Elucidating the relationships between two automated handwriting feature quantification systems for multiple pairwise comparisons.

Recent advances in complex automated handwriting identification systems have led to a lack of understandability of these systems' computational processes and features by the forensic handwriting examiners that they are designed to support. To mitigate this issue, this research studied the relationship between two systems: FLASH ID® , an automated handwriting/black box system that uses measurements extracted from a static image of handwriting, and MovAlyzeR® , a system that captures kinematic features from pen strokes. For this study, 33 writers each wrote 60 phrases from the London Letter using cursive writing and handprinting, which led to thousands of sample pairs for analysis. The dissimilarities between pairs of samples were calculated using two score functions (one for each system). The observed results indicate that dissimilarity scores based on kinematic spatial-geometric pen stroke features (e.g., amplitude and slant) have a statistically significant relationship with dissimilarity scores obtained using static, graph-based features used by the FLASH ID® system. Similar relationships were observed for temporal features (e.g., duration and velocity) but not pen pressure, and for both handprinting and cursive samples. These results strongly imply that both the current implementation of FLASH ID® and MovAlyzeR® rely on similar features sets when measuring differences in pairs of handwritten samples. These results suggest that studies of biometric discrimination using MovAlyzeR® , specifically those based on the spatial-geometric feature set, support the validity of biometric matching algorithms based on FLASH ID® output.

Advances toward validating examiner writership opinion based on handwriting kinematics.

A National Research Council report on strengthening forensic science raised concern over the lack of scientific studies supporting the validity of examining and interpreting forensic evidence. However, establishing the foundational validity of subjective methods can be challenging. The present study aimed to establish the scientific validity of expert writership opinions and the two-stage approach to evidence interpretation using measures derived from research on handwriting motor control. Regression-based procedures were used to address two experimental questions: 1) what are the relative contributions of kinematic and pressure features in predicting examiner support for alternate writership propositions when examining pairs of questioned handwriting samples; and 2) to what extent does information about the rarity of the kinematic feature dissimilarity scores improve the accuracy of a predictive model based on dissimilarity alone. Regarding the first question, we identified a multifactor model consisting of feature dissimilarity scores and their population distributions having correlation coefficients (R2) of 0.84 and 0.88 for the same-writer and different-writers propositions, respectively. Temporal features contributed up to 21% to the predictive value of the model, whereas spatial features contributed only 9% and pen pressure contributed up to 17%. When we compared models reflecting a single-stage process (based on feature dissimilarities) of forming opinions with models reflecting a two-stage process (based on feature dissimilarities and rarity) we found that the two-stage models had an average of 15.25% greater predictive value than single-stage models. These findings support the scientific validity of FDE writership determinations and underscore the importance of the two-stage approach for evidence interpretation.

Use of an Automated System to Evaluate Feature Dissimilarities in Handwriting Under a Two-Stage Evaluative Process*, †.

The two-stage evaluative process is an established framework utilized by forensic document examiners (FDEs) for reaching a conclusion about the source(s) of handwritten evidence. In the second, or discrimination, stage, the examiner attempts to estimate the rarity of observations in a relevant background population. Unfortunately, control samples from a relevant background population are often unavailable, leaving the FDE to reach this determination based on subjective experience. Automated handwriting feature recognition systems are capable of performing both feature comparison and discrimination, yet these systems have not been subjected to empirical validation studies. In the present study, we repurposed a commercially available automated system to generate empirical distributions for ranking feature dissimilarity scores among pairs of handwritten phrases. The blinded results of this automated process were used to survey an international cohort of 36 FDEs regarding their strength of support for same- and different-writer propositions. The survey served to cross-validate FDE decision-making under the two-stage approach. Results from the survey demonstrated a clear pattern of response consistent with ground truth. Predictive regression analyses indicated that the automated feature dissimilarity scores and the log of their cumulative distribution functions accounted for 72% of the variability in FDE opinions. This study demonstrated that feature dissimilarity scores acquired using automated processes and their distributions are closely aligned with FDE decision-making processes supporting the heuristic value of the two-stage evaluative framework.

Exploring the Relationship of Transdiagnostic Mood and Psychosis Symptom Domains with Motor Dysfunction.

BACKGROUND: A number of motor abnormalities have been reported in psychotic disorders, including dyskinesia and psychomotor slowing. There is also evidence for many of the same motor abnormalities in biological first-degree relatives and accruing evidence for motor abnormalities in bipolar disorder. In addition to motor dysfunction, there are also shared symptom domains amongst these populations. OBJECTIVES: We explored the associations of (1) current and lifetime psychosis and mood symptom domains and (2) domains of psychosis proneness with various domains of motor function in a transdiagnostic sample (n = 149). METHOD: Individuals with schizophrenia, schizoaffective disorder, or bipolar disorder, biological first-degree relatives of individuals with a psychotic disorder, and controls completed measures of psychomotor speed and movement fluidity, and neural activity related to motor preparation (stimulus-locked lateralized readiness potential, S-LRP) and execution (response-locked LRP) was assessed using EEG. All participants completed the Brief Psychiatric Rating Scale; patients were additionally assessed for lifetime psychosis and mood episode symptoms, and relatives and controls completed the Chapman psychosis proneness scales. RESULTS: Multiple regression revealed levels of current negative symptoms and mania were significantly positively associated with psychomotor slowing even after accounting for current antipsychotic medication dosage and duration of illness. S-LRP onset latency was significantly positively associated with magical ideation. CONCLUSION: Domains of motor function are associated with various mood and psychosis symptom domains in a transdiagnostic sample, which may provide insight into brain abnormalities relevant to the expression of symptoms across disorders.

Signature dynamics in Alzheimer's disease.

Forensic document examiners are often called upon to opine on the authenticity of handwritten signatures by individuals with diminished mental capacity. Legal arguments surrounding the decisional capacity of an individual with dementia can be found in many cases involving wills, deeds, trusts, and contracts. The purpose of this study was to provide estimates of feature variability derived from dynamic analyses of signatures written by individuals with dementia of the Alzheimer type (AD) compared with age-comparable healthy individuals. Dynamic features of digitally captured signatures were analyzed to test the hypothesis that AD signature features will show greater variability compared with signatures from age-comparable healthy subjects. The study enrolled 69 AD and 74 age comparable healthy subjects. Results revealed four main findings from AD signatures: (1) that the temporal, spatial and fluency characteristics of signature formation did not differ from signatures of healthy writers; (2) variability in dynamic features over a series of repetitive signatures fell within 10% of the natural variation of healthy subjects; (3) there was a significant association between increased dynamic signature feature variability and increased dementia severity for stylized and mixed signatures only; and (4) despite significant decline in cognitive status over a 1-year period, dynamic signature features remained stable. Overall, these results suggest that signature writing is preserved in AD. The association between dementia severity and dynamic feature variability among AD subjects with stylized or mixed signatures warrants further research.

The nature of bradykinesia in schizophrenia treated with antipsychotics.

Recognizing drug-induced parkinsonian bradykinesia in psychosis patients can be challenging due to overlapping presentation with psychomotor slowing associated with depression, negative symptoms, or cognitive disturbances. In this study, we apply prior findings on the pathophysiology of bradykinesia in Parkinson's disease to gain an understanding of motor slowing in psychosis patients. Handwriting movements from 57 healthy participants and 70 psychosis patients were recorded on a digitizing tablet. Temporal and kinematic features were extracted from handwritten loops and circles. An independent objective measure based on peak velocity for circles written at maximum speed was used to classify patients as bradykinetic. Using a statistical cut-point derived from normative data, 64% of the patients met criterion for bradykinesia compared with 46% using a conventional observer-based severity rating scale. Bradykinetic patients produced handwriting movements with longer stroke durations, smaller amplitudes and lower peak velocities compared with non-bradykinetic patients. Thirty-six percent of the pen strokes produced by the bradykinetic patients were non-ballistic compare with 20% for the non-bradykinetic patients. The proportion of nonballistic movements observed in handwriting was unrelated to current antipsychotic dose, severity of negative psychosis or depression. The ease-of-use and standardization of a tablet-based approach to quantifying parkinsonian bradykinesia can aid in diagnosing parkinsonian bradykinesia in patients treated with antipsychotics.

Instrument-based assessment of motor function yields no evidence of dyskinesia in adult first-degree biological relatives of individuals with schizophrenia and schizoaffective disorder.

There is accruing evidence of spontaneous dyskinesia in individuals with schizophrenia that is independent of medication exposure. Dyskinetic motor behavior is also present in individuals who are at high risk of schizophrenia and appears to have prognostic value for the development of psychosis. Nonetheless, it remains unclear whether dyskinesia is present in first-degree relatives of individuals with schizophrenia and thus associated with genetic liability for schizophrenia (i.e., an endophenotype), or whether the motor abnormality is a biomarker specific to the disease state spectrum. There is also limited information about links between dyskinesia and clinically relevant phenomena such as symptoms and cognition. Because dyskinesia marking genetic liability is likely to be subtle, we used sensitive instrument-based measurement of handwriting fluency to quantify dyskinesia in medicated individuals with schizophrenia or schizoaffective disorder, unaffected first-degree biological relatives of individuals with schizophrenia and schizoaffective disorder, and control participants. Results indicated that medicated individuals with schizophrenia or schizoaffective disorder exhibited more dyskinesia than both relatives and controls, with no difference between relatives and controls. Dyskinesia in individuals with schizophrenia or schizoaffective disorder was unrelated to current antipsychotic medication dosage, but associated with worse working memory function and greater positive formal thought disorder. These results provide evidence that dyskinesia is not associated with unexpressed genetic liability for schizophrenia.

A quantitative measure of handwriting dysfluency for assessing tardive dyskinesia.

Tardive dyskinesia (TD) is a movement disorder commonly associated with chronic exposure to antidopaminergic medications, which may be in some cases disfiguring and socially disabling. The consensus from a growing body of research on the incidence and prevalence of TD in the modern era of antipsychotics indicates that this disorder has not disappeared continues to challenge the effective management of psychotic symptoms in patients with schizophrenia. A fundamental component in an effective strategy for managing TD is its reliable and accurate assessment. In the present study, we examined the clinical utility of a brief handwriting dysfluency measure for quantifying TD. Digitized samples of handwritten circles and loops were obtained from 62 psychosis patients with or without TD and from 50 healthy subjects. Two measures of dysfluent pen movements were extracted from each vertical pen stroke, including normalized jerk and the number of acceleration peaks. Tardive dyskinesia patients exhibited significantly higher dysfluency scores than non-TD patients and controls. Severity of handwriting movement dysfluency was correlated with Abnormal Involuntary Movement Scale severity ratings for some tasks. The procedure yielded high degrees of test-retest reliability. These results suggest that measures of handwriting movement dysfluency may be particularly useful for objectively evaluating the efficacy of pharmacotherapeutic strategies for treating TD.

Kinematics of signature writing in healthy aging.

Forensic document examiners (FDE) called upon to distinguish a genuine from a forged signature of an elderly person are often required to consider the question of age-related deterioration and whether the available exemplars reliably capture the natural effects of aging of the original writer. An understanding of the statistical relationship between advanced age and handwriting movements can reduce the uncertainty that may exist in an examiner's approach to questioned signatures formed by elderly writers. The primary purpose of this study was to systematically examine age-related changes in signature kinematics in healthy writers. Forty-two healthy subjects between the ages of 60-91 years participated in this study. Signatures were recorded using a digitizing tablet, and commercial software was used to examine the temporal and spatial stroke kinematics and pen pressure. Results indicated that vertical stroke duration and dysfluency increased with age, whereas vertical stroke amplitude and velocity decreased with age. Pen pressure decreased with age. We found that a linear model characterized the best-fit relationship between advanced age and handwriting movement parameters for signature formation. Male writers exhibited stronger age effects than female writers, especially for pen pressure and stroke dysfluency. The present study contributes to an understanding of how advanced age alters signature formation in otherwise healthy adults.

Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in schizophrenia and schizoaffective disorder: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To examine the efficacy and safety of modafinil on parkinsonism and excessive daytime sleepiness (EDS), as well as on negative symptoms and cognitive abilities in patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) in a randomized double-blind placebo-controlled 8-week study. METHODS: Twenty-four male patients, who were aged 20-63 years and on stable dose of second generation antipsychotic medications and with a negative symptom score of ≥ 20 on the Positive and Negative Syndrome Scale (PANSS), were randomized into either the modafinil (n=12) or placebo (n=12) group. The modafinil group received flexible does of modafinil 50-200mg/day. Primary measurements were the Simpson-Angus Scale (SAS) for extrapyramidal side effects (EPS), the Epworth Sleepiness Scale (ESS), the PANSS and a neuropsychological (NP) test battery. Data were collected on Days 0, 14, 28, 42 and 56 for rating scales, and on Days 0, 28 and 56 for NP tests. RESULTS: Mixed model analyses showed a significant group-x-time interaction for total SAS scores (P<0.006), with scores decreasing in the modafinil group but remaining the same in the placebo group. There were no significant group-x-time interactions for scores of ESS (total), PANSS (total, positive and negative), and NP tests (composite and domains) (all P's>0.5). No significant adverse events were observed. CONCLUSION: The data suggest that modafinil was a safe adjunctive treatment which improved parkinsonian symptoms and signs in patients with schizophrenia or schizoaffective disorder. Further studies in larger samples and with longer study time are needed to test/confirm the beneficial effects of modafinil on motor function.

Quantitative assessment of motor abnormalities in untreated patients with major depressive disorder.

The primary purpose of this study was to examine motor physiology disturbances in a group of patients with untreated major depressive disorder using sensitive instrumental procedures. The secondary aim of the study was to examine the relationship of the affective symptom state to these motor assessments. The authors studied 40 individuals meeting DSM-IV criteria for unipolar major depressive disorder and 40 healthy comparison subjects. Electromechanical measures of force steadiness (FS), simple reaction time (RT), movement time (MT) and scaling of movement velocity to distance (velocity scaling, VS) were performed. The authors found that performance on the force steadiness, movement time, and velocity scaling measures was significantly poorer in the subjects with depression. There was no difference between the groups on the measure of reaction time. The force steadiness, reaction time, movement time, and velocity scaling scores were not associated with affective state. This study demonstrates that motor abnormalities suggestive of basal ganglia dysfunction occur in many patients with major depressive disorder, and that these abnormalities may exist in the absence of current psychotropic medication treatment. The finding of impaired movement time and velocity scaling in the presence of normal reaction time suggests a neuromotor or parkinsonian pathophysiology for slowness in depression.

Nonadherence to the isochrony principle in forged signatures.

Highly programmed skilled movements are executed in such a way that their kinematic features adhere to certain rules referred to as minimization principles. One such principle is the isochrony principle, which states that the duration of voluntary movement remains approximately constant across a range of movement distances; that is, movement duration is independent of movement extent. The concept of isochrony suggests that some information stored in the motor program is constant, thus reducing the storage demands of the program. The aim of the present study was to examine whether forged signatures can be distinguished from genuine signatures on the basis of isochrony kinematics. Sixty writers were asked to write their own signatures and to forge model signatures representing three different writing styles: text-based, stylized, and mixed. All signatures were digitized to enable high precision dynamic analyses of stroke kinematics. Vertical stroke duration and absolute amplitude were measured for each pen stroke of the signatures using MovAlyzeR(®) software. Slope coefficients derived from simple regression models of the relationship between stroke duration and amplitude served as our measure of isochrony. The slope coefficient reflects the degree to which stroke duration increases in relation to stroke amplitude. Higher coefficients indicate greater increases in stroke duration for a given stroke amplitude and thus violate the isochrony principle. We hypothesized that the duration-amplitude coefficients for forged signatures would be significantly greater than for genuine signatures suggesting non-adherence to the isochrony principle. Results indicated that regardless of the style of the writer, genuine signatures were associated with low slope coefficients Pen strokes forming forged signatures had significantly greater duration-amplitude slope coefficients than genuine signatures. These findings suggest that when forging signatures, writers execute pen movements having steeper duration-amplitude relationships than for genuine signatures.

Voxel-based morphometry of patients with schizophrenia or bipolar I disorder: a matched control study.

Controlled trials provide critical tests of hypotheses generated by meta-analyses. Two recent meta-analyses have reported that gray matter volumes of schizophrenia and bipolar I patients differ in the amygdala, hippocampus, or perigenual anterior cingulate. The present magnetic resonance imaging study tested these hypotheses in a cross-sectional voxel-based morphometry (VBM) design of 17 chronic schizophrenia and 15 chronic bipolar patients and 21 healthy subjects matched for age, gender and duration of illness. Whole brain gray matter volume of both the schizophrenia and bipolar groups was smaller than among healthy control subjects. Regional voxel-wise comparisons showed that gray matter volume was smallest within frontal and temporal regions of both patient groups. Region of interest analyses found moderately large to large differences between schizophrenia and healthy subjects in the amygdala and hippocampus. There were no group differences in the perigenual anterior cingulate. When schizophrenia and bipolar groups were directly compared, the schizophrenia group showed smaller gray matter volumes in right subcortical regions involving the right hippocampus, putamen, and amygdala. The hippocampal and amygdala findings confirm predictions derived from recent meta-analyses. These structural abnormalities may be important factors in the differential manifestations of these two functional psychotic disorders.

Handwriting movement kinematics for quantifying extrapyramidal side effects in patients treated with atypical antipsychotics.

Ongoing monitoring of neuroleptic-induced extrapyramidal side effects (EPS) is important to maximize treatment outcome, improve medication adherence and reduce re-hospitalization. Traditional approaches for assessing EPS such as Parkinsonism, tardive akathisia, or dyskinesia rely upon clinical ratings. However, these observer-based EPS severity ratings can be unreliable and are subject to examiner bias. In contrast, quantitative instrumental methods are less subject to bias. Most instrumental methods have only limited clinical utility because of their complexity and costs. This paper describes an easy-to-use instrumental approach based on handwriting movements for quantifying EPS. Here, we present findings from psychiatric patients treated with atypical (second generation) antipsychotics. The handwriting task consisted of a sentence written several times within a 2 cm vertical boundary at a comfortable speed using an inkless pen and digitizing tablet. Kinematic variables including movement duration, peak vertical velocity and the number of acceleration peaks, and average normalized jerk (a measure of smoothness) for each up or down stroke and their submovements were analyzed. Results from 59 psychosis patients and 46 healthy comparison subjects revealed significant slowing and dysfluency in patients compared to controls. We observed differences across medications and daily dose. These findings support the ecological validity of handwriting movement analysis as an objective behavioral biomarker for quantifying the effects of antipsychotic medication and dose on the motor system.

Handwriting movement analyses for monitoring drug-induced motor side effects in schizophrenia patients treated with risperidone.

Epidemiologic studies indicate that nearly 60% of schizophrenia (SZ) patients treated with conventional antipsychotic drugs develop extrapyramidal side effects (EPS) such as parkinsonism and tardive dyskinesia. Although the prevalence of EPS has decreased due to the newer antipsychotics, EPS continue to limit the effectiveness of these medicines. Ongoing monitoring of EPS is likely to improve treatment outcome or compliance and reduce the frequency of re-hospitalization. A quantitative analysis of handwriting kinematics was used to evaluate effects of antipsychotic medication type and dose in schizophrenia patients. Twenty-seven schizophrenia patients treated with risperidone, six schizophrenia patients who received no antipsychotic medication and 47 healthy comparison participants were enrolled. Participants performed a 20-min handwriting task consisting of loops of various sizes and a sentence. Data were captured and analyzed using MovAlyzeR software. Results indicated that risperidone-treated participants exhibited significantly more dysfluent handwriting movements than either healthy or untreated SZ participants. Risperidone-treated participants exhibited lower movement velocities during production of simple loops compared to unmedicated patients. Handwriting dysfluency during sentence writing increased with dose. A 3-factor model consisting of kinematic variables derived from sentence writing accounted for 83% (r=.91) of the variability in medication dose. In contrast, we found no association between observer-based EPS severity ratings and medication dose. These findings support the importance of handwriting-based measures to monitor EPS in medicated schizophrenia patients.

Reduction in neuroleptic-induced movement disorders after a switch to quetiapine in patients with schizophrenia.

BACKGROUND: Persistent neuroleptic-induced movement disorders limit effective pharmacological management of psychotic disorders. Although antipsychotic switching is a common strategy for managing extrapyramidal side effects (EPSs), there is insufficient empirical support to guide the clinician. We designed the present study to examine whether patients with preexisting EPS switched to quetiapine would show greater reduction in EPS compared with control patients. METHODS: Twenty-two patients with schizophrenia meeting clinical criteria for tardive dyskinesia or coexisting parkinsonism were randomized either to switch from their current antipsychotic to quetiapine (n = 13) or to remain on their current treatment (n = 9). A battery of standard clinical assessments for EPS along with electromechanical instrumental measures was administered before randomization and again 1 and 3 months postrandomization. RESULTS: We observed significant reduction in parkinsonism (P < 0.001) and akathisia (P = 0.02) based on clinical assessments and dyskinesia (P < 0.05) based on instrumental assessment for the quetiapine group. Subjects remaining on current treatment exhibited an increase in rigidity (P < 0.05) based on instrumental measures. CONCLUSIONS: These findings support the switching to quetiapine in the management of preexisting neuroleptic-induced extrapyramidal side effects.

Internal versus external: oral-motor performance as a function of attentional focus.

PURPOSE: Previous studies (e.g., G. Wulf, M. Höss, & W. Prinz, 1998; G. Wulf, B. Lauterbach, & T. Toole, 1999; for a review, see G. Wulf & W. Prinz, 2001) have reported that limb motor performance is enhanced when individuals adopt an external focus (focusing on the effect of the movement) versus an internal focus of attention (focusing on body parts such as the muscles of the hand). This study tested the hypothesis that the effects of attentional focus on limb performance would also occur in the oral-facial system. METHOD: Two groups of 23 participants were administered both hand and tongue impulse force control tasks in which each group was randomly assigned either an internal or an external focus of attention. Participants were required to exert rapid pressure bursts to achieve a target force level of 20% of their maximal strength. RESULTS: Consistent with limb studies, findings revealed a significant advantage of an external focus (greater accuracy, less variability) for both the hand and tongue control tasks, as opposed to an internal focus of attention. CONCLUSIONS: Results are discussed relative to a constrained-action theory of motor control and future application to speech motor learning.

Predictors of neuroleptic-induced dyskinesia and parkinsonism: the influence of measurement methods and definitions.

The accurate and objective measurement of abnormal, involuntary movements remains highly desirable, whether the movements are secondary to pharmacotherapy or an expression of the primary illness. In a previous study, we found that the prevalence of tardive dyskinesia in a sample of 100 subjects ranged from 28% when using the Abnormal Involuntary Movement Scale (AIMS) or the Dyskinesia Identification Scale, Condensed User Version (DISCUS) to 62% using an instrumental measurement (IM) of peripheral dyskinesia. The goal of this study was to examine the relationship between various risk factors for tardive dyskinesia as predictor variables, and the AIMS, DISCUS, and IMs of dyskinesia, tremor, and velocity of motor movement as dependent variables. The sample consisted of 100, mostly patients with schizophrenia. Poor performance on the Mini-Mental State Examination (MMSE) and increasing age were the most consistent predictors of dyskinetic and parkinsonian movements. Various predictors were associated with specific abnormal movements. Head injury was related to slower speed of motor movements and the total DISCUS score. A history of smoking was associated with less IM dyskinesia. For those with coexisting parkinsonism and dyskinesia, significant associations were found with head injury, diabetes mellitus, and an AIMS score of 2 or greater in 2 body areas. Various classes of psychotropic agents seemed to have little influence on the MMSE or the development of dyskinesia and parkinsonism. Increasing age and a lower score on the MMSE seem to be particularly helpful in gauging the risk for parkinsonian and dyskinetic movements.

Abnormalities in motor physiology in bipolar disorder.

The primary purpose of this study was to examine motor physiology disturbances in a group of patients with bipolar disorder by using sensitive instrumental procedures. The secondary aim of the study was to examine the effects of the affective state on motor functions. The authors studied 67 individuals meeting DSM-IV criteria for bipolar disorder and 47 healthy comparison subjects. Electromechanical measures of force steadiness and scaling of movement velocity to distance were performed. The authors found that performance on the force steadiness and velocity scaling measures was significantly poorer in the subjects with bipolar disorder, with 58% and 63% of the patients scoring outside the normal range on the force steadiness and velocity scaling measures, respectively. Eighty-four percent of subjects showed impairment on either measure, and 37% showed impairment on both measures. The force steadiness and velocity scaling abnormalities appeared to occur independently of one another and also were not associated with affective state or current medication status. This study demonstrates that motor abnormalities suggestive of basal ganglia dysfunction occur in many patients with bipolar disorder.