Psychosocial intervention to optimal treatment to patients with schizophrenia: neurocognitive perspectives

TANG Tze-ChunDepartment of psychiatry

KMUH

Pharmacotherapy alone or combination with psychotherapy?

Pharmacotherapy: optimal dose and strategies to the titration of

antipsychotics

Psychosocial intervention: add-on therapy

• Meta-analyses of the efficacy of psychotherapeutic interventions for schizophrenia.

Longer intervention period required

• Psychosocial family interventions, regarding the outcome measure "leaving study early" in the time period between 13 /24months, shown to be efficacious

Schizophr Res. 2012.

Cognitive therapy (CT) and antidepressant (ADM): response rate after 8 and 16 weeks-- DeRubeis RJ et al.,2008

Changes in blood-oxygen-level-dependent (Bold) signal in response to cognitive and emotional tasks associated with

cognitive therapy --- DeRubeis RJ et al.,2008

Less relapse after cognitive therapy compared to

antidepressant medication: Compliant, nice adherence subgroup

DeRubeis RJ et al.,2008

Schizophrenia: hyper-arousal response dissociated with reduced amygdala activities

• arousal dissociated amygdala/medial prefrontal ("visceral") networks and hippocampus/lateral prefrontal ("context") networks for fear perception.

• Excessive arousal responses elicited in schizophrenia subjects, but an associated reduction in amygdala/medial prefrontal activity.

• Paranoid patients also showed a relatively greater prefrontal deficit for "without-arousal" responses.

• Am J Psychiatry. 2004 Mar;161(3):480-9.

Social cognition, meta-cognition and social intervention

• Social function training– affect recognition– Cognitive Behavioral Social Skills Training– Meta-cognition training: CBT + social skills training

• Cognitive training– Cognitive behavior therapy/group– Cognitive remediation therapy

• Mindfulness training

Facial recognition and social function

Social cognition inferences

Voice and facial recognition

• Communication and interpersonal deficits are major stumbling blocks that stand between persons with severe mental illness

Hasson-Ohayon I, Kravetz S, Levy I, Roe D.(2009)

• these communication and interpersonal limitations of persons with psychosis to impairments of metacognition – empathy – theory of mind [ToM] – mind reading

• Training of affect recognition (TAR) in schizophrenia-Impact on functional outcome.

Schizophr Res. 2012 Mar 28

Mechanism of TAR

• Training of Affect Recognition (TAR) effects on – prosodic affect recognition– theory of mind (ToM) performance– social competence in a role-play task– more general social and occupational functioning

Facial recognition training• 40 stabilized schizophrenic patients

randomized to a 6-week training on affect recognition (TAR) or TAU

• assessments of emotion recognition, cognition, quality of life and clinical symptoms.

Facial recognition training• TAR group significant improvements in

– facial affect recognition, in particular in recognizing sad faces

– in quality of life domain social relationship– changes were not found in TAU group

Social and cognitive training

• Randomized Controlled Trial of Cognitive Behavioral Social Skills Training for Older Consumers With Schizophrenia: Defeatist Performance Attitudes and Functional Outcome.

Am J Geriatr Psychiatry. 2012 Jan 10.

• cognitive behavioral social skills training (CBSST) is an effective psychosocial intervention to improve functioning in older consumers with schizophrenia

• age 45-78

• 36-session, weekly group therapy that combined cognitive behavior therapy with social skills training (CBTSST)

• TAU : goal-focused supportive contact (GFSC)

• Functioning trajectories over time were significantly more positive in CBSST than in GFSC– especially for participants with more severe

defeatist attitudes

• Defeatist Beliefs as a Mediator of Cognitive Impairment, Negative Symptoms, and Functioning in Schizophrenia

Schizophrenia Bulletin, (35): 798-806

• Clinical Measures• Dysfunctional Attitude Scale (DAS) • Neurocognitive Performance

Path Analysis (N = 54).

Grant P M , Beck A T Schizophr Bull 2008;35:798-806

© The Author 2008. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Cognitive enhancement training(cognitive remediation therapy,CRT)

• Compensatory cognitive training for psychosis: who benefits? Who stays in treatment?

Schizophr Bull. 2011 Sep;37 Suppl 2:S55-62.

• primary psychotic disorder who enrolled in a randomized controlled trial of compensatory CT (cognitive training) and assessed at baseline, 3 months (posttest), and 6 months (follow-up)

• Study completers had more formal education and lower daily doses of antipsychotic medications

• lower baseline functioning may have more room to improve following CT

Cognitive remediation therapy: design and efficacy

• CRT is a therapy engages the patient in learning activities enhance neurocognitive skills to chosen recovery goals

• vary in extent and reflect narrow or broader perspectives

• Meta-analytic study reports moderate range effect sizes on cognitive test performance, and daily functioning

• Encephale. 2011 Dec;37 Suppl 2:S155-60.

Interaction and motivation for CRT

• type of instructional techniques ,member’s interaction, and motivation provide explanatory power for heterogeneity in patient response to cognitive remediation

• results of studies suggest intrinsic motivation be a viable treatment target in CRT

• Dorsolateral Prefrontal Cortex Activity Predicts Responsiveness to Cognitive–Behavioral Therapy in Schizophrenia

• Biological Psychiatry 66, (6), 2009, P 594–602

• DLPFC activity of both hemispheres predictive of CBT responsiveness

• left DLPFC showed more robust pattern of activity and connectivity with the cerebellum in association with CBT responsiveness.

Left hemisphere benefit from CBT more

• left hemisphere is more strongly associated with a beneficial outcome of CBT in schizophrenia, as reported previously in depression

• Although cerebellum has traditionally implicated in motor control, stronger cerebellar projections from PFC in humans (30.85%) than in nonhuman primates (16.4%)

DLPFC and cerebellum

• recent data demonstrate cerebellar contributions to higher-order cognitive functions – especially task management and multitasking components

of executive processing

• DLPFC-cerebellum connectivity and CBT responsiveness association explained by PFC–cerebellum contributions to executive control, facilitating CBT responsiveness in same way as DLPFC activity itself

corticocerebellar-thalamo-cortical circuitry deficits in schzophrenia

• disruption in the corticocerebellar-thalamo-cortical circuitry results in – deficient processing, prioritizing, retrieval,

coordination– responding to information processing deficits in

schizophrenia

Poor attention and poor responsive CBT

• Low response to CBT and reduced deactivation of regions deactivated during rest/0-back, relative to the memory load

• reduced ability to maintain focus on, or switch to, a goal (task in this case) associated with a less favorable response to CBT

default network and CBT

• default network is a network of brain regions that are active when individual is not focused on the outside world and brain is at wakeful rest– preferentially activates when individuals focus on internal

tasks such as daydreaming, envisioning the future, retrieving memories, and gauging others' perspectives

• The findings suggest that default mode of brain action has a role in CBT efficacy in schizophrenia

CBT vs. CRT• Multicenter, RCT showed both feasible for negative symptom control• Moderate improvement of negative symptoms• no indication for specific effects of CBT compared with CRT• Patients receiving CBT showed a greater mean reduction in avolition-

apathy• CBT promoting clinically meaningful improvements in

– functional outcome, – motivation, and positive symptoms – in low-functioning patients with significant cognitive impairment

Schizophr Bull. 2011 Sep;37 Suppl 2:S98-110Arch Gen Psychiatry. 2012 Feb;69(2):121-7.

Mindfulness training

• Mindfulness-induced changes in gamma band activity - implications for the default mode network, self-reference and attention.

•Clin Neurophysiol. 2012 Apr;123(4):700-10

Task deactivate default mode

• default mode network (DMN) deactivation identified during transition from resting state to a time production task

mindfulness meditation (MM) practitioners – exhibited a trait lower frontal gamma activity – related to narrative self-reference and DMN

activity, producing longer durations– negatively correlated with frontal gamma activity

Frontal DMN vs. posterior mindfulness

• MM practitioners exhibit lower trait frontal gamma activity (as well as a state and trait) increases in posterior gamma power – increased attention and sensory awareness

Duration of effective treatment

• Effect of antipsychotic medication alone vs combined with psychosocial intervention on outcomes of early-stage schizophrenia: A randomized, 1-year study

Arch Gen Psychiatry. 2010 Sep;67(9):895-904.

• Intervention Patients randomly assigned to – receive antipsychotic medication only – antipsychotic medication plus 12 months

of psychosocial intervention • psychoeducation, family intervention, skills training,

and cognitive behavior therapy • during 48 group sessions

• The rates of treatment discontinuation – 32.8% in combined treatment group – 46.8% in the medication-alone group.

• lower risk of relapse with combined treatment (0.57; 0.44-0.74; P < .001)

• greater improvement in combination treatment– insight (P < .001), – social functioning (P = .002), – activities of daily living (P < .001), – 4 domains of quality of life

• a significantly higher proportion of patients receiving combined treatment – obtained employment – accessed education

• Neurocognitive enhancement therapy with vocational services: Work outcomes at two-year follow-up

Schizophrenia Research 105, Issues 1–3, 2008, P18–29

NET(CRT) enhance competitive employment

Treatment recommendations

Schizophrenia psychosocial treatment recommendations

• employment • cognitive behavioral therapy • family-based services • token economy • skills training • psychosocial intervention

» Schizophr Bull. 2010 Jan;36(1):48-70

Philippe Pinel (1745-1826)

Thank you