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Psychomotor slowing has consistently been observed in schizophrenia, however research on motor learning in schizophrenia is limited. Additionally, motor learning in schizophrenia has never been compared with the waning of motor learning abilities in the elderly. Therefore, in an extensive study, 30 individuals with schizophrenia, 30 healthy age-matched controls and 30 elderly participants were compared on sensorimotor learning tasks including sequence learning and adaptation (both explicit and implicit), as well as tracking and aiming. This paper presents new findings on an explicit motor sequence learning task, an explicit verbal learning task and a simple aiming task and summarizes all previously published findings of this large investigation. Individuals with schizophrenia and elderly had slower Movement Time (MT)s compared with controls in all tasks, however both groups improved over time. Elderly participants learned slower on tracking and explicit sequence learning while individuals with schizophrenia adapted slower and to a lesser extent to movement perturbations in adaptation tasks and performed less well on cognitive tests including the verbal learning task. Results suggest that motor slowing is present in schizophrenia and the elderly, however both groups show significant but different motor skill learning. Cognitive deficits seem to interfere with motor learning and performance in schizophrenia while task complexity and decreased movement precision interferes with motor learning in the elderly, reflecting different underlying patterns of decline in these conditions. In addition, evidence for motor slowing together with impaired implicit adaptation supports the influence of cerebellum and the cerebello-thalamo-cortical-cerebellar (CTCC) circuits in schizophrenia, important for further understanding the pathophysiology of the disorder., (© 2024. The Author(s).)

Background: The "cognitive dysmetria hypothesis" of schizophrenia proposes a disrupted communication between the cerebellum and cerebral cortex, resulting in sensorimotor and cognitive symptoms. Sensorimotor adaptation relies strongly on the function of the cerebellum., Objectives: This study investigated whether sensorimotor adaptation is reduced in schizophrenia compared with age-matched and elderly healthy controls., Methods: Twenty-nine stably treated patients with schizophrenia, 30 age-matched, and 30 elderly controls were tested in three motor adaptation tasks in which visual movement feedback was unexpectedly altered. In the "rotation adaptation task" the perturbation consisted of a rotation (30° clockwise), in the "gain adaptation task" the extent of the movement feedback was reduced (by a factor of 0.7) and in the "vertical reversal task," up- and downward pen movements were reversed by 180°., Results: Patients with schizophrenia adapted to the perturbations, but their movement times and errors were substantially larger than controls. Unexpectedly, the magnitude of adaptation was significantly smaller in schizophrenia than elderly participants. The impairment already occurred during the first adaptation trials, pointing to a decline in explicit strategy use. Additionally, post-adaptation aftereffects provided strong evidence for impaired implicit adaptation learning. Both negative and positive schizophrenia symptom severities were correlated with indices of the amount of adaptation and its aftereffects., Conclusions: Both explicit and implicit components of sensorimotor adaptation learning were reduced in patients with schizophrenia, adding to the evidence for a role of the cerebellum in the pathophysiology of schizophrenia. Elderly individuals outperformed schizophrenia patients in the adaptation learning tasks., (© 2021 S. Karger AG, Basel.)

Abnormal fine motor function is a frequent finding in schizophrenia and has been linked to structural and functional brain alterations. However, whether fine motor function is related to functional alterations within the motor system remains unclear. The aim of this study was to assess whether abnormalities in resting-state functional connectivity are present in schizophrenia patients and to investigate how these abnormalities may be related to fine motor function. We examined 19 schizophrenia patients and 16 healthy controls using resting-state functional connectivity for 11 bilateral regions of interest. Fine motor function was assessed on a set of copying tasks and the Symbol-Digit-Substitution Test. We found significantly reduced functional connectivity between the left caudate nucleus and bilateral dorsolateral prefrontal cortex (DLPFC) and between the left putamen and bilateral supplementary motor area (SMA) proper in patients compared to controls. Altered connectivity from DLPFC to caudate nucleus was related to fine motor tasks, which are sensitive to psychomotor speed, whereas aberrant connectivity between the SMA proper and putamen was associated to both, fine motor task, which are sensitive to psychomotor speed and to speed of information processing. Our findings emphasize the role of fronto-striatal connections in the pathogenesis of fine motor impairments in schizophrenia., (Copyright © 2019. Published by Elsevier B.V.)

Activated microglia express the translocator protein (TSPO) on the outer mitochondrial membrane. 18 F-PBR111 is a second-generation PET ligand that specifically binds the TSPO, allowing in vivo visualization and quantification of neuroinflammation. The aim of this study was to evaluate whether the test-retest variability of 18 F-PBR111 in healthy controls is acceptable to detect a psychosis-associated neuroinflammatory signal in schizophrenia. Methods: Dynamic 90-min 18 F-PBR111 scans were obtained in 17 healthy male controls (HCs) and 11 male schizophrenia patients (SPs) during a psychotic episode. Prior genotyping for the rs6917 polymorphism distinguished high-affinity binders (HABs) and mixed-affinity binders (MABs). Total volume of distribution (V T ) was determined from 2-tissue-compartment modeling with vascular trapping and a metabolite-corrected plasma input function. A subgroup of HCs ( n = 12; 4 HABs and 8 MABs) was scanned twice to assess absolute test-retest variability and intraclass correlation coefficients of the regional V T values. Differences in TSPO binding between HC and SP were assessed using mixed model analysis adjusting for age, genotype, and age*cohort. The effect of using different scan durations (V T-60 min versus V T-90 min ) was determined based on Pearson r. Data were mean ± SD. Results: Mean absolute variability in V T ranged from 16% ± 14% (19% ± 20% HAB; 15% ± 11% MAB) in the cortical gray matter to 22% ± 15% (23% ± 15% HAB; 22% ± 16% MAB) in the hippocampus. Intraclass correlation coefficients were consistently between 0.64 and 0.82 for all tested regions. TSPO binding in SP compared with HC depended on age (cohort*age: P < 0.05) and was increased by +14% ± 4% over the regions. There was a significant effect of genotype on TSPO binding, and V T of HABs was 31% ± 8% (HC: 17% ± 5%, SP: 61% ± 14%) higher than MABs. Across all clinical groups, V T-60 min and V T-90 min were strongly correlated ( r > 0.7, P < 0.0001). Conclusion: 18 F-PBR111 can be used for monitoring of TSPO binding, as shown by medium test-retest variability and reliability of V T in HCs. Microglial activation is present in SPs depending on age and needs to be adjusted for genotype., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Avolition is a core feature of schizophrenia and may arise from altered brain connectivity. Here we used diffusion kurtosis imaging (DKI) to investigate the association between white matter (WM) microstructure and volitional motor activity. Multi-shell diffusion MRI and 24-h actigraphy data were obtained from 20 right-handed patients with schizophrenia and 16 right-handed age and gender matched healthy controls. We examined correlations between fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), and motor activity level, as well as group differences in these measures. In the patient group, increasing motor activity level was positively correlated with MK in the inferior, medial and superior longitudinal fasciculus, the corpus callosum, the posterior fronto-occipital fasciculus and the posterior cingulum. This association was not found in control subjects or in DTI measures. These results show that a lack of volitional motor activity in schizophrenia is associated with potentially altered WM microstructure in posterior brain regions associated with cognitive function and motivation. This could reflect both illness related dysconnectivity which through altered cognition, manifests as reduced volitional motor activity, and/or the effects of reduced physical activity on brain WM., (Copyright © 2016. Published by Elsevier B.V.)

Although there still is conflicting evidence whether schizophrenia is a neurodegenerative disease, cognitive changes in schizophrenia resemble those observed during normal aging. In contrast to extensively demonstrated deficits in explicit learning, it remains unclear whether implicit sequence learning is impaired in schizophrenia and normal aging. Implicit sequence learning was investigated using a computerized drawing task, the 'implicit pattern learning task (IPLT)' in 30 stable patients with schizophrenia, 30 age-matched controls and 30 elderly subjects on two consecutive days and after 1 week (sessions 1, 2 and 3). Fixed sequence trials were intermixed with random trials, and sequence learning was assessed by subtraction of the response time in fixed sequence trials from random trials. Separate analyses of response times and movement accuracy (i.e., directional errors) were performed. Explicit sequence knowledge was assessed using three different awareness tasks. All groups learned equally during sessions 1 and 2. In session 3, control subjects showed significantly larger learning scores than patients with schizophrenia (p = .012) and elderly subjects (p = .021). This group difference is mainly expressed in movement time and directional errors. Patients with schizophrenia demonstrated less subjective sequence awareness, and both patients with schizophrenia and elderly subjects had less explicit sequence recall. Explicit recall was positively correlated with task performance in all groups. After a short 24 h interval, all subjects showed similar improvements in implicit sequence learning. However, no benefit of prior task exposure 1 week later was observed in patients with schizophrenia and elderly subjects compared to controls. As patients with schizophrenia and elderly both display less explicit sequence recall, the control group superiority after 1 week could be explained by an explicit learning component. The few patients with schizophrenia and elderly subjects who had some sequence recall could possibly utilize this explicit knowledge to improve their task performance but did this by distinct mechanisms.

Introduction: Cognitive control impairments have been suggested to be a critical component in the overall cognitive deficits observed in patients diagnosed with schizophrenia. Here, we zoom in on a specific function of cognitive control, conflict adaptation. Abnormal neural activity patterns have been observed for patients diagnosed with schizophrenia in core conflict adaptation areas such as anterior cingulate cortex and prefrontal cortex. On the one hand, this strongly indicates that conflict adaptation is affected. On the other hand, however, outcomes at the behavioural level are needed to create a window into a precise interpretation of this abnormal neural activity., Methods: We present a narrative review of behavioural work within the context of conflict adaptation in schizophrenia, focusing on various major conflict adaptation markers: congruency sequence effects, proportion congruency effects, and post-error and post-conflict slowing. The review emphasises both methodological and theoretical aspects that are relevant to the understanding of conflict adaptation in schizophrenia., Results: Based on the currently available set of behavioural studies on conflict adaptation, no clear-cut answer can be provided as to the precise conflict adaptation processes that are impaired (and to what extent) in schizophrenia populations., Conclusions: Future work is needed in state-of-the-art designs in order to reach better insight into the specifics of conflict adaptation impairments associated with schizophrenia.

Schizophrenia is characterized by social deficits. Correctly monitoring own and others' performance is crucial for efficient social behavior. Deficits in monitoring own performance as reflected in reduced error-related negativity (rERN) amplitudes, have been demonstrated repeatedly in schizophrenia. A similar ERP component (observed ERN; oERN) is elicited when observing others' mistakes. However, possible deficits in monitoring others' performance have never been investigated in schizophrenia. The current ERP-study compared a group of schizophrenia patients (N=22) and healthy controls (N=21) while performing a Simon task and the social Simon task, enabling the investigation of own (rERN) and others' (oERN) performance monitoring. Patients showed slower reaction times, but comparable accuracy and compatibility effects in both tasks. As expected, patients' rERN amplitudes were reduced. Importantly however, oERN amplitudes were comparable between both groups. While monitoring own performance is compromised in schizophrenia, monitoring others' performance seems intact. This divergence between internal and external performance monitoring in patients is in line with studies showing normal neurophysiological responses to negative feedback. The presently found dissociation may improve our understanding of cognitive and neural mechanisms underlying monitoring of own and others' performance and may stimulate treatment development aimed at learning from external rather than internal error information in schizophrenia., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Many people with schizophrenia suffer from social impairments characterized by active social avoidance, which is related to social phobia common in schizophrenia, while motivational impairments can also result in passive social withdrawal. Although social avoidance is frequently reported in this population, this is the first study to directly compare approach-avoidance tendencies in schizophrenia patients (N = 37) and healthy controls (N = 29). Participants performed two tasks: a computerized approach-avoidance task (AAT) to assess response tendencies toward images of happy and angry faces with direct or averted gaze and a one-to-one personal space test (PST) to gauge more naturalistic approach-avoidance behaviors toward a real person bearing a neutral expression. The AAT results showed that both groups showed faster avoidance responses to angry faces and faster approach responses to happy faces with a direct gaze. Happy faces with averted gaze, however, resulted in faster avoidance responses in the patient group only. On the PST, the patients approached the experimenter less than healthy controls did. This measure of interpersonal distance was positively related to positive symptom severity. Delusions of reference and increased sensitivity to social rejection may explain the patients' avoidance tendencies in response to pictures of happy faces with averted gaze and in the presence of an actual person. The current findings demonstrate the importance of others adopting positive and unambiguous attitudes when interacting with schizophrenia patients to minimize behavioral avoidance patterns, which is particularly relevant for relatives and clinicians whose interactions with the patients are crucial to facilitating treatment and promoting healthy social relationships., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Deficits in the initiation and persistence of goal-directed behaviour are key aspects of schizophrenia. In this study, the association between these motivational deficits and discounting of reward value in function of increasing physical effort costs was investigated., Methods: Effort-based decision-making was investigated in 40 patients with a DSM-IV diagnosis of schizophrenia and 30 age- and sex-matched healthy control subjects by means of an effort discounting task. To assess negative symptom severity, we made use of the Scale for the Assessment of Negative Symptoms as well as objective measurements of hedonic response to stimuli and motor activity levels., Results: Patients as well as control subjects discounted the subjective value of rewards significantly with increasing physical effort costs. However, we failed to find a difference in the discounting curves between patients and controls. Furthermore, effort discounting was not associated with any of the negative symptoms measures., Conclusions: Physical effort discounting was not found to be associated with motivational symptoms in schizophrenia if other decision costs are constant. However, recent findings show that more cognitive effort and/or an interaction between effort and other decision costs (e.g. temporal delay or uncertainty) are associated with negative symptoms in schizophrenia. This should be investigated further in future research.

Little is known about the longitudinal course of psychomotor signs and symptoms after illness onset in schizophrenia. Therefore, a 1-year follow-up study was conducted in which patients with schizophrenia were assessed three times with an extensive battery of psychomotor rating scales and tests. The syndromic structure of psychomotor symptoms was also studied. In accordance with a neurodevelopmental view on schizophrenia, psychomotor functioning was found to remain stable or improve slightly. Prospective studies with longer follow-up periods are needed to rule out the possibility of neurodegeneration in subgroups of patients and to evaluate possible covariation in the course of psychomotor symptoms.

Aims: This review provides evidence of which interventions need to be part of effective outpatient integrated treatment for patients with comorbid schizophrenia and substance use disorders., Methods: A total of 14 randomized controlled trials were included. Effect sizes are provided to assess the magnitude of the treatments' efficacy., Results: Despite the studies' heterogeneity, we can conclude that certain programs (e.g. Behavioral Treatment for Substance Abuse in Severe and Persistent Mental Illness ) and specific interventions (e.g. motivational interviewing, family interventions) seem to be effective. Moreover, programs integrating multiple interventions are more likely to be positively related to better outcomes than single interventions. Finally, the lack of difference between effect sizes of assertive community treatment compared to case management suggests that a lower caseload is not necessary for positive treatment outcomes., Conclusion: Integrated treatment seems advantageous, although effect sizes are mostly modest. More homogeneous and qualitative sound studies are needed., (© 2013 S. Karger AG, Basel.)

Introduction: Psychomotor slowing is an important feature of schizophrenia and the relation with negative symptoms is not fully understood. This study aims, first, to investigate the association between negative symptoms and psychomotor slowing. Second, we want to investigate whether fine motor slowing reflects clinically observable gross motor slowing., Methods: In 53 stabilised adult patients with schizophrenia, negative symptoms were assessed using the Positive and Negative Syndrome Scale negative subscale (PANSS-N) with two calculated factors entering the analysis: an expressivity factor and a volitional factor. Psychomotor slowing was assessed by using a modified version of the Salpêtrière Retardation Rating Scale, the Finger Tapping Test, and a writing task measuring fine psychomotor slowing., Results: Negative symptomatology is associated with difficulties in the initiation of fine motor movements, r=.334, p<.05, whilst planning and execution are not. The volitional factor, r=-.407, p=.005, but not the expressivity factor, r=.060, p=.689, is significantly associated with psychomotor slowing. No associations between fine and clinically observable gross psychomotor functioning were found., Conclusions: These findings indicate that higher values of negative symptomatology-more specifically the volitional deficit cluster-affect motor initiation, indicating a heterogeneity in the PANSS-N factorial structure, and that gross and fine psychomotor functioning are affected independently.

Over the last years, genome-wide studies consistently showed an increased burden of rare copy number variants (CNVs) in schizophrenia patients, supporting the "common disease, rare variant" hypothesis in at least a subset of patients. We hypothesize that in families with a high burden of disease, and thus probably a high genetic load influencing disease susceptibility, rare CNVs might be involved in the etiology of schizophrenia. We performed a genome-wide CNV analysis in the index patients of eight families with multiple schizophrenia affected members, and consecutively performed a detailed family analysis for the most relevant CNVs. One index patient showed a DRD5 containing duplication. A second index patient presented with an NRXN1 containing deletion and two adjacent duplications containing MYT1L and SNTG2. Detailed analysis in the subsequent families showed segregation of the identified CNVs. With this study we show the importance of screening high burden families for rare CNVs, which will not only broaden our knowledge concerning the molecular genetic mechanisms involved in schizophrenia but also allow the use of the obtained genetic data to provide better clinical care to these families in general and to non-symptomatic causal CNV carriers in particular., (Copyright © 2013 Wiley Periodicals, Inc.)

Aims: The aim of the present study was to investigate the predictive value of qualitative psychomotor performance levels and subaspects of the negative syndrome for quantitative motor activity levels in patients with schizophrenia., Methods: Twenty-seven stabilized patients with schizophrenia and 22 age- and sex-matched healthy controls were included in the study. An extensive battery of psychomotor performance tests (Finger Tapping Test, Purdue Pegboard Test, Line Copying Test, Neurological Evaluation Scale, Salpêtrière Retardation Rating Scale), clinical rating scales (Positive and Negative Syndrome Scale) and 24-hour actigraphy were administered to all participants., Results: Correlational analyses showed that motor activity levels were associated with avolition as well as clinically assessed psychomotor slowing. However, in a regression model, only avolition was found to be a significant predictor for motor activity levels in patients with schizophrenia; none of the psychomotor performance tests nor the severity of emotional expressivity deficits contributed to the model., Conclusion: Qualitative and quantitative psychomotor deficits seem to be independent phenomena in stabilized patients with schizophrenia. The diminishing in motor activity in patients with schizophrenia is related to a loss of drive and not to problems in the quality of movement execution., (© 2013 S. Karger AG, Basel.)

Background: Second-generation antipsychotics have gradually replaced first-generation antipsychotics as first-line treatment for patients with schizophrenia. Some positive effects on verbal cognition have been shown for the second-generation antipsychotics, but most studies are based on relatively small numbers of patients., Objective: In the frame of the prospective, multi-centre, open-label study ESCAPE (A Prospective, Multicenter, Open-Label Study to Evaluate the Effectiveness and the Effect on Cognitive Function of a Treatment With Aripiprazole in a Broad Range of Schizophrenic Patients; clinicaltrials.gov identifier NCT00329810) evaluating the effectiveness and effect on cognitive functioning of aripiprazole in schizophrenic patients, we conducted a post hoc analysis to examine changes in verbal cognition and investigate the predictive value of a cognitive improvement on quality of life., Study Design: This was a prospective, multi-centre, non-comparative, open-label study of aripiprazole in schizophrenic patients. At study enrolment, these patients were being treated with various first- or second-generation antipsychotics or were without previous antipsychotic treatment. On entering the study, all patients were treated with aripiprazole (Abilify(®); Otsuka, Tokyo, Japan) monotherapy; those patients who had received prior treatment with antipsychotics had their current drug(s) tapered off over a 2-week period. A post hoc analysis of the effect of aripiprazole on two verbal cognitive measures and their correlation with efficacy measures and quality of life was conducted., Setting: Patients with schizophrenia were recruited in 56 psychiatric hospitals., Patients: A total of 361 patients with schizophrenia, ranging from 18 to 65 years, entered the study., Intervention: Patients were treated with aripiprazole monotherapy at a dosage of 10-30 mg/day. Those who were receiving first- or second-generation antipsychotics at enrolment were switched to aripiprazole monotherapy by tapering off their current drug(s) over a 2-week period., Main Outcome Measure: Physician- and patient-rated parameters were measured to gain a complete view of the effectiveness of aripiprazole on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) at baseline and at weeks 4, 8 and 12 and on the Clinical Global Impression-Severity of Illness (CGI-S) scale at baseline and at weeks 1, 2, 4, 8 and 12. A secondary endpoint of verbal cognitive function was measured by the California Verbal Learning Test (CVLT) and the Verbal Fluency (VF) test at baseline and at weeks 4 and 12. The hypothesis of an improvement in verbal cognition and its predictive value on the quality of life was formulated during data collection., Results: 238 patients completed the study. A significant improvement in verbal cognition was observed from week 4 with the long term free recall (LTFR) in the CVLT over the scheduled visits in the trial (F(2,519) = 29.67, p < 0.0001). For the phonemic (letter) subtest of the VF test, patients scored significantly better at week 12 in comparison with baseline (F(2,519) = 3.57, p = 0.0289). There was no significant effect on the semantic (categories) subtest of the VF test (F(2,518) = 0.57, p = 0.5614). Improvement in CGI-S scores at a particular moment in time predicted improvement in LTFR scores at that same moment (F(1,519) = 38.38, p < 0.0001) and in the phonemic (F(1,519) = 42.77, p < 0.0001) and semantic (F(1,518) = 67.43, p < 0.0001) subtests of the VF test. Similarly, CGI-S score improvement globally predicted quality-of-life improvement over visits. The Q-LES-Q scales leisure (F(1,144) = 14.03, p < 0.0001) and social relations (F(1,469) = 5.28, p = 0.0220) also directly correlated with verbal cognition., Conclusion: The findings suggest that switching to, or initiating aripiprazole in schizophrenic patients results in improvement in verbal cognitive functioning. The observed improvement on quality of life is explained by the effect of aripiprazole on the CGI-S score, though the leisure and social relations scales of the Q-LES-Q also independently correlated with verbal fluency. Randomized, controlled, clinical trials of this effect of aripiprazole for selected patients are needed.

We report on a young female patient diagnosed with Marfan syndrome upon admission to the psychiatric hospital for a first psychosis. Mutation analysis of FBN1 identified a de novo nonsense mutation (p.Glu178X). This finding implies co-occurrence of schizophrenia and Marfan syndrome, an observation that has been reported several times in the past. Although, this co-occurrence can be coincidental, several arguments provide strong evidence that Marfan syndrome and schizophrenia might share common etiological pathways. This observation can be important in light of both the etiology of schizophrenia and the diagnosis of Marfan syndrome., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: The rs1344706 single nucleotide polymorphism in the ZNF804A gene is a common variant with strong evidence for association with schizophrenia. Recent studies show an association of rs1344706 with cognitive functioning, and there is some evidence suggesting that the risk allele may increase susceptibility for a subtype of schizophrenia with relatively spared cognition., Methods: We tested the effect of rs1344706 genotype in 89 schizophrenia patients on 3 basic cognitive domains (working memory, processing speed and attention) shown to be severely impaired in schizophrenia. Also we investigated the effect of rs1344706 on the severity of neurological soft signs, subtle impairments in motor and sensory functions highly frequent in schizophrenia patients. Neurological soft signs and cognitive deficits are central features of schizophrenia and are tightly linked with clinical, social and functional outcome., Results: Our results show an association of higher rs1344706 risk allele load with improved performance on processing speed and with fewer neurological soft signs., Conclusions: Together with other studies, our findings suggest that ZNF804A is associated with a subtype of schizophrenia with better cognitive and neurological functioning. Discovery of the specific pathways through which ZNF804A is exerting this effect may lead to better prevention, diagnosis and treatment for a specific group of schizophrenia patients., (Copyright © 2012 S. Karger AG, Basel.)

Background: About half of all schizophrenic patients have a co-occurring substance use disorder, leading to poorer social and functional outcomes than obtained in non-abusing patients. To improve outcomes, integrated treatments have been designed that address the two conditions simultaneously. Results are, however, conflicting because the available effect studies are hampered by various methodological issues, among which are heterogeneous patient samples., Methods: In this comparative study, two well-described patient samples diagnosed with schizophrenia and co-morbid substance abuse disorders either received an integrated treatment (IDDT) or treatment as usual (TAU)., Results: Patients in the IDDT condition showed significant reductions in illicit drug and alcohol use, improvements on all psychiatric symptom domains, reported higher quality of life and improved on social and community functioning. In contrast, patients' improvements in the TAU group were moderate and limited to a few substance use and psychiatric outcomes. The TAU group had significantly higher dropout rates 6 and 12 months after baseline, suggesting that the IDDT programme was more successful in committing patients., Conclusions: Our results suggest that an integrated approach to schizophrenic patients and co-morbid substance use disorders is superior to standard treatment and may be considered as the treatment of choice for this patient group., (Copyright © 2011 S. Karger AG, Basel.)

Background: Neurocognitive impairment and psychiatric symptoms have been associated with deficits in psychosocial and occupational functioning in patients with schizophrenia. This post-hoc analysis evaluates the relationships among cognition, psychopathology, and psychosocial functioning in patients with schizophrenia at baseline and following sustained treatment with antipsychotic drugs., Methods: Data were obtained from a clinical trial assessing the cognitive effects of selected antipsychotic drugs in patients with schizophrenia. Patients were randomly assigned to 24 weeks of treatment with olanzapine (n = 159), risperidone (n = 158), or haloperidol (n = 97). Psychosocial functioning was assessed with the Heinrichs-Carpenter Quality of Life Scale [QLS], cognition with a standard battery of neurocognitive tests; and psychiatric symptoms with the Positive and Negative Syndrome Scale [PANSS]. A path-analytic approach was used to evaluate the effects of changes in cognitive functioning on subdomains of quality of life, and to determine whether such effects were direct or mediated via changes in psychiatric symptoms., Results: At baseline, processing speed affected functioning mainly indirectly via negative symptoms. Positive symptoms also affected functioning at baseline although independent of cognition. At 24 weeks, changes in processing speed affected changes in functioning both directly and indirectly via PANSS negative subscale scores. Positive symptoms no longer contributed to the path-analytic models. Although a consistent relationship was observed between processing speed and the 3 functional domains, variation existed as to whether the paths were direct and/or indirect. Working memory and verbal memory did not significantly contribute to any of the path-analytic models studied., Conclusion: Processing speed demonstrated direct and indirect effects via negative symptoms on three domains of functioning as measured by the QLS at baseline and following 24 weeks of antipsychotic treatment.

Background: Psychomotor slowing is regarded as an important clinical phenomenon in schizophrenia and simple graphic tasks consistently revealed deficits in the (implicit) planning and execution of motor actions in patients with chronic schizophrenia. The aim of the present study is to test the hypothesis that such deficits are already present in patients with recent-onset schizophrenia., Methods: Psychomotor performance and several aspects of movement planning were analyzed in 36 patients with recent-onset schizophrenia and a group of 33 matched healthy controls. Participants were required to draw patterns varying in complexity in three different figure-copying tasks, match and draw simple symbols in the Digit Symbol Substitution Test (DSST) and connect target circles with varying orientations in a newly developed Line Sequencing Task., Results: Relative to the controls, the patients showed significantly longer initiation times when the patterns in the copying tasks became more complex, suggesting increased difficulty in movement planning. Overall, they were not slowed in the execution stages. In the cognitively more demanding DSST, the patients were significantly slowed in both the initiation and movement phases. Moreover, they selected less optimal movement directions in the Line Sequencing Task., Conclusions: Psychomotor planning deficits are already present in the early stages of schizophrenia and involve deficient planning but intact motor action. Planning difficulties can be detected in motor sequences as well. The results indicate that the cognitive deficit in schizophrenia also affects the implicit planning of very simple movements.

Objective: The aim of this review was to discuss data from double-blind, randomized controlled trials (RCTs) that have investigated the effects of oral and long-acting injectable risperidone on cognitive and psychomotor functioning in patients with schizophrenia or schizoaffective disorder., Methods: PubMed/MEDLINE and the Institute of Scientific Information Web of Science database were searched for relevant English-language double-blind RCTs published between March 2000 and July 2008, using the terms schizophrenia, schizoaffective disorder, cognition, risperidone, psychomotor, processing speed, attention, vigilance, working memory, verbal learning, visual learning, reasoning, problem solving, social cognition, MATRICS, and long-acting. Relevant studies included patients with schizophrenia or schizoaffective disorder. Cognitive domains were delineated at the Consensus Conferences of the National Institute of Mental Health-Measurement And Treatment Research to Improve Cognition in Schizophrenia (NIMH-MATRICS). The tests employed to assess each domain and psychomotor functioning, and the within-group and between-group comparisons of risperidone with haloperidol and other atypical antipsychotics, are presented. The results of individual tests were included when they were individually presented and interpretable for either drug; outcomes that were presented as cluster scores or factor structures were excluded., Results: A total of 12 articles were included in this review. Results suggested that the use of oral risperidone appeared to be associated with within-group improvements on the cognitive domains of processing speed, attention/vigilance, verbal and visual learning and memory, and reasoning and problem solving in patients with schizophrenia or schizoaffective disorder. Risperidone and haloperidol seemed to generate similar beneficial effects (on the domains of processing speed, attention/vigilance, [verbal and nonverbal] working memory, and visual learning and memory, as well as psychomotor functioning), although the results for verbal fluency, verbal learning and memory, and reasoning and problem solving were not unanimous, and no comparative data on social cognition were available. Similar cognitive effects were found with risperidone, olanzapine, and quetiapine on the domains of verbal working memory and reasoning and problem solving, as well as verbal fluency. More research is needed on the domains in which study results were contradictory. For olanzapine versus risperidone, these were verbal and visual learning and memory and psychomotor functioning. No comparative data for olanzapine and risperidone were available for the social cognition domain. For quetiapine versus risperidone, the domains in which no unanimity was found were processing speed, attention/vigilance, nonverbal working memory, and verbal learning and memory. The limited available reports on risperidone versus clozapine suggest that: risperidone was associated with improved, and clozapine with worsened, performance on the nonverbal working memory domain; risperidone improved and clozapine did not improve reasoning and problem-solving performance; clozapine improved, and risperidone did not improve, social cognition performance. Use of long-acting injectable risperidone seemed to be associated with improved performance in the domains of attention/vigilance, verbal learning and memory, and reasoning and problem solving, as well as psychomotor functioning. The results for the nonverbal working memory domain were indeterminate, and no clear improvement was seen in the social cognition domain. The domains of processing speed, verbal working memory, and visual learning and memory, as well as verbal fluency, were not assessed., Conclusions: The results of this review of within-group comparisons of oral risperidone suggest that the agent appeared to be associated with improved functioning in the cognitive domains of processing speed, attention/vigilance, verbal and visual learning and memory, and reasoning and problem solving in patients with schizophrenia or schizoaffective disorder. Long-acting injectable risperidone seemed to be associated with improved functioning in the domains of attention/vigilance, verbal learning and memory, and reasoning and problem solving, as well as psychomotor functioning, in patients with schizophrenia or schizoaffective disorder.

Background: Psychomotor slowing is an intrinsic feature of schizophrenia, but little is known about its nature or to what extent it is influenced by antipsychotics. The Symbol-Digit Substitution Test (SDST) is an appropriate tool for assessing reduced processing speed, whereas performance on copying tasks may be more useful in evaluating psychomotor slowing., Objective: The primary aim of this study was to investigate the effects of different antipsychotic agents on psychomotor slowing in patients with schizophrenia., Methods: This cross-sectional study compared performance on line- and figure-copying tasks in schizophrenic inpatients (matched for symptomatology, demographic variables, and duration of illness) treated with risperidone, olanzapine, other atypical antipsychotics (amisulpride, aripiprazole, clozapine, or quetiapine), or conventional antipsychotics (bromperidol, flupentixol, haloperidol, pimozide, or zuclopenthixol) and in healthy controls. Other tests administered included the SDST to assess processing speed, the California Verbal Learning Test to gauge verbal memory, the Letter-Number Sequencing task to assess working memory, and the Wisconsin Card Sorting Test to measure executive function. Comparisons were made between each patient group and healthy controls; between patient groups; and, post hoc, between atypical and conventional antipsychotics., Results: The study included 26 patients treated with risperidone, 24 treated with olanzapine, 25 treated with other atypical antipsychotics, 21 treated with conventional antipsychotics, and 25 healthy controls. The groups were well matched in terms of sex, educational level, mean doses, and duration of illness. The conventional-antipsychotic group was significantly older (P=0.026) and had significantly higher positive symptoms scores (P=0.031) on the Positive and Negative Syndrome Scale compared with the risperidone group. Patients treated with conventional antipsychotics had significantly greater slowing on the copying tasks compared with patients treated with atypical antipsychotics (P

Psychomotor slowing (PS) is a cluster of symptoms that was already recognized in schizophrenia by its earliest investigators. Nevertheless, few studies have been dedicated to the clarification of the nature and the role of the phenomenon in this illness. Moreover, slowed psychomotor functioning is often not clearly delineated from reduced processing speed. The current, first review of all existing literature on the subject discusses the key findings. Firstly, PS is a clinically observable feature that is most frequently established by neuropsychological measures assessing speed of fine movements such as writing or tasks that require rapid fingertip manipulations or the maintenance of maximal speed over brief periods of time in manual activities. Moreover, the slowed performance on the various psychomotor measures has been demonstrated independent of medication and has also been found to be associated with negative symptoms and, to a lesser extent, with positive and depressive symptoms. Importantly, performance on the psychomotor tasks proved related to the patients' social, clinical, and functional outcomes. Several imaging studies showed slowed performance to coincide with dopaminergic striatal activity. Finally, conventional neuroleptics do not improve the patients' PS symptoms, in contrast to the atypical agents that do seem to produce modestly improving effects.

The aim of the current study was to replicate the finding that cognitive impairments are not or inversely associated with sensitivity to stress in a sample of 25 patients diagnosed with psychotic disorder. The results indicated that impairments in performance on the Trailmaking Test and the Stroop Color Word Test were inversely associated with sensitivity to stress in daily life, whereas impairment in a subtest of the Behavioral Assessment of Dysexecutive Syndrome (BADS) was not associated with stress-sensitivity. The data thus show that in some instances cognitive functioning is not, and in other instances is inversely associated with momentary sensitivity to stress. Cognitive impairment and affective reactivity thus appear to be independent or mutually exclusive mechanisms in psychosis, suggesting competing causal pathways.

Objectives: In schizophrenia, stereotypy is observed, a symptom characterized by repetitive, functionless motor behaviour. Whereas cognitive dysfunctioning is known to remain stable throughout the illness, less is known about the course of the motor symptoms. The Zeigeversuch [Mittenecker, E., 1953. Perseveration und Persönlichkeit: 1. Teil: experimentelle Untersuchungen. Z. Exp. Angew. Psychol. 1, 5-31], which entails the generation of a random sequence of button presses, was claimed to capture stereotypy. We used a newly designed computerized version of the Zeigeversuch, the Stereotypy Test Apparatus (STA) to evaluate the evolution of STA performance through the course of the illness., Methods: To assess stereotyped and perseverative behaviour, 58 schizophrenic inpatients and 48 healthy controls performed the STA and the Wisconsin Card Sorting Test (WCST), respectively, as well as several other traditional neuropsychological tests and the Symbol Digit Substitution Test (SDST) on a writing digitizer., Results: The STA correlated only weakly with the WCST and SDST measures but not with the cognitive or motor slowing on the SDST, nor with the other cognitive measures. Stereotyped and perseverative idiosyncrasies both seem to increase in the course of the illness, in contrast with other cognitive dysfunctions. However, whereas perseveration is already present in the early stages of the illness, stereotyped behaviour only manifests itself in the later stages of schizophrenia. Failure of cognitive inhibition may result in an activation of prepotent stereotyped responses captured by the STA.

• Awareness of illness is positively associated with suicidality. • Demoralization fully mediated between awareness of illness and suicidality. • Recognition and treatment of demoralization in schizophrenia is important. The lifetime risk of suicide is significantly higher in patients with schizophrenia than in the general population. It has been suggested that insight is an important risk factor for suicidality in schizophrenia, but only in the presence of feelings of hopelessness and demoralization more generally. This study set out to investigate these assumptions in a sample of patients diagnosed with schizophrenia (n = 81) with the Structured Clinical Interview for DSM-IV Axis I. We hypothesized that there would be a positive association between insight in schizophrenia, measured by the Insight Scale for Psychosis, and suicidality among these patients, measured by the Beck Scale for Suicide Ideation. Furthermore, we expected demoralization, measured by the Demoralization Scale, to mediate the association between insight and suicidality. With regard to the association between insight and suicidality, only the dimension awareness of illness was significantly positively associated with suicidality (r =.34, p ≤.01**). Demoralization fully mediated the relationship between awareness of illness and suicidality (Sobel test z = 1.93, p <.05). This was a cross-sectional study in a relatively small sample, based on self-report questionnaires only. This study emphasizes the importance of recognizing and treating demoralization features in schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: Different patterns of immune system upregulation are present in the acute vs. post-treatment states of psychotic illness. We explored the existence of state and trait markers in the peripheral immune system and two immune-associated neuroendocrine pathways (IDO and GTP-CH1 pathway) in a longitudinal sample of psychosis patients. We also evaluated the association of these markers with neuropsychiatric symptomatology. Method: Plasma concentrations of peripheral blood markers were measured in a transdiagnostic group of 49 inpatients with acute psychosis and 52 matched healthy control subjects. Samples were obtained in patients within 48 h after hospital admission for an acute psychotic episode (before initiation of antipsychotics), after 1–2 weeks and again after 8 weeks of treatment. Kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), phenylalanine, tyrosine, nitrite, and neopterin were measured using HPLC and LC-MS/MS analysis. Concentrations of CRP, CCL2 (MCP1) and cytokines were determined with multiplex immunoassay. PANSS interviews and cognitive tests were performed at baseline and follow-up. Mixed model analyses were used to identify trait and state markers. Results: Patients had significantly higher plasma concentrations of CRP, CCL2, IL1RA, and lower concentrations of KA and KA/Kyn at all time points (F7.5–17.5, all p < 0.001). Increased concentrations of IL6, IL8, IL1RA, TNFα, and CCL2 and decreased QA and 3-HK (F8.7–21.0, all p < 0.005) were found in the acute psychotic state and normalized after treatment. Low nitrite concentrations at admission rose sharply after initiation of antipsychotic medication (F42.4, p < 0.001). PANSS positive scale scores during the acute episode correlated with pro-inflammatory immune markers (r ≥ |0.5|), while negative scale scores correlated inversely with IDO pathway markers (r ≥ |0.4|). Normalization of KA and 3-HK levels between admission and follow-up corresponded to a larger improvement of negative symptoms (r = 0.5, p < 0.030) A reverse association was found between relative improvement of SDST scores and decreasing KA levels (r = 0.5, p < 0.010). Conclusion: The acute psychotic state is marked by state-specific increases of immune markers and decreases in peripheral IDO pathway markers. Increased CRP, CCL2, and IL1RA, and decreased KA and KA/Kyn are trait markers of psychotic illness. [ABSTRACT FROM AUTHOR]

Confronted with any kind of critical event, people tend to develop an urgent need for answers that provide a useful interpretation of what they experience as a painfully intruding disaster. This urge results from the often-unbearable suffering and the disruption of everyday life, routines, and relations. Moreover, dreams and aspirations one had for the future, the realization of which they perceived as important in leading a meaningful life, may be lost or have to be reconsidered. Accompanying feelings of disappointment, demoralization, or even desperation are often treated as symptoms of depression. This approach is called into question by the concept of demoralization, which points to the presence of healthy modes of functioning in a state of lucid awareness of one's condition. In this article, we focus on the case of schizophrenia, as we suppose that having to deal with recurring psychotic episodes constitutes such a pervasive experience, possibly leading to meaning deficiency. We propose then a treatment perspective that integrates care for the processes of mourning and of meaning making. This view, described here in the case of schizophrenic psychosis, is offered as a paradigm that can serve the approach to other serious conditions requiring prolonged care. [ABSTRACT FROM AUTHOR]

Background/Aims: In addition to affective and cognitive symptomatology, psychomotor deficits are known to be present in bipolar disorder (BD). Psychomotor functioning includes all of the processes necessary for completing a movement, from planning to initiation and execution. While these psychomotor symptoms have been studied extensively in schizophrenia and major depressive disorder, only simple measures have been conducted in BD. The present study examines psychomotor functioning in BD. Methods: Twenty-two euthymic BD patients and 21 healthy controls performed three computerized copying tasks varying in cognitive load. Movement times (MT), reflecting fine motor processing, and initiation times (IT), reflecting cognitive processing of visual-spatial information, were separately measured in each group. Results: The BD patients had longer IT but not MT in the simplest task and the opposite pattern of longer MT but not IT in the complex task. However, when controlling for residual mood symptoms, the MT were no longer significantly slower in the BD group. Conclusions: The longer MT and IT in BD reflect overall psychomotor slowing. Specifically, the results provide evidence for cognitive slowing in BD. In addition, the longer MT in the complex task reflect a slowed motor component of movement when the cognitive load is high and when depressive symptoms are present. These findings extend the current knowledge of the nature of psychomotor slowing in BD and may have important prognostic implications for patients. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Speed of processing, one of the main cognitive deficits in schizophrenia is most frequently measured with a digit-symbol-coding test. Performance on this test is additionally affected by writing speed and the rate at which symbol-digit relationships are learned, two factors that may be impaired in schizophrenia.This study aims to investigate the effects of sensorimotor speed, short-term learning, and long-term learning on task performance in schizophrenia. In addition, the study aims to explore differences in learning effects between patients with schizophrenia and elderly individuals. Methods: Patients with schizophrenia (N D30) were compared with age-matched healthy controls (N D30) and healthy elderly volunteers (N D30) during the Symbol-Digit Substitution Test (SDST). The task was administered on a digitizing tablet, allowing precise measurements of the time taken to write each digit (writing time) and the time to decode symbols into their corresponding digits (matching time). The SDST was administered on three separate days (day 1, day 2, day 7). Symbol-digit repetitions during the task represented short-term learning and repeating the task on different days represented long-term learning. Results: The repetition of the same symbol-digit combinations within one test and the repetition of the test over days resulted in significant decreases in matching time. Interestingly, these short-term and long-term learning effects were about equal among the three groups. Individual participants showed a large variation in the rate of short-term learning. In general, patients with schizophrenia had the longest matching time whereas the elderly had the longest writing time. Writing time remained the same over repeated testing. Conclusion:The rate of learning and sensorimotor speed was found to have a substantial influence on the SDST score. However, a large individual variation in learning rate should be taken into account in the interpretation of task scores for processing speed. Equal learning rates among the three groups suggest that unintentional learning in schizophrenia and in the elderly is preserved. These findings are important for the design of rehabilitation programs for schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: To compare sensorimotor performance and learning in stable schizophrenia patients, healthy age- and sex-matched controls and elderly controls on two variations of the rotary pursuit: circle pursuit (true motor learning) and figure pursuit (motor and sequence learning). Method: In the circle pursuit, a target circle, rotating with increasing speed along a predictable circular path on the computer screen, must be followed by a cursor controlled by a pen on a writing tablet. In the eight-trial figure pursuit, subjects learn to draw a complex figure by pursuing the target circle that moves along an invisible trajectory between and around several goals. Tasks were administered thrice (day 1, day 2, day 7) to 30 patients with stable schizophrenia (S), 30 healthy age- and sex-matched controls (C), and 30 elderly participants (>65 years; E) and recorded with a digitizing tablet and pressure-sensitive pen. The outcome measure accuracy (% of time that cursor is within the target) was used to assess performance. Results:We observed significant group differences in accuracy, both in circle and figure pursuit tasks (E

Background: The possible link between creativity and psychopathology has been a long-time focus of research up to the present day. However, the research results in this field are heterogeneous and contradictory. Links between creativity and specific psychiatric disorders have been confirmed and refuted in different studies. This disparity is partly explained by the methodological challenges peculiar to this field. Methods: In this systematic review of the literature from 1950, research articles in the field of creativity and psychopathology are presented, focusing on the methodology and results of the collected studies. Results: This review confirms the methodological problems and the heterogeneity of the study designs and results. The assessment of psychopathology, but more so of creativity, remains a fundamental challenge. On the whole, study results cautiously confirm an association between creativity and both bipolar disorder and schizotypy. Conclusion: The research on creativity and psychopathology is hampered by serious methodological problems. Study results are to be interpreted with caution and future research needs more methodological rigor. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction.Abnormal psychomotor behaviour in schizophrenia might be based on separate deficits. Here we studied the relationship between trajectory planning, action planning, psychomotor speed, and indices of cognitive functioning in a large group of stabilised patients with schizophrenia. Method.Sixty-one patients and 30 controls were tested. Trajectory planning was assessed in a graphic task in which sequences of single lines, gradually changing in direction, had to be drawn. Shifts to a comfortable drawing direction reflect anticipatory trajectory planning. Action planning was evaluated in a task in which figures varying in complexity and familiarity had to be copied. Psychomotor speed was measured by use of a simple line copying task. Measures of information processing speed, attention, working memory, and problem solving were derived from neuropsychological tests. Results.Patients much more often opted for the unusual bottom-to-top direction to draw the vertical lines in the drawing task. They changed the line orientation less often than the controls did. In the patient group, these trajectory planning indices did not correlate with measures of action planning, psychomotor speed, or neuropsychological test scores. Conclusion.Deviant trajectory planning strongly characterises schizophrenia, and is independent from action planning deficits and reduced psychomotor speed. [ABSTRACT FROM AUTHOR]

INTRODUCTION: IN THE FOLLOWING ARTICLE THE COLLABORATIVE ANTWERP PSYCHIATRIC RESEARCH INSTITUTE (CAPRI), THE RESEARCH CENTRE IN MEDICAL PSYCHOLOGY AND PSYCHIATRY OF THE FACULTY OF MEDICINE AND HEALTH SCIENCES, UNIVERSITY OF ANTWERP, BELGIUM, PRESENTS ITS CURRENT RESEARCH PROJECTS. SUBJECTS AND METHOD: THE TEAM LEADERS WERE ASKED TO PRESENT AND SUMMARIZE THE PROJECT THEY HAD BEEN WORKING ON. THE FIELDS IN WHICH RESEARCH WAS CONDUCTED ARE: CHILD AND YOUTH PSYCHIATRY, COGNITIVE AND PSYCHOMOTOR DYSFUNCTIONS IN SCHIZOPHRENIA AND BIPOLAR DISORDER, COGNITIVE AND PSYCHOMOTOR DYSFUNCTIONS IN MAJOR DEPRESSIVE DISORDER, CONSULTATION AND LIAISON PSYCHIATRY, ADDICTION PSYCHIATRY AND FORENSIC PSYCHIATRY. RESULTS: RESULTS OF STUDIES THAT HAVE BEEN FINISHED WILL BE PRESENTED. AS MOST PROJECTS ARE ONGOING OR IN PREPARATION, THE FINDINGS WILL BE PUBLISHED AT A LATER DATE. THIS ARTICLE IS MEANT AS AN OVERVIEW OF THE CURRENT PROJECTS, IN ORDER TO INFORM OTHER RESEARCHERS AND ALL STAKEHOLDERS OF OUR PROGRESS. [ABSTRACT FROM AUTHOR]

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Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years). All subjects received farampator (500 mg) and placebo. Testing took place 1 h after drug intake, which was around Tmax for farampator. Subjects performed tasks assessing episodic memory (wordlist learning and picture memory), working and short-term memory (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Information processing was assessed with a tangled lines task, the symbol digit substitution test (SDST) and the continuous trail making test (CTMT). Farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory. Furthermore, it tended to decrease the number of switching errors in the CTMT. Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. The positive results on short-term memory and the favorable trends in the trail making test (CTMT) are interesting in view of the development of ampakines in the treatment of Alzheimer's disease and schizophrenia.Neuropsychopharmacology (2007) 32, 1272–1283. doi:10.1038/sj.npp.1301257; published online 22 November 2006 [ABSTRACT FROM AUTHOR]

The mixed 5-HT receptor agonist/antagonist meta-chlorophenylpiperazine (mCPP) is known to suppress locomotor activity in mice and rats. This study aimed: (1) to determine whether mCPP induces cognitive and motor changes in normal human volunteers and how these changes relate to the neuroendocrine effects of mCPP; and (2) to compare these cognitive and motor changes to the known cognitive and motor slowing patterns in depression and schizophrenia. A computerized method (used in previous research) analyzed fine motor behavior during figure-copying tasks. In 14 normal male volunteers behavioral responses, body temperature, plasma levels of prolactin and cortisol, and cognitive and motor performance during figure-copying tasks were measured after a single oral dose of mCPP (0.5 mg/kg). mCPP-induced prolongation of the reaction times in all copying tasks, parallel to increases in cortisol and prolactin and some self-reported behavioral effects. There were no changes in the movement times or the velocities of the writing movements. In conclusion, mCPP induced cognitive, but not motor slowing, in normal male volunteers. This indicates that the human serotonin system is also implicated in psychomotor behavior. This pattern of slowing was different from that in depressed and schizophrenic patients. [Copyright &y& Elsevier]

Highlights • Patients show age-dependent changes in TSPO binding from psychosis to follow-up. • Acutely psychotic patients' TSPO binding increases with age. • TSPO binding during psychosis correlates with severity of psychotic symptoms. • Peripheral CRP and kynurenines correlate negatively with TSPO binding. Abstract Objective To determine whether state-associated changes in microglial activity, measured with translocator-protein positron emission tomography (TSPO PET), can be identified in psychosis patients through longitudinal evaluation of their regional tracer uptake over the clinical course from acute psychosis to post-treatment follow-up, and comparison to healthy controls. We also evaluated the relation between tracer uptake, clinical symptoms and peripheral immunological markers. Method Second-generation radioligand [18F]-PBR111 TSPO PET-CT was used for longitudinal dynamic imaging in 14 male psychosis patients and 17 male age-matched healthy control subjects. Patients were first scanned during an acute psychotic episode followed by a second scan after treatment. Prior genotyping of subjects for the rs6917 polymorphism distinguished high- and mixed-affinity binders. The main outcome was regional volume of distribution (V T), representing TSPO binding. Plasma concentrations of CRP, cytokines and kynurenines were measured at each timepoint. Results We found a significant three-way interaction between time of scan, age and cohort (cortical grey matter F6.50, p.020). Age-dependent differences in V T existed between cohorts during the psychotic state, but not at follow-up. Patients' relative change in V T over time correlated with age (cortical grey matter Pearson's r.574). PANSS positive subscale scores correlated with regional V T during psychosis (cortical grey matter r.767). Plasma CRP and quinolinic acid were independently associated with lower V T. Conclusions We identified a differential age-dependent pattern of TSPO binding from psychosis to follow-up in our cohort of male psychosis patients. We recommend future TSPO PET studies in psychosis patients to differentiate between clinical states and consider potential age-related effects. [ABSTRACT FROM AUTHOR]

Abstract: In schizophrenia, psychomotor slowing and stereotypy are poorly delineated from cognitive deficits like diminished processing speed. Inpatients'' performance outcomes on a line-copying task, a task assessing stereotypy and a processing-speed task are compared. Results suggested that psychomotor slowing and stereotypy are related and may represent a catatonic symptom cluster. [Copyright &y& Elsevier]

Abstract: Purpose. – Evidence indicates that classical antipsychotics may aggravate non-malignant and malignant catatonia (MC). Atypical antipsychotics are less likely to cause movement disorders than classical antipsychotics and they are being frequently prescribed in disorders that can be associated with catatonia. Therefore, the important question that arises is whether atypical antipsychotics have a role to play in the treatment of catatonia. Materials and methods. – A Medline search was performed to locate papers on the use of atypical antipsychotics in catatonia published between 1970 and 31st December 2004. Results. – The literature on the use of atypical antipsychotics in catatonia consists of case reports and retrospective studies. In most cases of non-MC a reduction of the catatonic symptoms is reported upon treatment with atypical antipsychotics. Cases of MC relate mainly to the neuroleptic malignant syndrome (NMS), which is considered as an iatrogenic stuporous variant of MC caused by antipsychotics. Conclusion. – There are indications that atypical antipsychotics may be useful in non-MC. As a consequence, one should not only focus on the possible extrapyramidal and autonomic side effects of these drugs, but also on the possible beneficial effects on certain brain functions and on the catatonic symptomatology. However, randomized controlled trials are needed to evaluate the effect of these drugs, and caution is advisable, since cases of NMS have been linked to treatment with atypical antipsychotics. There is no evidence to prescribe atypical antipsychotics in MC. [Copyright &y& Elsevier]