
TH2 cytokines (-) US 1959-1965 Allswede et al 2020
markers during weeks)
C- reactive protein Finland 1983 Canetta et al 2014
pregnancy

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FAMILY TREE!
 RISK AND VULNERABILITY: AT KEY POINT
THROUGHOUT LIFESPAN
Perinatal Risk Postnatal Risk

Obstetrical complication: hypoxia Stress: season of birth, ACE, migrant status and urbanity,
Lower birth weight, short gestation drug use
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WHAT GENES ARE
RESPONSIBLE FOR
THE DISORDER?
 WHAT DO THESE
GENES AFFECT?
In total there are 108 different gens
that are associated with the
disorder.
This however does not account for
every population set.
Some estimates state 270 gens.
This study examined European and
Asian ancestry. Consolidating many
other studies.
 SHARED
GENETICS

CACNA1C appears to be more

strongly associated to BP and SCZ
than any other disorder.
CACNA1C: is responsible for calcium
channel production.
Strong correlation between BP
polygenic score and the manic
symptom dimension in SCZ cases.
EPIGENETIC

the study of how your behaviour and

environment can cause changes that affect
the way your genes work. Epigenetic
changes are reversible and do not change
your DNA sequences but can change how
your body reads a DNA sequence.
WHY IS SCHIZOPHRENIA STILL AROUND?
Evolutionary causes.
PERINATAL RISK

Hypoxia
Obstetric complication Severe stress and anxiety = permeability of the
.Brain trauma placenta to cortisol.
.Lateral and third – ventricle Maternal prenatal stress affect the
size(enlargement) dopaminergic system of prefrontal cortex.
.Left and right hippocampi
size
.Prolonged delivery time
What is the association between the
birth weight infant and risk of
schizophrenia?

Low birth weight(<2500g) and short gestion

period + Genetic link to father with the disorder

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 AREA OF CONCENTRATION
Postnatal Risk

Adverse Childhood Experiences

Migration
First- and second-generation Stressful life events and trauma;
migrants and refugees; .Parental separation
.Poverty and minority status(for .Neglect
example, skin color)
.Police involvement
.Social exclusion and isolation
stress .financial struggles
.Language barrier/verbal .Physical/emotional abuse
communication .death of family member
.Inadequate vitamin D levels (parental/spouse)
.Vulnerability to infection Supports GXE mechanism
.Discrimination

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 AREA OF CONCENTRATION
Postnatal Risk

Cannabis Use

.Prolonged use of cannabis

.Relapse
.Cannabis use in adolescence
.Cocaine/stimulant use
.Potential for harm reduction?
Cannabis use and COMT gene
and AKT1 gene.

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 SCENARIOS

Fe ma le , 3 2 , 2 child r e n, Ma le , 3 5 , 3 child r e n, mov e d

Ma le , 2 4 , Ad op t e d a t a ge 6 ,
d ur ing t he se cond fr om r ur a l a r e a in Mor occo
a nd migr a t e d t o a n ur b a n Fe ma le , 2 0 , colle ge s t ud e nt
p r e gna ncy e sca p e d d e a t h t o S we d e n . Low cla s s
cit y , N e w Yo r k . status.
a ft e r a n a ccid e nt .
B ac k gr ound hi s t or y : p ar ent s ar e
B ac k gr ound hi s t or y : A s i an k i d s e p ar at e d , b r ok e up wi t h he r B ac k gr ound hi s t or y : Shar e Backgr ou n d h i s tor y
who was ad op t ed , s ep ar at ed d is or d er p r om ot ing genes wit h
f r om b i ol ogi c al p ar ent s wi t h
hi gh s c hool s weet hear t ,
s i b l i ng wi t h s c hi z op hr eni a.
E x p e r i e nc e s s t r e s s o r f r o m
gr and m ot he r p as s e d away discrimination, social
s c hiz op hr enia who d evelop ed r ec ent l y and i s f ac i ng a Dr i nk i ng p r ob l e m , t ak e s p s y c hi c
the d is or d er f r om the ep id em ic
c r i m i nal of f ens e f or d r ugs , m al nut r i t i on, and i s o l at i o n , po ve r t y,
t hat t ook p l ac e b et ween 1957 - t r aum a.
s hop lif t ing. language and cultural
1958 . di f f e r e n ces .

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 WHAT DOES THE FUTURE HOLD

Genetic risk factors Environmental risk factors

.The development relationship between intestinal

-Gene editing tools microbiota and the risk of developing schizophrenia.
-Examine other associated .New developed innovative techniques to
genetics. characterize ecosystem has produced data on the
-Focus attention on relationship between gut microbiota and
demographic differences schizophrenia.
–What are these genes .Interactions estimate just for 4% of the variance
schizophrenia.
affecting
.Further research is needed to understand how risk
factors exert influences biologically to shape an
individual propensity

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 THANK YOU
Take aways thoughts:

QUESTION: HOW DO GENETIC AND

ENVIRONMENTAL RISK FACTOR FIT IN
TOGETHER?

WITH A SUPRROTIVE COMMUNITY LIVIING

STRUCTURE, CAN THE DISORDER BE
REDUCED?
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