This document discusses several studies related to childhood mental health and schizophrenia. It describes a study by Dr. Kristin Laurens that found negative schemas in childhood are associated with psychotic-like experiences in children, and that changing these schemas through cognitive-behavioral interventions may have benefits. It also discusses how childhood trauma can interact with genes like FKBP5 to influence cognition in schizophrenia through stress response pathways. Finally, it summarizes an animal study that found teasaponin supplementation improved cognition in obese mice by enhancing leptin signaling in the brain.

1. Schizophrenia Research Institute | Margarete Ainsworth Building Barker Street Randwick NSW 2031 www.schizophreniaresearch.org.au
October 2015
Protecting kids’
mental health
Improving how children feel about themselves
and others may have an important knock-on
effect for their future mental health, especially
if they experience psychotic-like symptoms.
Dr Kristin Laurens
In the first study of its kind, Dr Kristin Laurens
has been part of a group of researchers
interested in how schematic beliefs –
that is, beliefs formed early in life and
shaped by childhood experience – may
be associated with unusual, or psychotic-
like, experiences in children. It is thought
that improving negative schematic
beliefs in young people may be a useful
therapeutic target for those at risk of
developing psychosis.
Schemas influence how we interpret the
actions of others, process our emotions
and behave. If the schemas are negative
they may cause a person to believe they
are unlovable or worthless, or that other
people are untrustworthy or judgemental.
These negative beliefs about the self
or others are more often seen in people
with psychosis, when compared with
the beliefs held by healthy individuals.
Psychotic-like experiences are non-clinical
forms of symptoms that are reported by
people with psychosis, such as hearing
voices that others can’t hear, feelings of
being watched or having special powers.
These are common in young people in
the general population, but persistence
of these experiences is associated with
distress and increases the likelihood of
later mental health problems.
If addressed early, for example as part
of a cognitive-behavioural intervention,
the chance to improve negative schemas
before they become fixed beliefs in
adulthood may have beneficial outcomes
for young people who have experienced
distressing, psychotic-like experiences.
“Our study found that negative schemas
in childhood are associated with
psychotic-like experiences in children and
that schema-change work is an important
therapeutic focus,” says Dr Laurens.
“Such interventions include considering
how the negative beliefs arose, how
they are maintained, their influence on
day-to-day functioning and the benefits
of changing the incorrect beliefs.”
An associated study has also found
that these negative beliefs about self
and others influence how the experience
of being bullied impacts on children’s
psychotic-like experiences.
“If we intervene early, we can teach these
children ways to reduce their negative
beliefs and build the kind of resilience
that will help them better deal with
victimisation experiences like bullying,”
says Dr Laurens. “Creating resilience is
a great way to protect the future mental
health of our children.”

2. 2 Schizophrenia Research Institute | HeadLines
Although he started his degree in
psychology, it was a neuroscience
unit that led Juan Olaya to become
interested in understanding the possible
causes of schizophrenia. “What I found
really fascinating was what causes
mental illness to occur,” he explains.
“I’m fascinated by the biological,
mechanistic basis. Studying
neuroscience allows me to explore
the ‘how’ of mental illness. The brain
is incredibly complex and intricate.
Studying it makes me want
to know more about how things can
go wrong and how we can fix it.”
This interest in the “how” of mental
illness has led him to explore the
Neuregulin 1 type III (NRG1 III) mRNA
that is increased in the brains of people
at risk of developing schizophrenia.
Using a mouse model that has an
overexpression of this particular
transcript, Juan has found that not only
do these mice display schizophrenia-
like symptoms, they may also be able
to explain how an overabundance of
NRG1 III may lead to the development
of schizophrenia.
Exposure to traumatic experiences in
the early stages of life – including various
forms of abuse or neglect, parental
divorce or mental illness, and poverty –
are known to influence the development
of disorders such as schizophrenia.
These early experiences impact the
development of brain systems that
regulate the body’s response to stress,
including the hypothalamic-pituitary-
adrenal (HPA) axis. Previous studies have
noted that exposure to trauma in
childhood can affect cognition later
in life for healthy adults as well as
people with schizophrenia.
At the same time, individual variation in
the genes involved in regulating the HPA
axis have been shown to affect stress-
responses in people prone to psychosis.
These associations led our researchers
to investigate whether individual variation
in one of these genes (FKBP5), would
moderate the effects of childhood
trauma on cognitive function in people
with schizophrenia.
The effects of childhood stress
Early life experiences can have different influences on behaviour
depending on our genes. Associate Professor Melissa Green has
recently led an investigation of the impact of childhood experiences
on cognition in schizophrenia.
The study found that people with a
particular variant of the FKBP5 gene
performed worse on measures of
attention if they had been exposed
to childhood trauma, compared to
participants with the same genetic
variant who were not exposed to trauma.
This pattern was found in people with
and without schizophrenia, and suggests
that this interaction between genes and
environment is not restricted to people
with schizophrenia, but can certainly
exacerbate their cognitive deficits.
In addition to this finding, another variant
of this gene was associated with poor
cognition in schizophrenia regardless
of adverse experiences in childhood,
which suggests that genes regulating
stress-responses may also contribute to
cognitive impairments in ways that are
specific to the disorder.
“The extent to which adverse childhood
experiences affect brain function in later
life appears to depend on individual
variation in genes that regulate stress
responses,” says Associate Professor
Melissa Green, “and this may be important
in the development of psychosis. Our
next steps will explore the way in which
early life trauma changes the expression
of these genes. We hope the results
will help us find new ways to improve
cognition.”
The group used genetic material obtained from the
Australian Schizophrenia Research Bank, a bio-bank
facility run by the Institute.
Melissa Green
Understanding these mechanisms
has the potential to lead to new
therapeutic targets for a particular
subset of schizophrenia patients.
Indeed, identifying new therapies
to treat schizophrenia is an aspect
of future research that most appeals
to Juan.
“Due to the heterogeneity of the
disease, two patients can have similar
symptoms, such as hallucinations,
delusions and social withdrawal,”
says Juan, “however what may cause
their symptoms may be very different.
Person A may have an inflammatory
response, while person B may have
a genetic mutation on the NRG1 gene.
So I think a large part of the research
should look at how to identify a subset
of patients who are defined not by their
symptoms, but by the underlying cause
of schizophrenia. We need to hone in
on that. We can then find a tailored
therapeutic response that is effective
in preventing or treating that particular
subset of schizophrenia. I think that is
the future of schizophrenia research.”
FOCUS ON
Juan Olaya
Research Area:
Animal models for schizophrenia
Educated:
Bachelor of Science Major
in Psychology with Honours
in Neuroscience, UNSW
PhD in Psychiatry Candidate, UNSW
Personal Interests:
Gym, outdoor activities,
mountain biking, bushwalking

3. An animal study conducted by
Dr Yinghua Yu at the University of
Wollongong has found that teasaponin
supplementation may be used to prevent
neurodegeneration and improve cognitive
deficits associated with obesity.
There is a high incidence of obesity and
metabolic issues in mental disorders
such as schizophrenia. The obesity can
be caused by the disorder itself, or it
could be a result of medication side
effects or due to lifestyle factors. Dr Yu
and Prof Huang are searching for a way
to improve cognitive function by
dealing with the first two causes.
People classified as obese are often
leptin-resistant, which means that their
brain has reduced levels of leptin, the
hormone that stops us from feeling
hunger once we’ve eaten. Leptin
also facilitates learning and memory
functioning in the brain.
Brain-derived neurotrophic factor (BDNF)
promotes the brain’s ability to grow new
neurones, which are also important for
learning and memory. A high fat diet,
which often results in obesity, reduces
the amount of BDNF in the brain,
however this can be reversed with
the administration of leptin.
So, leptin is an important part of the brain’s
ability to maintain particular cognitive
functions and is an integral part of the
body’s way of maintaining a healthy
weight, which made it an interesting
therapeutic target to explore.
The recent study from Dr Yu found that
teasaponin supplementation improved
leptin signalling in the brain as well as
the amount of BDNF growth caused by
leptin. This may have beneficial effects
in reducing cognitive decline associated
with obesity.
It must be noted, however, that the dose
of teasaponin obtained by frequently
drinking tea is significantly lower than
the doses in the study. Clinical trials are
needed to determine the optimal dose
in humans, as well as any risk of toxicity
over long-term use.
3HeadLines | Shining a Light on Schizophrenia | October 2015
Teasaponin
supplementation
offers promising
results
In the future, a cup of tea may
be just what the doctor orders to
reduce the cognitive impairments
associated with antipsychotic-
induced obesity.
New screening test identified
The Australian Schizophrenia Research Bank has assisted researchers internationally
with genetic and biological samples to support studies. Most recently, they have
supplied a young Newcastle researcher with participants for her study.
Cognitive impairment in schizophrenia
has been well-established in research.
Individuals with schizophrenia have
been found to have deficits in the areas
of memory, executive functioning and
attention. These impairments often
don’t change too much over time and
can impact on a person’s ability to live
independently, retain employment and
function comfortably in social settings.
In order to reduce these impacts,
it is important for clinicians to be able
to address and treat any cognitive
difficulties. However, there is currently
no screening test that is accurate,
easy-to-use and widely available that
can inform clinicians of the cognitive
strengths or weaknesses of their patient.
The current study identified that the
Audio Recorded Cognitive Screen
(ARCS) could fill this gap. The ARCS
is unique in that it is administered via
an audio device such as an MP3 or
CD player and participants record their
answers in a response booklet, making
it a test that is both easy to use and
access. The administration of the tool
requires minimal clinician supervision,
no special training, and takes only
35 minutes.
Researchers tested a small group of
people from the Australian Schizophrenia
Research Bank database with and
without schizophrenia and found that
ARCS may be able to detect cognitive
deficits associated with schizophrenia,
particularly with regards to memory
and verbal fluency.
“The minimal resources required
to administer this test may make it
attractive for many community-based
clinical settings such as community
mental health and disability employment
services and could be useful in guiding
treatment planning,” said study author
Brooke Gelder.
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4. 4 Schizophrenia Research Institute | HeadLines
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