Neurological soft signs and brain morphology in first-episode schizophrenia

Thomann, Philipp A.; Wüstenberg, Torsten; Santos, Vasco Dos; Bachmann, Silke; Essig, Marco; Schröder, Johannes

doi:10.1017/s0033291708003656

Cited by 100 publications

(105 citation statements)

References 38 publications

(72 reference statements)

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“…Implicated motor systems include the cerebellum [13,54,55] and corticospinal tract [70,72], where we have previously described defects in Sema6A mutants [30,39]. The abnormalities in gait that we report here may reflect disrupted cellular organisation in the cerebellum [73].…”

Section: Comparison With the Pathology Of Psychiatric Disorderssupporting

confidence: 50%

“…Neuropathological studies of post mortem brains of SZ patients provide evidence for variable and subtle cytoarchitectural disturbances in cell positioning, packing, density and size in various parts of the brain, most notably the prefrontal cortex, hippocampal formation [4], thalamus [53] and cerebellum [54,55]. [56,57].…”

Section: Comparison With the Pathology Of Psychiatric Disordersmentioning

confidence: 99%

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[P2.14]: Mutation of Semaphorin‐6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology

Rünker

O’Tuathaigh

Dunleavy

et al. 2010

Intl J of Devlp Neuroscience

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Psychiatric disorders such as schizophrenia and autism are characterised by cellular disorganisation and dysconnectivity across the brain and can be caused by mutations in genes that control neurodevelopmental processes. To examine how neurodevelopmental defects can affect brain function and behaviour, we have comprehensively investigated the consequences of mutation of one such gene, Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour and physiology in mice. These analyses reveal a spectrum of widespread but subtle anatomical defects in Sema6A mutants, notably in limbic and cortical cellular organisation, lamination and connectivity. These mutants display concomitant alterations in the electroencephalogram and hyper-exploratory behaviour, which are characteristic of models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory. Mice with mutations in Sema6A or the interacting genes may thus represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting, either directly or through reactive mechanisms, in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. The biological data presented here also make these genes plausible candidates to explain human linkage findings for schizophrenia and autism.

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Section: Comparison With the Pathology Of Psychiatric Disorderssupporting

confidence: 50%

Section: Comparison With the Pathology Of Psychiatric Disordersmentioning

confidence: 99%

[P2.14]: Mutation of Semaphorin‐6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology

Rünker

O’Tuathaigh

Dunleavy

et al. 2010

Intl J of Devlp Neuroscience

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“…It is important to note that the detection of localized changes is not exclusive to FIRST but is also possible using voxel-based morphometry, a technique that was most commonly used in previous MRI studies on NSS in schizophrenia [12,16,29]. Inference in the latter technique relies on locally averaged gray matter segmentations and is therefore sensitive to the inaccuracy of tissue-type classification and arbitrary smoothing extents.…”

Section: Discussionmentioning

confidence: 99%

“…According to previous structural magnetic resonance imaging (MRI) studies, increased NSS scores were found to be related to atrophic processes within the caudate nucleus [7,11,12,13], putamen [7,14], globus pallidus [7,13], thalamus [7,11,12,13,15], cerebellum [12,16], inferior and middle frontal gyri [12], and corpus callosum [17]. Studies using functional MRI techniques reported abnormal activation in the pre- and postcentral gyrus, the premotor area, and the middle and inferior frontal gyri in patients with higher NSS scores [18,19].…”

Section: Introductionmentioning

confidence: 99%

Neurological Soft Signs and Brainstem Morphology in First-Episode Schizophrenia

Hirjak

Stieltjes²,

Hauser

et al. 2013

Neuropsychobiology

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Background: Minor motor and sensory deficits or neurological soft signs (NSS) have frequently been reported in patients with schizophrenia at any stage of their illness. NSS have been demonstrated to correlate with neuroanatomical abnormalities in various brain regions. Despite its important role in the integration and coordination of automatic motor actions, the brainstem has so far rather been ignored in previous neuroimaging studies on NSS in schizophrenia. Method: We investigated 21 right-handed first-episode schizophrenia patients using high-resolution magnetic resonance imaging at 3 T. The severity of NSS was measured with the Heidelberg Scale. Associations between NSS and both brainstem volume and shape changes were examined. Results: Higher NSS scores were significantly associated with structural alterations in the brainstem. According to volume measurements higher NSS scores correlated with global changes of the brainstem. Using shape analyses these associations referred to regionally specific morphometric alterations predominantly in the midbrain and pons. Conclusion: The findings suggest that brainstem morphometric alterations are associated with the severity of NSS in patients with first-episode schizophrenia. They further indicate the involvement of the brainstem in the pathogenesis of schizophrenia.

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“…58,59 NSS are also indicative of basal ganglia dysfunction, because a reduction of grey matter volume in different basal ganglia structures has been reported in a number of studies. [60][61][62] Furthermore, a recent study of functional and structural MRI in schizophrenia patients 63 showed that those with high levels of negative symptoms had diminished striatal activity during a working memory task. Despite converging evidence of basal ganglia dysfunction in deficit schizophrenia, and given the marked influence of antipsychotic medication on basal ganglia structures, 64 neuroimaging research on drug-naive patients with deficit schizophrenia is clearly warranted to confirm this hypothesis.…”

Section: Deficit Features and Primary Neurological Abnormalitiesmentioning

confidence: 99%

Characterization of the Deficit Syndrome in Drug-Naive Schizophrenia Patients: The Role of Spontaneous Movement Disorders and Neurological Soft Signs

Peralta

Moreno-Izco

Sánchez‐Torres

et al. 2012

Schizophrenia Bulletin

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This study aimed to characterize the deficit syndrome in drug-naive schizophrenia patients and to examine the relationship between deficit features and primary neurological abnormalities. Drug-naive schizophrenia patients (n = 102) were examined at baseline for demographics, premorbid functioning, duration of untreated illness (DUI), psychopathology, neurological signs, and deficit symptoms, and reassessed at 1-year follow-up. Neurological abnormalities were examined before inception of antipsychotic medication and included four domains of spontaneous movement disorders (SMD) and four domains of neurological soft signs (NSS). Patients fulfilling the deficit syndrome criteria at the two assessments (n = 20) were compared with nondeficit patients (n = 82) across demographic, clinical, and neurological variables. Deficit and nondeficit groups showed similar demographic characteristics and levels of psychotic, disorganization, and depressive symptoms. Compared with nondeficit patients, deficit patients showed poorer premorbid adjustment, higher premorbid deterioration, a lengthier DUI, and much poorer functional outcome. Relative to the nondeficit patients, those with the deficit syndrome showed higher levels of SMD-excepting akathisia-and NSS. This association pattern was also evident for deficit and neurological ratings in the whole sample of schizophrenia patients. Parkinsonism, motor sequencing, and release signs were all independently related to the deficit syndrome. These findings confirm that the deficit/nondeficit categorization is replicable and reliable in first-admission patients and raise the possibility that premorbid deterioration, deficit symptoms, and neurological abnormalities represent a triad of manifestations that share common underlying neurobiological mechanisms. More specifically, the data are consistent with a neurodevelopmental model of deficit symptoms involving basal ganglia dysfunction.

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Neurological soft signs and brain morphology in first-episode schizophrenia

Cited by 100 publications

References 38 publications

[P2.14]: Mutation of Semaphorin‐6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology

[P2.14]: Mutation of Semaphorin‐6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology

Neurological Soft Signs and Brainstem Morphology in First-Episode Schizophrenia

Characterization of the Deficit Syndrome in Drug-Naive Schizophrenia Patients: The Role of Spontaneous Movement Disorders and Neurological Soft Signs

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