From Biology to Belief Exploring Biological and Psychosocial

Interventions in Psychosis

Mahesh Menon, Ph.D., R.Psych. Psychologist, BC Psychosis Program and Mood Disorders

Program, Vancouver Coastal Health

Clinical Assistant Professor, Department of Psychiatry,

University of British Columbia

Outline

• The bio-psycho-social model- Current theories of schizophrenia

• Creating a model of psychosis- putting it all together

• Recovery and wellness- what does it mean in the big picture?

• Acknowledgements

What is schizophrenia?

• Schizophrenia is characterised by

– Positive symptoms- delusions, hallucinations,

thinking problems

– Negative symptoms- lack of motivation,

reduced emotional expression etc

– decline in everyday functioning

Hallucinations

• “Aberrant perceptual experiences”

• Auditory, visual, tactile, olfactory, gustatory

• Auditory hallucinations are the most

common

Delusions

• Fixed, false belief about external reality firmly held despite evidence to the contrary

• Not held by person‟s culture or extremely unlikely

Diathesis- stress model

• Born with a genetic/ biological vulnerability

• Environmental and external stressors

increase risk

• Additional risk due to drugs, head injury

etc

The bio-psycho-social model

• Vulnerabilities at different levels

• Neurodevelopmental

• Neuroanatomy and Neurochemistry

• Developmental delays

• Social impairments

• Cognitive difficulties and cognitive biases

• Environmental stressors/ greater effects of

external stressors

From comas to chlorpromazine

The dopamine hypothesis of

psychosis

• Chlorpromazine

– Initially used as an anti-emetic and sedative

– Found to help patients with schizophrenia

– The birth of the „antipsychotic‟ or „neuroleptic‟

• Antipsychotics shown to be act on the

Dopamine receptor (Carlsson, 1957-

Nobel prize, 2000)

What is dopamine?

• Produced by

midbrain nuclei

• Transported to many

parts of the brain

• Three distinct

dopamine pathways

•Many different kinds

of dopamine

receptors

• Focus on

mesolimbic pathway

and D1 and D2

families of receptors

What is dopamine?

Are there dopaminergic

abnormalities in schizophrenia?

• Amphetamines (which cause increased DA release)

– induce psychotic symptoms in healthy individuals

– Exacerbate psychotic symptoms in patients

• Studies have found that patients with schizophrenia show increased levels of DA synthesis, release and synaptic dopamine

• Therefore, probably.. YES

11C-Raclopride

PET Scan Coregistered

MRI Scan

Before

Treatment

Haloperidol

2 mg/d (74% Occ.)

11C-Raclopride

PET Scan

Dopamine D2 Receptor occupancy

and Antipsychotic drug action

D2 occupancy predicts clinical

response

Striatal D2 Occupancy

<65% > 65%

Pe

rce

nt R

esp

on

de

rs (

CG

I)

0

20

40

60

80

100

Non Responders

Responders

Kapur et al. Am. J Psychiatry, 2000

D2 occupancy predicts response on CGI (p < 0.001)

Predicts change in positive symptoms PANSS (p = 0.07)

Understanding drug action

• How do the drugs work?

• How does blockade of the dopamine D2

receptor cause a person to change their

beliefs?

• What does dopamine do?

What does dopamine do?

• Dopamine does many things..

– Movement (Parkinson‟s disease)

– Attention and Decision making (Frontal lobes)

– Reward and punishment (Striatum)

– We shall focus on the dopamine D2 receptors

in the striatum

Dopamine and reward

Environmental

stimuli

motivationally

relevant event

•The firing of DA neurons are

observed when an unexpected

reward is presented.

•These responses transfer to the

onset of a conditioned stimulus

after repeated pairings with the

reward.

•Further, DA neurons are

depressed when the expected

reward is omitted.

•Thus, DA neurons seem to

encode the prediction error of

rewarding outcomes.

Dopamine and salience

• Dopamine neurons fire not only in response to positive stimuli, but also to negative stimuli and unexpected or salient stimuli

• i.e. Dopamine mediates the “attribution of salience” whereby external events (or internal thoughts) grab attention or motivate behavior because they are unexpected or have positive or negative consequences

• The midbrain dopamine regions in turn connect with the limbic (emotional) regions and the frontal (decision making) regions of the brain

The prodromal stage

• Before the onset of delusions, patients report..

• “I noticed things I hadn‟t noticed before”

• “..even little things seemed very significant”

• “..like something significant was about to

happen”

• “I felt like I was solving a puzzle”

• The Matrix feeling

• The Truman Show feeling

Dopamine, salience and delusions

• The psychotic state is characterized by greater dopamine release and stimulus independent dopamine release

• Thus creating a state of Aberrant salience

• Delusions are thus an explanation given to explain these experiences of aberrant salience

• And these explanations are maintained as a result of other aberrant psychological processes

• Hallucinations are the heightened internal sensory representations

Neural and cognitive biases in

hallucinations • Increased „salience‟ of internal perceptions

may result in increased activity in auditory

processing regions

• When we look at brain activity in people

when the listen to speech and contrast

that with when the imagine someone

speaking..

•Hallucinating patients demonstrate hyperactivity in neural network that includes voice-selective

cortical regions during perception.

Rapin,

Lovevenbruck,

Dohen, Metzak,

Whitman, &

Woodward 2012,

Psychiatry

Research:

Neuroimaging).

•Hallucinating patients demonstrate schizophrenia-typical activity in a neural network that

includes voice-selective cortical regions during silent thought.

Rapin,

Lovevenbruck,

Dohen, Metzak,

Whitman, &

Woodward 2012,

Psychiatry

Research:

Neuroimaging).

• Hyperactivation of functional networks involving voice-selective

cortical regions is seen in individuals prone to hallucinations. These

“unbidden” thoughts (Ford & Hoffman, 2013) may partially explain

hallucinations.

• Perhaps as a result, hallucination prone individuals have a

tendency to misattribute thoughts (and memories) as coming from

outside of themselves.

• Other personalizing factors must interact with hyperactivation of

voice-selective cortical regions: expectations, hypervigilance,

delusional beliefs, imagination/fantasy, memories/trauma

• Medications can help with reducing activity within the network, and

psychotherapy can help with changing beliefs associated with

voices.

Neural and cognitive biases in

hallucinations

Cognitive biases in delusions

• As outlined earlier, delusions may be

developed as an explanation to instances

of aberrant salience.

• There are also specific biases in thinking

which play a role in creating and

maintaining delusional ideas..

• We will look at two thinking processes?

– How do people arrive at a decision (form a

belief?

– How do people hold onto their belief?

Probabilistic Reasoning

Probabilistic Reasoning

Probabilistic Reasoning

Jumping to Conclusions (JTC)

0

0.2

0.4

0.6

0.8

1

Nonmatching Lake Matching Lake

Lik

elih

oo

d R

atin

gHealthy ControlsBipolar ControlsNon-Delusional SzDelusional Sz

Speechley,

Whitman &

Woodward

(2010). Journal

of Psychiatry

and

Neuroscience

Cognitive biases in delusions

• Even in a neutral context, individuals who are

prone to delusions seem to use less information

to arrive at a decision, and are more confident in

a decision which is consistent with their initial

expectation.

• We call this a „hypersalience of matches‟

between a delusional idea (e.g., I think the CIA

is spying on me) and evidence (e.g., people are

staring at me).

Cognitive biases in delusions

• Once we have a belief, why is it difficult to

change our beliefs?

• We can look at how people use

information consistent with their beliefs,

and information inconsistent with their

beliefs.

• Studies find that people prone to delusions

show a „bias against disconfirmatory

information‟, and a greater bias towards

self generated information.

Psychological interventions for

psychosis • Two of the most well validated methods

are-

• Cognitive Behaviour Therapy for

psychosis (CBTp)

• Metacognitive Therapy for psychosis

(MCT)

What is CBT?

“A structured, short-term, present-oriented

psychotherapy directed towards solving

current problems, and modifying

dysfunctional thinking and behaviour” (Beck,

1964)

• A treatment model that assumes that maladaptive thoughts and behaviours serve to maintain psychological disorders • A goal-oriented, directive, time-limited psychotherapy focused on the “here and now”

Slide courtesy of Dr. Amanda Beaman

CBT Model

Trigger

Thoughts

Behaviours Feelings

Antecedent

Beliefs

Consequences

Slide courtesy of Dr. Amanda Beaman

CBT MODEL

• Trigger (Antecedent/ Situation): Any external or internal event E.g. noticing heart beating faster, making a mistake, entering a crowded room

• Thoughts (Beliefs/ cognitions, appraisals, interpretations): How the client thinks about events E.g. “This means I‟m having a heart attack”; “I never get anything right”; “what-if I embarrass myself?”

CBT MODEL

• Feelings (Consequences): The client‟s

emotional reaction to thoughts or behaviours,

often come with physical sensations

E.g. anxious, depressed, scared

• Behaviours (Actions): What the client does in

response to feelings or thoughts

E.g. checking pulse, procrastinating, using a hidden

entrance/exit

Morrison (2001) - An integrative cognitive

approach to hallucinations and delusions

• Positive symptoms are conceptualised as intrusions into awareness (e.g. hallucinations) and culturally unacceptable interpretations of these intrusions (e.g. delusions)

• Symptoms are maintained by mood, arousal and mal-adaptive cognitive-behavioural responses (e.g. avoidance)

•The interpretation, rather than simply the intrusion, causes distress and disability

Putting it all together – Formulation/ Case

conceptualization

• Collaboratively construct a model that makes

symptoms and distress understandable and

explainable

• Connect up seemingly unconnected factors -

beliefs, life events, emotions, thoughts,

behaviours and symptoms

•Develop a plausible „biases-in-psychological-

processing‟ explanation of experiences

• Develop a model that is non-stigmatizing

Metacognitive Therapy (MCT)

• MCT was developed as a knowledge translation tool- to inform consumers of the results of over 20 years of cognitive neuroscience research on psychosis

• Based on clinical gains and feedback from the early sessions, it was developed into a structured clinical intervention

• Metacognitive Training- group intervention

• Metacognitive Therapy (or MCT plus)- individualized treatment

MCT and CBT

• Both methods aim to help individuals

understand and explore cognitive biases

and ways of thinking about their beliefs

and symptoms.

• CBT helps individuals look at their

thoughts

• MCT takes a slight different approach and

helps individuals think about the cognitive

biases outlined earlier.

www.uke.de/mkt

Module 2

Target domains: bias against disconfirmatory evidence,

jumping to conclusions

Picture 1

Several alternative interpretations are provided.

How likely is each option?

Discuss your decision with your group members.

Understanding cognitive biases

• smiling face

• bowl

• boat

• sled

• rocking chair

• elephant‟s head

• smiling face

• bowl

• boat

• sled

• rocking chair

• elephant‟s head

• smiling face

• bowl

• boat

• sled

• rocking chair

• elephant‟s head

• smiling face

• bowl

• boat

• sled

• rocking chair

• elephant‟s head

• smiling face

• bowl

• boat

• sled

• rocking chair

• elephant‟s head

• smiling face

• bowl

• boat

• sled

• rocking chair

• elephant‟s head

• smiling face

• bowl

• boat

• sled

• rocking chair

• elephant‟s head

Event Catastrophic thinking

Positive/constructive evaluation

Your boss does not say hello to you.

“I will be fired”

“Did she see me at all?”; “Perhaps she is thinking about something”

Challenging thinking biases

Skills acquired from MCT/ CBT

• Learning to consider multiple explanations

• Looking for evidence that may help

disprove a belief

• Take your time making a judgment when

you‟re uncertain.

• Recognize that our memories may be

imperfect

• Work on self-esteem

Wellness & Recovery

• Integrating biological, environmental and psychological approaches to wellness and recovery

• Prevent relapse through integrating biological and psychological treatments – Medication adherence (& side effect management)

– Psychotherapy (increase adherence, psychoeducation, symptom amelioration)

– Family therapy (reduce Expressed Emotion and thus relapse)

– Improved role functioning

Acknowledgements

Special thanks to:

Todd Woodward

Emma Davis

Ariel Graff

Shitij Kapur

Gary Remington

Jimmy Jensen

Michele Korostil

Adam Anderson

Taylor Schmitz

Jean Addington

Irina Vitcu

Adrian Crawley

Rosaleen McCarthy

If you are interested in taking part in

research studies on Metacognitive

Therapy, please contact Emma Davis at

ubc.cnos.lab@gmail.com