Alterations of the Brain Reward System in Antipsychotic Naïve Schizophrenia Patients

Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne; Bak, Nikolaj; Lublin, Henrik; Kapur, Shitij; Glenthøj, Birte

doi:10.1016/j.biopsych.2012.02.007

Cited by 190 publications

(223 citation statements)

References 61 publications

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“…Moreover, these regions are key components of the reward network (McClure et al, 2004;Sesack and Grace, 2010). We and other have reported on changes in frontostriatal reward processing in schizophrenia patients (Morris et al, 2012;Nielsen et al, 2012), siblings (Grimm et al, 2014;de Leeuw et al, 2015b), and offspring (Vink et al, 2016b).…”

Section: Discussionmentioning

confidence: 88%

Changes in White Matter Organization in Adolescent Offspring of Schizophrenia Patients

Leeuw

Bohlken

Mandl

et al. 2016

Neuropsychopharmacol

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Schizophrenia is associated with frontostriatal network impairments underlying clinical and cognitive symptoms. We previously found disruptions in anatomical pathways, including the tract connecting the left nucleus accumbens and left dorsolateral prefrontal cortex (DLPFC). Similar deficits are observed in unaffected siblings of schizophrenia patients, indicating that these deficits are linked to a genetic vulnerability for the disorder. Frontostriatal tract disruptions may arise during adolescence, preceding the clinical manifestation of the disorder. However, to date, no studies have been performed to investigate frontostriatal tract connections in adolescents who are at increased familial risk for schizophrenia. In this study, we investigate the impact of familial risk on frontostriatal tract connections using diffusion tensor imaging in 27 adolescent offspring of schizophrenia patients and 32 matched control adolescents, aged 10-18 years. Mean fractional anisotropy (FA) was calculated for the tracts connecting the striatum (caudate nucleus, putamen, nucleus accumbens) and frontal cortex regions (DLPFC, medial orbital frontal cortex, inferior frontal gyrus). As expected, based on siblings data, we found an impact of familial risk on frontostriatal development: schizophrenia offspring showed increased FA in the tracts connecting nucleus accumbens and DLPFC as compared with control adolescents. Moreover, while FA increased across age in control adolescents, it did not in schizophrenia offspring. We did not find differences in FA in other frontostriatal tracts. These results indicate altered development of white matter in subjects who are at familial risk for schizophrenia and may precede frontostriatal white matter alterations in adult schizophrenia patients and siblings.

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Section: Discussionmentioning

confidence: 88%

Changes in White Matter Organization in Adolescent Offspring of Schizophrenia Patients

Leeuw

Bohlken

Mandl

et al. 2016

Neuropsychopharmacol

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“…Details of recruitment procedures have been reported elsewhere. 10,11 We excluded patients with a current ICD-10 diagnosis of drug dependency, but previous diagnoses of drug dependency or intermittent recreational use of drugs were accepted. Current drug use was measured using a urine test (Rapid Response, Jepsen HealthCare).…”

Section: Participantsmentioning

confidence: 99%

Frontal fasciculi and psychotic symptoms in antipsychotic-naive patients with schizophrenia before and after 6 weeks of selective dopamine D2/3 receptor blockade

Ebdrup

Raghava

Nielsen

et al. 2016

jpn

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“…Compared to healthy controls (HCs), differences in ventral striatal activity were observed in studies in patients with first-episode schizophrenia (FEP-SZ) and first-degree relatives of patients with schizophrenia. [15][16][17][18] Other studies including patients with broadly defined first-episode psychosis (not restricted to schizophrenia and schizophreniform disorder) or individuals at-risk for psychosis did not report any group differences, but focused more on the relationship with symptom expression. [19][20][21][22][23] This work supports the idea that on a group level reduced activation of the striatum may be more strongly related to schizophrenia or chronic forms of psychosis than to psychotic disorders in general.…”

Section: Introductionmentioning

confidence: 99%

“…18 Concerning positive symptoms, the literature strongly suggests an association with diminished striatal activity to relevant stimuli in unmedicated first-episode psychosis patients and individuals at ultra-high risk, which is consistent with the aberrant salience model of psychosis. 15,21 However, on a meta-analytic level including studies with unmedicated and medicated patients the association of neural alterations during reward processing and positive symptoms is less clearly delineated. 24 Furthermore, the association between striatal dysfunction and depressive symptoms is well described within depressive disorders 28,29 but data are limited for schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Ventral Striatal Dysfunction and Symptom Expression in Individuals With Schizotypal Personality Traits and Early Psychosis

Kirschner

Hager

Muff

et al. 2016

SCHBUL

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Striatal abnormalities play a crucial role in the pathophysiology of schizophrenia. Growing evidence suggests an association between aberrant striatal activity during reward anticipation and symptom dimensions in schizophrenia. However, it is not clear whether this holds across the psychosis continuum. The aim of the present study was to investigate alterations of ventral striatal activation during reward anticipation and its relationship to symptom expression in persons with schizotypal personality traits (SPT) and first-episode psychosis. Twenty-six individuals with high SPT, 26 patients with non-affective first-episode psychosis (including 13 with brief psychotic disorder (FEP-BPD) and 13 with first-episode schizophrenia [FEP-SZ]) and 25 healthy controls underwent event-related functional magnetic resonance imaging while performing a variant of the Monetary Incentive Delay task. Ventral striatal activation was positively correlated with total symptom severity, in particular with levels of positive symptoms. This association was observed across the psychosis continuum and within each subgroup. Patients with FEP-SZ showed the strongest elevation of striatal activation during reward anticipation, although symptom levels did not differ between groups in the psychosis continuum. While our results provide evidence that variance in striatal activation is mainly explained by dimensional symptom expression, patients with schizophrenia show an additional dysregulation of striatal activation. Trans-diagnostic approaches are promising in order to disentangle dimensional and categorical neural mechanisms in the psychosis continuum.

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Alterations of the Brain Reward System in Antipsychotic Naïve Schizophrenia Patients

Cited by 190 publications

References 61 publications

Changes in White Matter Organization in Adolescent Offspring of Schizophrenia Patients

Changes in White Matter Organization in Adolescent Offspring of Schizophrenia Patients

Frontal fasciculi and psychotic symptoms in antipsychotic-naive patients with schizophrenia before and after 6 weeks of selective dopamine D2/3 receptor blockade

Ventral Striatal Dysfunction and Symptom Expression in Individuals With Schizotypal Personality Traits and Early Psychosis

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