Biomedical subjects

Daniel C Javitt

Publications and source records attributed to Daniel C Javitt.

At least 37 records · Page 2Linked to original sources

PubMed2005

Brain morphometry using diffusion-weighted magnetic resonance imaging: application to schizophrenia.

Loss of cortical gray matter is accompanied by a commensurate increase in the sulcal and intraventricular cerebrospinal fluid volume. On diffusion-weighted magnetic resonance imaging, this would be reflected as a higher apparent diffusion coefficient in affected brain regions. On the basis of the above premise, we suggest that the apparent diffusion coefficient may be used as a surrogate marker for the assessment of regional brain volume deficits. We demonstrate this approach by voxelwise analysis of registered apparent diffusion coefficient images from a group of 15 patients with schizophrenia and 15 age-matched healthy controls. We found widespread regional apparent diffusion coefficient increases in patients. Affected areas included the bilateral insular cortex, hippocampus, temporal lobe, and occipital areas. These results largely concur with previous findings of cortical volume deficits in schizophrenia.

Adult↗

PubMed2005

Sensory contributions to impaired prosodic processing in schizophrenia.

BACKGROUND: Deficits in affect recognition are prominent features of schizophrenia. Within the auditory domain, patients show difficulty in interpreting vocal emotional cues based on intonation (prosody). The relationship of these symptoms to deficits in basic sensory processing has not been previously evaluated. METHODS: Forty-three patients and 34 healthy comparison subjects were tested on two affective prosody measures: voice emotion identification and voice emotion discrimination. Basic auditory sensory processing was measured using a tone-matching paradigm and the Distorted Tunes Test (DTT). A subset of subjects was also tested on facial affect identification and discrimination tasks. RESULTS: Patients showed significantly impaired performance on all emotion processing tasks. Within the patient group, a principal components analysis demonstrated significant intercorrelations between basic pitch perception and affective prosodic performance. In contrast, facial affect recognition deficits represented a distinct second component. Prosodic affect measures correlated significantly with severity of negative symptoms and impaired global outcome. CONCLUSIONS: These results demonstrate significant relationships between basic auditory processing deficits and impaired receptive prosody in schizophrenia. The separate loading of auditory and visual affective recognition measures suggests that within-modality factors may be more significant than cross-modality factors in the etiology of affect recognition deficits in schizophrenia.

Adult↗

PubMed2005

Timing of pure tone and noise-evoked responses in macaque auditory cortex.

We compared onset latencies for characteristic frequency pure tone and broadband noise responses in AI and posterior belt regions of the auditory cortex in awake macaques. We found that (1) in AI, responses to characteristic frequency tones and broadband noise have similar latencies, (2) in belt regions, characteristic frequency tone and broadband noise latencies differ significantly; broadband noise latencies are shorter, while characteristic frequency tone latencies are longer than corresponding values in AI, (3) for both pure tone and broadband noise responses in AI, latency decreases with increasing characteristic frequency and (4) despite a similar inverse relationship of tone latency and local characteristic frequency in belt areas, broadband noise latencies are uniformly short, and appear unrelated to local characteristic frequency. Dissociation of broadband noise and pure tone latencies may reflect the use of parallel anatomical routes into belt regions.

Acoustic Stimulation↗

PubMed2005

Filling-in in schizophrenia: a high-density electrical mapping and source-analysis investigation of illusory contour processing.

Evidence is accumulating that patients with schizophrenia exhibit relatively severe deficits in early visual sensory processing within the dorsal stream, while processing within the ventral stream appears to be relatively more intact. Here, illusory contour (IC) processing was investigated in a cohort of schizophrenia patients and age-matched healthy controls using high-density visual evoked potentials (VEPs), spatiotemporal topographic analyses and the Local Auto-Regressive Average distributed linear inverse source estimation. IC processing was assessed because it is now known to be an excellent metric of early processing within regions of the ventral visual stream. Results in the present study show that IC processing (106-194 ms) is spared in patients with schizophrenia, providing strong evidence that early ventral stream processing is essentially normal. This is so despite equally strong evidence that early dorsal stream processing is severely impaired in this population, as indexed by a robust decrement in amplitude of the P1 component in patients and a large topographic difference between groups for this component (54-104 ms). Source analysis confirmed that the flow of activity into the dorsal stream was substantially decreased in patients. As such, these results suggest that some aspects of early ventral processing are not entirely reliant on intact inputs from the dorsal stream. Lastly, we show that later phases of visual processing (240-400 ms) also rely on the activity of different brain networks in controls and patients, with the latter recruiting strong frontal activity perhaps as compensation for impaired ventral stream processing during this period. We interpret the present findings in the context of a two-stage processing model. Under this model, it is suggested that the second stage of ventral stream processing is dependent on the fidelity of inputs from the dorsal visual stream and that impairment of this critical modulatory input may underlie the failure of 'higher-level' ventral stream processes in this population.

Adult↗

PubMed2005

D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia.

BACKGROUND: D-serine, a selective full agonist at the glycine site of N-methyl-D-aspartate glutamate receptor, might presently be the compound of choice for counteracting the hypothesized dysfunction of this receptor class in schizophrenia. Studies performed with Taiwanese patients indicate that D-serine significantly improves schizophrenia symptoms when used as adjuvant to conventional neuroleptics but not to clozapine. We assessed the efficacy and safety of D-serine adjuvant treatment for Occidental schizophrenia patients treated with newer atypical antipsychotics. METHODS: Thirty-nine risperidone- or olanzapine-treated schizophrenia patients participated in a double-blind, placebo-controlled, 6-week crossover trial with 30 mg/kg/day D-serine added to their antipsychotic medication. Measures of clinical efficacy and side effects were determined biweekly throughout the study. Clinical laboratory parameters and amino acid serum levels were monitored. RESULTS: D-serine administration induced increased serine serum levels (p < .001) and resulted in significant (p < .001) improvements in negative, positive, cognitive, and depression symptoms, as measured by the Positive and Negative Syndrome Scale. For approximately one third of the sample, D-serine treatment resulted in significant (>20%) reductions in Brief Psychiatric Rating Scale total scores. D-serine was well tolerated, and no detrimental changes in clinical laboratory parameters were noted. CONCLUSIONS: These findings 1) indicate that risperidone and olanzapine efficacy might be augmented with D-serine adjuvant treatment; 2) confirm D-serine efficacy against main schizophrenia symptom domains; and 3) warrant the assessment of D-serine antipsychotic monotherapy for this illness.

Adult↗

PubMed2005

Early-stage visual processing and cortical amplification deficits in schizophrenia.

BACKGROUND: Patients with schizophrenia show deficits in early-stage visual processing, potentially reflecting dysfunction of the magnocellular visual pathway. The magnocellular system operates normally in a nonlinear amplification mode mediated by glutamatergic (N-methyl-D-aspartate) receptors. Investigating magnocellular dysfunction in schizophrenia therefore permits evaluation of underlying etiologic hypotheses. OBJECTIVES: To evaluate magnocellular dysfunction in schizophrenia, relative to known neurochemical and neuroanatomical substrates, and to examine relationships between electrophysiological and behavioral measures of visual pathway dysfunction and relationships with higher cognitive deficits. DESIGN, SETTING, AND PARTICIPANTS: Between-group study at an inpatient state psychiatric hospital and outpatient county psychiatric facilities. Thirty-three patients met DSM-IV criteria for schizophrenia or schizoaffective disorder, and 21 nonpsychiatric volunteers of similar ages composed the control group. MAIN OUTCOME MEASURES: (1) Magnocellular and parvocellular evoked potentials, analyzed using nonlinear (Michaelis-Menten) and linear contrast gain approaches; (2) behavioral contrast sensitivity measures; (3) white matter integrity; (4) visual and nonvisual neuropsychological measures, and (5) clinical symptom and community functioning measures. RESULTS: Patients generated evoked potentials that were significantly reduced in response to magnocellular-biased, but not parvocellular-biased, stimuli (P = .001). Michaelis-Menten analyses demonstrated reduced contrast gain of the magnocellular system (P = .001). Patients showed decreased contrast sensitivity to magnocellular-biased stimuli (P<.001). Evoked potential deficits were significantly related to decreased white matter integrity in the optic radiations (P<.03). Evoked potential deficits predicted impaired contrast sensitivity (P = .002), which was in turn related to deficits in complex visual processing (P< or =.04). Both evoked potential (P< or =.04) and contrast sensitivity (P = .01) measures significantly predicted community functioning. CONCLUSIONS: These findings confirm the existence of early-stage visual processing dysfunction in schizophrenia and provide the first evidence that such deficits are due to decreased nonlinear signal amplification, consistent with glutamatergic theories. Neuroimaging studies support the hypothesis of dysfunction within low-level visual pathways involving thalamocortical radiations. Deficits in early-stage visual processing significantly predict higher cognitive deficits.

Adult↗

PubMed2005

Impairments in generation of early-stage transient visual evoked potentials to magno- and parvocellular-selective stimuli in schizophrenia.

OBJECTIVE: Patients with schizophrenia demonstrate significant impairments of early visual processing, potentially implicating dysfunction of the magnocellular visual pathway. The present study evaluates transient visual evoked potential (tVEP) responses to stimuli biased toward the magnocellular (M) or parvocellular (P) systems in patients with schizophrenia vs. normal volunteers first to evaluate relative contributions of M and P systems to specific tVEP components in schizophrenia and, second, to evaluate integrity of early M and P processing in schizophrenia. METHODS: Seventy-four patients with schizophrenia and schizoaffective disorder were compared with 59 control subjects using separate stimuli to assess the tVEP response to M, P and mixed M/P conditions. Stimuli were biased toward M vs. P processing by manipulation of chromatic and achromatic contrast. C1, P1, N1 and P2 components were compared between patients and controls. All subjects showed 20/32 vision or better. RESULTS: Waveforms were obtained to low contrast (M), chromatic contrast (P) and high contrast (mixed M/P) stimuli in both patients and controls. C1 was present to P and mixed M/P stimuli. Patients showed a significant reduction in amplitude and an increase in latency of the C1 component. P1 was elicited primarily by M and mixed M/P stimuli, whereas N1 was elicited primarily by P and mixed M/P stimuli. Patients showed reductions in both P1 and N1 amplitudes across conditions. However, only reductions in P1 amplitude survived covariation for between group differences in visual acuity. Further, P1 amplitude reductions in the M condition correlated with a proxy measure of global outcome. CONCLUSIONS: M- and P-selective stimuli elicit differential components of the tVEP. Patients with schizophrenia show significant reductions in response even to simple visual stimuli. Deficits, particularly within the M system, may correlate significantly with global outcome and level of community functioning. SIGNIFICANCE: Whereas deficits in high-order cognitive processing have been extensively documented in schizophrenia, integrity of early-stage sensory processing has been studied to a lesser degree. The present findings suggest that deficits in early-stage visual processing are significantly related to overall clinical outcome in schizophrenia. Further, between-group differences in visual acuity may influence VEP results, even for subjects with 'normal' vision (20/32 or better).

Activities of Daily Living↗

PubMed2005

Modulation of striatal dopamine release by glycine transport inhibitors.

Traditional models of schizophrenia have focused primarily upon dopaminergic (DA) dysregulation. In contrast, more recent models focus on dysfunction of glutamatergic systems, acting particularly through N-methyl-D-aspartate (NMDA) receptors. NMDA receptors in brain are regulated by glycine, acting via a strychnine-insensitive regulatory site, and by glycine (GlyT1) transporters that maintain low glycine levels in the immediate vicinity of the NMDA receptor complex. The present study investigates the role of NMDA receptors in the modulation of striatal dopamine release in vitro, and of glycine transport inhibitors (GTIs) as potential psychotherapeutic agents in schizophrenia. In striatum, NMDA receptors exert dual excitatory/inhibitory effects, with inhibition reflecting activity of local GABAergic feedback regulation. We have previously demonstrated effectiveness of glycine in regulating [3H]DA release both in vivo and in vitro, consistent with its beneficial clinical effects. In the present study, similar effects were observed for the high-affinity GTI (+)N[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy-)propyl]sarcosine (NFPS), and for a range of high-affinity GTIs with appropriate rank order of potency. In addition, (+)NFPS significantly stimulated NMDA-induced [3H]GABA release. Effects, of GTIs, were blocked by the glycine-site antagonists L689,560 and HA-966, and the GABA(B) antagonists phaclofen and CGP 52432, confirming the roles of both the NMDA-associated glycine-site and presynaptic GABA(B) receptors in NMDA receptor-mediated regulation of striatal DA release in vitro. Endogenous DA hyperactivity is associated with prominent positive symptoms in schizophrenia. The present results are consistent with recent clinical studies showing significant effectiveness of glycine-site agonists and GTIs in reduction of persistent positive, as well as negative, symptoms in schizophrenia.

Amino Acid Transport Systems, Neutral↗

PubMed2005

Early-stage visual processing deficits in schizophrenia.

PURPOSE OF REVIEW: While cognitive dysfunction including memory and attentional deficits are well known in schizophrenia, recent work has also shown basic sensory processing deficits. Deficits are particularly prominent in the visual system and may be related to cognitive deficits and outcome. This article reviews studies of early-stage visual processing in schizophrenia published during the past year. These studies reflect the growing interest and importance of sensory processing deficits in schizophrenia. RECENT FINDINGS: The visual system is divided into magnocellular and parvocellular pathways which project to dorsal and ventral visual areas. Recent electrophysiological and behavioral investigations have found preferential magnocellular/dorsal stream dysfunction, with some deficits in parvocellular function as well. These early-stage deficits appear to be related to higher level cognitive, social, and community function. Structural studies of occipital cortex and particularly optic radiations provide anatomical support for early visual processing dysfunction. SUMMARY: These findings highlight the importance of sensory processing deficits, in addition to higher cognitive dysfunction, for understanding the pathophysiology of schizophrenia. Understanding the nature of sensory processing deficits may provide insight into mechanisms of pathology in schizophrenia, such as N-methyl-D-aspartate dysfunction or impaired signal amplification, and could lead to treatment strategies including sensory processing rehabilitation that may improve outcome.

Journal Article↗

PubMed2005

Relation of plasma glycine, serine, and homocysteine levels to schizophrenia symptoms and medication type.

OBJECTIVE: Altered glycine and homocysteine levels may contribute to N-methyl-D-aspartate receptor dysfunction in schizophrenia. The authors measured plasma levels of these amino acids in a group of patients with chronic schizophrenia and related them to the patients' symptom profiles and types of antipsychotic medication. METHOD: Plasma levels of amino acids in 94 patients with schizophrenia were compared with those in 34 age- and sex-matched normal subjects. The Positive and Negative Syndrome Scale was used to evaluate the patients' psychopathology. RESULTS: Plasma glycine levels and glycine-serine ratios were lower and homocysteine levels were higher in patients than in comparison subjects. Low glycine levels correlated with a greater number of negative symptoms. The glycine-serine ratios of normal subjects and patients being treated with clozapine did not differ significantly. CONCLUSIONS: These findings support the hypothesis that altered levels of glycine and homocysteine may coexist in patients with schizophrenia and contribute to pathophysiological aspects of this illness.

Adult↗

PubMed2004

Dysfunction of early-stage visual processing in schizophrenia: harmonic analysis.

Schizophrenia is associated with severe neurocognitive deficits that constitute a core feature of the disorder. Deficits have been most extensively studied in relationship to higher-order processes. This study evaluated the integrity of early visual processing in order to evaluate the overall pattern of visual dysfunction in schizophrenia. Steady-state visual-evoked potentials (ssVEPs) were recorded over the occipital cortex (Oz) in patients with schizophrenia and schizoaffective disorder (N=26) and in age-matched comparison volunteers (N=22). Two stimuli were used: windmill-dartboard and partial-windmill, which are contrast-reversing ( approximately 4 Hz), radial patterns with dominant low spatial-frequency content. Each stimulus was presented for 1 min. Fourier analysis was performed on the ssVEP data to extract the relevant temporal frequency (i.e., harmonic) components. Magnitude-squared coherence (MSC) was computed to estimate the relative signal level for each frequency component. The patients showed reduced amplitude and coherence of second harmonic responses in both conditions, but intact first harmonic responses in the windmill-dartboard condition. This finding of a differential deficit may indicate a significant loss in the magnocellular pathway, which contributes to the generation of the second harmonic component under these conditions. Early sensory deficits may lead to impairments in subsequent stages of processing.

Adult↗

PubMed2004

DTI and impulsivity in schizophrenia: a first voxelwise correlational analysis.

Compromised white matter (WM) integrity in inferior frontal WM has been related to impulsivity in men with schizophrenia. However, these relationships may be more widespread. Fractional anisotropy (FA) derived from diffusion tensor imaging of 25 men with schizophrenia was transformed into Talairach space. Correlations between FA and impulsiveness were examined on a voxelwise basis. We found negative correlations between FA and impulsivity in inferior frontal WM, anterior cingulate, caudate, insula, and inferior parietal lobule. Positive correlations were obtained in the left postcentral gyrus, right superior/middle temporal gyrus, and bilateral fusiform gyrus. These areas may comprise a fronto-temporo-limbic circuit that modulates impulsivity. The voxelwise correlation method can serve as a hypothesis-generation method for relating target behaviors to their underlying neural networks.

Adult↗

PubMed2004

Grabbing your ear: rapid auditory-somatosensory multisensory interactions in low-level sensory cortices are not constrained by stimulus alignment.

Multisensory interactions are observed in species from single-cell organisms to humans. Important early work was primarily carried out in the cat superior colliculus and a set of critical parameters for their occurrence were defined. Primary among these were temporal synchrony and spatial alignment of bisensory inputs. Here, we assessed whether spatial alignment was also a critical parameter for the temporally earliest multisensory interactions that are observed in lower-level sensory cortices of the human. While multisensory interactions in humans have been shown behaviorally for spatially disparate stimuli (e.g. the ventriloquist effect), it is not clear if such effects are due to early sensory level integration or later perceptual level processing. In the present study, we used psychophysical and electrophysiological indices to show that auditory-somatosensory interactions in humans occur via the same early sensory mechanism both when stimuli are in and out of spatial register. Subjects more rapidly detected multisensory than unisensory events. At just 50 ms post-stimulus, neural responses to the multisensory 'whole' were greater than the summed responses from the constituent unisensory 'parts'. For all spatial configurations, this effect followed from a modulation of the strength of brain responses, rather than the activation of regions specifically responsive to multisensory pairs. Using the local auto-regressive average source estimation, we localized the initial auditory-somatosensory interactions to auditory association areas contralateral to the side of somatosensory stimulation. Thus, multisensory interactions can occur across wide peripersonal spatial separations remarkably early in sensory processing and in cortical regions traditionally considered unisensory.

Adult↗

PubMed2004

Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia.

BACKGROUND: Lamotrigine, a novel anticonvulsant drug having modulatory effects on glutamatergic neurotransmission, improves mood and cognition parameters in bipolar disorder. Recent studies suggest that when added to clozapine, lamotrigine treatment may result in significant positive symptoms reductions in schizophrenia. Similar effects were not observed in an open trial in which lamotrigine was used as adjuvant to nonclozapine antipsychotics. METHODS: Thirty-eight treatment-resistant schizophrenia inpatients receiving conventional and atypical antipsychotics enrolled in a 10-week, double-blind, placebo-controlled study, in which they were randomized in a 2:1 ratio to receive adjuvant treatment with lamotrigine, gradually titrated to a 400 mg/day dose, or placebo. Of these, 31 completed the trial. Measures of clinical efficacy and side effects were determined every other week. Serum levels of amino acids were assessed at the beginning and end of the study. RESULTS: In primary last observation carried forward analysis, no statistically significant between-group differences were observed; however, the completers' analyses revealed that lamotrigine treatment resulted in significant (p < or = .05) reductions in positive and general psychopathology symptoms, as measured by the Positive and Negative Syndrome Scale. No significant differences in lamotrigine effects were noted between conventional versus atypical antipsychotics. Lamotrigine treatment was well tolerated, and glutamate serum levels remained stable throughout the study. CONCLUSIONS: These preliminary findings 1) support the hypothesis that lamotrigine adjuvant treatment may improve positive symptoms and general psychopathology in schizophrenia, 2) suggest that beneficial effects may be achieved when lamotrigine is added to both conventional and atypical antipsychotics, and 3) warrant additional, larger scale trials.

Adult↗

PubMed2004

The neural circuitry of pre-attentive auditory change-detection: an fMRI study of pitch and duration mismatch negativity generators.

Electrophysiological studies have revealed a pre-attentive change-detection system in the auditory modality. This system emits a signal termed the mismatch negativity (MMN) when any detectable change in a regular pattern of auditory stimulation occurs. The precise intracranial sources underlying MMN generation, and in particular whether these vary as a function of the acoustic feature that changes, is a matter of some debate. Using functional magnetic resonance imaging, we show that anatomically distinct networks of auditory cortices are activated as a function of the deviating acoustic feature--in this case, tone frequency and tone duration--strongly supporting the hypothesis that MMN generators in auditory cortex are feature dependent. We also detail regions of the frontal and parietal cortices activated by change-detection processes. These regions also show feature dependence and we hypothesize that they reflect recruitment of attention-switching mechanisms.

Adult↗

PubMed2004

Setting boundaries: brain dynamics of modal and amodal illusory shape completion in humans.

Normal visual perception requires differentiating foreground from background objects. Differences in physical attributes sometimes determine this relationship. Often such differences must instead be inferred, as when two objects or their parts have the same luminance. Modal completion refers to such perceptual "filling-in" of object borders that are accompanied by concurrent brightness enhancement, in turn termed illusory contours (ICs). Amodal completion is filling-in without concurrent brightness enhancement. Presently there are controversies regarding whether both completion processes use a common neural mechanism and whether perceptual filling-in is a bottom-up, feedforward process initiating at the lowest levels of the cortical visual pathway or commences at higher-tier regions. We previously examined modal completion (Murray et al., 2002) and provided evidence that the earliest modal IC sensitivity occurs within higher-tier object recognition areas of the lateral occipital complex (LOC). We further proposed that previous observations of IC sensitivity in lower-tier regions likely reflect feedback modulation from the LOC. The present study tested these proposals, examining the commonality between modal and amodal completion mechanisms with high-density electrical mapping, spatiotemporal topographic analyses, and the local autoregressive average distributed linear inverse source estimation. A common initial mechanism for both types of completion processes (140 msec) that manifested as a modulation in response strength within higher-tier visual areas, including the LOC and parietal structures, is demonstrated, whereas differential mechanisms were evident only at a subsequent time period (240 msec), with amodal completion relying on continued strong responses in these structures.

Adult↗

PubMed2004

Sensitive and simple gas chromatographic-mass spectrometric determination for amphetamine in microdialysate and ultrafiltrate samples.

A gas chromatographic-mass spectrometric (GC-MS) method is described for the measurement of amphetamine (AMP) using negative chemical ionization (NCI) mode. Without prior extraction AMP was derivatized with 2,3,4,5,6-pentafluorobenzoyl chloride (PFBC) and simultaneously extracted into toluene. The toluene extract was injected directly into GC-MS equipped with a HP-1 capillary column. The method is simple and more sensitive than most of the previously published methods. The limit of quantification of amphetamine is 25pg (1.4pg on column) with a very limited sample volume (25microl). The within-day precision was from 1.7 to 5.1% and between-day precision was from 2.2 to 7.3%. The method has been used for the measurement of several thousand microdialysate and ultrafiltrate samples and proven reliable.

Amphetamine↗

PubMed2004

Glycine and D-cycloserine attenuate vacuous chewing movements in a rat model of tardive dyskinesia.

Presently there is no established treatment for antipsychotic drugs-induced tardive dyskinesia (TD), which remains a major clinical issue in psychiatry. Based on the principles of the glutamatergic hypothesis of schizophrenia, the amino acid glycine (GLY) and the antituberculosis drug D-cycloserine (DCS) have been assessed, during the last decade, as adjuvants to antipsychotic drugs. Observations stemming from these studies suggest that, in addition to improving schizophrenia symptoms, these compounds may also be beneficial against drug-induced dyskinesias. In order to investigate this hypothesis, GLY and DCS effects were studied using the putative TD analogue vacuous chewing movements (VCM) rat model. Following 24 weeks of treatment with haloperidol decanoate (0.38 mg/kg/4 weeks) rats (N=40) were randomized to receive one intraperitoneal injection with 1.6 g/kg GLY, 10 mg/kg ("low dose") DCS; 100 mg/kg ("high dose") DCS or saline ("placebo"), respectively. Behavior was videotaped at intervals during the experiment and all VCM, rearing, grooming and immobility episodes were analyzed and scored. A control group (N=9) received saline for 24 weeks. Haloperidol administration decreased motor activity and significantly induced VCM. High dose DCS significantly reduced VCM without affecting other motor parameters. GLY treatment resulted in significantly less VCM but also reduced rearing, grooming and mobility. In contrast, low dose DCS and placebo did not significantly affect any of these parameters. These findings indicate that the use of GLY and DCS results in attenuation of VCM in rats and may have an effect on TD in humans. Clinical trials with this type of compounds for patients suffering from TD are warranted.

Animals↗