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Biomarkers in psychiatry
1. By:
Dr. Hani Hamed Dessoki, M.D. Psychiatry
Associate Prof. Psychiatry
Acting
Head, Psychiatry Department
Beni Suef University
2012
2. Introduction
Psychiatry has long been a second-class
citizen in science and medicine.
Despite much effort, the causes of many
psychiatric disorders remain unclear, and it
has been difficult even to categorize such
disorders precisely.
The identification of genetic biomarkers that
predict treatment response can improve
current clinical practice in psychiatry.
3. Introduction
The identification of genetic biomarkers that
predict treatment response can improve
current clinical practice in psychiatry.
4. Introduction
This is an emerging field known as
pharmacogenetics, which comprises of
genetic studies on both the
pharmacokinetics and pharmacodynamics
of treatment response.
Recent studies on antidepressant-treatment
response have focused on both aspects of
pharmacogenetics research, identifying new
candidate genes that may predict better
treatment response for patients.
5. Introduction
Ultimately, the use of genetic testing which
can be considered as a valuable guide in the
use of antidepressants and other
psychotropics in clinical practice.
The use of biomarkers to predict human
behaviors and psychiatric disorders raises
social and ethical issues, which must be
resolved by collaborative efforts.
6. Biomarkers
Biomarkers tell us who is sick, who will get sick, which
patients should be treated with what and when, how
well does the patient respond to treatment, and when
has the patient returned to health.
For countless diseases today, biomarkers are providing
physicians with valuable information.
It is a long-cherished dream of the medical profession to
be able to individually tailor diagnosis and treatment for
every patient.
This dream of personalised medicine could come true
with the help of biomarkers.
7. Biomarkers
Measuring biomarkers to identify and
assess illness is a strategy growing in
popularity and relevance.
Although already in clinical use for treating
and predicting cancer, no biological
measurement is used clinically for any
psychiatric disorder.
8. Biomarkers in Psychiatry
Here diagnostic tools are restricted to the
evaluation of behavioral and clinical phenotypes, a
severe limitation for any scientific study.
As in any other disease area a major goal is
therefore the identification of markers that can
categorize subsets of patients in a consistent
manner.
This will allow a more precise definition of
psychiatric disorders and in turn facilitate
investigations of the pathophysiology and enhance
the ability for patient treatment.
9. Biomarkers in Psychiatry
Biomarkers could predict the course of a
medical problem, and aid in determining
how and when to treat.
Several studies have indicated that of
candidate psychiatric biomarkers detected
such as cholesterol and associated proteins,
specifically apolipoproteins (Apos), may be
of interest.
10. Biomarkers in Psychiatry
Cholesterol is necessary for brain
development and its synthesis continues at
a lower rate in the adult brain.
Apos are the protein component of
lipoproteins responsible for lipid transport.
There is extensive evidence that the levels
of cholesterol and Apos may be disturbed in
psychiatric disorders, including autistic
spectrum disorders (ASD).
11. Neuroimaging:
Why Important in Psychiatry?
To understand the functional neural basis of
psychiatric disorders
To obtain neural markers / disease biomarkers
and endophenotypes to aid diagnosis
To identify disease enophenotypes
predict treatment response
to help
12. Inflammation and behaviour
There is a relationship between stress, inflammation
and different forms of psychiatric pathology.
The way the brain reacts to stress, especially in
relationship to personality factors, is still
insufficiently known.
One way to look at the brain is to study
cerebrospinal fluid (CSF) (Anckarsäter 2005,
Söderström 2001), another to look at different
13. Inflammation and psychiatric disorders
Classical sickness behavior after cytokine therapy
(Dantzer et al 2004)
Increased risk of schizophrenia and autism after
prenatal maternal infections (Freedman et al 2010)
Inflammatory dysbalance in several psychiatric
disorders
14. Inflammation and aggression
Hostility is associated with increased levels of
several inflammatory markers (Marsland et al 2008)
There seems to be a connection between variants
of the CRP gene and impulsive personality traits
(Suchankova et al 2009)
Measures of hostility/anger are increased in
persons undergoing cytokine therapy (Kraus et al 2003)
15. Pharmacogenetics of Antidepressant Drugs
While antidepressant drugs are widely
prescribed to treat depression and anxiety
disorders, only one-third of drug-treated
patients exhibit a beneficial therapeutic
response.
Response and tolerability to medication are
highly variable, with some patients
responding to one treatment but not
another.
16. Uncertainty in Psychiatry
There are several potential explanations for
these poor drug-response rates, including
clinical heterogeneity and diagnostic
uncertainty, environmental and social
factors, and genetics factors.
17. Pharmacogenetics
Early studies suggested that specific clinical
phenotypes, such as melancholic or anxious
depression, might predict differential responses to
antidepressants; however, the clinical phenotypes
were often variable and difficult to translate into
clinical practice.
Pharmacogenetics, which is the identification and
development of genetic biomarkers that predict
therapeutic response and the risk of side effects,
takes a different approach to ultimately help the
practitioner in choosing effective and safe treatment
for patients suffering from psychiatric disorders.
18. Pharmacogenetics
Pharmacogenetic studies are often
subdivided into studies concerned with
pharmacokinetics and those concerned with
pharmacodynamics of antidepressant
medications.
Pharmacokinetics refers to the mechanisms
controlling the absorption, distribution,
metabolism and excretion of a drug.
19. Pharmacogenetics
Knowledge of the genetic metabolizer status of a
patient may be helpful to the clinician in order to
avoid potential side effects and to reach therapeutic
levels faster.
However, the well-documented correlations
between CYP alleles and plasma concentrations of
antidepressants do not translate well to differences
in clinical response to the same antidepressants.
Some small studies have found a significant
association between CYP2D6 genotypes and
antidepressant-treatment response
20. Pharmacogenetics
The term pharmacodynamics is used to describe the effects a
drug has on the body.
Pharmacodynamics includes interactions of a drug with
receptors, transporters and downstream targets.
Although the primary mechanism of action for
antidepressants is thought to involve predominantly
monoaminergic neurotransmitter systems, the exact
mechanisms by which antidepressant medications work
remain unknown.
Most pharmacogenetic studies in MDD to date have focused
on candidate genes involved in monoaminergic
neurotransmission.
25. Future of Behavioral Health has Arrived
Patients with depression and anxiety are frustrated with drug
treatments because of poor response (up to 5 trials).
Also, some of these medications increase anxiety, resistance
to treatment, insomnia, and sexual dysfunction.
Sometimes they may quit medications.
It is better to choose psychotropic medications based on the
individual genetic characteristics, metabolizing pathways
leading to better medication tolerance.
This give the patient the confidence to continue treatment.
Test can done by a simple cheek swab (Assure RxGeneSightRx).
26.
27. Future
The FDA has approved several drug labels to contain
information about pharmacogenetic biomarkers.
Currently, approximately 17% of these pharmacogenetic labels
are for psychiatric drugs, and most of them contain
information about the CYP450 enzymes.
However, most of these labels do not offer any clinical
recommendations or require the use of this information before
treatment prescription.
The ultimate goal of future studies is to expand the
pharmacogenetic information on antidepressant labels and
incorporate them into wide clinical use.
However, there are several limitations that need to be
considered before the field can advance to this stage.
28. Problems
The main problem with current pharmacogenetic
studies is the lack of standardization, making it
difficult to distinguish between positive and
negative findings in the same candidate gene.
Current studies often have very different inclusion
criteria, use of medications, outcome measures,
recording of side effects, ethnicity of study
population and genetic coverage.
Furthermore, many of these studies have small
sample sizes with limited power and a short-term
follow-up of patients, leading to possible false
negative or false positive results.
29. Take Home Massage
The mere existence of biomarkers in psychiatric illness
does not mean we should ignore the cultural,
psychosocial, and existential components of our
patients’ problems, or attribute their psychopathology to
biochemical factors alone.
Nonetheless, accurate biomarkers, along with more
reliable and valid disease criteria, will help psychiatry
achieve greater objectivity in diagnosis.
Even more promising, biomarkers may soon help us
diagnose psychiatric disorders in their earliest stages,
potentially enhancing the care of our patients.
Notas do Editor
Ökande data talar för ass mellan psykop och immunsyst, class sickn beh 1 6 tnf ifn, NK cell upp hos vissa, TNF upp hostility upp, IL6 och tnf upp schiz, genvarianter i CRP ass med ökad impul. Icke-psykiatriskt material! BBB can be disrupted and altered by ck. R and utsöndra.
Kieseppa et al., 2004 (Am J Psychiatry):
Finnish study. All Finnish same-sex twins (N=19124) were screened for a diagnosis of Bipolar I Disorder.
38 pairs were detected. 26 pairs accepted to participate.