| 1 | Am J Psychiatry 2002 Nov 159: 1921-6 |
|---|---|
| PMID | 12411229 |
| Title | Applications of errorless learning for improving work performance in persons with schizophrenia. |
| Abstract | Until recently, few training methods used in the psychosocial rehabilitation of persons with schizophrenia have taken into account the neurocognitive deficits common to this illness. The present study tested a training method called errorless learning (which theoretically compensates for neurocognitive impairments) for efficacy at teaching entry-level job tasks to persons with serious and persistent mental illness. Sixty-five unemployed, clinically stable outpatients with schizophrenia or schizoaffective disorder were randomly assigned to training by means of either errorless learning or conventional instruction for two entry-level job tasks (index card filing and toilet TANK assembly). Training was conducted in small groups of four subjects for 90-120 minutes in a simulated workshop. Efficacy-as measured by accuracy, speed, and overall productivity-was assessed immediately after training and at a 3-month follow-up evaluation. Significant group differences in accuracy that favored errorless learning were found on both job tasks. In terms of productivity, the errorless learning group was superior to the conventional instruction group on the card filing task, and differences for the TANK assembly task approached significance. There were no significant group differences in speed. Both groups showed significant drops in accuracy and productivity on the TANK assembly task from immediately after training to the 3-month follow-up evaluation; performance levels were more stable for both groups on the card filing task. Errorless learning appears to be a useful training method for establishing introductory high levels of performance in the work rehabilitation of persons with schizophrenia. Future studies may wish to test its long-term durability by embedding it within supported employment programs. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Hum. Mol. Genet. 2003 Oct 12: 2431-48 |
| PMID | 12915444 |
| Title | Complexin II is essential for normal neurological function in mice. |
| Abstract | Complexins (CPLXs) are modulators of synaptic vesicle release. At 1 year of age, CPLXII knockout (KO) mice appear normal. However, behavioral testing reveals underlying deficits of motor and cognitive function in these mice. We found motor deficits on the rotarod, and learning deficits in the Morris water maze (both acquisition and reversal) and the two-choice swim TANK (reversal). The reversal learning deficits are particularly noticeable, being present from the earliest time of testing, when most other behaviors are normal. CPLXII KO mice also fail to develop adult patterns of exploratory behavior in the open field and show deficits in interactive grooming behaviors. The behavioral deficits worsen with age. For example, while rotarod performance is normal until 10 weeks, it is impaired from 24 weeks onwards. Similarly, deficits in spatial learning in the Morris water maze are mild at 8 weeks, but pronounced by 1 year of age. The deficits seen in CPLXII KO mice are not due to physical weakness, since their ability to run, swim and grip is unimpaired. Rather, the mice appear to have deficits of higher function. The deficits seen in CPLXII KO mice are strikingly similar to those seen in the R6/2 model of Huntington's disease (HD) where a progressive depletion of CPLXII is seen. This suggests that depletion of CPLXII contributes to cognitive abnormalities in R6/2 mice. Given that decreased expression of CPLXII is seen in HD and schizophrenic patients, a role for CPLXII depletion should be considered in other diseases where motor, cognitive and psychiatric symptoms co-exist. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Psychol Med 2003 Apr 33: 433-42 |
| PMID | 12701664 |
| Title | Does 'errorless learning' compensate for neurocognitive impairments in the work rehabilitation of persons with schizophrenia? |
| Abstract | Because neurocognitive impairments of schizophrenia appear to be 'rate limiting' in the acquisition of skills for community functioning, it is important to develop efficacious rehabilitative interventions that can compensate for these impairments. Procedures based on errorless learning may facilitate work rehabilitation because they effectively automate training of work and other skills, thereby reducing the cognitive burden on persons with schizophrenia. The present study examined the ability of a training method based on errorless learning to compensate for neurocognitive deficits in teaching two entry-level job tasks (index card filing and toilet-TANK assembly) to a sample of 54 unemployed, clinically stable schizophrenic and schizoaffective disorder out-patients. Participants were randomly assigned to one of two training groups, errorless learning v. conventional trial-and-error type instruction. Prior to randomization, all subjects were administered a neurocognitive battery. Job task performance was assessed by percentage accuracy scores immediately after training. For three of the six inter-relationships among neurocognitive functioning and training condition, the pattern was the same: the errorless learning group scored high in job task performance regardless of neurocognitive impairment, whereas the conventional instruction group showed a close correspondence between job task performance and degree of neurocognitive impairment. These findings support errorless learning as a technique that can compensate for neurocognitive deficits as they relate to the acquisition of new skills and abilities in the work rehabilitation of persons with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Psychol Med 2003 Apr 33: 433-42 |
| PMID | 12701664 |
| Title | Does 'errorless learning' compensate for neurocognitive impairments in the work rehabilitation of persons with schizophrenia? |
| Abstract | Because neurocognitive impairments of schizophrenia appear to be 'rate limiting' in the acquisition of skills for community functioning, it is important to develop efficacious rehabilitative interventions that can compensate for these impairments. Procedures based on errorless learning may facilitate work rehabilitation because they effectively automate training of work and other skills, thereby reducing the cognitive burden on persons with schizophrenia. The present study examined the ability of a training method based on errorless learning to compensate for neurocognitive deficits in teaching two entry-level job tasks (index card filing and toilet-TANK assembly) to a sample of 54 unemployed, clinically stable schizophrenic and schizoaffective disorder out-patients. Participants were randomly assigned to one of two training groups, errorless learning v. conventional trial-and-error type instruction. Prior to randomization, all subjects were administered a neurocognitive battery. Job task performance was assessed by percentage accuracy scores immediately after training. For three of the six inter-relationships among neurocognitive functioning and training condition, the pattern was the same: the errorless learning group scored high in job task performance regardless of neurocognitive impairment, whereas the conventional instruction group showed a close correspondence between job task performance and degree of neurocognitive impairment. These findings support errorless learning as a technique that can compensate for neurocognitive deficits as they relate to the acquisition of new skills and abilities in the work rehabilitation of persons with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Schizophr Bull 2005 Jan 31: 67-72 |
| PMID | 15888426 |
| Title | Learning potential and the prediction of work skill acquisition in schizophrenia. |
| Abstract | This study examined whether a measure of learning potential could predict work skill acquisition in schizophrenia beyond the prediction offered by a single administration assessment. Fifty-seven outpatients with schizophrenia or schizoaffective disorder completed a test-train-test version of the Wisconsin Card Sorting Test as a measure of their learning potential. The outpatients were randomly assigned to training by errorless learning or conventional instruction on two work skills (index card filing and toilet TANK assembly). Work skills were assessed both immediately and 3 months after training. Generally, patients with high learning potential performed better on the work skill tasks. Learning potential explained an additional 15 percent of variance beyond single administration assessment in participants' accuracy immediately after work skill training and an additional 13 percent of variance in participants' accuracy 3 months after training. These findings indicate that measures of learning potential contribute to the prediction of work skill acquisition, going beyond the predictive power of single administration assessments. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Hum. Mol. Genet. 2007 Oct 16: 2288-305 |
| PMID | 17652102 |
| Title | Complexin 1 knockout mice exhibit marked deficits in social behaviours but appear to be cognitively normal. |
| Abstract | Complexins are presynaptic proteins that modulate neurotransmitter release. Abnormal expression of complexin 1 (Cplx1) is seen in several neurodegenerative and psychiatric disorders in which disturbed social behaviour is commonplace. These include Parkinsons's disease, Alzheimer's disease, schizophrenia, major depressive illness and bipolar disorder. We wondered whether changes in Cplx1 expression contribute to the psychiatric components of the diseases in which Cplx1 is dysregulated. To investigate this, we examined the cognitive and social behaviours of complexin 1 knockout mice (Cplx1(-/-)) mice. Cplx1(-/-) mice have a profound ataxia that limits their ability to perform co-ordinated motor tasks. Nevertheless, when we taught juvenile Cplx1(-/-) mice to swim, they showed no evidence of cognitive impairment in the two-choice swim TANK. In contrast, although olfactory discrimination in Cplx1(-/-) mice was normal, Cplx1(-/-) mice failed in the social transmission of food preference task, another cognitive paradigm. This was due to abnormal social interactions rather than cognitive impairments, increased anxiety or neophobia. When we tested social behaviour directly, Cplx1(-/-) mice failed to demonstrate a preference for social novelty. Further, in a resident-intruder paradigm, male Cplx1(-/-) mice failed to show the aggressive behaviour that is typical of wild-type males towards an intruder mouse. Together our results show that in addition to the severe motor and exploratory deficits already described, Cplx1(-/-) mice have pronounced deficits in social behaviours. Abnormalities in complexin 1 levels in the brain may therefore contribute to the psycho-social aspects of human diseases in which this protein is dysregulated. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Behav. Brain Res. 2010 Dec 214: 417-22 |
| PMID | 20600350 |
| Title | Antipsychotic drugs prevent the motor hyperactivity induced by psychotomimetic MK-801 in zebrafish (Danio rerio). |
| Abstract | Glutamate N-methyl-d-aspartate (NMDA) receptor antagonists, such as dizocilpine (MK-801), elicit schizophrenia-like symptoms in humans and a behavioral syndrome in rodents, characterized by hyperlocomotion and stereotyped actions, which is antagonized by antipsychotic drugs. Animal models of schizophrenia have been established and used for the development of new antipsychotic drugs. In this work we characterized the behavioral effects of MK-801 and investigated the effect of typical and atypical antipsychotic treatments on locomotor activity as well on the hyperlocomotion induced by MK-801 in zebrafish. MK-801 (20 microM) increased the locomotor behavior as measured by the number of line crossings, distance traveled, and the mean speed in the TANK test after 15, 30, and 60 min of exposure. All tested antipsychotics counteracted MK-801-induced hyperactivity on all parameters analyzed and at doses that, given alone, had no effect on spontaneous locomotor activity. The results suggest a similar profile between typical and atypical antipsychotics in the reversal of locomotor disorders induced by MK-801. Moreover, an anxiolytic effect was verified at 30 and 60 min of MK-801 exposure, which was not reversed by antipsychotics tested in this work. In addition, olanzapine, which alone caused an anxiolytic response, when given with MK-801 potentiated the latter's effect on anxiety. In this work we demonstrated the value of the zebrafish, a simple to use animal model, in developing some behavioral features observed in schizophrenia, which may indicate a new approach for drug screening. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2012 Mar 36: 258-63 |
| PMID | 22019856 |
| Title | Behavioral changes induced by long-term proline exposure are reversed by antipsychotics in zebrafish. |
| Abstract | Hyperprolinemia is an inherited disorder of proline metabolism and patients affected by this disease may present neurological manifestations, including seizures and cognitive dysfunctions. Moreover, an association between adulthood schizoaffective disorders and moderate hyperprolinemia has been reported. However, the mechanisms underlying these behavioral phenotypes still remain unclear. In the present study, we investigated the effect of proline treatments on behavioral parameters in zebrafish, such as locomotor activity, anxiety, and social interaction. Adult zebrafish (Danio rerio) were exposed to proline (1.5 and 3.0 mM) during 1h or 7 days (short- or long-term treatments, respectively). Short-term proline exposure did not promote significant changes on the behavioral parameters observed. Long-term exposure at 1.5 mM proline significantly increased the number of line crossing (47%), the total distance (29%), and the mean speed (33%) when compared to control group. A significant increase in the time spent in the upper portion of the test TANK was also observed after this treatment (91%), which may be interpreted as an indicator of anxiolytic behavior. Proline at 1.5 mM also induced social interaction impairment (78%), when compared to the untreated group after long-term treatment. Moreover, these proline-induced behavioral changes in zebrafish were completely reversed by acute administration of an atypical antipsychotic drug (sulpiride), but not by a typical (haloperidol). These findings demonstrate that proline is able to induce schizophrenia-like symptoms in zebrafish, which reinforce the use of this species as a complementary vertebrate model for studying behavioral phenotypes associated with neurological dysfunctions characteristic of metabolic diseases. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Int. J. Neuropsychopharmacol. 2015 Sep 18: pyv042 |
| PMID | 25899066 |
| Title | Biomarkers for Psychiatry: The Journey from Fantasy to Fact, a Report of the 2013 CINP Think Tank. |
| Abstract | A think TANK sponsored by the Collegium Internationale Neuropsychopharmacologium (CINP) debated the status and prospects of biological markers for psychiatric disorders, focusing on schizophrenia and major depressive disorder. Discussions covered markers defining and predicting specific disorders or domains of dysfunction, as well as predicting and monitoring medication efficacy. Deliberations included clinically useful and viable biomarkers, why suitable markers are not available, and the need for tightly-controlled sample collection. Different types of biomarkers, appropriate sensitivity, specificity, and broad-based exploitability were discussed. Whilst a number of candidates are in the discovery phases, all will require replication in larger, real-life cohorts. Clinical cost-effectiveness also needs to be established. Since a single measure is unlikely to suffice, multi-modal strategies look more promising, although they bring greater technical and implementation complexities. Identifying reproducible, robust biomarkers will probably require pre-competitive consortia to provide the resources needed to identify, validate, and develop the relevant clinical tests. |
| SCZ Keywords | schizophrenia, schizophrenic |