Name: handwriting analysis indicates spontaneous dyskinesias in neuroleptic na&#239;ve adolescents at high risk for psychosis
Uploaded: 2013-11-21T14:30:00
Description: Watch this Scientific Journal Video about Handwriting Analysis Indicates Spontaneous Dyskinesias in Neuroleptic NaÃƒÂ¯ve Adolescents at High Risk for Psychosis at JoVE.com

This work was supported by National Institute of Health Grants R01MH094650 to Dr. Mittal.

1. Participants
<ol>
	<li>Provide approval for the protocol and informed consent procedures from the University Institutional Review Board.</li>
	<li>Recruit adolescent and young adult UHR participants by using Craigslist (i.e. local classified advertisements on the internet), email postings, newspaper ads, and community professional referrals.</li>
	<li>Recruit healthy control participants by craigslist, flyers and newspaper announcements.
	<ol>
		<li>Advertise that the study looks at healthy development for ...

<ol>
	<li>Cannon, T. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prediction+of+psychosis+in+youth+at+high+clinical+risk:+a+multisite+longitudinal+study+in+North+America.">Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America.</a> Arch. Gen. Psychiatry. 65, 28-37 (2008).</li><li>Yung, A. R., Phillips, L. J., Yuen, H. P., McGorry, P. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Risk+factors+for+psychosis+in+an+ultra+high-risk+group:+psychopathology+and+clinical+features.">Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features.</a> Schizophr. Res. 67, 131-142 (2004).</li><li>Miller, T. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prodromal+assessment+with+the+structured+interview+for+prodromal+syndromes+and+the+scale+of+prodromal+symptoms:+predictive+validity,+interrater+reliability,+and+training+to+reliability.">Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability.</a> Schizophr. Bull. 29, 703-715 (2003).</li><li>Cornblatt, B. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+schizophrenia+prodrome+revisited:+a+neurodevelopmental+perspective.">The schizophrenia prodrome revisited: a neurodevelopmental perspective.</a> Schizophr. Bull. 29, 633-651 (2003).</li><li>Mittal, V. A., Dean, D. J., Pelletier, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dermatoglyphic+asymmetries+and+fronto-striatal+dysfunction+in+young+adults+reporting+non-clinical+psychosis.">Dermatoglyphic asymmetries and fronto-striatal dysfunction in young adults reporting non-clinical psychosis.</a> Acta Psychiatr. Scand. 126, 290-297 (2012).</li><li>Mittal, V. A., Neumann, C., Saczawa, M., Walker, E. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Longitudinal+progression+of+movement+abnormalities+in+relation+to+psychotic+symptoms+in+adolescents+at+high+risk+of+schizophrenia.">Longitudinal progression of movement abnormalities in relation to psychotic symptoms in adolescents at high risk of schizophrenia.</a> Arch. Gen. Psychiatry. 65, 165-171 (2008).</li><li>Mittal, V. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Abnormal+movements+are+associated+with+poor+psychosocial+functioning+in+adolescents+at+high+risk+for+psychosis.">Abnormal movements are associated with poor psychosocial functioning in adolescents at high risk for psychosis.</a> Schizophr. Res. 130, 164-169 (2011).</li><li>Mittal, V. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Markers+of+basal+ganglia+dysfunction+and+conversion+to+psychosis:+neurocognitive+deficits+and+dyskinesias+in+the+prodromal+period.">Markers of basal ganglia dysfunction and conversion to psychosis: neurocognitive deficits and dyskinesias in the prodromal period.</a> Biol. Psychiatry. 68, 93-99 (2010).</li><li>Walker, D., Diforio, <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Schizophrenia:+a+neural+diathesis-stress+model.">Schizophrenia: a neural diathesis-stress model.</a> Psychol. Rev. 104, 667-685 (1997).</li><li>Walker, E. F., Savoie, T., Davis, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuromotor+precursors+of+schizophrenia.">Neuromotor precursors of schizophrenia.</a> Schizophr. Bull. 20, 441-451 (1994).</li><li>Mittal, V. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Striatal+volumes+and+dyskinetic+movements+in+youth+at+high-risk+for+psychosis.">Striatal volumes and dyskinetic movements in youth at high-risk for psychosis.</a> Schizophr. Res. 123, 68-70 (2010).</li><li>Bechdolf, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interventions+in+the+initial+prodromal+states+of+psychosis+in+Germany:+concept+and+recruitment.">Interventions in the initial prodromal states of psychosis in Germany: concept and recruitment.</a> Br. J. Psychiatry Suppl. 48, s45-s48 (2005).</li><li>Mittal, V. A., Dean, D. J., Pelletier, A., Caligiuri, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Associations+between+spontaneous+movement+abnormalities+and+psychotic-like+experiences+in+the+general+population.">Associations between spontaneous movement abnormalities and psychotic-like experiences in the general population.</a> Schizophr. Res. 132, 194-196 (2011).</li><li>Mittal, V. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=BDNF+Val66Met+and+spontaneous+dyskinesias+in+non-clinical+psychosis.">BDNF Val66Met and spontaneous dyskinesias in non-clinical psychosis.</a> Schizophr. Res. 140, 65-70 (2012).</li><li>Caligiuri, M. P., Teulings, H. L., Dean, C. E., Niculescu, A. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handwriting+movement+analyses+for+monitoring+drug-induced+motor+side+effects+in+schizophrenia+patients+treated+with+risperidone.">Handwriting movement analyses for monitoring drug-induced motor side effects in schizophrenia patients treated with risperidone.</a> Hum. Mov. Sci. 28, 633-642 (2009).</li><li>Caligiuri, M. P., Teulings, H. L., Dean, C. E., Niculescu, A. B., 3rd, J. B., Lohr, <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handwriting+movement+kinematics+for+quantifying+extrapyramidal+side+effects+in+patients+treated+with+atypical+antipsychotics.">Handwriting movement kinematics for quantifying extrapyramidal side effects in patients treated with atypical antipsychotics.</a> Psychiatry Res. 177, 77-83 (2010).</li><li>Caligiuri, M. P., Teulings, H. L., Filoteo, J. V., Song, D., Lohr, J. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+measurement+of+handwriting+in+the+assessment+of+drug-induced+parkinsonism.">Quantitative measurement of handwriting in the assessment of drug-induced parkinsonism.</a> Hum. Mov. Sci. 25, 510-522 (2006).</li><li>Schizophr Bull, . <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> 19, 303-315 (1993).</li><li>Andersson, K., Fuxe, K., Agnati, L. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+single+injections+of+nicotine+on+the+ascending+dopamine+pathways+in+the+rat.+Evidence+for+increases+of+dopamine+turnover+in+the+mesostriatal+and+mesolimbic+dopamine+neurons.">Effects of single injections of nicotine on the ascending dopamine pathways in the rat. Evidence for increases of dopamine turnover in the mesostriatal and mesolimbic dopamine neurons.</a> Acta Physiol. Scand. 112, 345-347 (1981).</li><li>Lane, R. D., Glazer, W. M., Hansen, T. E., Berman, W. H., Kramer, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+tardive+dyskinesia+using+the+Abnormal+Involuntary+Movement+Scale.">Assessment of tardive dyskinesia using the Abnormal Involuntary Movement Scale.</a> J. Nerv. Ment. Dis. 173, 353-357 (1985).</li><li>Zhang, X. Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Smoking+and+tardive+dyskinesia+in+male+patients+with+chronic+schizophrenia.">Smoking and tardive dyskinesia in male patients with chronic schizophrenia.</a> Prog. Neuropsychopharmacol. Biol. Psychiatry. 35, 1765-1769 (2011).</li><li>Tucha, O., Lange, K. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+nicotine+chewing+gum+on+a+real-life+motor+task:+a+kinematic+analysis+of+handwriting+movements+in+smokers+and+non-smokers.">Effects of nicotine chewing gum on a real-life motor task: a kinematic analysis of handwriting movements in smokers and non-smokers.</a> Psychopharmacology. 173, 49-56 (2004).</li><li>Teulings, H. L., Contreras-Vidal, J. L., Stelmach, G. E., Adler, C. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Parkinsonism+reduces+coordination+of+fingers,+wrist,+and+arm+in+fine+motor+control.">Parkinsonism reduces coordination of fingers, wrist, and arm in fine motor control.</a> Exp. Neurol. 146, 159-170 (1997).</li><li>Lin, C. Y., Yeh, C. H., Chang, T. T., Kao, C. H., Tsai, S. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Smoking,+dopamine+transporter,+and+hand+tremor.">Smoking, dopamine transporter, and hand tremor.</a> Clin. Nucl. Med. 37, 35-38 (2012).</li><li>Van Gemmert, A. W., Teulings, H. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Advances+in+graphonomics:+studies+on+fine+motor+control,+its+development+and+disorders.">Advances in graphonomics: studies on fine motor control, its development and disorders.</a> Hum. Mov. Sci. 25, 447-453 (2006).</li><li>Gharabawi, G. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Abnormal+Involuntary+Movement+Scale+(AIMS)+and+Extrapyramidal+Symptom+Rating+Scale+(ESRS):+cross-scale+comparison+in+assessing+tardive+dyskinesia.">Abnormal Involuntary Movement Scale (AIMS) and Extrapyramidal Symptom Rating Scale (ESRS): cross-scale comparison in assessing tardive dyskinesia.</a> Schizophr. Res. 77, 119-128 (2005).</li><li>Cortese, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Relationship+of+neuromotor+disturbances+to+psychosis+symptoms+in+first-episode+neuroleptic-naive+schizophrenia+patients.">Relationship of neuromotor disturbances to psychosis symptoms in first-episode neuroleptic-naive schizophrenia patients.</a> Schizophr. Res. 75, 65-75 (2005).</li><li>Howes, O. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Elevated+striatal+dopamine+function+linked+to+prodromal+signs+of+schizophrenia.">Elevated striatal dopamine function linked to prodromal signs of schizophrenia.</a> Arch. Gen. Psychiatry. 66, 13-20 (2009).</li><li>Van Gemmert, A. W., Teulings, H. L., Contreras-Vidal, J. L., Stelmach, G. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Parkinson's+disease+and+the+control+of+size+and+speed+in+handwriting.">Parkinson's disease and the control of size and speed in handwriting.</a> Neuropsychologia. 37, 685-694 (1999).</li></ol>

This study found significant evidence of more dysfluent pen movements and the presence of dyskinesia in an UHR sample using a handwriting analysis program to examine movement abnormalities.
Traditionally, observer based rating scales have been utilized to measure movement abnormalities in order to monitor drug side effects15-17. However, the observer ratings suffer from significant drawbacks including long training times for raters, experimenter error, and suboptimal reliability<sup...

The period preceding the onset of psychosis is of clinical and research interest as it may shed light on formal psychosis (prior to when a number of third variable confounds such as medication obfuscate our understanding), and also serves as a viable point of intervention (roughly &#8531; of youth showing a prodromal syndrome go on to develop schizophrenia in a 2 year period, and several studies suggest that psychosocial, cognitive training, and pharmacological interventions may ameliorate the course of illness)1. This prodromal period is marked by attenuated positive symptoms (perceptual abnormalities, suspiciousness, feelings of grandiosity, or unusual thoughts) and a decline in functioning2. Individuals who report a moderate degree of positive symptoms during a structured clinical interview, and/or a decline in functioning accompanying the presence of schizotypal personality disorder and/or a family history of schizophrenia are considered to have a prodromal or ultra high-risk (UHR) syndrome1-3. Current etiological conceptions of psychosis suggest that it is a neurodevelopmental disorder that affects an individual during late adolescence or early adulthood4. Constitutional factors such as genetics and prenatal insults result in vulnerability for psychosis4. Movement abnormalities are of keen interest to this model, as the same mechanisms believed to be contributing to psychotic symptoms are also responsible for governing the motor system5. Researchers argue that by understanding movement behavior prior to the onset of schizophrenia, we may improve our ability to predict, understand, and intervene in the development of schizophrenia6.
It is well known that individuals who later go on to develop schizophrenia often show subtle movement abnormalities prior to the onset of illness7,8. Walker and colleagues collected videotapes of patients with schizophrenia during childhood and rated the videos for movement abnormalities, showing that movement abnormalities are present long before the onset of illness and are indicative of a neurological constitutional vulnerability9,10. Research suggests that the basal ganglia may be implicated in this neurological constitutional vulnerability, as UHR individuals show impaired neural development and neurocognitive deficits related to basal ganglia function8,11. Additionally, Mittal and colleagues have used observer ratings to show that movement abnormalities, closely linked to basal ganglia function, could successfully classify UHR individuals likely to convert to psychosis8,12. Another at risk group, nonclinical psychosis&#160;individuals who report having a psychotic-like experience at least once a year,&#160;show dyskinesia during a finger force stability task5,13,14. These findings provide strong evidence for the idea that movement abnormalities may be a core feature of risk of psychosis. Clearly, research that can improve detection and understanding of movement abnormalities is crucial for the understanding of the etiology of psychosis and for preventive efforts.
Efforts to understand medication side-effects that affect dopamine regulation in schizophrenia and Parkinson&#39;s patients have guided technological improvements, such as the development of computerized tablets for handwriting analysis, in measuring movement abnormalitie15-17. Antipsychotic medication may lead to the development of tardive dyskinesia, characterized by slow involuntary repetitive movements18. Nicotine use has also been shown to affect dopamine regulation and handwriting kinematics19-21. For example, Tucha and Lange showed that pen movement fluency improved during a computerized handwriting task when healthy participants were given chewing gum containing nicotine22. During assessment, participants generally write in a western cursive handwriting with larger and smaller vertical strokes. Western cursive handwriting is optimal for examining pen movement smoothness because of the predominance of vertical strokes that require complex coordination of muscles to perform well23. Dysfluent pen movements result when the muscles that coordinate the movement receive disregulated signals from the basal ganglia15,16.
The software segments and analyzes pen movements per stroke and extracts a variable that is thought to be a proximal measure of dyskinesia, called average normalized jerk15-17. Jerk is defined as the change in acceleration over time per stroke23. Because of the different lengths in vertical strokes in most western style handwritings, jerk is normalized across strokes. Within each stroke, dysfluent pen movements are characterized by a greater number of acceleration peaks over a given distance. Thus, dysfluent pen movements are characterized by a lack of smoothness, a greater number of acceleration peaks, and a larger value of jerk.
The improvement of measures used to rate movement abnormalities in UHR youth is critical for improving our etiological conceptions of the illness and our understanding of movement disorders in general. In that effort to understand movement disorders in those at risk for psychosis, we examined handwriting kinematics from 36 neuroleptic na&#239;ve research participants using handwriting analysis software. Despite its wide use in investigating dyskinesia in Parkinson&#39;s and schizophrenia patients, this is surprisingly the first study to report on handwriting kinematics in an ultra-high-risk group for psychosis. We hypothesized that the UHR individuals would show more dysfluent pen movements, characterized by a larger value of jerk, when asked to write on a tablet computer than a group of healthy controls.

<table border="1">
 <tbody>
		 <tr>
			<td>Material Name</td>
			<td>Company</td>
			<td></td>
			<td>Website </td>
		 </tr>
		 <tr>
			<td>Fujitsu Lifebook T901 Tablet Computer</td>
			<td>Fujitsu Ltd. </td>
			<td></td>
			<td><a href="http://www.shopfujitsu.com/store/" target="_blank">http://www.shopfujitsu.com/store/</a></td>
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			<td>Neuroscript MovAlyzeR</td>
			<td>Neuroscript LLC</td>
			<td></td>
			<td><a href="http://www.neuroscript.net/movalyzer.php" target="_blank">http://www.neuroscript.net/movalyzer.php</a></td>
		 </tr>
 </tbody>
 </table>

handwriting analysis indicates spontaneous dyskinesias in neuroleptic na&#239;ve adolescents at high risk for psychosis

Growing evidence suggests that movement abnormalities are a core feature of psychosis. One marker of movement abnormality, dyskinesia, is a result of impaired neuromodulation of dopamine in fronto-striatal pathways. The traditional methods for identifying movement abnormalities include observer-based reports and force stability gauges. The drawbacks of these methods are long training times for raters, experimenter bias, large site differences in instrumental apparatus, and suboptimal reliability. Taking these drawbacks into account has guided the development of better&#160;standardized and more efficient procedures to examine movement abnormalities through handwriting analysis software and tablet. Individuals at&#160;risk for psychosis showed significantly more dysfluent pen movements (a proximal measure for dyskinesia) in a handwriting task. Handwriting kinematics offers a great advance over previous methods of assessing dyskinesia, which could clearly be beneficial for understanding the etiology of psychosis.

There were no significant differences between groups on demographic characteristics including age, years of education, or parental education (see Table 1 for a demographic breakdown of the participants). Chi Square tests revealed significant differences between groups on gender &#967;2 (1, N = 36) = 5.46, p&#8804;0.05, with more males in the UHR group and more females in the control group. There was a significant group differences in tobacco usage frequency, t(22.9) = 2.15, p&#8804;0.05, showi...

Watch this Scientific Journal Video about Handwriting Analysis Indicates Spontaneous Dyskinesias in Neuroleptic NaÃƒÂ¯ve Adolescents at High Risk for Psychosis at JoVE.com

Handwriting Analysis Indicates Spontaneous Dyskinesias in Neuroleptic NaÃƒÆ’Ã‚Â¯ve Adolescents at High Risk for Psychosis

Handwriting analysis software significantly improves upon existing instruments measuring movement disorders. Individuals at&#160;risk for psychosis and healthy controls completed handwriting tasks to test for dyskinesia. Results suggest that youth at&#160;risk for psychosis exhibit dyskinesia and that handwriting analysis could significantly contribute to wider dissemination of early identification efforts

Handwriting Analysis Indicates Spontaneous Dyskinesias in Neuroleptic Na&#239;ve Adolescents at High Risk for Psychosis

Growing evidence suggests that movement abnormalities are a core feature of psychosis. One marker of movement abnormality, dyskinesia, is a result of ...

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