Negative symptoms in schizophrenia are associated with aberrant striato-cortical connectivity in a rewarded perceptual decision-making task

Reckless, Greg E.; Andreassen, Ole A.; Server, Andrés; Østefjells, Tiril; Jensen, Jimmy

doi:10.1016/j.nicl.2015.04.025

Cited by 26 publications

(14 citation statements)

References 65 publications

(104 reference statements)

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“…Our findings may be consistent with findings of disrupted hemispheric specialization 34 and decreased global connectivity of the caudate 35 as well as those demonstrating deficient striato-cortical connectivity in schizophrenia 3637–39 and altered caudate-cortical connectivity in subjects at high-risk for psychosis 37,40 . Although dysfunction 41 and dysconnectivity 42 of the (ventral) striatum may relate to negative symptoms, we failed to find such a relationship, although more work in this direction is warranted. Together with findings highlighting the role of striatal dopamine dysregulation in schizophrenia 1 , our results suggest that disruptions of striatal circuitry may plausibly mediate the deleterious effects of dopamine dysregulation on cortical processes involved in perception and cognition 43–45 .…”

Section: Discussionmentioning

confidence: 56%

Dopamine-Related Disruption of Functional Topography of Striatal Connections in Unmedicated Patients With Schizophrenia

Horga

Cassidy

et al. 2016

JAMA Psychiatry

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Importance Despite the well-established role of striatal dopamine in psychosis, current views generally agree that cortical dysfunction is likely necessary for the emergence of psychotic symptoms. The topographical organization of striatal-cortical connections is central to gating and integration of higher-order information, so a disruption of such topography via dysregulated dopamine could lead to cortical dysfunction in schizophrenia. However, this hypothesis remains to be tested using multivariate methods ascertaining the global pattern of striatal connectivity and without the confounding effects of anti-dopaminergic medication. Objective To determine whether the pattern of brain connectivity across striatal subregions is abnormal in unmedicated patients with schizophrenia, and whether this abnormality relates to psychotic symptoms and extrastriatal dopaminergic transmission. Design and Participants In this multimodal, case-control study, we obtained resting-state functional Magnetic Resonance Imaging (fMRI) data in 18 unmedicated patients with schizophrenia and 24 matched healthy controls. A subset of these (12 and 17, respectively) underwent Positron Emission Tomographic (PET) imaging with the dopamine D2-receptor radiotracer [11C]FLB457, before and after amphetamine. Data were acquired between June 16, 2011, and February 25, 2014. Main Outcomes (1) Group differences in the striatal connectivity pattern (assessed via multivariable logistic regression) across striatal subregions, and the relationship between the multivariate striatal connectivity pattern (2) with extrastriatal baseline D2-receptor binding potential and its change following amphetamine (BPND and ΔBPND), and (3) with severity of positive symptoms evaluated with the PANSS scale. Results Patients exhibited an abnormal pattern of striatal connectivity, which included abnormal caudate connections with a distributed set of associative cortex regions (p=0.0036). In patients, more deviation from the multivariate pattern of striatal connectivity found in controls correlated specifically with more severe positive symptoms (p=0.0021). Striatal connectivity also correlated with baseline BPND across cortical and extrastriatal subcortical regions (p=0.0116, Bonferroni-corrected) but not with ΔBPND. Conclusions and Relevance Using a multimodal, circuit-level interrogation of striatal-cortical connections, we provide a first demonstration that the functional topography of these connections is globally disrupted in unmedicated patients with schizophrenia. These findings suggest that striatal-cortical dysconnectivity may underlie the effects of dopamine dysregulation on the pathophysiology of psychotic symptoms.

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Section: Discussionmentioning

confidence: 56%

Dopamine-Related Disruption of Functional Topography of Striatal Connections in Unmedicated Patients With Schizophrenia

Horga

Cassidy

et al. 2016

JAMA Psychiatry

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“…A prior study showed that patients with persistent negative symptoms following first‐episode psychosis had significantly reduced left amygdala and right hippocampal volumes . Severity of negative symptoms is also related to reduced gray and white matter volumes in the frontal cortex . A single photon emission computed tomography study found a negative correlation between negative symptom scores and prefrontal perfusion in schizophrenia .…”

Section: Discussionmentioning

confidence: 99%

Comparison of emotional processing assessed with fear conditioning by interpersonal conflicts in patients with depression and schizophrenia

Tani

Tada

Maeda

et al. 2018

Psychiatry Clin Neurosci

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Aim While emotional processing is implicated in various psychiatric illnesses, its differences among diagnoses are unclear. We compared associative learning of social values in patients with depression and schizophrenia by measuring skin conductance response to interpersonal stimuli. Methods We included 20 female outpatients each with depression and schizophrenia. They underwent Pavlovian conditioning experiments in response to a classical aversive sound, and an interpersonal stimulus that was designed to cause aversive social conditioning with actors’ faces coupled with negative verbal messages. Multiple regression analysis was performed to examine the associations between the degree of conditioned response and the clinical characteristics of the participants. Results Conditioned responses during the acquisition phase in both conditions were higher in depression compared to schizophrenia. Patients with depression successfully showed fear conditioning in both conditions, and they exhibited slower extinction in the interpersonal condition. The conditioned response during the extinction phase showed a positive association with Emotion Regulation Questionnaire Expressive Suppression score, and a negative association with the Emotion Regulation Questionnaire Cognitive Reappraisal score and the use of antidepressants. Patients with schizophrenia did not become conditioned in either of the conditions. The Positive and Negative Syndrome Scale Negative Syndrome score was negatively associated with the degree of conditioned response during the acquisition phase in the interpersonal condition. Conclusion Female patients with schizophrenia, especially those who prominently demonstrated negative symptoms, suggested their intrinsic impairments in the associative learning of social context. Antidepressants and adaptive emotional regulation strategy may enhance the extinction learning of aversive social conditioning in depression.

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“…A recent fMRI study that observed normal VS response, but abnormal striatal-cortical connectivity to motivational cues that was related to negative symptom severity in patients with schizophrenia, may support that hypothesis. 46 A more complete understanding of the etiology of apathy in schizophrenia will therefore require further investigation of the structural and functional integrity of subregions within the frontal-striatal circuitry, as well as functional connectivity of the circuitry.…”

Section: Discussionmentioning

confidence: 99%

Apathy Is Associated With Ventral Striatum Volume in Schizophrenia Spectrum Disorder

Roth

Garlinghouse

Flashman

et al. 2016

JNP

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Apathy is prevalent in schizophrenia, but its etiology has received little investigation. The ventral striatum (VS), a key brain region involved in motivated behavior, has been implicated in studies of apathy. We therefore evaluated whether apathy is associated with volume of the VS on MRI in 23 patients with schizophrenia using voxel-based morphometry. Results indicated that greater self-reported apathy severity was associated with smaller volume of the right VS even when controlling for age, gender, depression, and total gray matter volume. The finding suggests that apathy is related to abnormality of brain circuitry subserving motivated behavior in patients with schizophrenia.

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Negative symptoms in schizophrenia are associated with aberrant striato-cortical connectivity in a rewarded perceptual decision-making task

Cited by 26 publications

References 65 publications

Dopamine-Related Disruption of Functional Topography of Striatal Connections in Unmedicated Patients With Schizophrenia

Dopamine-Related Disruption of Functional Topography of Striatal Connections in Unmedicated Patients With Schizophrenia

Comparison of emotional processing assessed with fear conditioning by interpersonal conflicts in patients with depression and schizophrenia

Apathy Is Associated With Ventral Striatum Volume in Schizophrenia Spectrum Disorder

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