Time In Schizophrenia Research Articles

Linking the Developmental and Degenerative Theories of Schizophrenia: Association Between Infant Development and Adult Cognitive Decline

Neurodevelopmental and neurodegenerative theories may be viewed as incompatible accounts that compete to explain the pathogenesis of schizophrenia. However, it is possible that neurodevelopmental and neurodegenerative processes could both reflect common underlying causal mechanisms. We hypothesized that cognitive dysfunction would gradually deteriorate over time in schizophrenia and the degree of this deterioration in adulthood would be predicted by an infant measure of neurodevelopment. We aimed to examine the association between age of learning to stand in infancy and deterioration of cognitive function in adulthood. Participants were nonpsychotic control subjects (n = 76) and participants with schizophrenia (n = 36) drawn from the Northern Finland 1966 Birth Cohort study. The schizophrenia group showed greater deterioration in abstraction with memory than controls, but there were no differences between schizophrenia and controls in rate of change of other cognitive measures. Age of learning to stand in infancy significantly inversely predicted later deterioration of abstraction with memory in adult schizophrenia (later infant development linked to greater subsequent cognitive deterioration during adulthood), possibly suggesting a link between abnormal neurodevelopmental and neurodegenerative processes in schizophrenia.

Resting-state connectivity in the prodromal phase of schizophrenia: Insights from EEG microstates

IntroductionResting-state EEG microstates are thought to reflect the momentary local states and interactions of distributed neural networks in the brain. Several changes in resting-state EEG microstates have been described in acutely ill patients with schizophrenia, but it is not known whether these represent trait or state abnormalities. The present study aimed to investigate this issue by assessing EEG microstate characteristics in high-risk individuals (HR) and clinically stable first-episode patients with schizophrenia (SZ) with low symptom levels, compared to each other and healthy controls (HC). MethodParticipants were 18 HR, 18 SZ, and 22 HC subjects. 64-channel resting-state EEG recordings were used for microstate analyses. Microstates were clustered into four classes (A–D) according to their topography. Temporal parameters and topographies of microstates were compared among groups. ResultsMicrostate class A displayed higher coverage and occurrence in HR than SZ and HC, while microstate class B covered significantly more time in SZ compared to both HR and HC. Microstate class B displayed an aberrant spatial configuration in SZ, and to a lesser extent also in HR, compared to HC, with patients exhibiting significantly higher activity in the vicinity of the left posterior cingulate. DiscussionMicrostate abnormalities observed in HR were similar to those previously reported in acutely ill patients with schizophrenia. Moreover, there was evidence that HR and SZ might share specific disturbances in brain functional connectivity. These findings raise the possibility that certain abnormalities in resting-state EEG microstates might be associated with an increased risk for psychosis.

Impaired Representation of Time in Schizophrenia Is Linked to Positive Symptoms and Cognitive Demand

Time processing critically relies on the mesencephalic dopamine system and striato-prefrontal projections and has thus been suggested to play a key role in schizophrenia. Previous studies have provided evidence for an acceleration of the internal clock in schizophrenia that may be linked to dopaminergic pathology. The present study aimed to assess the relationship between altered time processing in schizophrenia and symptom manifestation in 22 patients and 22 controls. Subjects were required to estimate the time needed for a visual stimulus to complete a horizontal movement towards a target position on trials of varying cognitive demand. It was hypothesized that patients – compared to controls – would be less accurate at estimating the movement time, and that this effect would be modulated by symptom manifestation and task difficulty. In line with the notion of an accelerated internal clock due to dopaminergic dysregulation, particularly patients with severe positive symptoms were expected to underestimate movement time. However, if altered time perception in schizophrenia was better explained in terms of cognitive deficits, patients with severe negative symptoms should be specifically impaired, while generally, task performance should correlate with measures of processing speed and cognitive flexibility. Patients underestimated movement time on more demanding trials, although there was no link to disease-related cognitive dysfunction. Task performance was modulated by symptom manifestation. Impaired estimation of movement time was significantly correlated with PANSS positive symptom scores, with higher positive symptom scores associated with stronger underestimation of movement time. The present data thus support the notion of a deficit in anticipatory and predictive mechanisms in schizophrenia that is modulated both by symptom manifestation and by cognitive demand.

IQ change over time in schizophrenia and healthy individuals: A meta-analysis

BackgroundCognitive deficits have been recognized as a key feature of schizophrenia, since the first description by Kraepelin. Specifically, lower intelligence is considered a core feature of the disorder and may represent a risk factor for its development. However, whether global intelligence decreases over time in schizophrenia is not known. The aims of this quantitative meta-analysis are to gather, integrate and estimate the overall mean effect size of IQ change over time in schizophrenia as compared to healthy individuals. MethodsA systematic search was conducted to identify relevant studies. Longitudinal studies with at least two intelligence assessments in schizophrenia cohorts were retrieved. Studies had to report sufficient data on IQ-change and include data from healthy comparisons for computation of effect sizes. For each study, the Cohen d was calculated as well as a combined mean effect size. ResultsFourteen studies were identified. Eight studies with a total of 280 patients and 306 healthy controls were suitable to be included. The mean weighted baseline IQ was 97.20 for patients and 109.26 for controls. The mean weighted IQ-change per year was +0.33 for patients and +2.08 for controls. The combined effect size was Cohen's d=−0.48, p=0.01. ConclusionsA global cognitive deficit is present in patients with schizophrenia expressed as a lower test score increase over repeated testing as compared to healthy subjects possibly due to the lack of practice effects in patients. Thus, schizophrenia is characterized by a relative lack of gain in global cognitive abilities over time.

2589 – Reaction time in schizophrenia and mood disorder

Introduction In experimental psychopathology there is a long tradition of reaction time studies. Especially in schizophrenia there has reliably been observed deficits in attention and reaction time. Objectives To examine if patients with schizophrenia can be differentiated from patients with mood disorder on the basis of their reaction time patterns. Aims To evaluate if reaction time measures might be useful in the diagnostic process. Methods 58 patients with schizophrenia, 55 patients with mood disorder, and 30 healthy controls participated in a computerbased reaction time experiment. The stimuli were short visual and auditory stimuli presented in a randomized sequence. The subjects were instructed to press a button each time they saw or heard a signal from the computer. Results The reaction times of the patients with schizophrenia and mood disorder to both light and sound stimuli were significantly slower than those of the control group. Furthermore, the patient groups’ reaction times were significantly less stable than those of the control group, and they made significantly more errrors. However, no significant differences in reaction times, stability of reaction times, and number of errors were found between the two patient groups. No clear or consistent differences were observed when comparing the reaction time patterns of subgroups of schizophrenia patients with positive, mixed and negative symptoms, and mood disorder patients in manic and depressive phases. Conclusion On the basis of simple reaction measures it is not possible to differentiate between patients with schizophrenia and mood disorder.

Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies

Cortical gray matter deficits have been found in patients with schizophrenia, with evidence of progression over time. The aim of this study was to determine the extent of progressive cortical gray matter volume changes over time in schizophrenia, their site and time of occurrence, and the role of potential moderators of brain changes. English language articles published between 1 January 1983 and 31 March 2012 in the MEDLINE and EMBASE databases were searched. Longitudinal magnetic resonance imaging studies comparing changes in cortical gray matter volume over time between patients with schizophrenia and healthy controls were included. Hedges g was calculated for each study. Analyses were performed using fixed- and random-effects models. A subgroup analysis was run to explore the pattern of brain changes in patients with first-episode schizophrenia. A meta-regression statistic was adopted to investigate the role of potential moderators of the effect sizes (ESs). A total of 19 studies, analyzing 813 patients with schizophrenia and 718 healthy controls, were included. Over time, patients with schizophrenia showed a significantly higher volume loss of total cortical gray matter, left superior temporal gyrus (STG), left anterior STG, left Heschl gyrus, left planum temporale and posterior STG bilaterally. Meta-analysis of first-episode schizophrenic patients showed a more significant pattern of progressive loss of whole cerebral gray matter volume involving the frontal, temporal and parietal lobes, and left Heschl gyrus compared with healthy controls. Clinical, pharmacologic and neuroradiological variables were found to be significant moderators of brain volume changes in patients with schizophrenia. The meta-analysis demonstrates that progressive cortical gray matter changes in schizophrenia occur with regional and temporal specificity. The underlying pathological process appears to be especially active in the first stages of the disease, affects the left hemisphere and the superior temporal structures more and is at least partly moderated by the type of pharmacological treatment received.

Temporal event structure and timing in schizophrenia: Preserved binding in a longer “now”

Patients with schizophrenia experience a loss of temporal continuity or subjective fragmentation along the temporal dimension. Here, we develop the hypothesis that impaired temporal awareness results from a perturbed structuring of events in time—i.e., canonical neural dynamics. To address this, 26 patients and their matched controls took part in two psychophysical studies using desynchronized audiovisual speech. Two tasks were used and compared: first, an identification task testing for multisensory binding impairments in which participants reported what they heard while looking at a speaker's face; in a second task, we tested the perceived simultaneity of the same audiovisual speech stimuli. In both tasks, we used McGurk fusion and combination that are classic ecologically valid multisensory illusions. First, and contrary to previous reports, our results show that patients do not significantly differ from controls in their rate of illusory reports. Second, the illusory reports of patients in the identification task were more sensitive to audiovisual speech desynchronies than those of controls. Third, and surprisingly, patients considered audiovisual speech to be synchronized for longer delays than controls. As such, the temporal tolerance profile observed in a temporal judgement task was less of a predictor for sensory binding in schizophrenia than for that obtained in controls. We interpret our results as an impairment of temporal event structuring in schizophrenia which does not specifically affect sensory binding operations but rather, the explicit access to timing information associated here with audiovisual speech processing. Our findings are discussed in the context of curent neurophysiological frameworks for the binding and the structuring of sensory events in time.

The causal relationships between neurocognition, social cognition and functional outcome over time in schizophrenia: a latent difference score approach

Social cognition has been identified as a significant construct for schizophrenia research with relevance to diagnosis, assessment, treatment and functional outcome. However, social cognition has not been clearly understood in terms of its relationships with neurocognition and functional outcomes. The present study sought to examine the empirical independence of social cognition and neurocognition; to investigate the possible causal structure among social cognition, neurocognition and psychosocial functioning. The sample consists of 130 individuals diagnosed with schizophrenia. All participants were recruited as they were admitted to four community-based psychosocial rehabilitation programs. Social cognition, neurocognition and psychosocial functioning were measured at baseline and 12 months. The empirical independence of social cognition and neurocognition was tested using confirmatory factor analysis (CFA) and the possible causal structure among social cognition, neurocognition and psychosocial functioning was investigated using latent difference score (LDS) analysis. A two-factor model of social cognition and neurocognition fit the data very well, indicating the empirical independence of social cognition, whereas the longitudinal CFA results show that the empirical independence of neurocognition and social cognition is maintained over time. The results of the LDS analysis support a causal model that indicates that neurocognition underlies and is causally primary to social cognition, and that neurocognition and social cognition are causally primary to functional outcome. Social cognition and neurocognition could have independent and distinct upward causal effects on functional outcome. It is also suggested that the approaches for remediation of neurocognition and social cognition might need to be distinct.

P-789 - Time-dependent activation of theory of mind neural networks in schizophrenia patients-a 3 t fMRI study

Introduction Functional magnetic resonance imaging (fMRI) studies in schizophrenia found altered brain activation patterns during Theory of Mind (ToM) task performance in the so-called ToM-network, recently focusing on over- rather than under-activation. Even though most fMRI-studies applied tasks that might gradually activate the ToM-network, no study so far has investigated the time-course of ToM-performance. Some of the varying activation results might thus be due to time-course of performance. Aim Our aim was to investigate neural activation over time in schizophrenia compared with a healthy control sample. Methods Using a block design in fMRI, we presented a sophisticated paradigm that depicts moving geometrical shapes interacting in social patterns. 14 patients with schizophrenia and 15 healthy controls participated in the study. Functional activation patterns were investigated for the first and second half of the videos separately. Results Both groups activated brain areas related to the ToM-network during performance of ToM videos as compared to a baseline condition. Most importanly, schizophrenia patients showed activation in ToM-related brain areas only in the second part, while healthy controls activated the ToM-network in the first part of the video presentation. Conclusions Results confirm recent findings of an increased activation in ToM-related brain areas in schizophrenia. Moreover, patients activated ToM-related brain areas later than healthy controls. This delay might be due to a general cognitive slowing, symptom-related inhibition of cognition-associated processes or specific delay in task processing. As this is the first study to investigate this time-course of ToM, more research is needed to classify results.

Cognitive functioning in subjects with recent-onset psychosis from a low-middle-income environment: Multiple-domain deficits and longitudinal evaluation

Cognitive deficits are a key feature of recent-onset psychosis, but there is no consensus on whether such deficits are generalized or confined to specific domains. Besides, it is unclear whether cognitive deficits: a) are found in psychotic patients in samples from outside high-income countries; and b) whether they progress uniformly over time in schizophrenia and affective psychoses. We applied 12 tests organized into eight cognitive domains, comparing psychosis patients ( n = 56, time from initial contact = 677.95 ± 183.27 days) versus healthy controls ( n = 70) recruited from the same area of São Paulo, Brazil. Longitudinal comparisons (digit span and verbal fluency) were conducted between a previous assessment of the subjects carried out at their psychosis onset, and the current follow-up evaluation. Psychosis patients differed significantly from controls on five domains, most prominently on verbal memory. Cognitive deficits remained detectable in separate comparisons of the schizophrenia subgroup and, to a lesser extent, the affective psychosis subjects against controls. Longitudinal comparisons indicated significant improvement in schizophrenia, affective psychoses, and control subjects, with no significant group-by-time interactions. Our results reinforce the view that there are generalized cognitive deficits in association with recent-onset psychoses, particularly of non-affective nature, which persist over time.

Why treating early, treating well, and treating for life is important in schizophrenia

Schizophrenia is a progressive illness, with many psychotic episodes. Brain imaging studies have consistently demonstrated brain abnormalities in patients with schizophrenia. These changes are largely confined to decreases in gray matter volumes and enlargement of the lateral and third ventricles. To date schizophrenia has been considered to result from abnormalities in neurodevelopment, with brain changes to be static. However, schizophrenia has long been thought to be a progressive or a degenerative, not a developmental, disorder. Indeed, Kraepelin considered the progressive clinical deterioration to be the hallmark of the disorder, naming it dementia praecox to reflect this particular aspect. Lately, others have re-emphasized the importance of the decline in functioning in schizophrenia as a clue to its pathogenesis, suggesting that the brain abnormalities in schizophrenia could be expected to reflect this clinical progression. Indeed, we and others have reported brain abnormalities to increase over time in schizophrenia. Interestingly, not all patients show changes in brain volumes over time: we demonstrated that the changes are particularly pronounced in those patients with a poor prognosis in the first years of illness. Moreover progressive changes are most pronounced in the frontal and temporal areas as postulated by Kraepelin over a hundred years ago. Interestingly, white matter did not change over time. Also we found that brain loss over time was most pronounced in patients who had been psychotic longest. Finally, the progression in these frontal brain changes appeared to be attenuated by treatment with atypical, but not by typical antipsychotics. Thus, not only are brain changes progressive in schizophrenia, they are clinically relevant since they are related to outcome and may be reversed by some of the atypical antipsychotics. With the evidence pointing to a link between progressive disease and patient outcomes, it is becoming increasingly clear that every effort should be made to prevent psychotic relapses. Using medications with maximal effect is therefore warranted.

Discrimination Learning, Reversal, and Set-Shifting in First-Episode Schizophrenia: Stability Over Six Years and Specific Associations with Medication Type and Disorganization Syndrome

BackgroundThe intradimensional/extradimensional (IDED) task assesses different forms of learning from feedback. Limited evidence suggests that attentional set-shifting deteriorates over time in schizophrenia. We tested this hypothesis and examined the specificity of learning impairments identified by this task.MethodTwo hundred sixty-two first-episode patients and 76 healthy control subjects, matched for age and premorbid IQ, were tested; 104 patients and 25 control subjects were reassessed 1 and 3 years later, and 31 patients were reassessed additionally 6 years later.ResultsPatients showed impaired set-shifting that correlated with current IQ and working memory, but there were no impairments when subgroups were matched on current IQ. In contrast, patients showed marked impairments in rule reversal learning that survived correction for IQ, were present in the context of intact rule abstraction, and correlated with disorganization symptoms. Patients prescribed second-generation antipsychotics were worse on set-shifting compared with first-generation, a finding not explained by demographic data, illness characteristics, or IQ. Patients and control subjects showed stable IDED performance over the first 6 years of illness, although set-shifting was inconsistent over the first year. Those with residual negative symptoms were more likely to fail the set-shifting stage at follow-up.ConclusionsFirst-episode schizophrenia patients can learn and generalize rules but are inflexible when rules change, reflecting reduced responsiveness to negative feedback and difficulty in switching attention. Rule-reversal is a promising target for translational studies, because it is specific, clinically relevant, and might reflect orbitofrontal dysfunction. Set-shifting is related to poor function more generally but might be sensitive to medication effects and valuable for clinical trials.

Relationship between exploratory eye movement, P300, and reaction time in schizophrenia

Exploratory eye movement (EEM), P300 and reaction time (RT) tests may relate to the important parts of information processing in the human brain. Therefore the aim of the present study was to compare EEM, P300 and RT test data in schizophrenic and normal control groups to investigate whether schizophrenic patients have information processing abnormalities. In addition, the potential correspondence between the three tests was examined in order to investigate the information processing dysfunctions seen in schizophrenic patients. The EEM, P300 and RT performances were recorded in 34 schizophrenic and 36 normal control subjects. Ten parameters were measured: four from the EEM test (number of eye fixations, total eye scanning length, cognitive search score and responsive search score [RSS]); two from the P300 test (amplitude and latency); and four from the RT test (simple reaction time, index of reaction time crossover [IRT-crossover], set index and coefficient of variation). These parameters in the schizophrenic patients differed significantly from those in the control group. Additionally, there was a significant correlation between the RSS and the IRT-crossover in the schizophrenic patients. The present group comparisons (schizophrenia vs normal controls) are consistent with previous studies in that the abnormalities in EEM, P300 and RT tests in schizophrenic patients were able to be replicated. Moreover, based on the former psychological theory, it is reasonable to propose that the RSS is associated with the IRT-crossover. The present results may contribute to elucidation of the pathophysiological signature of schizophrenia.

Treating early and treating well: the importance of restoring global functioning for the brains of schizophrenia patients

Brain imaging studies have consistently demonstrated brain abnormalities in patients with schizophrenia. These changes are largely confined to decreases in gray matter volumes and enlargement of the lateral and third ventricles. To date schizophrenia has been considered to result from abnormalities in neurodevelopment, with brain changes to be static. However, schizophrenia has long been thought to be a progressive or a degenerative, not a developmental, disorder. Indeed, Kraepelin considered the progressive clinical deterioration to be the hallmark of the disorder, naming it dementia praecox to reflect this particular aspect. Lately, others have re-emphasised the importance of the decline in functioning in schizophrenia as a clue to its pathogenesis, suggesting that the brain abnormalities in schizophrenia could be expected to reflect this clinical progression. Indeed, we and others [1,2] have reported brain abnormalities to increase over time in schizophrenia. Interestingly, not all patients show changes in brain volumes over time: we demonstrated that the changes are particularly pronounced in those patients with a poor prognosis in the first years of illness. Moreover progressive changes are most pronounced in the frontal and temporal areas as postulated by Kraepelin over a hundred years ago. Interestingly, white matter did not change over time. Finally, the progression in these frontal brain changes appeared to be attenuated by treatment with atypical, but not by typical antipsychotics. Thus, not only are brain changes progressive in schizophrenia, they are clinically relevant since they are related to outcome and my be reversed by some of the atypical antipsychotics. With the evidence pointing to a link between progressive disease and patient outcomes, questions such as whether these changes can be reversed with early pharmacological intervention and whether there is a point at which the brain changes become irreversible, become pertinent.

Excessive Brain Volume Loss Over Time in Cannabis-Using First-Episode Schizophrenia Patients

Cerebral gray matter volume reductions have been found to progress over time in schizophrenia, with larger decreases related to poorer outcome, which has also been associated with cannabis use in schizophrenia patients. Progressive gray matter changes in patients who use cannabis may be more extensive than in those who do not. Patients with recent-onset schizophrenia (N=51) and matched healthy subjects (N=31) were included. For all subjects, magnetic resonance imaging scans were obtained at inclusion (T0) and at 5-year follow-up (T5). Nineteen patients used cannabis but no other illicit drugs; 32 patients did not use any drugs during the 5-year follow-up. At T5, clinical outcome was measured. Cumulative amount of antipsychotic medication during the interval was calculated. At T0 and T5, total brain, gray and white matter, and lateral and third ventricle volumes were measured. Univariate analysis of covariance and pairwise comparisons were performed. Schizophrenia patients showed a larger gray matter volume decrease over time than healthy subjects. They also showed larger increases in lateral and third ventricle volumes than healthy subjects and patients who did not use cannabis during follow-up. This decrement was significantly more pronounced in the patients who continued to use cannabis. These differences could not be attributed to outcome or baseline characteristics. First-episode schizophrenia patients who use cannabis show a more pronounced brain volume reduction over a 5-year follow-up than patients with schizophrenia who do not use cannabis. These results may help explain some of the detrimental effects of cannabis use in schizophrenia.

Temporal processing dysfunction in schizophrenia

Schizophrenia may be associated with a fundamental disturbance in the temporal coordination of information processing in the brain, leading to classic symptoms of schizophrenia such as thought disorder and disorganized and contextually inappropriate behavior. Despite the growing interest and centrality of time-dependent conceptualizations of the pathophysiology of schizophrenia, there remains a paucity of research directly examining overt timing performance in the disorder. Accordingly, the present study investigated timing in schizophrenia using a well-established task of time perception. Twenty-three individuals with schizophrenia and 22 non-psychiatric control participants completed a temporal bisection task, which required participants to make temporal judgments about auditory and visually presented durations ranging from 300 to 600 ms. Both schizophrenia and control groups displayed greater visual compared to auditory timing variability, with no difference between groups in the visual modality. However, individuals with schizophrenia exhibited less temporal precision than controls in the perception of auditory durations. These findings correlated with parameter estimates obtained from a quantitative model of time estimation, and provide evidence of a fundamental deficit in temporal auditory precision in schizophrenia.

Semantic priming in schizophrenia: Systematic review and meta-analysis

Increased semantic priming is an influential theory of thought disorder in schizophrenia. However, studies to date have had conflicting findings. To investigate semantic memory in patients with schizophrenia with and without thought disorder. Data were pooled from 36 studies comparing patients with schizophrenia and normal controls in semantic priming tasks. Data from 18 studies comparing patients with thought disorder with normal controls, and 13 studies comparing patients with and without thought disorder were also pooled. There was no support for altered semantic priming in schizophrenia as a whole. Increased semantic priming in patients with thought disorder was supported, but this was significant only in comparison with normal controls and not in comparison with patients without thought disorder. Stimulus onset asynchrony (SOA) and general slowing of reaction time moderated the effect size for priming in patients with thought disorder. Meta-analysis provides qualified support for increased semantic priming as a psychological abnormality underlying thought disorder. However, the possibility that the effect is an artefact of general slowing of reaction time in schizophrenia has not been excluded.

Dendritic distributions of dopamine D1 receptors in the rat nucleus accumbens are synergistically affected by startle-evoking auditory stimulation and apomorphine

Prepulse inhibition of the startle response to auditory stimulation (AS) is a measure of sensorimotor gating that is disrupted by the dopamine D1/D2 receptor agonist, apomorphine. The apomorphine effect on prepulse inhibition is ascribed in part to altered synaptic transmission in the limbic-associated shell and motor-associated core subregions of the nucleus accumbens (Acb). We used electron microscopic immunolabeling of dopamine D1 receptors (D1Rs) in the Acb shell and core to test the hypothesis that region-specific redistribution of D1Rs is a short-term consequence of AS and/or apomorphine administration. Thus, comparisons were made in the Acb of rats killed 1 h after receiving a single s.c. injection of vehicle (VEH) or apomorphine (APO) alone or in combination with startle-evoking AS (VEH+AS, APO+AS). In both regions of all animals, the D1R immunoreactivity was present in somata and large, as well as small, presumably more distal dendrites and dendritic spines. In the Acb shell, compared with the VEH+AS group, the APO+AS group had more spines containing D1R immunogold particles, and these particles were more prevalent on the plasma membranes. This suggests movement of D1Rs from distal dendrites to the plasma membrane of dendritic spines. Small- and medium-sized dendrites also showed a higher plasmalemmal density of D1R in the Acb shell of the APO+AS group compared with the APO group. In the Acb core, the APO+AS group had a higher plasmalemmal density of D1R in medium-sized dendrites compared with the APO or VEH+AS group. Also in the Acb core, D1R-labeled dendrites were significantly smaller in the VEH+AS group compared with all other groups. These results suggest that alerting stimuli and apomorphine synergistically affect distributions of D1R in Acb shell and core. Thus adaptations in D1R distribution may contribute to sensorimotor gating deficits that can be induced acutely by apomorphine or develop over time in schizophrenia.

Estimating transitions between symptom severity states over time in schizophrenia: a Bayesian meta-analytic approach

We obtain the posterior predictive distribution of transition probabilities between symptom severity states over time for patients with schizophrenia by (i) employing a Bayesian meta-analysis of published clinical trials and observational studies to estimate the posterior distribution of parameters that guide changes in Positive and Negative Syndrome Scale (PANSS) scores over time and under the influence of various drugs and (ii) by propagating the variability from the posterior distributions of the parameters through a micro-simulation model that is formulated based on schizophrenia progression. Results show detailed differences among haloperidol, risperidone and olanzapine in controlling various levels of severities of positive, negative and joint symptoms over time. For example, risperidone seems best in controlling severe positive symptoms while olanzapine is the worst in that during the first quarter of drug treatment; however, olanzapine seems to be best in controlling severe negative symptoms across all four quarters of treatment while haloperidol is the worst in this regard. These details may further serve to better estimate quality of life of patients and aid in resource utilization decisions in treating schizophrenic patients. In addition, consistent estimation of uncertainty in the time-profile parameters also has important implications for the practice of cost-effectiveness analysis and for future resource allocation policies in schizophrenia treatment.

Relationship of impaired processing speed and flexibility of abstract thought to improvements in work performance over time in schizophrenia

Vocational impairments in schizophrenia have been widely linked to deficits in neurocognition. This study examined the possibility that deficits in visuomotor processing speed and flexibility in abstract thought may in combination be an especially potent risk factor for poorer levels of work performance in rehabilitation. Fifty-seven participants with confirmed diagnoses of schizophrenia spectrum disorders were administered the Digit Symbol Subtest and the Wisconsin Card Sorting Test and then offered work placements in a vocational rehabilitation program. Work performance was assessed biweekly over two months using the Work Behavior Inventory. Multivariate and univariate repeated ANOVA revealed that participants classified as having no impairments in either visuomotor processing speed and flexibility in abstract thought ( n=14) had superior work performance compared to participants with deficits in either one area ( n=20) or both areas ( n=23). Additionally, participants with no impairments were the only group to show significant improvement in work performance over 7 weeks of rehabilitation. Participants with only one deficit had significantly better work performance than participants with both deficits but showed no statistically significant improvement in work performance. Results suggest assessments of these domains of neurocognition may provide important information about individual needs for adjunct services.