T161. THE RELATIONSHIP BETWEEN FRONTAL CORTICAL VOLUME AND STRIATAL DOPAMINE SYNTHESIS CAPACITY IN PSYCHOSIS

AbstractPreclinical models propose that increased hippocampal activity drives subcortical dopaminergic dysfunction and leads to psychosis-like symptoms and behaviors. Here, we used multimodal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis and investigated its association with subsequent clinical and functional outcomes. Ninety-five participants (67 CHR and 28 healthy controls) underwent arterial spin labeling MRI and 18F-DOPA PET imaging at baseline. CHR participants were followed up for a median of 15 months to determine functional outcomes with the global assessment of function (GAF) scale and clinical outcomes using the comprehensive assessment of at-risk mental states (CAARMS). CHR participants with poor functional outcomes (follow-up GAF < 65, n = 25) showed higher rCBF in the right hippocampus compared to CHRs with good functional outcomes (GAF ≥ 65, n = 25) (pfwe = 0.026). The relationship between rCBF in this right hippocampal region and striatal dopamine synthesis capacity was also significantly different between groups (pfwe = 0.035); the association was negative in CHR with poor outcomes (pfwe = 0.012), but non-significant in CHR with good outcomes. Furthermore, the correlation between right hippocampal rCBF and striatal dopamine function predicted a longitudinal increase in the severity of positive psychotic symptoms within the total CHR group (p = 0.041). There were no differences in rCBF, dopamine, or their associations in the total CHR group relative to controls. These findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of adverse outcomes in the CHR state.

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Frontostriatal functional connectivity and striatal dopamine synthesis capacity in schizophrenia in terms of antipsychotic responsiveness: an [18F]DOPA PET and fMRI study

Psychological Medicine ◽

10.1017/s0033291718003471 ◽

2018 ◽

Vol 49 (15) ◽

pp. 2533-2542 ◽

Cited By ~ 3

Author(s):

Seoyoung Kim ◽

Wi Hoon Jung ◽

Oliver D. Howes ◽

Mattia Veronese ◽

Federico E. Turkheimer ◽

...

Keyword(s):

Functional Connectivity ◽

Antipsychotic Drugs ◽

Striatal Dopamine ◽

University Hospital ◽

Dopamine Synthesis ◽

Control Group ◽

First Line ◽

Influx Rate ◽

Significant Difference ◽

The Relationship

AbstractBackgroundGiven that only a subgroup of patients with schizophrenia responds to first-line antipsychotic drugs, a key clinical question is what underlies treatment response. Observations that prefrontal activity correlates with striatal dopaminergic function, have led to the hypothesis that disrupted frontostriatal functional connectivity (FC) could be associated with altered dopaminergic function. Thus, the aim of this study was to investigate the relationship between frontostriatal FC and striatal dopamine synthesis capacity in patients with schizophrenia who had responded to first-line antipsychotic drug compared with those who had failed but responded to clozapine.MethodsTwenty-four symptomatically stable patients with schizophrenia were recruited from Seoul National University Hospital, 12 of which responded to first-line antipsychotic drugs (first-line AP group) and 12 under clozapine (clozapine group), along with 12 matched healthy controls. All participants underwent resting-state functional magnetic resonance imaging and [18F]DOPA PET scans.ResultsNo significant difference was found in the total PANSS score between the patient groups. Voxel-based analysis showed a significant correlation between frontal FC to the associative striatum and the influx rate constant of [18F]DOPA in the corresponding region in the first-line AP group. Region-of-interest analysis confirmed the result (control group: R2 = 0.019, p = 0.665; first-line AP group: R2 = 0.675, p < 0.001; clozapine group: R2 = 0.324, p = 0.054) and the correlation coefficients were significantly different between the groups.ConclusionsThe relationship between striatal dopamine synthesis capacity and frontostriatal FC is different between responders to first-line treatment and clozapine treatment in schizophrenia, indicating that a different pathophysiology could underlie schizophrenia in patients who respond to first-line treatments relative to those who do not.

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Glutamatergic and dopaminergic function and the relationship to outcome in people at clinical high risk of psychosis: a multi-modal PET-magnetic resonance brain imaging study

Neuropsychopharmacology ◽

10.1038/s41386-019-0541-2 ◽

2019 ◽

Vol 45 (4) ◽

pp. 641-648 ◽

Cited By ~ 6

Author(s):

Oliver D. Howes ◽

Ilaria Bonoldi ◽

Robert A. McCutcheon ◽

Matilda Azis ◽

Mathilde Antoniades ◽

...

Keyword(s):

High Risk ◽

Imaging Study ◽

Striatal Dopamine ◽

Psychotic Symptoms ◽

Dopamine Synthesis ◽

Clinical High Risk ◽

Magnetic Resonance Brain Imaging ◽

The Relationship ◽

Brain Imaging Study

Abstract Preclinical models of psychosis propose that hippocampal glutamatergic neuron hyperactivity drives increased striatal dopaminergic activity, which underlies the development of psychotic symptoms. The aim of this study was to examine the relationship between hippocampal glutamate and subcortical dopaminergic function in people at clinical high risk for psychosis, and to assess the association with the development of psychotic symptoms. 1H-MRS was used to measure hippocampal glutamate concentrations, and 18F-DOPA PET was used to measure dopamine synthesis capacity in 70 subjects (51 people at clinical high risk for psychosis and 19 healthy controls). Clinical assessments were undertaken at baseline and follow-up (median 15 months). Striatal dopamine synthesis capacity predicted the worsening of psychotic symptoms at follow-up (r = 0.35; p < 0.05), but not transition to a psychotic disorder (p = 0.22), and was not significantly related to hippocampal glutamate concentration (p = 0.13). There were no differences in either glutamate (p = 0.5) or dopamine (p = 0.5) measures in the total patient group relative to controls. Striatal dopamine synthesis capacity at presentation predicts the subsequent worsening of sub-clinical total and psychotic symptoms, consistent with a role for dopamine in the development of psychotic symptoms, but is not strongly linked to hippocampal glutamate concentrations.

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T137. THE RELATIONSHIP BETWEEN CORTICOSTRIATAL CONNECTIVITY AND STRIATAL DOPAMINE FUNCTION IN SCHIZOPHRENIA: AN 18F-DOPA PET AND DIFFUSION TENSOR IMAGING STUDY

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa029.697 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S282-S283

Author(s):

Sangho Shin ◽

Euitae Kim

Keyword(s):

Prefrontal Cortex ◽

Dorsolateral Prefrontal Cortex ◽

Striatal Dopamine ◽

Dopamine Synthesis ◽

Treatment Resistant ◽

Control Subjects ◽

Dorsolateral Prefrontal ◽

Healthy Control ◽

The Relationship ◽

And Diffusion

Abstract Background Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis of schizophrenia pathophysiology, which underlies in majority of treatment-responsive patients. Although supported by findings that prefrontal cortical lesions lead to striatal dopamine dysregulation and that recently, prefrontal structural volume is negatively correlated with striatal dopamine synthesis, the relationship between corticostriatal connectivity and striatal dopamine synthesis has not been tested in patients with schizophrenia. We therefore investigated the relationship between corticostriatal connectivity and striatal dopamine synthesis capacity in treatment-responsive patients with schizophrenia, and compared them to treatment-resistant patients and healthy control subjects. Methods Twenty-four patients with schizophrenia and twelve matched healthy control subjects underwent 18F-DOPA PET scans to measure dopamine synthesis capacity (indexed as the influx rate constant Kicer), structural and diffusion 3T MRI. Connectivity(indexed as Fractional anisotropy, FA) were assessed in 3 major corticostriatal tracts (dorsolateral prefrontal cortex-associative striatum, ventromedial prefrontal cortex-limbic striatum, and pre/primary motor cortex-sensorimotor striatum). Furthermore, these measures were tested whether they were correlated with a measure of Wisconsin Card Sorting Test (WCST). Results Treatment responsive patients showed a negative correlation between connectivity of dorsolateral prefrontal cortex-associative striatum and striatal dopamine synthesis capacity of associative striatum, but this was not evident in treatment-resistant patients. Furthermore, WCST negatively correlated with Kicer in associative striatum and positively correlated with FA in dorsolateral prefrontal cortex-associative striatum in whole subjects and treatment responsive patients but not in treatment-resistant patients. Discussion These findings demonstrate that different mechanisms underlie the pathophysiology of treatment-responsive and treatment-resistant schizophrenia and especially, connectivity of dorsolateral prefrontal cortex-associative striatum is a core part for the different pathophysiology.

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Interactions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to clinical outcomes

10.1101/2020.12.08.20245902 ◽

2020 ◽

Author(s):

Gemma Modinos ◽

Anja Richter ◽

Alice Egerton ◽

Ilaria Bonoldi ◽

Matilda Azis ◽

...

Keyword(s):

High Risk ◽

Functional Outcome ◽

Clinical Outcomes ◽

Striatal Dopamine ◽

Psychotic Symptoms ◽

Dopamine Synthesis ◽

Clinical High Risk ◽

Hippocampal Activity ◽

The Relationship

AbstractBackgroundPreclinical models propose that the onset of psychosis involves increased hippocampal activity which drives subcortical dopaminergic dysfunction. We used multi-modal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis, and investigated its association with subsequent clinical outcomes.MethodsNinety-five participants (67 CHR and 28 healthy controls) underwent pseudo-continuous arterial spin labelling and 18F-DOPA PET imaging at baseline. Clinical outcomes in CHR participants were determined after a median of 15 months follow-up, using the Comprehensive Assessment of At Risk Mental States (CAARMS) and the Global Assessment of Function (GAF) scale.ResultsCHR participants with a poor functional outcome (follow-up GAF<65, n=25) showed higher rCBF in the right hippocampus compared to CHRs with a good functional outcome (GAF≥65, n=25) (familywise error [FWE] p=0·026). The relationship between right hippocampal rCBF and striatal dopamine synthesis capacity was also significantly different between groups (pFWE=0·035); the association was negative in CHR with poor outcomes (pFWE=0·012), but non-significant in CHR with good outcomes. The correlation between rCBF in this right hippocampal region and striatal dopamine function also predicted a longitudinal increase in the severity of positive psychotic symptoms (p=0·041). The relationship between hippocampal rCBF and striatal dopamine did not differ in the total CHR group relative to controls.InterpretationThese findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of psychosis-related outcomes.

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SPECT and fMRI analysis of motor and cognitive indices of early Parkinson's disease: The relationship of striatal dopamine and cortical function

PsycEXTRA Dataset ◽

10.1037/e446682006-001 ◽

2000 ◽

Author(s):

John D. E. Gabrieli

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Striatal Dopamine ◽

Cortical Function ◽

Fmri Analysis ◽

Relationship Of ◽

The Relationship ◽

Early Parkinson’S Disease

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The relationship between brain structure and general psychopathology in preadolescents

10.31234/osf.io/r4pxy ◽

2020 ◽

Author(s):

Louise Mewton ◽

Briana Lees ◽

Lindsay Squeglia ◽

Miriam K. Forbes ◽

Matthew Sunderland ◽

...

Keyword(s):

Mental Disorders ◽

Surface Area ◽

Brain Structure ◽

Parental Education ◽

Mental Illnesses ◽

General Psychopathology ◽

Control Approach ◽

Cortical Volume ◽

Subcortical Regions ◽

The Relationship

Categorical mental disorders are being recognized as suboptimal targets in clinical neuroscience due to poor reliability as well as high rates of heterogeneity within, and comorbidity between, mental disorders. As an alternative to the case-control approach, recent studies have focused on the relationship between neurobiology and latent dimensions of psychopathology. The current study aimed to investigate the relationship between brain structure and psychopathology in the critical preadolescent period when psychopathology is emerging. This study included baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study® (n = 11,721; age range = 9-10 years; male = 52.2%). General psychopathology, externalizing, internalizing, and thought disorder dimensions were based on a higher-order model of psychopathology and estimated using Bayesian plausible values. Outcome variables included global and regional cortical volume, thickness, and surface area. Higher levels of psychopathology across all dimensions were associated with lower volume and surface area globally, as well as widespread and pervasive alterations across the majority of cortical and subcortical regions studied, after adjusting for sex, race/ethnicity, and parental education. The relationships between general psychopathology and brain structure were attenuated when adjusting for cognitive functioning. There was evidence of a relationship between externalizing psychopathology and frontal regions of the cortex that was independent of general psychopathology. The current study identified lower cortical volume and surface area as transdiagnostic biomarkers for general psychopathology in preadolescence. The widespread and pervasive relationships between general psychopathology and brain structure may reflect cognitive dysfunction that is a feature across a range of mental illnesses.

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