A Test of the Transdiagnostic Dopamine Hypothesis of Psychosis Using Positron Emission Tomographic Imaging in Bipolar Affective Disorder and Schizophrenia

Jauhar, Sameer; Nour, Matthew M.; Veronese, Mattia; Rogdaki, Maria; Bonoldi, Ilaria; Azis, Matilda; Turkheimer, Federico; McGuire, Philip; Young, Allan H.; Howes, Oliver

doi:10.1001/jamapsychiatry.2017.2943

Cited by 194 publications

(173 citation statements)

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“…It is increasingly becoming evident that processing of motivation and reward are affected in all of these states (Ashok et al , 2017). This is supported by recent findings showing a transdiagnostic dopamine dysfunction spanning from bipolar disorder to schizophrenia (Jauhar et al , 2017). In order to understand the relationship between dysfunctional motivational processes and clinical disease manifestations within but also between different diagnostic entities, valid dimensional psychopathological constructs are essential (Cuthbert and Insel, 2013).…”

Section: Introductionsupporting

confidence: 84%

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Kirschner

Cathomas

Manoliu

et al. 2019

Preprint

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BackgroundBipolar disorder I (BD-I) is defined by episodes of mania, depression, and euthymic states. These episodes are among other symptoms characterized by altered reward processing and negative symptoms (NS), in particular apathy. However, the neural correlates of these deficits are not well understood.MethodsWe first assessed the severity of negative symptoms in 25 euthymic BD-I patients compared to 25 healthy controls (HC) and 27 patients with schizophrenia (SZ). Then, we investigated ventral and dorsal striatal activation during reward anticipation in a Monetary Incentive Delayed Task and its association with NS.ResultsIn BD-I patients NS were clearly present and the severity of apathy was comparable to SZ patients. Apathy scores in the BD-I group but not in the SZ group correlated with sub-syndromal depression scores. At the neural level, we found significant ventral and dorsal striatal activation in BD-I patients and no group differences with HC or SZ patients. In contrast to patients with SZ, apathy did not correlate with striatal activation during reward anticipation. Explorative whole brain analyses revealed reduced extra-striatal activation in BD-I patients compared to HC and an association between reduced activation of the inferior frontal gyrus and apathy.ConclusionThis study found that in BD-I patients apathy is present to an extent comparable to schizophrenia, but is more strongly related to sub-syndromal depressive symptoms. The findings support the view of different pathophysiological mechanisms underlying apathy in the two disorders and suggest that extra-striatal dysfunction may contribute to impaired reward processing and apathy in BD-I.

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Section: Introductionsupporting

confidence: 84%

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Kirschner

Cathomas

Manoliu

et al. 2019

Preprint

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“…Individuals with more striatal dopamine (itself a marker for psychosis risk [36]) are more susceptible to this impact of prior expectation on auditory perception: those with higher dopamine are more likely to perceive target auditory stimuli embedded in a stream consistent with their expectations rather than what was actually presented to them [37]. Visual hallucinations in Parkinson's disease have likewise been related to precise priors [38], which may be driven by dopaminergic, cholinergic, and serotonergic perturbations [39].…”

Section: Data Consistent With the Strong Prior Accountmentioning

confidence: 99%

Hallucinations and Strong Priors

Corlett

Horga

Fletcher

et al. 2019

Trends in Cognitive Sciences

415

339

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“…(ii) The interpretation of k i cer as index of DSC needs caution, as tyrosine hydroxylase is the rate-limiting step in DSC and not aromatic acid decarboxylase (for further limitations regarding the DSC measure such as premedication see Supplementary Discussion). 6, 72 (iii) Striatal-DSC and blood oxygenation-based cortico-thalamic-iFC, are indirect measures of brain activity, averaged over several minutes and reflecting mixed signals. Therefore, we are only able to examine relative coarse relations and we might have missed fast occurring effects (e.g.…”

Section: Discussionmentioning

confidence: 99%

Cortico-thalamic dysconnectivity links with aberrant striatal dopamine in schizophreniaA simultaneous¹⁸F-DOPA-PET/resting-state fMRI study

Avram

Knolle

Cabello

et al. 2019

Preprint

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In schizophrenia, among the most consistent brain changes are both aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei; however, it is unknown whether these changes are pathophysiologically related. Such a relationship is expected because cortico-thalamic-connectivity is modulated by striatal dopamine within topographically distinct, parallel but interacting cortico-basal-ganglia-thalamic circuits. We hypothesized: (1) Within-circuits, aberrant striatal dopamine contributes to aberrant cortico-thalamic-iFC, specifically, associative-striatum dopamine contributes to salience-network-thalamic-iFC, and sensorimotor-striatum dopamine to auditory-sensorimotor-network-thalamic-iFC. (2) Due to between-circuits interactions following an anterior-to-posterior gradient, salience-network-centered-system changes contribute to auditory-sensorimotor-network-centered-system changes. To test these hypotheses, 19 patients with schizophrenia during symptomatic remission of positive symptoms and 19 age- and sex-comparable controls underwent simultaneous fluorodihydroxyphenyl-L-alanine positron emission tomography (18F-DOPA-PET) and resting-state functional magnetic resonance imaging (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure dopamine synthesis capacity (DSC), indicating striatal dopamine function; correlation coefficients between rs-fMRI time-series of cortical networks and thalamic regions-of-interest were used to measure iFC. In the salience-network(SAL)-centered-system, patients had reduced associative-striatum-DSC, which correlated positively with SAL-mediodorsal-thalamus-iFC and mediated the reduction of SAL-thalamic-iFC in patients. In the auditory-sensorimotor-network(ASM)-centered-system, patients had reduced sensorimotor-striatum-DSC, which correlated positively with ASM-ventrolateral-thalamus-iFC, but did not mediate increased ASM-thalamic-iFC in patients. Finally, aberrant DSC and iFC of the SAL-centered-system mediated corresponding changes in the ASM-centered-system. Results demonstrate that cortico-thalamic-dysconnectivity links with aberrant striatal dopamine in schizophrenia - in a topographically distinct way, with an anterior-to-posterior gradient, and primary changes in the SAL-centered system.

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A Test of the Transdiagnostic Dopamine Hypothesis of Psychosis Using Positron Emission Tomographic Imaging in Bipolar Affective Disorder and Schizophrenia

Abstract: These findings are consistent with a transdiagnostic role for dopamine dysfunction in the pathoetiology of psychosis and suggest dopamine synthesis capacity as a potential novel drug target for bipolar disorder and schizophrenia.

Cited by 194 publications

References 69 publications

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Hallucinations and Strong Priors

Cortico-thalamic dysconnectivity links with aberrant striatal dopamine in schizophreniaA simultaneous¹⁸F-DOPA-PET/resting-state fMRI study

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A Test of the Transdiagnostic Dopamine Hypothesis of Psychosis Using Positron Emission Tomographic Imaging in Bipolar Affective Disorder and Schizophrenia

Abstract: These findings are consistent with a transdiagnostic role for dopamine dysfunction in the pathoetiology of psychosis and suggest dopamine synthesis capacity as a potential novel drug target for bipolar disorder and schizophrenia.

Cited by 194 publications

References 69 publications

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Hallucinations and Strong Priors

Cortico-thalamic dysconnectivity links with aberrant striatal dopamine in schizophreniaA simultaneous18F-DOPA-PET/resting-state fMRI study

Contact Info

Product

Resources

About

Cortico-thalamic dysconnectivity links with aberrant striatal dopamine in schizophreniaA simultaneous¹⁸F-DOPA-PET/resting-state fMRI study