Article about schizophrenia disorder

1. Por: Amelia Molina
Astrid Carolina Salazar

2. Introduction
SCHIZOPHRENIA Is a complex disorder affected by
genetic as well as enviromental factors
involving dysfunction in nearly all
aspects of higher order behaviour.
• abnormal
social
behavior
• failure to
recognize
what is
real.
Common symptoms include
• false beliefs
• unclear or confused thinking
• auditory hallucinations
• reduced social engagement and
emotional expression
• inactivity

3. • Symptoms begin typically in
young adulthood, and
about 0.3–0.7% of people
are affected during their
lifetime.
• People with schizophrenia
are likely to have additional
conditions, including major
depression and anxiety
disorders; the lifetime
occurrence of substance
use disorder is almost 50%

4. • The genetic
influence of
SZ remains
unknown.
• Among the multiple genes
implicated, those
enconding for 14-3-3
proteins at locus 8q, 22q,
17p, have been repoted
to be associated with SZ

5. PROTEINS The 14-3-3 protein family is formed by
seven distinct isoforms (β, ε, γ, η, ζ, σ) with
abundant presence in the brain.
Their function is exerted by
formig dimers.
Activates tyrosine
hydroxylase.
Are involved in multiple cellular process such
as neurotransmission, cell signalling, ion
channel functioning, intracellular
trafficking/targeting, transcription, cell
division and differenciation and apoptosis.

6. • 14-3-3 protein beta/alpha is
a protein that in humans is
encoded by the YWHAB
gene.
• Adapter protein implicated
in the regulation of a large
spectrum of both general and
specialized signaling
pathways.

7. • Negative regulator of
osteogenesis.
• Blocks the nuclear
translocation and apoptosis

8. • 14-3-3 protein zeta/delta
is a protein that in humans
is encoded by the YWHAZ
gene
• The encoded protein has a
role on the regulation of
insulin sensitivity
• A multifunctional
regulator of the cell
signaling processes.
• Interacts with α2
adrenoreceptor and could
have a role in the
supersensitivity of this
receptor in major
depression disorder (MD)

9. Biological process:
• response to drug
• platelet activation
• histamine secretion by mast cell
• establishment of Golgi localization
• gene expression
• blood coagulation
• signal transduction
• protein targeting to mitochondrion
• negative regulation of apoptosis

10. Psychotropic Treatment
• Psychotropic medications are drugs that are typically prescribed to treat
mental health conditions. These include:
1. depression
2. Anxiety
3. obsessive compulsive disorder
4. Schizophrenia
5. bipolar disorder
6. attention deficit disorder.
• The term, psychotropic refers to a drug whose primary or significant effects
are on the central nervous system.
• Most psychotropic act by altering neurotransmission process, stimulating or
inhibiting activity.
• The mainstay of treatment is antipsychotic medication, which primarily
suppresses dopamine receptor activity.

11. Example Queatiapina
is a neuroleptic drug belonging to the
group called antipsychotics used in the
treatment of schizophrenia and severe
manic and depressive episodes of
bipolar disorder.
• Exerts its antipsychotic effect in part
through its activity as an antagonist
of serotonin receptors and dopamine

12. Relay
• Various studies have reported descreases in mRNA and protein
expression of diverese 14-3-3 isoforms in different brain areas of
subjects with schizophrenia.
• Modulation of 14-3-3β and 14-3-3ζ isoforms has been described in
cellular and in animal models after chronic antidepressant
treatment.
• A number of studies have identified down-regulations of 14-3-3
mRNAs in the brain samples of schizophrenia patients.
• In addition, proteomic analyses have determined a reduction of 14-
3-3 proteins in schizophrenic brains, with 14-3-3ζ decreased
expression having been consistently reported in multiple studies

13. • Studies of prefrontal cortical show gene expression in
schizophrenia, reported that certain groups of genes
regulating presynaptic, postsynaptic, and metabolic functions
were consistently and significantly decreased in schizophrenia
• 14-3-3 protein family describes this alterations in SZ subjects:
1. Dopaminergic, serotonergic and/or glutaminergic
dysregulation
2. Epigenetic alterations
3. Neurodevelopmental deviances
4. Cortical atrophy

14. General Objective
• See if the expression of the 14-3-3 protein (ζ,β) in the
prefrontal cortex of schizophrenia subjects differs with control
subjects y and see in what way the psicothropic treatment
deacrease or increase levels of proteins and in what way this
contributes to the syntoms

15. Materiales y Métodos
• SUJETOS se obtuvieron cerebros humanos
postmortem del instituto Basque y de la universidad
centro de medicina legal.
• Se usaron muestras del área de broadman, se
diseccionaron y se almacenaron
• Control 52
( ninguna evidencia de desordenes neuropsiquiatricos o
abuso de drogas
• Sujetos con SZ 22
• Sujetos con MD 21
Fueron clasificados en
antipsicoticos/antidepresivos
libres o tratados

17. Materiales y Métodos
• Western blot es una técnica analítica usada para detectar
proteínas específicas en una muestra determinada.
1. Mediante una electroforesis en gel se separan las proteínas
atendiendo al criterio que se desee: peso molecular, estructura,
hidrofobicidad, etc.
2. Luego son transferidas a una membrana adsorbente (típicamente
de nitrocelulosa o de PVDF) para poder buscar la proteína de interés
con anticuerpos específicos contra ella.
3. Finalmente, se detecta la unión antígeno-anticuerpo por actividad
enzimática, fluorescencia entre otros métodos.
• De esta forma se puede estudiar la presencia de la proteína en el
extracto y analizar su cantidad relativa respecto a otras proteínas.

18. 3. Resultados
Se evaluaron 3 parámetros
3.1 Variables epidemiológicas y metodológicas que contribuyen
a los niveles de inmunoreactividad de las proteínas en la corteza
prefrontal humana
14-3-3β 14-3-3ζ
Género (β = −0.376, p = 0.007) Género (β = −0.297, p = 0.031)
PMD (β = 0.349, p = 0.011) Edad (β = −0.309, p = 0.025)
Línea de regresión positiva en PMD Línea de regresión negativa en edad
Edad y tiempo de almacenamiento PMD y tiempo de almacenamiento
Inmunoreactividad 29% mayor en hombres
Los niveles de etanol en la sangre no fueron significativos

19. 3. Resultados
• 3.2 Inmunoreactividad de 14-3-3β y 14-3-3ζ en las personas
con esquizofrenia tratadas con antipsicóticos y libres de
antipsicóticos
Sin antipsicóticos Con antipsicóticos
Niveles de 14-3-3β Significativo incremento
(∆: 25 ± 5% n:11 p:0,046)
No hay un incremento
significativo( p: 0,156)
14-3-3β fue 30% mas alta en sujetos con
esquizofrenia sin antipsicóticos (p:0,011)
Resultado independiente del género (p:0,012)y
PMD (p:0,015)
Sujetos con esquizofrenia Sujetos control
Niveles de 14-3-3β No se presento una diferencia significativa

20. Con antipsicótico Sin antipsicótico
Niveles de 14-3-3 ζ No hay incremento
significativo(∆: -5 ± 9%
n:10 p:0,697)
Hay incremento
significativo(∆: 29 ± 6%
n:12 p:0,012)
14-3-3 ζ fue 46% mas alta en sujetos con esquizofrenia
sin antipsicóticos (p:0,0007)
Resultado independiente del género (p:0,0015) y edad
(p:0,0012)

21. 3. Resultados
• 3.3 inmunoreactividad de 14-3-3β y 14-3-3ζ en sujetos con
trastornos depresivos
la inmunoreactividad de las proteínas 14-3-3β
y 14-3-3ζ en la corteza prefrontal de los sujetos
con trastornos depresivos no fue
significativamente diferente a los sujetos de
control.

22. 3. Resultados

23. 3. Resultados

24. 3. Resultados

25. 3.Resultados

26. 3. Resultados

28. 4. Discussion

29. 4. Discussion
Person or entity Contribution Agree or disagree
McCullumsmith, 2013 «The utilization of postmortem
tissue is of great relevance for
the study of complex mental
illnesses thaht are difficult to
model in animals »
Agree
Pandey and Dwivedi,
2010
«In the present study, the
majority of both SZ and MD
subjects were suicide victims (17
of 22 in the SZ group and 17 of
21 in the MD group) regardless of
the psychotropic treatment.
Some neurobiological
abnormalities associated with
suicide have been suggested to
be independent of psychiatric
diagnoses and to be a common
feature of suicidal behaviour»
Disagree

30. 4. Discussion
Person o entity Contribution Agree or disagree
Middleton , 2005 “In the present study, postmortem brain
samples of SZ and MD subjects were used
valuably reflecting neuroplastic changes
from a lifetime of mental illness and
psychopharmacological treatment”.
Disagree
Carboni, 2006;
Cecconi, 2007;
Malki, 2012.
“With respect to MD, no alteration was
observed in 14-3-3β and 14-3-3ζ protein
levels neither in antidepressant-free nor
in antidepressant-treated MD subjects. To
our knowledge, this is the first time 14-3-
3 protein status in MD is studied. The
unaltered levels suggest no role for these
proteins in MD and no modulation of
protein levels by antidepressant
treatment despite the modulation by
antidepressants suggested in cellular and
in animal models”.
Agree

31. 5. Conclusions
In depressive disorders we don’t see any
change in proteins so we could indicate
that this disease has nothing to do with
14-3-3ζ and 14-4-4β but can not
asegurate because it is the first time that
relate these variables
To make a good research is necessary to
understand very well the variables because
this allows us a good interpretation, one of
the foundations of this research is to
understand how no differences in levels of
proteins occurs in people with
schizophrenia and control, but the
treatment with antipsychotics alters
everything
14-3-3 regulatory proteins that are present
from the most primitive organisms bind to
signaling proteins, affecting its stability,
activity or cellular localization. Therefore,
they are involved in regulating various
cellular processes including apoptosis, cell
cycle and the stress response.
one of the objectives that need to be
evaluated more thoroughly was each
genetic polymorphism may influence the
response of patients to treatment with
antipsychotics because the study present a
possible consequence of suicides is that this
not responding to treatment
Conclusions

32. Mapa Conceptual.

33. Mapa Conceptual.