Neuropsychology of Delusions in Schizophrenia and Neuropsychiatric Syndromes

1. Neuropsychology of Delusions in Schizophrenia and Neuropsychiatric Syndromes Neuropsicología de los Delirios en Esquizofrenia y Síndromes Neuropsiquiátricos Vaughan Bell Departamento de Psiquiatría, Universidad de Antioquia Institute of Psychiatry, King’s College London

2. Outline • One symptom, two approaches • Brain injury and cognitive neuropsychiatry • Schizophrenia and the theories of pathology • Neurocognitive similarities, differences and convergences. • One symptom? • Conclusions

3. One Symptom, Two Approaches • Delusions are considered a single symptom but the literature is split into two camps (Bell et al., 2006): • Cognitive neuropsychiatry: • Cognitive neuropsychologists studying impossible, monothematic, brain injury-related delusions that are considered to categorically present or absent. • Traditional psychiatry: • Psychiatrists and clinical psychologists studying plausible, largely persecutory delusions, associated with idiopathic psychoses, considered to exist on a continuum.

4. One Symptom, Two Approaches • Theoretically, each uses very different theories to explain how delusions occur: • Cognitive neuropsychiatry: • Attempts to explain delusion as a breakdown in a model of normal belief formation. • Traditional psychiatry: • Attempts to identify which cognitive or neural biases produce delusions and little attempt is made to develop a theory of normal belief.

5. One Symptom, Two Approaches • Although this division is not absolute, it is clear that the two approaches are not entirely compatible, despite some crossover. • We will at two examples from the literature to illustrate this.

6. Freeman et al. (2002) model • A psychological model of persecutory delusions. • Almost entirely based on research with idiopathic psychosis patients. • Using psychometric and cognitive measures.

7. Precipitant Anomalous experiences / arousal Emotion: Beliefs about self, world, others Cognitive biases Search for meaning Selection of explanation DELUSION

8. Anomalous experiences / arousal Emotion: Beliefs about self, world, others Cognitive biases Search for meaning Selection of explanation DELUSION Precipitant

9. Langdon and Coltheart (2000) • A cognitive model of belief formation. • Largely based on patients with monothematic delusions, and often after brain injury. • Using single case and double dissociation method of cognitive neuropsychology.

10. Sensory information Monitoring Web of belief Hypotheses Prioritised list of explanations Evaluation Belief accepted Belief rejected

11. Factor One Anomalous Perceptual Experiences Factor Two Reasoning impairment Sensory information Monitoring Web of belief Hypotheses Prioritised list of explanations Evaluation DELUSION Belief accepted Belief rejected

12. Hemispheric Function • In the neuropsychiatry literature, delusions have been typically associated with right hemisphere damage (e.g. Malloy and Richardson, 1994) • Studies on subclinical psychosis-like belief and experience suggest a right hemisphere bias:

13. Hemispheric Function

14. Hemispheric Function • However, imaging studies in idiopathic delusional patients typically show left-sided dysfunction is more common (Gur and Chin, 1999). • e.g. this summary of fMRI findings from a study of persecutory delusions (Blackwood et al., 2001).

15. Brain Networks • Reviews of the structural imaging literature in schizophrenia (e.g: Wolkin and Rusinek, 2003) suggest: • prefrontal cortex white / grey matter differences • temporal lobe volume reduction (particularly in the medial temporal areas and the STG) • ventricular enlargement • corpus callosum abnormalities

16. Brain Networks • Frontal / temporal dysfunction is a common finding. • The DTI literature indicates pathways connecting these areas are most commonly abnormal (Kubicki et al., 2007) • Functional neuroimaging of delusions typically implicates frontal and temporal areas (Blackwood et al., 2001), although results can be task and delusion specific (e.g. Blakemore et al., 2000).

17. Brain Networks • Reviews of psychosis after brain damage also stress the importance of the temporal and frontal lobes. • Psychosis has been found most commonly after damage to these areas in studies of: • Cerebrovascular accident (Starkstein et al., 1992) • Tumour (Lisanby et al., 1998) • Traumatic brain injury (Fujii and Ahmed, 2002)

18. Dopamine / Glutamate • Both dopamine (e.g. Di Forti et al., 2007) and glutamate (e.g. Stone et al., 2007) theories are well developed in schizophrenia research. • However, they are difficult to integrate directly with the cognitive neuropsychiatry literature… • …owing to the complexity of linking cortical lesions to reliable disruptions in subcortical neurotransmitter function even with the known PFC pathways.

19. Dopamine • It is also not clear how the effects of acquired neurological impairments relate to the major theories that link dopamine dysregulation and psychosis: • Salience (Spitzer, 1995; Kapur, 2003) • Signal-noise ratio (Rolls et al., 2008) • Attentional gating (Gray and Snowden, 2005) • Reward prediction (Murray et al., 2008)

20. Prediction Error Studies • Some impressive recent studies are starting to bridge this gap. • Corlett et al. (2007) found prediction error activation in the RPFC was associated with extent of delusions in patients. • This is the same area identified by Coltheart et al. (2007) from cognitive neuropsychiatry studies. • Honey et al. (2008) found ketamine altered error-prediction and delusions.

21. Delusions in Dementia • Unlike idiopathic psychosis, more females than males, virtually no genetic loading, strongly associated with cog. impairment (Hasset et al., 2005) • ApoE ε4 allele carriers at higher risk specifically for delusions in AD (Zdanys et al., 2006). • This is not a gene identified in mol. genetic studies of idiopathic psychosis. • Types of most prevalent delusions differ – greater misidentification, theft, reference, phantom boarder (Ballard et al., 1995).

22. Delusions in Dementia • Neuroimaging studies on dementia typically implicate right frontal dysfunction (Bell and Halligan, in press) although less temporal involvement. Resting PET - Sultzer et al. (2003) Healthy AD No Delusions AD Delusions

23. A Single Symptom? • There is a single definition of delusion, but several authors have suggested that delusion may be more syndrome like (Bayne and Pacherie, 2005; Gilleen and David, 2005; Bell et al., 2006). • In part due to problems with the diagnostic criteria for delusion (Leeser and O’Donohue, 1999; Bell et al., 2003) • And in part due to problems with the concept of belief itself (Schwitzgebel, 2006)

24. A Single Symptom? • We suggest it is likely that while some neurocognitive commonalities might be present… • …we may eventually have distinct explanations for different types of delusions… • …or multiple pathways to seemingly identical cases of delusion formation. • This needs to be kept in mind when attempting to make sense of the cognitive and neuropsychological research.

25. Conclusions • There are two main traditions in delusion research, which are attempting to do different things. • Cognitive neuropsychiatry approach attempting to find a pathology in normal belief systems. • Traditional approach attempting to understand pathology only. • Not all findings from one are applicable to the other. • Right frontal cortex involvement seems common. • New paradigms attempting to link cognition, neurotransmitter function and networks.