Obiettivo del trattamento della schizofrenia:

RECOVERY FUNZIONALE

• Autonomia abitativa

• Relazioni interpersonali

• Attività del tempo libero

• Lavoro/scuola

• …

Symptom remission alone is inadequate for a definition

of recovery ...

Dimensions of improved psychosocial functioning must

also be integral to a definition of recovery... these

dimensions include work, school, family life, friends,

recreation, and independent living.

Liberman & Kopelowicz, Psychiatr Serv 2005

Schizofrenia e Recovery

A proportion of schizophrenia patients have a favourable prognosis and have a good clinical and functional outcomes

Systematic review of available data showed that 13.5% of patients met recovery criteria

Meta-analisi di 50 studi

Recovery:

• La persona deve mostrare un recupero sia sul piano clinico

che su quello psicosociale.

• In almeno uno di questi piani il recupero deve avere una

durata di almeno 2 anni.

Jääskeläinen et al. Schizophr Bull 2013

NEUROCOGNITIVE FUNCTIONING IN SCHIZOPHRENIA

Summary of results from meta-analytic studies presented in effect-size unitsReichenberg, Dialogues Clin Neurosci 2010

Meta-analysis of cognitive performance in drug-naïve patients with schizophreniaVerbal Memory

Speed of Processing Attention

Working Memory

Verbal memory, speed of processing and workingmemory were three of the domains with thegreatest impairments

The pattern of results is in line with previousmeta-analytic findings in antipsychotic treatedpatients

The present meta-analysis confirms the existence of significant cognitive impairments at the early stage of the illness in the absence of antipsychotic medication Fatouros-Bergman et al, Schizophr Res 2014

The Italian Network for Research on Psychoses StudyDegree of cognitive impairment in individual subjects with

schizophrenia (N=921)

0-0.5 SD below norms

1-1.5 SD below norms in at least 2 domains

2-2.5 SD below norms in at least 2 domains

2.5-3 SD below norms in at least 2 domains

Mucci et al, 2017

VELOCITÀ DI PROCESSAZIONE

ATTENZIONE

MEMORIA VERBALE

SINTOMI NEGATIVI

FUNZIONAMENTO

GLOBALE

PSICOSOCIALE

(Milev et al., Am J Psychiatry, 2005)

Baseline Follow-Up 7 anni

Neuropsychopharmacology: The Fifth Generation of Progress 2002

Neurocognitive constructs and functional outcome

• Social

• Occupational

• Independent

Living

• Rehabilitation

Success

Mediating

Variables

Neuro-

Cognition

Functional

Outcome

Domains

Social

Cognition

Negative

symptoms

Green and Horan, Current Directions 2010

Negative Symptoms, Cognitive Impairment and Real-Life Functioning

Negative symptoms of schizophrenia: Clinical characteristics, pathophysiological

substrates, experimental models and prospects for improved treatment

NS may, to a certain extent, channel the deleterious influence of other symptoms into poor functional

outcome with which NS are strongly correlated

SEM - Modello Finale

VARIABLES SHOWING SIGNIFICANT ASSOCIATION WITH FUNCTIONING

TOTAL(direct+indirect)

NEUROCOGNITIVE FUNCTIONING 0.30

PANSS DISORGANIZATION -0.26

BNSS AVOLITION -0.25

FUNCTIONAL CAPACITY 0.24

ENGAGEMENT WITH MENTAL HEALTH SERVICES -0.18

SOCIAL COGNITION 0.17

PANSS POSITIVE -0.15

INCENTIVES -0.14

RESILIENCE 0.11

INTERNALIZED STIGMA -0.06

The Italian Network for Research in Psychoses

Galderisi et al, World Psychiatry 2014

Is cognitive

remediation effective?

1982 participantsEffect size 0.45

Wykes et al., 2011

0

0,1

0,2

0,3

0,4

0,5

What differences really matter?

• Strategic approach produced a higher functional effect

– DP=0.34 (95% CI -0.11, 0.78); SC+=0.47 (95% CI 0.22, 0.73)

• Adjunctive psychiatric rehabilitation increases functional gains

– Rehab=0.59 (95% CI 0.30, 0.88);CRT only=0.28(95% CI -0.02, 0.58)

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

SC+

Rehab

DP+

Rehab

Effect sizes when rehab provided

Continuous treatment

Schizophrenia Research, 2017

• Cognition stable over time in both groupsBUT• CRT/SRT + only produced stable functional improvement (Time by

treatment effect F=11.48, p<0.001)

DesignCRT/SRT for 6 monthsCRT/SRT + post-therapy SRT

Follow-up after 5 years

VariableBefore

treatment

12 months after

treatment

36 months after

treatment

60 months after

treatment

Number of

hospitalizations in acute

unit per month

(mean±SD)

0.070±0.109 0.026±0.064* 0.020±0.037** 0.012±0.022**

Days of hospitalizations

in acute units per month

(mean±SD)1.855±3.300 0.450±1.431** 0.456±0.881** 0.486±1.165**

Number of admissions in

rehabilitative facilities per

month

(mean±SD)

0.048±0.082 0.023±0.047* 0.013±0.023** 0.030±0.027

Days of stay

in rehabilitative facilities

per month

(mean±SD)

5.743±9.638 3.083±6.690 2.052±3.708* 5.140±11.001

Number of total

outpatient interventions

per month

(mean±SD)

32.652±21.758 40.581±26.568** 40.810±27.907* 37.414±24.899

Number of total

rehabilitation

interventions per month

(mean±SD)

22.453±15.709 28.500±19.367** 27.416±19.650 26.531±18.375

USE OF PSYCHIATRIC SERVICES BEFORE AND AFTER

TREATMENT IN THE CR GROUP

* p<0.05 (Wilcoxon Signed Rank test, comparisons performed versus parameters before treatment)

* * p<0.01 (Wilcoxon Signed Rank test, comparisons performed versus parameters before treatment)

Sintomi, funzionicognitive, social

cognition

Funzionamento

sociale

Lavoro/Scuola

Relazioniinterpersonali

Addestramentoalle abilità

sociali

Rimediocognitivo

Inserimentolavorativo

Psicoeducazione

Farmacoterapia(efficace, tollerata, continuativa)

Cura di sé

Recoveryfunzionale

Interventipsicosociali

Qualitàdella vita

Autonomia

Benesseresoggettivo

Motivazioneestrinseca e intrinseca

MODELLO DI INTERVENTO INTEGRATO NELLA SCHIZOFRENIA

Vita et al., 2016

DEPRESSION AND COGNITION

Meta-analysis of cognitive deficits in 1st-episode

MDD: pooled effect sizes by cognitive domain

Cognitive flexibility

Verbal fluency

Attentional switching

Visual learning and memory

Verbal learning and memory

Working memory

Attention

Psychomotor speed

-2 -1 0 1 2

Patients performing worseControls performing worse

Std mean differenceIV, random, 95% CI

Co

gnit

ive

do

mai

n

0.48 [0.21, 0.75]

0.36 [0.13, 0.59]

0.16 [-0.20, 0.51]

0.13 [-0.18, 0.45]

0.53 [-0.05, 1.11]

0.22 [0.00, 0.44]

0.59 [0.10, 1.07]

0.53 [0.23, 0.83]

Std mean differenceIV, random, 95% CI

Lee RS et al. J Affect Disord 2012;140:113-24

MDD, major depressive disorder; CI, confidence interval

Conradi HJ et al. Psychol Med 2011;41:1165-74

Cognitive symptoms are common in

depression

94%

Proportion of time spent without cognitive symptoms

Cognitive symptoms during

depressive episodes

Proportion of time spent with

cognitive symptomsa

Proportion of time spent without cognitive

symptoms

Residual cognitive symptoms in between depressive episodes

44%

aAccording to Diagnostic and Statistical Manual of Mental Disorders 4th Edition: diminished ability to think or concentrate, or indecisivenessProspective study (n=267) assessed 12 times over 3 years

Proportion of time spent with

cognitive symptomsa