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Professor Lisa Nissen and Dr Esther Lau are from the
School of Clinical Sciences, Queensland University of
Technology, Brisbane, Queensland.
Raloxifene for improving
attention and memory in
BY PROFESSOR LISA NISSEN & DR ESTHER LAU
Schizophrenia can affect people’s thoughts, feelings, and behaviour, and it
can be as if your brain was playing tricks on you.
Schizophrenia is characterised by
the co-occurrence of at least two
symptoms (at least one positive
symptom) occurring for a significant
period of time over an ‘active phase’ of
a one-month period, and continuously
over at least a six-month period.
Examples of positive symptoms include
delusions, hallucinations, disorganised
speech, while negative symptoms
include attention deficit, diminished
or absence of emotional expressions
(affective flattening), or anhedonia,
which is an inability to find pleasure
in activities normally found to be
enjoyable e.g. hobbies.
Many people find schizophrenia
difficult to understand and empathise
with, especially since it is not possible
to experience or make sense of what
is going on in someone else’s mind.
Schizophrenia is not a feeling, emotion,
or occurrence that people can easily
empathise with, e.g. like pain when
you walk into the corner of the kitchen
bench, or when you scratch and dent
your brand new car after driving it for
the first time. So imagine if you were
not able to trust what your own brain
was telling you – that what you heard or
saw was not actually there. Or that you
are not able to make any sense of any
stimuli from the outside world and even
something that many people take for
granted, like watching television can just
come across as gibberish.
The cause of schizophrenia is not well
understood, but has been identified
as being associated with a range of
abnormalities in structure and function.
These abnormalities have been related
to imbalances in neurotransmitters,
with overactive doperminergic receptors
being identified as one of the culprits.
Schizophrenia management is around
psychosocial interventions such as
skills training and cognitive behavioural
therapy; and antipsychotic medications.
Non-adherence to medication is
challenging to manage as people with
schizophrenia can have diminished
insight into their condition.
Antipsychotic medications are
thought to produce their effects,
at least in part, though blocking
doperminergic transmission in parts
of the brain, particularly the limbic
system. Where other symptoms are
present, adjuvants may be added
to a patient’s therapy. Examples of
adjuvants include mood stabilisers
(e.g. lithium) when concurrent bipolar
spectrum symptoms are present,
antidepressants (e.g. fluoxetine) for
concurrent depression, or anxiolytics
(e.g. alprazolam) for concurrent anxiety.
However, patients often do not respond
adequately to existing antipsychotic
medication, and the evidence
supporting the use of some adjuvant
therapies is lacking, or controversial.
Cognitive impairment in memory and
attention is one of the characteristics of
schizophrenia that is least responsive
to pharmacological treatment. There is
reportedly no existing pharmacotherapy
that can restore cognitive
function, and only galantamine
and minocycline have shown small
beneficial effects. Galantamine works
as an acetylcholinesterase inhibitor;
while minocycline is thought to inhibit
nitric oxide-induced neurotoxicity,
attenuate dopaminergic overactivity
in parts of the brain, and inhibit
microglial activation (which mediates an
inflammatory process in the brain that is
thought to cause neuronal cell death in
numerous neurodegenerative diseases in
Increasing research has identified
the important role of hormones in
schizophrenia, more specifically oestrogen.
Women are more likely to develop their first
episode of psychosis when their oestrogen
levels are low, and symptoms can remit
when progesterone and oestrogen levels
are high. Similarly, in males, testosterone
is converted to oestrogen in the brain,
and men with schizophrenia had lower
testosterone levels compared to males
without schizophrenia, and lower
testosterone was correlated with more
severe negative symptoms. As such,
it was postulated that oestrogen played a
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