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Studies that examined sex differences in first-episode patients consistently show that males compared to females have poor premorbid adjustment, earlier age of onset, worse clinical characteristics, and poorer outcomes. However, little is known about potential mediators that could explain these sex differences.
Our sample consisted of 137 individuals with first episode schizophrenia (males, n = 105; 77%) with a mean age of 22.1(s.d. = 4.1) years and mean education of 12.5(s.d. = 1.7) years. At entry, patients were within 2 years of their first psychotic episode onset. Baseline assessments were conducted for premorbid adjustment, symptoms, cognitive functioning, insight, and at 6-months for role and social functioning.
Males as compared to females had poorer premorbid adjustment across several key developmental periods (p < 0.01), an earlier age of onset [M = 20.3(3.3) v. 22.8(5.6), p = 0.002], more negative symptoms (p = 0.044), poorer insight (p = 0.031), and poorer baseline and 6-month role (p = 0.002) and social functioning (p = 0.034). Several of these variables in which males showed impairment were significant predictors of 6-month role and social functioning. Premorbid adjustment and insight mediated the relationship between sex and role and social functioning at 6-months, but not negative symptoms.
Males compared to females were at lower levels across several key premorbid and clinical domains which are strongly associated with functional outcome supporting the hypothesis that males might have a more disabling form of schizophrenia. The relationship between sex with role and social functioning was mediated through premorbid adjustment and insight suggesting pathways for understanding why females might have a less disabling form of schizophrenia.
Cognitive development after schizophrenia onset can be shaped by interventions such as cognitive remediation, yet no study to date has investigated whether patterns of early behavioral development may predict later cognitive changes following intervention. We therefore investigated the extent to which premorbid adjustment trajectories predict cognitive remediation gains in schizophrenia.
In a total sample of 215 participants (170 first-episode schizophrenia participants and 45 controls), we classified premorbid functioning trajectories from childhood through late adolescence using the Cannon-Spoor Premorbid Adjustment Scale. For the 62 schizophrenia participants who underwent 6 months of computer-assisted, bottom-up cognitive remediation interventions, we identified MATRICS Consensus Cognitive Battery scores for which participants demonstrated mean changes after intervention, then evaluated whether developmental trajectories predicted these changes.
Growth mixture models supported three premorbid functioning trajectories: stable-good, deteriorating, and stable-poor adjustment. Schizophrenia participants demonstrated significant cognitive remediation gains in processing speed, verbal learning, and overall cognition. Notably, participants with stable-poor trajectories demonstrated significantly greater improvements in processing speed compared to participants with deteriorating trajectories.
This is the first study to our knowledge to characterize the associations between premorbid functioning trajectories and cognitive remediation gains after schizophrenia onset, indicating that 6 months of bottom-up cognitive remediation appears to be sufficient to yield a full standard deviation gain in processing speed for individuals with early, enduring functioning difficulties. Our findings highlight the connection between trajectories of premorbid and postmorbid functioning in schizophrenia and emphasize the utility of considering the lifespan developmental course in personalizing therapeutic interventions.
Cognitive training (CT) and aerobic exercise both show promising moderate impact on cognition and everyday functioning in schizophrenia. Aerobic exercise is hypothesized to increase brain-derived neurotrophic factor (BDNF) and thereby synaptic plasticity, leading to increased learning capacity. Systematic CT should take advantage of increased learning capacity and be more effective when combined with aerobic exercise.
We examined the impact of a 6-month program of cognitive training & exercise (CT&E) compared to cognitive training alone (CT) in 47 first-episode schizophrenia outpatients. All participants were provided the same Posit Science computerized CT, 4 h/week, using BrainHQ and SocialVille programs. The CT&E group also participated in total body circuit training exercises to enhance aerobic conditioning. Clinic and home-based exercise were combined for a target of 150 min per week.
The MATRICS Consensus Cognitive Battery Overall Composite improved significantly more with CT&E than with CT alone (p = 0.04), particularly in the first 3 months (6.5 v. 2.2 T-score points, p < 0.02). Work/school functioning improved substantially more with CT&E than with CT alone by 6 months (p < 0.001). BDNF gain tended to predict the amount of cognitive gain but did not reach significance. The cognitive gain by 3 months predicted the amount of work/school functioning improvement at 6 months. The amount of exercise completed was strongly associated with the degree of cognitive and work/school functioning improvement.
Aerobic exercise significantly enhances the impact of CT on cognition and functional outcome in first-episode schizophrenia, apparently driven by the amount of exercise completed.
Patients with schizophrenia spectrum disorders have been increasingly recognised to form cognitive subgroups with differential levels of impairment. Using cluster analytical techniques, this study sought to identify cognitive clusters in a sample of first-episode psychosis (FEP) patients and examine clinical and developmental differences across the resultant groups.
In total, 105 FEP patients in the University of California Los Angeles Aftercare Research Program were assessed for cognition, symptoms and premorbid developmental adjustment. Hierarchical cluster analysis with Ward's method and squared Euclidean distance was conducted, confirmed by discriminant function analysis and optimised with k-means clustering. The stability of the solution was evaluated through split-sample (random, 80 and 70% samples) and alternate method (average linkage method) replication via Cohen's κ analysis. Controlling for multiple comparisons, one-way analysis of variances examined group differences in symptom severity and premorbid adjustment.
Three groups were identified: severely impaired (n = 27), moderately impaired (n = 41) and relatively intact (n = 37). There were no significant differences in symptom severity across the groups. Significant differences were observed for scholastic performance at three different developmental stages: childhood, early adolescence and late adolescence, with the relatively intact group demonstrating significantly better scholastic performance at all three stages than both the moderately impaired and severely impaired groups (who did not significantly differ from each other).
The findings add to growing evidence that cognitive clusters in FEP mirror that of later-stage schizophrenia. They also suggest that premorbid scholastic performance may not just be a risk factor for developing schizophrenia, but is also related to cognitive impairment severity and potentially to prognosis.
Cognitive deficits at the first episode of schizophrenia are predictive of functional outcome. Interventions that improve cognitive functioning early in schizophrenia are critical if we hope to prevent or limit long-term disability in this disorder.
We completed a 12-month randomized controlled trial of cognitive remediation and of long-acting injectable (LAI) risperidone with 60 patients with a recent first episode of schizophrenia. Cognitive remediation involved programs focused on basic cognitive processes as well as more complex, life-like situations. Healthy behavior training of equal treatment time was the comparison group for cognitive remediation, while oral risperidone was the comparator for LAI risperidone in a 2 × 2 design. All patients were provided supported employment/education to encourage return to work or school.
Both antipsychotic medication adherence and cognitive remediation contributed to cognitive improvement. Cognitive remediation was superior to healthy behavior training in the LAI medication condition but not the oral medication condition. Cognitive remediation was also superior when medication adherence and protocol completion were covaried. Both LAI antipsychotic medication and cognitive remediation led to significantly greater improvement in work/school functioning. Effect sizes were larger than in most prior studies of first-episode patients. In addition, cognitive improvement was significantly correlated with work/school functional improvement.
These results indicate that consistent antipsychotic medication adherence and cognitive remediation can significantly improve core cognitive deficits in the initial period of schizophrenia. When combined with supported employment/education, cognitive remediation and LAI antipsychotic medication show separate significant impact on improving work/school functioning.
This study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling.
Individual Placement and Support (IPS) was adapted to meet the goals of individuals whose goals might involve either employment or schooling. IPS was combined with a Workplace Fundamentals Module (WFM) for an enhanced, outpatient, vocational intervention. Random assignment to the enhanced integrated rehabilitation program (N = 46) was contrasted with equally intensive clinical treatment at UCLA, including social skills training groups, and conventional vocational rehabilitation by state agencies (N = 23). All patients were provided case management and psychiatric services by the same clinical team and received oral atypical antipsychotic medication.
The IPS–WFM combination led to 83% of patients participating in competitive employment or school in the first 6 months of intensive treatment, compared with 41% in the comparison group (p < 0.005). During the subsequent year, IPS–WFM continued to yield higher rates of schooling/employment (92% v. 60%, p < 0.03). Cumulative number of weeks of schooling and/or employment was also substantially greater with the IPS–WFM intervention (45 v. 26 weeks, p < 0.004).
The results clearly support the efficacy of an enhanced intervention focused on recovery of participation in normative work and school settings in the initial phase of schizophrenia, suggesting potential for prevention of disability.
Our objective in the present study was to conduct the first empirical study of the effects of regular physical activity habits and their relationship with brain volume and cortical thickness in patients in the early phase of schizophrenia. Relationships between larger brain volumes and higher physical activity levels have been reported in samples of healthy and aging populations, but have never been explored in first-episode schizophrenia patients. Method: We collected MRI structural scans in 14 first-episode schizophrenia patients with either self-reported low or high physical activity levels. We found a reduction in total gray matter volume, prefrontal cortex (PFC), and hippocampal gray matter volumes in the low physical activity group compared to the high activity group. Cortical thickness in the dorsolateral and orbitofrontal PFC were also significantly reduced in the low physical activity group compared to the high activity group. In the combined sample, greater overall physical activity levels showed a non-significant tendency with better performance on tests of verbal memory and social cognition. Together these pilot study findings suggest that greater amounts of physical activity may have a positive influence on brain health and cognition in first-episode schizophrenia patients and support the implementation of physical exercise interventions in this patient population to improve brain plasticity and cognitive functioning. (JINS, 2015, 21, 868–879)
In experiments of hot surface ignition and subsequent flame propagation, a puffing flame instability is observed in mixtures that are stagnant and premixed prior to ignition. By varying the size of the hot surface, power input, and combustion vessel volume, it was determined that the instability is a function of the interaction of the flame, with the fluid flow induced by the combustion products rather than the initial plume established by the hot surface. Pressure ranges from 25 to 100 kPa and mixtures of n-hexane/air with equivalence ratios between $\phi = 0. 58$ and 3.0 at room temperature were investigated. Equivalence ratios between $\phi = 2. 15$ and 2.5 exhibited multiple flame and equivalence ratios above $\phi = 2. 5$ resulted in puffing flames at atmospheric pressure. The phenomenon is accurately reproduced in numerical simulations and a detailed flow field analysis revealed competition between the inflow velocity at the base of the flame and the flame propagation speed. The increasing inflow velocity, which exceeds the flame propagation speed, is ultimately responsible for creating a puff. The puff is then accelerated upward, allowing for the creation of the subsequent instabilities. The frequency of the puff is proportional to the gravitational acceleration and inversely proportional to the flame speed. A scaling relationship describes the dependence of the frequency on gravitational acceleration, hot surface diameter, and flame speed. This relation shows good agreement for rich n-hexane/air and lean hydrogen/air flames, as well as lean hexane/hydrogen/air mixtures.
Cognitive deficits in schizophrenia are increasingly accepted as core features of this disorder that play a role as vulnerability indicators, as enduring abnormalities during clinical remission, and as critical rate-limiting factors in functional recovery. This article demonstrates the lasting influence of Norman Garmezy through his impact on one graduate student and then through his later collaborative research with colleagues. The promise of core cognitive deficits as vulnerability indicators or endophenotypes was demonstrated in research with children born to a parent with schizophrenia as well as with biological parents and siblings of individuals with schizophrenia. In studies of patients with a recent onset of schizophrenia, cognitive deficits were found to endure across psychotic and clinically remitted periods and to have a strong predictive influence on likelihood of returning successfully to work or school. Converging lines of evidence for the enduring core role of cognitive deficit in schizophrenia have led in recent years to a burgeoning interest in developing new interventions that target cognition as a means of improving functional recovery in this disorder.
Background. While several personality characteristics are implicated in the etiology and phenotypic expression of schizophrenia, little is known about their trait status or clinical correlates during the early course of this disorder.
Method. The stability of five personality characteristics derived from the MMPI-168 was examined in recent-onset schizophrenia patients (n=59) during a psychotic period at study entry and at two out-patient assessments over the following 15 months and in non-patient controls (n=39) at similar time intervals. Among patients, associations between personality characteristics and clinical symptoms and exposure to stressful life events during the study period were also examined.
Results. Multilevel modeling analyses indicated that the between-subjects or trait-like variance components for these characteristics among patients were substantial, albeit smaller than those found for controls. Patients reported higher mean levels of Neuroticism, Cynicism, and Psychotic Ideation and lower mean levels of Psychopathic Tendencies and Denial of Somatic Complaints than controls. Among patients, several personality characteristics were systematically related to mean clinical symptom levels as well as frequency of exposure to dependent, but not independent, life events.
Conclusions. Stable individual differences in personality are detectable during the early course of schizophrenia and may help account for heterogeneity in clinical symptoms and functional outcome.
Background. Evidence has mounted that some patients with schizophrenia experience remission of symptoms and restoration of social and vocational functioning. The purpose of this study was to identify neurocognitive variables associated with recovery from schizophrenia.
Method. Twenty-eight patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder and who met our operational definition of recovery from schizophrenia underwent a battery of neurocognitive tests. These subjects were matched with schizophrenia patients who did not meet recovery criteria (‘non-recovered’) and with normal controls.
Results. On tests of executive functioning, verbal fluency and verbal working memory, recovered subjects performed significantly better than non-recovered subjects and were comparable to normal controls. Patient groups did not differ on a test that assessed early visual processing, but both groups performed significantly worse than normal controls.
Conclusions. Three measures of frontal lobe functioning appear to be neurocognitive domains associated with recovery from schizophrenia. These findings help narrow the search for targets for cognitive remediation that may have implications for improving community functioning.
Test–retest stability of electrodermal (EDA) variables
indexing both general autonomic arousal (e.g., skin conductance
level, number of nonspecific skin conductance responses) and
attention to external stimuli (e.g., number of skin conductance
orienting responses, electrodermal responder/nonresponder status)
was assessed in 71 young, recent-onset schizophrenia patients
and 36 demographically matched normal subjects. Significant
stability over a 1-year period was found for both patients and
normal subjects for most EDA variables and for
responder/nonresponder status, with test–retest correlations
generally being higher for normal subjects. The lower reliability
for patients was not attributable to symptomatic fluctuations
during the follow-up period and may reflect poorer arousal
regulation among the patients. Among measures of responding
to nontask stimuli, a simple count of the number of orienting
responses occurring was more stable than was a traditional
Research with schizophrenic out-patients has shown that antipsychotic medication reduces relapse rates. This protective factor may operate partially by raising the threshold for relapse in the face of environmental stressors such as life events and high levels of familial expressed emotion. A prospective, longitudinal design was employed in the monthly collection of life-events data with 23 recent-onset schizophrenic out-patients. In a between-subjects ANOVA, a significantly higher frequency of independent life events was found in the month prior to a relapse for ten patients on medication, as compared with the analogous month for 13 drug-free patients. These findings suggest that neuroleptic medication may produce a prophylactic effect by raising a patient's threshold of vulnerability to relapse.
The general view that relationships between factors within the patient and those in the environment are important in understanding schizophrenia has been widely accepted and is the basis for vulnerability/stress models of this disorder. However, the specifics of the patient-environment relationships that may be critical for schizophrenia continue to be largely a mystery. At the UCLA Clinical Research Center for the Study of Schizophrenia, we have developed a tentative working model of schizophrenic episodes that emphasises the mediating role of information-processing and autonomic abnormalities in the patient in interaction with stressful circumstances and protective factors in the patient's environment (Nuechterlein & Dawson, 1984a; Liberman, 1986; Dawson & Nuechterlein, 1987; Nuechterlein, 1987). Here we examine two examples of patient-environment relationships that may increase our understanding of such processes in schizophrenia.
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