White matter pathway organization of the reward system is related to positive and negative symptoms in schizophrenia

Bracht, Tobias; Horn, Helge; Strik, Werner; Federspiel, Andrea; Razavi, Nadja; Stegmayer, Katharina; Wiest, Roland; Dierks, Thomas; Müller, Thomas; Walther, Sebastian

doi:10.1016/j.schres.2014.01.015

Cited by 69 publications

(59 citation statements)

References 58 publications

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“…Consistently, we have demonstrated that gray matter abnormalities in a key region of the limbic system, i.e., the ventral striatum, were specifically related to emotional dysregulation in schizophrenia, but at the same time unrelated to schizophrenia in general [59]. Furthermore, the probability of a structural connection between the ventral striatum and the amygdala was increased as a function of paranoid symptoms [97]. Moreover, behavioral alterations in the BPS affectivity dimension – such as delusions of threat, suspiciousness, or unpleasant body sensations – were linked with an increased resting-state CBF in the left amygdala [60], and thus provide evidence for the hypothesized association between limbic dysfunction and clinical presentations of paranoid threat and persecutory delusions [94, 98].…”

Section: Mapping Symptoms Onto Brain Systems: Empirical Evidence For mentioning

confidence: 80%

Systems Neuroscience of Psychosis: Mapping Schizophrenia Symptoms onto Brain Systems

et al. 2017

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Schizophrenia research has been in a deadlock for many decades. Despite important advances in clinical treatment, there are still major concerns regarding long-term psychosocial reintegration and disease management, biological heterogeneity, unsatisfactory predictors of individual course and treatment strategies, and a confusing variety of controversial theories about its etiology and pathophysiological mechanisms. In the present perspective on schizophrenia research, we first discuss a methodological pitfall in contemporary schizophrenia research inherent in the attempt to link mental phenomena with the brain: we claim that the time-honored phenomenological method of defining mental symptoms should not be contaminated with the naturalistic approach of modern neuroscience. We then describe our Systems Neuroscience of Psychosis (SyNoPsis) project, which aims to overcome this intrinsic problem of psychiatric research. Considering schizophrenia primarily as a disorder of interindividual communication, we developed a neurobiologically informed semiotics of psychotic disorders, as well as an operational clinical rating scale. The novel psychopathology allows disentangling the clinical manifestations of schizophrenia into behavioral domains matching the functions of three well-described higher-order corticobasal brain systems involved in interindividual human communication, namely, the limbic, associative, and motor loops, including their corticocortical sensorimotor connections. The results of several empirical studies support the hypothesis that the proposed three-dimensional symptom structure, segregated into the affective, the language, and the motor domain, can be specifically mapped onto structural and functional abnormalities of the respective brain systems. New pathophysiological hypotheses derived from this brain system-oriented approach have helped to develop and improve novel treatment strategies with noninvasive brain stimulation and practicable clinical parameters. In clinical practice, the novel psychopathology allows confining the communication deficits of the individual patient, shifting attention from the symptoms to the intact resources. We have studied this approach and observed important advantages for therapeutic alliances, personalized treatment, and de-escalation strategies. Future studies will further conjoin clinical definitions of psychotic symptoms with brain structures and functions, and disentangle structural and functional deficit patterns within these systems to identify neurobiologically distinct subsyndromes. Neurobiologically homogeneous patient groups may provide new momentum for treatment research. Finally, lessons learned from schizophrenia research may contribute to developing a comprehensive perspective on human experience and behavior that integrates methodologically distinct, but internally consistent, insights from humanities and neuroscience.

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Section: Mapping Symptoms Onto Brain Systems: Empirical Evidence For mentioning

confidence: 80%

Systems Neuroscience of Psychosis: Mapping Schizophrenia Symptoms onto Brain Systems

et al. 2017

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“…Second, patients show decreased frontal and striatal volumes (Emsley et al, 2015;Harms et al, 2010). Finally, diffusion tensor imaging (DTI) studies points in the direction of altered white matter organization in tracts connecting frontal and striatal regions (Bracht et al, 2014;Quan et al, 2013). Importantly, we recently observed such reductions in unaffected siblings of schizophrenia patients (de Leeuw et al, 2015a), suggesting genetic factors underlying frontostriatal dysfunction in schizophrenia siblings.…”

Section: Introductionmentioning

confidence: 82%

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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“…Tracts were reconstructed using anatomically defined regions of interest (ROI). For reconstruction of the slMFB one horizontal ROI was placed surrounding the ventral tegmental area (VTA) (Bracht et al, 2014a(Bracht et al, , 2014b(Bracht et al, , 2014c. Anatomical borders were laterally the substantia nigra, anteriorly the mammillary bodies and posteriorly the red nucleus (Nieuwenhuys et al, 2008).…”

Section: Tractographymentioning

confidence: 99%

Limbic white matter microstructure plasticity reflects recovery from depression

Bracht

Jones

Müller

et al. 2015

Journal of Affective Disorders

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White matter pathway organization of the reward system is related to positive and negative symptoms in schizophrenia

Cited by 69 publications

References 58 publications

Systems Neuroscience of Psychosis: Mapping Schizophrenia Symptoms onto Brain Systems

Systems Neuroscience of Psychosis: Mapping Schizophrenia Symptoms onto Brain Systems

Changes in White Matter Organization in Adolescent Offspring of Schizophrenia Patients

Limbic white matter microstructure plasticity reflects recovery from depression

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