OXIDATIVE STRESS IN SCHIZOPHRENIA

PATIENTS WITH and WITHOUT DIABETES

MELLITUS
Mentor : dr. Sabar P Siregar, SpKJ
FK-UKI
(April 14
th
2014 May 9
th
2014 periode)
Gemeinial 07 610 50 129
Made Sanitca Indah 09 610 50 035
Anggraeni Parwati 09 610 50 036
Indri Patra Tarigan 09 610 50 037
Indriyanti N.A.U Kotten 09 610 50 038
Virginia Cynthiara M.A 09 610 50 039
Friska Karolina 09 610 50 041
Andhika Djajadi 09 610 50 043
OUTLINE
Introduction
Materials and
Methods
Statistical
Analysis
Results
Discussion
Critical
appraisal
INTRODUCTION
I
n
t
r
o
d
u
c
t
i
o
n


Schizophrenia is a common psychiatric disorder,
marked by gross distortion from reality.
Presents in young adulthood with auditory
hallucinations, paranoid or bizarre delusions, or
disorganized speech and thinking with significant social
or occupational dysfunction.
There are many important contributory factors in
development of the disease.
Increased dopamine activity in the mesolimbic
pathway which becomes mainstay of treatment in
antipsychotic medication.
INTRODUCTION
The prevalence of schizophrenia in
worldwide 3 4 %.
Free radicals are involved in schizophrenia
pathogenesis.
Cytoprotective enzymes and antioxidants
limit the damage from free radicals.
Malondialdehyde (MDA) is a secondary lipid peroxidation
end product and is specific marker of lipid peroxidation of
membrane.
Total thiols are the major antioxidants in the body and
they consists of free sulfhydryl (-SH) groups in plasma and
cells, and SH groups bound to proteins.
INTRODUCTION
Glutathione (GSH) plays a major role in protecting
nervous tissue against reactive oxygen species and in
modulating redox-sensitive sites, considering the N-
methyl D-aspartate (NMDA) receptor hypo function is
hypothesis for schizophrenia.
Number of studies in patients with schizophrenia has
found a positive association between schizophrenia and
diabetes mellitus.
In the present study, we have tried to determine the
levels of oxidative stress in schizophrenia with and
without diabetes mellitus, by analyzing MDA and total
thiols, and to know if the determined parameter relates
to each other.
MATERIALS AND METHODS
Subjects and Samples
Biochemical determinations
Total thiol assay
MDA assay
Other biochemical parameters
MATERIALS and METHODS (1)
Subject
and
Samples
60 schizofrenia
patients
Gender
Mean age
58 12 y.o
42 18
Groups
I
Without
diabetes
(n= 39)
II
With
Diabetes
mellitus
(n= 21)
50 healthy
controls
Mean age
52 12 y.o
Blood
samples
MATERIALS and METHODS (2)
5 5 dithio-bis (2-nitrobenzoic acid) (DTNB)
Reduced glutathione (GSH)
Standard MDA
Biochecmical
determinations

Reaction mixture contained 900 L 2 mM Na2 EDTA in 0.2

M Na2HPO4, 20 L 10 mM DTNB in 0.2 M Na2HPO4 and
100 L of serum.
Total thiol assay
Reaction mixture contained 1 mL 0.67% thiobarbituric
acid (TBA), 500 L 20% Tri carboxylic acid (TCA) and
100 L serum.
MDA assay
Fasting blood glucose (FBG) Alanine transaminase
Serum levels of urea Total bilirubin
Creatinine Direct bilirubin
Aspartate transaminase
Other biochemical
parameters
STATISTICAL ANALYSIS
The results were
expressed as
mean standard
error of mean
(SEM).
Performed using
the statistical
package for social
sciences (SPSS-16,
Chicago, USA).
Pearson
correlation was
applied to
correlate between
the parameters.
RESULTS
DISCUSSION
DISCUSSION (1)
Serum MDA levels in
schizophrenic
patients increased
presence of
oxidant damage to
biological
membranes
including neuronal
cells.
The brain tissue
contain large
amounts of
polyunsaturated
fatty acids and are
vulnerable to free
radical induced lipid
peroxidation which
will generate MDA.
MDA levels
increase in
schizophrenia
patients with
diabetes
mellitus
Hyperglycemia itself
can induce oxidative
stress and also
deplete antioxidants
which in turn cause
peroxidative
membrane damage.
DISCUSSION (2)
The positive
correlation between
MDA and FPG
indicates more
severe is the
diabetes mellitus
more will be
membrane damage.
There is increased risk
of diabetes mellitus in
schizophrenic patients
and which has been
attributed due to:
disease itself
genetic factors
antipsychotic medications
life style changes
obesity
There is increased risk
of schizophrenia in
babies born to
diabetic mother. Three
prenatal mechanism:
Hypoxia
Oxidation stress
Increased inflammation
DISCUSSION (3)
The role of GSH in
protecting nervous tissue
against free radical
induced membrane
damage in neuronal
tissues.
The negative correlation
between total thiols and
MDA indicates the role of
thiols in neutralizing
reactive free radicals, and
thereby preventing
oxidative membrane
damage.
Decrease in total
thiol levels in
schizophrenia
patients with
diabetes mellitus.
DISCUSSION (3)
Decrease in total thiol levels in
schizophrenia patients with
diabetes mellitus.
The role of GSH in
protecting nervous
tissue against free
radical induced
membrane damage in
neuronal tissues.
The negative
correlation between
total thiols and MDA
indicates the role of
thiols in neutralizing
reactive free radicals,
and thereby
preventing oxidative
membrane damage.
DISCUSSION (3)
Decrease in total thiol levels in
schizophrenia patients with
diabetes mellitus.
The negative correlation
between total thiols and
MDA indicates the role
of thiols in neutralizing
reactive free radicals,
and thereby preventing
oxidative membrane
damage.
The role of GSH in
protecting nervous
tissue against free
radical induced
membrane
damage in
neuronal tissues
CRITICAL APPRAISAL
CRITICAL APPRAISAL (1)
This has been thought to result from
numerous factors associated with
schizophrenia i.e the disease itself and
its genetic factors, antipsychotic
medication, lifestyle changes, and
possibly weight gain may play a
role.
Because the
nutrition has a real
significant role in this
study, the bias will
be smaller if the
nutrition from both
population arranged.