Biomarkers are objective measures that can provide information on a variety of different clinical characteristics. Cytokines as Biomarkers for Anti-inflammatory Treatments. Cytokines and psychosis. Hormonal Stress Biomarkers. LOWERED CORTISOL AWAKENING RESPONSE.

1. Stress and infalmmatory
Biomarkers
By
Mohamed Ghamry
BioMarkers for Treatment
Response in First-Episod
Psychosis

2. Biomarkers are objective
measures that can provide
information on a variety of
different clinical characteristics,
such as an individual's normal
biology, pathology, including the
trajectory of illness, or the
response to a therapeutic
intervention.

3.  pathology biomarkers have been
highly informative for understanding
the neural and genomic
heterogeneity of neuropsychiatric
disorders and appear promising for
the identification of individuals at
ultrahigh risk for developing
psychosis .

5. Inflammatory
biomarkers

6.  Cytokines as Biomarkers for
Anti-inflammatory Treatments

7. The effect on glutamine synthetase (found only in astrocytes) which is one
of the factors protecting neurons from glutamate induced excitotoxicity

8. the effect of excitotoxicity on neurons is to decrease the activity of choline acetyl
transferase (ChAT) in cholinergic neurons and to decrease the activity of
glutamate decarboxylase (GAD) in GABAergic neurons. IL-6 (10 units) reduces
the first effect, but not the second.

9. IL-6 appears to have multiple effects, some neuroprotective, and others damaging. The
effects depend on the duration of exposure and the cell type. IL-6 is known to protect
from NMDA induced excitotoxicity under some conditions, but to elevate calcium
currents that can lead to increased neuronal stress/death in other cases

10. Cytokines and
psychosis

11.  In first-episode psychosis, there
have been a number of studies to
report increased levels of cytokines
including interleukin (IL)-1β, IL-6,
IL-12, interferon (IFN)-γ, tumor
necrosis factor (TNF)-α,
transforming growth factor-β and
more recently IL-17, the
complement protein C1Q activation,
leukocyte activation, and

12.  All these baseline immune-
inflammatory disturbances may be
biomarkers of interest for future anti-
inflammatory add-on therapy.
 The adjunction of celecoxib( a
cyclooxygenase-2 inhibitor), to
amisulpride in first-episode psychosis
improved the clinical outcome as
assesseby diminished PANSS
(positive, negative, and general

13.  Several studies have so far
assessed the association between
cytokine levels and treatment
response in first episode psychosis:
decreased IL-6 levels, increased
levels of IL-10, and normalization of
Th17 cells were all associated with
positive treatment response.
Cytokines & ttt response

14. Hormonal Stress
Biomarkers

15.  Stress is known to play a key role in
the development and course of
many psychiatric disorders,
including psychosis.
 Hypothalamo-pituitary-adrenal
(HPA) axis function is often altered
in the major psychiatric disorders

16.  Multiple studies, but not all, found a
basal overactivity of the HPA axis in
male patients with first-episode
psychosis that was, however, only
inconsistently associated with
disease severity.
 HPA functioning was also found to
be impaired in the ultra-high-risk
stages of illness, with elevated
cortisol levels indicating increased

17.  HPA disturbances may be
maintained and worsened all along
the illness progression and
correlated with severity of illness
and aggressive behavior in male
patients with first-episode
psychosis.
 Antipsychotics drugs were found to
normalize diurnal cortisol
hypersecretion but not the blunted
cortisol awakening response in
patients with first-episode

18. Dehydroepiandrosterone
(DHEA) and its sulphated form
(DHEAS) are major circulating
corticosteroids that exert multiple
effects on the central nervous
system and have antistress and
neuroprotective properties.

19.  DHEA has potent antiglucocorticoid
actions
on the brain and can protect
hippocampal neurons from
glucocorticoid-induced
neurotoxicity.
 The corelease of DHEA in the
acute stress response is thought to
protect against the potentially
damaging effects of excessive

20. LOWERED CORTISOL
AWAKENING RESPONSE

21.  For the study, saliva and blood samples
were taken from 68 patients presenting
with early psychosis and 57 healthy
controls. In order to establish whether
symptoms had improved following the first
course of antipsychotic medication,
responses to treatment were measured at
the beginning of the study and 12 weeks
later.
 Those who did not respond to early
treatment showed lower levels of cortisol
awakening response (CAR). CAR refers to
an increase of around 50 per cent in levels
of cortisol 20-30 minutes after waking in

22.  Individuals at the onset of
psychosis typically show increased
levels of cortisol throughout the day
but a blunted CAR.
 The study also found higher levels
of inflammatory markers, in
particular IL-6 and IFN-γ, among
those who did not respond to
treatment. These differences in
cortisol and inflammatory
biomarkers were found to persist