Affect in Parkinson's disease: validation of the two-factor approach.

Depression in Idiopathic Parkinson's disease (IPD) is frequent, difficult to recognize, under managed and has a profound impact on quality of life. Current categorization of diagnosis in psychiatry poorly applies to the protean manifestations of mood disorders presented by parkinsonian patients. In this study we have chosen to dissect the state of depressive mood as assessed with the Beck Depression Inventory (BDI) at different points in time of pharmacological interventions using a dimensional approach. The 21 items of the BDI were classified in two new categories or factors: hyperkinetic and hypokinetic. The hyperkinetic factor included all items related to unbalanced intrusions of negative feelings and ideas, as well as to behavioral hyperactivity. The hypokinetic factor included all items related to loss of drive for appetitive behaviors and loss of mental and physical energy. The objectives were to (1) compare different pharmacological treatments on the two-factor approach in PD depression, (2) determine the influence of levodopa therapy on the two-factor approach, and (3) explore the two-factor approach in placebo conditions. Three sets of analyses using the hypo/hyperkinetic dichotomy favour a neurobiological dissociation of these factors in response to pharmacological intervention: symptoms of the hyperkinetic factor are responsive to serotonergic drugs while those of the hypokinetic one are not and may even show deterioration under SSRIs. In contrast, the hypokinetic factor is responsive to dopaminergic drugs and may show deterioration under serotonergic drugs. Furthermore, the two factors seem to transiently dissociate on placebo intervention aiming at correcting either mood or motor status. The dimensional approach to depression symptomatology may thus be of heuristic value in probing aminergic modulation of mood in IPD and establishing new correlations between affective and motor symptoms.

Long-term skill proceduralization in schizophrenia.

Previous studies had revealed no specific effect under haloperidol (typical) and risperidone (atypical) neuroleptic (NLP) treatments for schizophrenia (SZ) on a variety of neurocognitive functions relying on the dopaminergic meso-cortico-limbic system (Rémillard et al., 2005, 2008). Considering the different affinities of D2 dopamine receptors for typical and atypical NLPs, these drugs may differentially affect the functions of the striatum, a determinant brain structure involved in procedural learning. The influence of risperidone (2-6 mg) and haloperidol (2-40 mg) on a nonmotor procedural task involving semantically related pairs of words with inverted letters was investigated in this double-blind study. The performance of 26 patients with SZ, randomly assigned to risperidone or haloperidol, was compared to that of 18 healthy controls at baseline, 3, 6, and 12 months. Results revealed that all patients with SZ exhibited slower reading speed of the word pairs than healthy controls at all assessment periods. In addition, procedural learning - characterized as a significant decrease in the time taken to read aloud the target word pairs - was more impaired in the haloperidol- than in the risperidone-treated group at all assessment periods. Healthy controls showed steady improvement in reading speed over the 12 months of the study, in contrast to SZ patients, who reached a plateau in their capacity to improve mirror-reading skill over time. However, all SZ participants in the study showed near normal learning profiles from exposure to semantic associations embedded in the procedural memory task, providing evidence for the preservation of associative connections in the semantic network of these patients. The observed impairment in procedural learning in SZ may thus reflect, at least in part, the influence of neuroleptic medication on striatal functions.

Compulsive habits in restless legs syndrome patients under dopaminergic treatment.

Since the introduction of levodopa therapy and dopaminergic replacement therapy to abate symptoms of idiopathic Parkinson's disease, repetitive compulsive behaviors have been reported and are now considered to be drug-related response complications. As dopamine (DA) agonists are the licensed treatment in Restless Legs Syndrome (RLS), a survey was conducted to determine the extent to which patients with RLS present compulsive behaviors. The aim of this study was to investigate the relationship between DA agonists and the occurrence of motor or behavioral compulsions, stress, depression, and sleep disturbance in RLS patients. A questionnaire was mailed three times, at four-month intervals over a period of 8 months to all patients of the Quebec Memory and Motor Skills Disorders Clinic diagnosed with RLS. In addition to recording all medication information for RLS treatment, patients were assessed on the International Restless Legs Syndrome Study Group Rating Scale (IRLS), the Beck Depression Inventory-II (BDI-II), the Sleep Scale from the Medical Outcomes Study (MOS) and on a visual analog scale for current level of stress. A section pertaining to hobby, mania, and compulsion was also included. Analyses are based on 97 out of 151 patients (64.2%) with RLS who returned the three questionnaires. Twelve patients (12.4%) on stable DA agonist therapy (average dose 0.52+/-0.59 mg Pramipexole equivalent) developed a new compulsive behavioral repertoire. Eating (3 women, 1 man), buying food or clothes (2 women, 1 man), trichotillomania (1 woman, 1 man), and gambling (1man) were among the compulsions developed under DA treatment. In addition, two women presented new tic-like phenomena. In contrast to the RLS patients without compulsive behaviors (53 treated with DA agonist; 32 untreated), those with compulsive habits reported experiencing more stress, depression and sleep problems. Patients with RLS with mood and stress states may be at greater risk of developing compulsive behaviors while receiving standard dosage DA agonist treatment. These behaviors are clearly linked to short-term satisfaction and underline the role of dopaminergic mesolimbic stimulation in the reinforcement process of rewarding behavioral sequences.

Long-term effects of risperidone versus haloperidol on verbal memory, attention, and symptomatology in schizophrenia.

There is evidence in the literature that cognitive functions in schizophrenia (SC) may be improved by atypical neuroleptics (NLPs) in contrast to typical medication, but there is still controversy regarding this apparent superiority of atypical drugs. In this study, we assessed the differential effects of risperidone and haloperidol on verbal memory, attention, and psychiatric symptoms in SC. The performance of 28 SC participants, randomly assigned to risperidone (2-6 mg/day) or haloperidol (2-40 mg/day), was compared with that of healthy controls. The California Verbal Learning Test (CVLT), the d2 Cancellation Test, and the Positive and Negative Symptoms Scale were administered at baseline and 3, 6, and 12 months. Relative to controls, all SC participants showed markedly impaired verbal memory and processing speed at each assessment period. There was no differential effect between the two NLPs on CVLT and d2 performance. However, risperidone was more effective than haloperidol in reducing psychiatric symptoms. Improvement in symptom severity was not associated with improvement in neurocognitive performance on these specific tests. Neither conventional nor atypical neuroleptic medications improved neurocognitive functioning over a 12-month follow-up, suggesting that psychopathological improvement under risperidone is independent of cognitive function.

The effect of neuroleptic treatments on executive function and symptomatology in schizophrenia: a 1-year follow up study.

Cognitive dysfunctions (as in memory, attention and executive function) have been recognized as fundamental features of schizophrenia. Executive dysfunction is a major obstacle to functional outcome, community functioning and rehabilitation success and it is crucial to assess the effects of so-called neuroleptic (NLP) medications in this domain of cognitive functioning. Risperidone, an atypical NLP, has been reported to improve executive function in schizophrenia (SZ), but there is controversy regarding these findings. The aim of the current study was to assess the differential effects of risperidone (2-6 mg) and conventional (2-40 mg haloperidol) NLPs on executive skills in 31 individuals with SZ over a 12-month period. The performance of both NLP groups was compared to the performance of 17 age- and education-matched healthy controls. In this randomized, double blind study, the Wisconsin Card Sorting Test (WCST) was administered at baseline, 3, 6, and 12 months after initiating medication. The relationship between executive functioning and the course of clinical symptoms, as assessed by the Positive and Negative Syndrome Scale (PANSS) was also investigated. Results showed that, relative to healthy controls, individuals with SZ showed marked impairment in WCST from baseline through 12 months of treatment. Also, participants under haloperidol or risperidone NLP medication performed similarly on the WCST at all assessment periods showing that risperidone and haloperidol do not differ in their effect on executive functioning. Risperidone treatment, however, was more effective in the reduction of negative symptoms. The differential efficacy of risperidone over negative symptoms and WCST performance strongly suggests that the executive impairments are to some extent the result of brain abnormalities independent of those that produce the major psychopathology manifestations seen in SZ.