Markers of Basal Ganglia Dysfunction and Conversion to Psychosis: Neurocognitive Deficits and Dyskinesias in the Prodromal Period

Mittal, Vijay A.; Walker, Elaine F.; Bearden, Carrie E.; Walder, Deborah J.; Trottman, Hanan D.; Daley, Melita; Simone, Anthony; Cannon, Tyrone D.

doi:10.1016/j.biopsych.2010.01.021

Cited by 84 publications

(89 citation statements)

References 71 publications

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“…42 In support of this theory, prospective investigations in youth with prodromal syndromes have observed that the presence of specific motor abnormalities significantly increases the odds of developing psychosis in a brief 2-year period. 10,43 In a new exciting direction, some work also suggests that cerebellar-specific motor behavior (i.e., balance) may also have unique predictive value for negative symptoms as well. 29,44 This series of findings has significant practical use for the refinement of risk calculators 45 as well as efforts to understand unique potential subtypes.…”

Section: At Issuementioning

confidence: 99%

“…8,9 Indeed, if schizophrenia is a disorder characterized by domains of symptoms as well as cognitive and emotive deficits spanning a host of disparate mechanisms and structures, then perhaps these circuits, responsible for dynamic communication with frontal areas, may be a good target for explaining this heterogeneity. 10 Although theories have pointed to this idea in the past, 11,12 sophisticated cross-disciplinary empirical work is now filling in the missing pieces. One of the most exciting developments in this area focuses on new evidence suggesting direct 2-way communication between the basal ganglia and the cerebellum, independent of the cortex.…”

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confidence: 99%

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Cross-Cutting Advancements Usher in a New Era for Motor Research in Psychosis

Mittal

2016

SCHBUL

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As gesture serves as an interaction point between motor, language, and sensory-integration processes, an intersection also implicated in psychosis, schizophrenia researchers have recently turned toward this area as well. 1 The findings of Walther et al 2 move our understanding of this nascent field significantly ahead, with results indicating that deficits in gesture performance and perception are closely tied with clinical and functional outcome in individuals with schizophrenia over a 6-month period. More broadly, this article suggests that a test of hand gesture may provide a viable method for predicting clinical course and potentially highlighting a novel vulnerability subtype in schizophrenia patients. Given the importance of these findings, and the relative ease of such assessments, the questions remain-why are we not seeing more studies like this, and where are the translational applications? Further, in addition to aberrant gesture, schizophrenia has been linked with a range of motor signs including delays in developmental milestones, clumsiness, poor coordination, abnormalities in gait, posture and neuromusculature, diffuse neurological soft signs, catatonia, psychomotor slowing, and both medication-induced and spontaneous hyper/hypo dyskinesias spanning muscle groups throughout the body. Despite the broad array of affected behaviors and characteristics, and the long history of movement and motor research in this area, 3 the question remains, why is this such a neglected area in our field?There are several factors that have been impeding more widespread use of motor variables in cuttingedge research. First, rigid intradisciplinary boundaries between neurology and psychiatry have historically kept abnormalities in movement and socio-emotional behavior distinct. In a related issue, until recently, key relevant target structures such as the basal ganglia and cerebellum have been viewed primarily as a motor centers and related movement behaviors have not been linked into the sophisticated comprehensive models or etiological theories that are often necessary generate enthusiasm about a domain or target. Second, the advent of first-generation antipsychotic medications, which produce characteristic movement disorders in some patients, contributed to further confusion about etiology of movement signs. More broadly, both generations of neuroleptics have also continued to serve as a tricky barrier for definitive research in this area. 4 Third, empirical studies have relied almost entirely on drug-induced motor abnormality assessments, 5 or scales designed to follow diffuse markers (eg, neurological soft signs). 6 While these instruments can be reliable at a particular site, they require highly specialized training, miss more subtle movements, and can press investigators to impose subjective categories on continuous phenotypes. Fourth, although it has been clear for some time that there are motor abnormalities present in psychosis, the translational relevance of these markers is uncertain. Finally, motor behaviors...

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Section: At Issuementioning

confidence: 99%

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Cross-Cutting Advancements Usher in a New Era for Motor Research in Psychosis

Mittal

2016

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“…Motor dysfunction in psychosis populations varies greatly and includes relatively diffuse neurological soft signs (Mittal et al 2014), dyspraxia (Schiffman et al 2015), postural control deficits (Marvel et al 2004; Bernard et al 2014), and both hypo- and hyper-kinesias (Mittal et al 2010; Pappa & Dazzan 2009), catatonia and psychomotor slowing (Walther & Strik 2012), and motor learning deficits (Marvel et al 2007). What is particularly interesting is that in psychosis risk populations where confounds such as drug abuse and medications are less prevalent, movement abnormalities have been useful in predicting symptom course and disease progression (Dean et al .…”

Section: Motor Dysfunction Across Disordersmentioning

confidence: 99%

“…Critically, in many cases motor systems dysfunction is present in the absence of medication (Caligiuri & Lohr 1994; Fenton et al 1994), indicating that these deficits are not merely a side effect of pharmacological treatments. Furthermore, evidence also indicates that motor systems dysfunction is present prior to disease onset (e.g., Mittal et al 2010). Together this suggests that it may be a trait feature of psychopathology, though it is likely that there are state effects with respect to the severity of this dysfunction associated with disease course, symptom severity, and medications.…”

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Updating the research domain criteria: the utility of a motor dimension

Mittal

2015

Psychol. Med.

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Within the NIMH Research Domain Criteria (RDoC) framework, dimensions of behavior are investigated across diagnoses with the goal of developing a better understanding of their underlying neural substrates. Currently, this framework includes five domains: cognitive, social, arousal/regulatory, and negative and positive valence systems. We argue that the inclusion of a motor systems domain is sorely needed as well. Independent of medication, distinct areas of motor dysfunction (e.g., motor planning/inhibition/learning/coordination, involuntary movements) commonly appear across a number of mental disorders (e.g., schizophrenia, bipolar disorder, autism, ADHD, Alzheimer’s, depression) as well as neurological disorders accompanied by significant psychological symptoms (e.g., Parkinson’s disease). In addition, motor systems are amenable to study across multiple levels of analysis from the cellular molecular level focusing on cytoarchitechtonics and neurotransmitter systems, to networks and circuits measured using neuroimaging, and finally at the level of overt behavioral performance. Critically, the neural systems associated with motor performance have been relatively well defined, and different circuits have been linked to distinct aspects of motor behavior. As such, they may also be differentially associated with symptoms and motor dysfunction across diagnoses, and be uniquely informative about underlying etiology. Importantly, motor signs can change across stages of illness; they are also often present in the prodromal phases of disease and closely linked with course, suggesting that these behaviors represent a core feature reflective of pathogenic processes. The inclusion of a motor domain would allow researchers to better understand psychopathology more broadly, and may also reveal important contributions to disease processes across diagnoses.

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“…The negative finding in Southeast Asians suggests an ethnicity effect [59]. In addition, spontaneous abnormal movements were reported in schizophrenia spectrum disorders and prodromal states [60,61,62,63], suggesting that the vulnerability for schizophrenia was associated with these movement disorders [11,62]. …”

Section: Clinical Perspectivesmentioning

confidence: 99%

Motor Symptoms and Schizophrenia

Walther¹,

Strik²

2012

Neuropsychobiology

300

233

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Classical schizophrenia literature reports motor symptoms as characteristic of the disorder. After the introduction of neuroleptic drugs, the existence of genuine motor disorders was challenged. Renewed interest arose as symptoms were found in never-medicated patients. Reports focused on abnormal involuntary movements, parkinsonism, neurological soft signs, catatonia, negative symptoms, or psychomotor slowing. Since these syndromes refer to different concepts, however, the definitions are not congruent and the symptoms overlap. The prevalence rates of motor symptoms in schizophrenia are surprisingly high, and recent studies indicate a possible pathobiology. In particular, the development and maturation of the human motor system appears to be closely linked to the emergence of motor symptoms observed in schizophrenia. Post-mortem and neuroimaging results demonstrated aberrant structure and function of premotor and motor cortices, basal ganglia, thalamus, and the connecting white matter tracts. Animal models have focused on aberrant neurotransmission and genetic contributions. Findings of localized abnormal oligodendrocyte function and myelination point to the special role of the white matter in schizophrenia, and recent studies specifically found an association between motor abnormalities and white matter structure in schizophrenia. This review of the literature supports the idea that motor symptoms are closely related to the neurodevelopmental disturbances of schizophrenia and a distinct syndromal dimension with its own pathophysiology.

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Markers of Basal Ganglia Dysfunction and Conversion to Psychosis: Neurocognitive Deficits and Dyskinesias in the Prodromal Period

Cited by 84 publications

References 71 publications

Cross-Cutting Advancements Usher in a New Era for Motor Research in Psychosis

Cross-Cutting Advancements Usher in a New Era for Motor Research in Psychosis

Updating the research domain criteria: the utility of a motor dimension

Motor Symptoms and Schizophrenia

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