potencial terapeutico de los acidos grasos omega-3 en el prodromos de la psicosis
TRANSCRIPT
Potencial Terapéutico de los Acidos Grasos Omega 3 en el Pródromos de la Psicosis
Guillermo Rivera, MD, MPHS, PhD.WPA Research Fellow
Orygen Youth Health.
Agenda
La intervención temprana en psicosis
Ácidos grasos Omega 3
Efectos clínicos de Omega 3 en la fase prodrómica de la psicosis.
Conclusiones
Edad de inicio de los trastornos mentales
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Years
Relative dominance
Affect Mood disorders Personality disorders Schizophrenia, pos. sxs. Schizophrenia, Neg. sxs.
Disfuncionalidad asociada al número de episodios psicoticos
0
20
40
60
80
100
120
0 1 2 3 4 5 6Number of episodes
Fu
nc
tio
nin
g
Efectos de las múltiples recaidas
47
76,5
130
0
20
40
60
80
100
120
140
1st 2nd 3rd
Days toremission
Adapted from Lieberman, J., et al., J Clin, Psychiatry, 1996; 57: 5-9
Neurological disease (Cerebral AIDS, SLE, MS. etc.)
Dementia praecox, deficit schizophrenia
Chronic undifferentiated schizophrenia
Paranoid schizophrenia
Schizo-obsessive disorder.
Schizo-affective disorder
“NRG-1 disorder”
Psychotic bipolar disorder
Psychotic depressive disorder
Severe agoraphobia
tiempo
Val
idity
of
clin
ica
l diff
eren
tial d
iagn
osis
0
Hig
hH
igh Periodo
Premorbido
Diagnostico
DefinidoPeriodo
Prodromico
Validez diagnostica a traves de las fases de lapsicosis
22% - 54% de sujetos identificados en prodromos desarrollaron Psicosis 12 meses después
Estudio NAPLS: 35% desarrollaron psicosis 30 meses después.
Copyright restrictions may apply.
Cannon, T. D. et al. Arch Gen Psychiatry 2008;65:28-37.
Cumulative survival distribution function modeling time to conversion to psychosis in 291clinical high-risk (prodromal) patients and 134 demographically comparable normal control
subjects (dashed line)
Estudios de prevencion de psicosis: Tasas de conversion 12 meses después
32
9,9
0
5
10
15
20
25
30
35
40
% c
onve
rtin
g to
psy
chos
is
Controls Experimental
PACEPRIMEOPUSPIEREDIEAmmingerMean rate
Lipidos en el cerebro
El cerebro es el segundo organo con mayor contenido De lipidos, hasta un 50%, porcentaje proximo a losadipocitos
LA
GLA
ARA
24:4(n-6)
24:5(n-6)
EPA
DPA
24:5(n-3)
24:6(n-3)
DHA
18:2(n-6)
18:3(n-6)
DGLA20:3(n-6)
20:4(n-6)
22:4(n-6)
DPA22:5(n-6)
ALA18:3(n-3)
18:4(n-3)
20:4(n-3)
20:5(n-3)
22:5(n-3)
22:6(n-3)
6-Desaturase
6-Desaturase
5-Desaturase
Elongase
Elongase
Elongase
-Oxidation
PGs of series 1
Omega-6
PGs of series 2
PGs of series 1
Omega-3
Senalizacion lipidica y Neuroplasticidad Neuronal, Reparacion Cerebral, y Neuroprotección
Bazan, 2005
Mecanismos
Neurotransmisores (dopamina, serotonina)
Citoquinas (BNDF, IL6, IL10)
Glutatione
Neuroprotectina D-1
El vinculo metabolico de los acidos grasos
La fiebre mejora los síntomas de la esquizofrenia
• Menor incidencia de artritis ↓
“Schizophrenia as a Prostaglandin Deficiency Disease”David Horrobin, Lancet, 1977.
• Sensibilidad al dolor y la temperatura
Date of download: 9/15/2012
Copyright © American Psychiatric Association. All rights reserved.
From: Randomized, Placebo-Controlled Study of Ethyl-Eicosapentaenoic Acid as Supplemental Treatment in Schizophrenia
Am J Psychiatry. 2002;159(9):1596-1598. doi:10.1176/appi.ajp.159.9.1596
Mean Total Scores on the Positive and Negative Syndrome Scale of Patients Who Received Ethyl-Eicosapentaenoic Acid (E-EPA) or Placebo in a 12-Week Randomized, Parallel-Group, Double-Blind Study of Supplemental Treatment for Schizophreniaa
aLast observation carried forward.bSignificant difference between groups (t=2.20, df=38, p<0.05).cSignificant difference between groups (t=2.90, df=38, p<0.05).dSignificant difference between groups (t=2.20, df=38, p<0.05).
Figure Legend:
© 2012 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 6
Eicosapentaenoic Acid Interventions in Schizophrenia: Meta-Analysis of Randomized, Placebo-Controlled Studies.
Fusar-Poli, Paolo; Berger, GregorJournal of Clinical Psychopharmacology. 32(2):179-185, April 2012.DOI: 10.1097/JCP.0b013e318248b7bb
treatment) on psychotic symptoms.20,34-38FIGURE 1 . Meta-analysis of double-blind placebo-controlled EPA studies in DSM-IV schizophrenia. Random-effects model of individual and overall (last line of the plot) Hedges' g estimate (95% confidence interval) of the effect of EPA augmentations strategies as compared with placebo (standard antipsychotic
Diseño del Estudio
Doble ciego, aleatroizado, contra placebo, estudio en un solo centro
Individuos con Ultra Alto Riesgo, entre 13–25 a.
Tratamientos: 2g Ac 2g Placebo
Seguimiento: 1, 2, 3, 4, 8, 12, 26, y 52 semanas
Por 12 semanasPor 12 semanas
Effects SizesBaseline and Follow-up mean
difference scores converted to Cohen's D effect sizes
0,24
0,48
0,18
0,07
0,660,61
0,39
0,53
-0,2
0
0,2
0,4
0,6
0,8
Effe
ct s
ize
PANSS Global
PANSS Positive
GAF
PANSS Negative
PANSS Global
PANSS Positive
GAF
PANSS NegativeOlanzapine vs. PlaceboEPA/DHA vs. Placebo
Woods et al., 2003
Positive
Symptoms
Negative
Symptoms
General
Symptoms
Depressi ve
Symptoms
GAF
Score
NA
DHA
ARA
-.144
.010
.048
-.457**
-.223*
-.029
-.395**
-.065
-.028
-.239*
.018
-.049
.336**
.149
.046
**P≤0.01 *P≤0.05
Relationship: Fatty Acids with Clinical Variables at Baseline
Non-psychotic Non-psychotic Non-psychoticPsychotic PsychoticPsychotic
Figure 1 Baseline erythrocyte fatty acids in ultra-high risk patients who did or did not transition to psychosis by 12-month follow-upa
a Fatty acid values represent percent of the total fatty acids. Error bars are means, 95% CIs.b Significant difference between groups (P<0.05).
b
Prediction of Psychosis Transition
Amminger et al., resubmitted
The NEURAPRO-E Study: A comparison study The NEURAPRO-E Study: A comparison study of fish oil capsules and psychological therapy of fish oil capsules and psychological therapy versus placebo capsules and psychological versus placebo capsules and psychological therapy in patients at risk of developing therapy in patients at risk of developing a a psychotic disorderpsychotic disorder
Conclusiones
La intervención temprana se dirige a promover la recuperación de la psicosis a través de la prevención, la detección temprana y los tratamientos más efectivos para los inicios de la enfermedad
El requerimiento de ácidos grasos en el cerebro asegura el recambio de las membranas de las células y de preservar la integridad de las funciones celulares.
Conclusiones 2
Evidencia creciente apoya fuertemente que los PUFAs ω-3 puede ofrecer una prevencion viable y una estrategia de tratamiento con minimos riesgos asociados en gente joven en riesgo ultra alto de psicosis, lo que debe continuar siendo explorado.