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

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1 Psychosocial intervention to optimal treatment to patients with schizophrenia: neurocognitive perspectives TANG Tze-Chun Department of psychiatry KMUH

2 Pharmacotherapy alone or combination with psychotherapy?

3 Pharmacotherapy: optimal dose and strategies to the titration of antipsychotics

4 Psychosocial intervention: addon therapy

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

6 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

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

8 Changes in blood-oxygen-level-dependent (Bold) signal in response to cognitive and emotional tasks associated with cognitive therapy --- DeRubeis RJ et al.,2008

9 Less relapse after cognitive therapy compared to antidepressant medication: Compliant, nice adherence subgroup DeRubeis RJ et al.,2008

10 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 Mar;161(3):480-9.

11 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

12 Facial recognition and social function

14 Social cognition inferences

15 Voice and facial recognition

16 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)

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

18 Training of affect recognition (TAR) in schizophrenia-impact on functional outcome. Schizophr Res Mar 28

19 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

20 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.

21 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

22 Social and cognitive training

23 Randomized Controlled Trial of Cognitive Behavioral Social Skills Training for Older Consumers With Schizophrenia: Defeatist Performance Attitudes and Functional Outcome. Am J Geriatr Psychiatry Jan 10.

24 cognitive behavioral social skills training (CBSST) is an effective psychosocial intervention to improve functioning in older consumers with schizophrenia age 45-78

25 36-session, weekly group therapy that combined cognitive behavior therapy with social skills training (CBTSST) TAU : goal-focused supportive contact (GFSC)

26 Functioning trajectories over time were significantly more positive in CBSST than in GFSC especially for participants with more severe defeatist attitudes

27 Defeatist Beliefs as a Mediator of Cognitive Impairment, Negative Symptoms, and Functioning in Schizophrenia Schizophrenia Bulletin, (35):

28 Clinical Measures Dysfunctional Attitude Scale (DAS) Neurocognitive Performance

29 Path Analysis (N = 54). Grant P M, Beck A T Schizophr Bull 2008;35: The Author Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please journals. permissions@oxfordjournals.org.

30 Cognitive enhancement training (cognitive remediation therapy,crt)

31 Compensatory cognitive training for psychosis: who benefits? Who stays in treatment? Schizophr Bull Sep;37 Suppl 2:S55-62.

32 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)

33 Study completers had more formal education and lower daily doses of antipsychotic medications lower baseline functioning may have more room to improve following CT

34 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 Dec;37 Suppl 2:S

35 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

36 Dorsolateral Prefrontal Cortex Activity Predicts Responsiveness to Cognitive Behavioral Therapy in Schizophrenia Biological Psychiatry 66, (6), 2009, P

39 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.

41 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%)

42 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

43 corticocerebellar-thalamo-cortical circuitry deficits in schzophrenia disruption in the corticocerebellar-thalamocortical circuitry results in deficient processing, prioritizing, retrieval, coordination responding to information processing deficits in schizophrenia

44 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

45 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

46 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 avolitionapathy CBT promoting clinically meaningful improvements in functional outcome, motivation, and positive symptoms in low-functioning patients with significant cognitive impairment Schizophr Bull Sep;37 Suppl 2:S98-110

47 Mindfulness training

48 Mindfulness-induced changes in gamma band activity - implications for the default mode network, self-reference and attention. Clin Neurophysiol Apr;123(4):700-10

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

50 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

51 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

53 Duration of effective treatment

54 Effect of antipsychotic medication alone vs combined with psychosocial intervention on outcomes of early-stage schizophrenia: A randomized, 1-year study Arch Gen Psychiatry Sep;67(9):

55 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

56 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; ; P <.001)

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

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

59 Neurocognitive enhancement therapy with vocational services: Work outcomes at twoyear follow-up Schizophrenia Research 105, Issues 1 3, 2008, P18 29

60 NET(CRT) enhance competitive employment

61 Treatment recommendations

services token economy skills training psychosocial

62 Schizophrenia psychosocial treatment recommendations employment cognitive behavioral therapy family-based services token economy skills training psychosocial intervention Schizophr Bull Jan;36(1):48-70 Philippe Pinel ( )

63 Thank you

Concise Reference Cognitive Dysfunction in Schizophrenia Richard Keefe, Martin Lambert, Dieter Naber

Concise Reference Cognitive Dysfunction in Schizophrenia Richard Keefe, Martin Lambert, Dieter Naber Concise Reference Cognitive Dysfunction in Schizophrenia Extracted from Current Schizophrenia, Third