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

Ventanas de prevención

Institute of Medicine, 2010

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

Impacto Potencial de la Intervencion Temprana en Psicosis

Mc Gorry, 1998

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)

Prevention And Promotion

Institute of Medicine, 2010

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

Indicaciones de Omega 3

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

Evidencia Epidemiologica

Hedelin et al., BMC Psychiatry 2010,

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

Gas Chromatography (GC)

Gas Chromatography (GC)

Change n-6/n-3 Ratio

P=0.000000000012

Resultado Primario - Psicosis

Resultados Secundarios

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.