Background and purpose: The lack of appropriate measures has hindered the research on anxiety syndromes in Parkinson's disease (PD). The objective of the present cross-sectional, international study was to identify shared elements and grouping of components from anxiety scales as a basis for designing a new scale for use in PD.Methods: For this purpose, 342 consecutive PD patients were assessed by means of the Mini International Neuropsychiatric Inventory (depression and anxiety sections), the Clinical Global Impression of severity of the anxiety symptoms, the Hamilton Anxiety Rating Scale (HARS), the Neuropsychiatric Inventory (section E), the Beck Anxiety Inventory (BAI) and the Anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A).Results: As the HADS-A showed a weak correlation with the HARS and BAI, it was not considered for more analyses. HARS and BAI exploratory factor analysis identified nine factors (62% of the variance), with only two of them combining items from both scales. Therefore, a canonical correlation model (a method to identify relations between components of two groups of variables) was built and it showed four factors grouping items from both scales: the first factor corresponded to 'generalized anxiety'; the second factor included muscular, sensory and autonomic 'non-specific somatic symptoms'; the third factor was dominated by 'respiratory symptoms'; and the fourth factor included 'cardiovascular symptoms'.Conclusions: BAI is heavily focused on panic symptoms, whilst HARS is more focused towards generalized anxiety symptoms. The new scale should include additional components in order to assess both episodic and persistent anxiety as well as items for evaluation of avoidance behaviour.

Animal models of drug discrimination have been used to examine the subjective effects of addictive substances. The cAMP system is a crucial downstream signaling pathway implicated in the long-lasting neuroadaptations induced by addictive drugs. We examined effects of rolipram, nefiracetam, and dopamine D2-like receptor antagonists, all of which have been reported to modulate cAMP level in vivo, on the discriminative-stimulus effects of methamphetamine (METH) and morphine in rats. All these compounds inhibited the discriminative-stimulus effects of METH, while only rolipram and nefiracetam attenuated the discriminative-stimulus effects of morphine. In addition, neither nifedipine nor neomycin, two voltage-sensitive calcium channel blockers, was found to modulate the effect of nefiracetam on METH-associated discriminative stimuli, suggesting that the inhibitory effect of nefiracetam may not involve the activation of calcium channels. These findings suggest that the cAMP signaling cascade may play a key role in the discriminative-stimulus effects of METH and morphine and may be a potential target for the development of therapeutics to counter drugs of abuse.

BACKGROUND:Deficits in a patient's 'theory of mind' (TOM) have been proposed to lead to psychosis. However, it remains unclear whether TOM deficits constitute a trait- or a state-related deficit and whether they respond to antipsychotic treatment, and also whether the change in TOM and change in psychosis are associated.METHOD:In the cross-sectional component of this study, 71 patients with psychotic disorders were included and TOM ability was measured using a hinting task in which subjects had to infer real intentions behind indirect speech. In the longitudinal study, a different cohort of 17 drug-free patients were included wherein they received antipsychotic treatment for 6 weeks and the effect on psychotic symptoms and TOM was measured every 2 weeks. Associations between TOM and psychopathology were assessed and a mixed effects model was used to investigate the rate of change over time.RESULTS:Positive and Negative Syndrome Scale (PANSS) total scores were significantly associated with TOM scores. The hinting task was not associated with positive symptoms but was significantly associated with negative and general symptoms. The longitudinal arm of the study showed that both PANSS positive scores and TOM improved after medication was started, particularly during the first 2 weeks of antipsychotic treatment, but these changes were not associated. The TOM response at 2 weeks of antipsychotic treatment reached similar values to those obtained in the cross-sectional sample.CONCLUSIONS:Although TOM and psychotic symptoms are related to each other, antipsychotic treatment impacts each independently, suggesting a dissimilar cognitive or neurobiological substrate for the two.

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Conventional antipsychotic agents can induce extrapyramidal symptoms (EPS) that may be alleviated by switching patients to novel agents such as olanzapine. Patients with schizophrenia and related disorders (ICD-10) who were taking haloperidol (N = 94; mean dose = 12.7 mg/day) and had EPS (Simpson-Angus Scale [SAS] > 3) were directly switched to 6 weeks of open-label olanzapine treatment (mean dose = 11.4 mg/day). There were significant mean improvements (p < 0.001 for all measurements) from baseline to endpoint on the SAS (-9.69 +/- 5.33; percentage change, 87.2%), the Barnes Akathisia Scale (-1.00 +/- 1.19; percentage change, 82.5%), and the Abnormal Involuntary Movement Scale (-1.48 +/- 2.89; percentage change, 81.1%), and anticholinergic use decreased from 47.9% to 12.8% (mean baseline to endpoint change: -1.52 +/- 1.91-mg equivalents of benztropine; p < 0.001). Significant mean baseline to endpoint improvements (p 0.001 for all measurements) were observed on the Positive and Negative Syndrome Scale (PANSS; -25.28 +/- 18.67; percentage change, 30.3%), the PANSS-extracted Brief Psychiatric Rating Scale (0-6 scale, -13.41 +/- 10.16; percentage change, 54.4%), and the Clinical Global Impressions Severity scale (-1.16 +/- 1.19; percentage change, 26.4%). Spontaneously reported treatment- emergent adverse events with a greater than 5% incidence were somnolence (16.0%), increased appetite (14.9%), weight gain (11.7%), headache (8.5%), anxiety (7.4%), dizziness (6.4%), and insomnia (5.3%). Criteria for a successful switch were met by 90.5% of patients. Psychotic symptom exacerbation was experienced by 30.9% of patients at any time during the study and by 11.7% of patients at endpoint. Results suggest that a direct switch to olanzapine is a therapeutic option when patients with haloperidol-induced EPS are unable to tolerate a more gradual switch.

Whether patients with Parkinson's disease develop cognitive impairments or improvements after ventral pallidotomy is still a debated issue.1 Recent studies produced contradictory findings which may have resulted from methodological factors such as differences in surgical techniques, neuropsychological assessments, duration of follow up, and the lack of evaluations of non-operated controls with Parkinson's disease.1 We assessed a consecutive series of 27 patients with Parkinson's disease who received unilateral pallidotomy using the microelectrode registration technique.2 Sixteen of these patients received a 3–6 month follow up evaluation, and 10 of them received a 12 month follow up evaluation. They were compared with a non-operated control group of 20 patients with Parkinson's disease matched for age, severity of extrapyramidal symptoms, and overall cognitive status who received the same neuropsychological evaluation at baseline and 12 months later. The neuropsychological examination included the Raven's progressive matrices, the Wisconsin card sorting test …

OBJECTIVE:Posteroventral pallidotomy (PVP) has proved to be an effective method for the treatment of Parkinson's disease. However, data on bilateral procedures are still limited. To assess the effects of bilateral globus pallidus (GPi) lesion and to compare it with a combination of unilateral GPi lesion plus contralateral GPi stimulation (PVP+PVS), an open blind randomised trial was designed.METHODS:A prospective series of patients with severe Parkinson's disease refractory to medical treatment, and severe drug induced dyskinesias, were randomised either to simultaneous bilateral PVP or simultaneous PVP+PVS. All patients were assessed with the core assessment programme for intracerebral transplantation (CAPIT), and a comprehensive neuropsychological and neuropsychiatric battery both before surgery and 3 months later.RESULTS:The severe adverse effects found in the first three patients subjected to bilateral PVP led to discontinuation of the protocol. All three patients developed depression and apathy. Speech, salivation, and swallowing, as well as freezing, walking, and falling, dramatically worsened. By contrast, all three patients undergoing PVP+PVS had a significant motor improvement.CONCLUSION:Bilateral simultaneous lesions within the GPi may produce severe motor and psychiatric complications. On the other hand, a combination of PVP+ PVS significantly improves parkinsonian symptoms not associated with the side effects elicited by bilateral lesions.

Patients with basal ganglia diseases may exhibit ideomotor apraxia. To define the nature of the impairment of the action production system, we studied a repetitive gesture of slicing bread by three-dimensional computergraphic analysis in eight nondemented patients with Parkinson's disease in the "on" state, five with progressive supranuclear palsy and four with multiple system atrophy. Two patients with Parkinson's disease and two with progressive supranuclear palsy showed ideomotor apraxia for transitive movements on standard testing. A Selspott II system was used for kinematic analysis of wrist trajectories and angular motions of the shoulder and elbow joints. Patients with Parkinson's disease, progressive supranuclear palsy, and even some with multiple system atrophy exhibited kinematic deficits in the spatial precision of movement and velocity-curvature relationships; in addition, they failed to maintain proper angle/angle relationships and to apportion their relative joint amplitudes normally. Spatial disruption of wrist trajectories was more severe in patients with ideomotor apraxia. We posit that the basal ganglia are part of the parallel parieto-frontal circuits devoted to sensorimotor integration for object-oriented behavior. The severity and characteristics of spatial abnormalities of a transitive movement would therefore depend on the location and distribution of the pathologic process within these circuits.

Microelectrode-guided posteroventral pallidotomy (PVP) has shown to be an effective method in the treatment of a group of patients with advanced Parkinson's disease. A nonlesioning approach by means of deep brain electrodes connected to a programmable neuropacemaker has also been used to inhibit the internal segment of globus pallidus (posteroventral stimulation [PVS]) reporting comparable clinical efficacy to the one obtained with the ablative method. Nevertheless, no controlled studies have been performed to compare the efficacy of both procedures. A prospective series of 13 patients with a clinical indication for globus pallidus surgery was randomized either to a pallidotomy or stimulator implantation, and comparisons on motor and neuropsychologic measurements were made on a 3-month follow-up basis. Primary measurements of efficacy showed a comparable effect on Unified Parkinson's Disease Rating Scale and activities of daily living score after both procedures. Secondary measurements of efficacy showed that although both techniques improve hand tapping score and dyskinesia score, the bilateral improvement in the former was greater after PVS whereas the latter improved more significantly after PVP. No significant changes in neuropsychologic parameters were observed after either PVP or PVS. Side effects and surgery complications occurred in six of 13 patients (three after PVP and three after PVS): they were mild, transient, and unrelated to optic tract injury. In conclusion, the short-time effect and safety of both procedures is comparable.