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To clarify, in a national sample, associations between risk for seven psychiatric and substance use disorders and five key transitions in Sweden's public educational system.
Methods
Swedish-born individuals (1972–1995, N = 1 997 910) were followed through 12-31-2018, at mean age 34.9. We predicted, from these educational transitions, risk for major depression (MD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), anorexia nervosa (AN), alcohol use disorder (AUD), and drug use disorder (DUD), assessed from Swedish national registers, by Cox regression, censoring individuals with onsets ⩽17. We also predicted risk from the deviation of grades from family-genetic expectations (deviation 1) and from changes in grades from ages 16 to 19 (deviation 2).
Results
We observed four major risk patterns across transitions in our disorders: (i) MD and BD, (ii) OCD and SZ, (iii) AUD and DUD, and (iv) AN. Failing early educational transitions had the greatest impact on risk for OCD and SZ while for other disorders, not progressing from basic to upper high school had the largest effect. Completing vocational v. college-prep upper high school was strongly associated with risk for AUD and DUD, had little relation with MD, OCD, BD, and SZ risk, and was protective for AN. Deviation 1 predicted risk most strongly for SZ, AN, and MD. Deviation 2 predicted risk most strongly for SZ, AUD, and DUD.
Conclusions
The pattern of educational transitions and within family and within person development deviations are strongly and relatively specifically associated with future risk for seven psychiatric and substance-use disorders.
Earlier studies examining structural brain abnormalities associated with cognitively derived subgroups were mainly cross-sectional in design and had mixed findings. Thus, we obtained cross-sectional and longitudinal data to characterize the extent and trajectory of brain structure abnormalities underlying distinct cognitive subtypes (“preserved,” “deteriorated,” and “compromised”) seen in psychotic spectrum disorders.
Methods.
Data from 364 subjects (225 patients with psychotic conditions and 139 healthy controls) were first used to determine the relationship of cognitive subtypes with cross-sectional measures of subcortical volume and cortical thickness. To probe neurodevelopmental abnormalities, brain structure laterality was examined. To examine whether neuroprogressive abnormalities persist, longitudinal brain structural changes over 5 years were examined within a subset of 101 subjects. Subsequent discriminant analysis using the identified brain measures was performed on an independent subject group.
Results.
Cross-sectional comparisons showed that cortical thinning and limbic volume reductions were most widespread in “deteriorated” cognitive subtype. Laterality comparisons showed more rightward amygdala lateralization in “compromised” than “preserved” subtype. Longitudinal comparisons revealed progressive hippocampal shrinkage in “deteriorated” compared with healthy controls and “preserved” subtype, which correlated with worse negative symptoms, cognitive and psychosocial functioning. Post-hoc discrimination analysis on an independent group of 52 subjects using the identified brain structures found an overall accuracy of 71% for classification of cognitive subtypes.
Conclusion.
These findings point toward distinct extent and trajectory of corticolimbic abnormalities associated with cognitive subtypes in psychosis, which can allow further understanding of the biological course of cognitive functioning over illness course and with treatment.
Cognitive impairment is considered a central feature of schizophrenia. Many aspects of cognition are impaired in schizophrenia. Careful evaluation of the relationship between cognitive impairment and the other symptoms of schizophrenia has revealed several important findings. In this article, we discuss these findings, the effects of typical neuroleptic therapy on cognitive impairment, and important issues to address in cognitive enhancement studies in schizophrenia.
The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project identified tests that measure cognition in clinical trials and outlined clinical trial designs believed to best test the treatment effects of a compound on cognition in patients with schizophrenia. The MATRICS project focused primarily on later-phase trials that would satisfy regulatory requirements for product registration and deriving a cognitive test battery that could be used to measure treatment effects consistently across clinical studies. Cognitive neuroscience tasks are developed in individual laboratories, their methods allow great attention to detail and essentially no need for clear communication of assessment procedures to other investigators. The Schizophrenia Cognition Rating Scale (SCoRS) is a 20-item interview-based assessment covering all seven cognitive domains tested in the MATRICS battery. The advantages of computerized test batteries allow standardized stimulus presentation and scoring, response measures of response latencies, and immediate direct data transfer to study databases.
CNS drug development is rapidly evolving to meet the unique and changing demands of the fields of psychiatry and neurology. Phase I studies are traditionally focused on determining the safety, tolerability, and pharmacokinetics of a new molecular entity in young healthy volunteers: first in a single ascending dose (SAD) study and then in a multiple ascending dose (MAD) study. The use of an adaptive design to examine data and modify the study in real time may also promote time- and cost-efficient identification of novel molecular entities (NMEs) that have the characteristics necessary to be successful in confirm stages of drug development research. This chapter discusses how use of biomarkers as surrogate endpoints can be incorporated into early clinical trials to determine if a drug modulates the appropriate targets, which enhances the likelihood of demonstrating efficacy in the confirm phase of clinical testing.
The finding that women are attracted to men older than themselves whereas men are attracted to relatively younger women has been explained by social psychologists in terms of economic exchange rooted in traditional sex-role norms. An alternative evolutionary model suggests that males and females follow different reproductive strategies, and predicts a more complex relationship between gender and age preferences. In particular, males' preferences for relatively younger females should be minimal during early mating years, but should become more pronounced as the male gets older. Young females are expected to prefer somewhat older males during their early years and to change less as they age. We briefly review relevant theory and present results of six studies testing this prediction. Study 1 finds support for this gender-differentiated prediction in age preferences expressed in personal advertisements. Study 2 supports the prediction with marriage statistics from two U.S. cities. Study 3 examines the cross-generational robustness of the phenomenon, and finds the same pattern in marriage statistics from 1923. Study 4 replicates Study 1 using matrimonial advertisements from two European countries, and from India. Study 5 finds a consistent pattern in marriages recorded from 1913 through 1939 on a small island in the Philippines. Study 6 reveals the same pattern in singles advertisements placed by financially successful American women and men. We consider the limitations of previous normative and evolutionary explanations of age preferences and discuss the advantages of expanding previous models to include the life history perspective.
This chapter describes the cognitive findings from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project, including analyses of the baseline cognitive assessments in 1,331 patients, one of the largest schizophrenia cohorts to be studied with neuropsychological measures, and the effects of treatment on these measures in over 800 patients randomized to five different antipsychotic treatments. The choice of tests for a neurocognitive battery is often controversial. Since the CATIE project promised to yield a rich database, it is important that the batteries of tests chosen for the project receive consensus approval from the leaders in schizophrenia and dementia research. The aim of the CATIE Neurocognitive Assessment Unit training program is for testers and investigators to achieve thorough understanding of the rationale and methods of the neurocognitive assessment protocol, and considerable preparation preceded the production of manuals and training materials.
Since 1998, Dow has been actively developing and applying high throughput research (HTR) methodologies to increase the speed to market and the probability of successful product introductions. Initially Dow implemented this approach in the area of homogeneous catalysis. Based upon the success in this area, high throughput methods have been expanded into other research areas such as waterborne coatings. Paint formulations offer an excellent opportunity to use the strengths of high throughput research to understand how complex interactions between many components affect final properties. High throughput tools enable the rapid and reproducible development of paints, preparation of coating on substrates, and evaluation of performance. Rapid formulation and testing allows the interactions between formulation variables to be investigated in much more depth and breadth than has been possible in the past. Finally, statistical anaylsis and data mining tools can be used to optimize a desired balance of properties within customer defined constraints. This paper presents an example of using Dow's HTR coatings workflow to improve properties for low VOC / low odor architectural coatings.
There are claims that second-generation antipsychotics produce fewer
extrapyramidal side-effects (EPS) compared with first-generation
drugs.
Aims
To compare the incidence of treatment-emergent EPS between
second-generation antipsychotics and perphenazine in people with
schizophrenia.
Method
Incidence analyses integrated data from standardised rating scales and
documented use of concomitant medication or treatment discontinuation for
EPS events. Mixed model analyses of change in rating scales from baseline
were also conducted.
Results
There were no significant differences in incidence or change in rating
scales for parkinsonism, dystonia, akathisia or tardive dyskinesia when
comparing second-generation antipsychotics with perphenazine or comparing
between second-generation antipsychotics. Secondary analyses revealed
greater rates of concomitant antiparkinsonism medication among
individuals on risperidone and lower rates among individuals on
quetiapine, and lower rates of discontinuation because of parkinsonism
among people on quetiapine and ziprasidone. There was a trend for a
greater likelihood of concomitant medication for akathisia among
individuals on risperidone and perphenazine.
Conclusions
The incidence of treatment-emergent EPS and change in EPS ratings
indicated that there are no significant differences between
second-generation antipsychotics and perphenazine or between
second-generation antipsychotics in people with schizophrenia.
Efficient and reliable assessments of cognitive treatment effects are essential for the comparative evaluation of procognitive effects of pharmacologic therapies. Yet, no studies have addressed the sensitivity and efficiency with which neurocognitive batteries evaluate cognitive abilities before and after treatment. Participants were primarily first episode schizophrenia patients who completed baseline (n = 367) and 12-week (n = 219) assessments with the BACS (Brief Assessment of Cognition in Schizophrenia) and CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) neuropsychological batteries in a clinical trial comparing olanzapine, quetiapine, and risperidone. Exploratory factor analysis revealed that performance on both batteries was characterized by a single factor of generalized cognitive deficit for both baseline performance and cognitive change after treatment. Both batteries estimated similar levels of change following treatment, although the BACS battery required half the administration time. Because a unitary factor characterized baseline cognitive abilities in early psychosis as well as cognitive change after treatment with atypical antipsychotic medications, short batteries such as the BACS may efficiently provide sufficient assessment of procognitive treatment effects with antipsychotic medications. Assessment of cognitive effects of adjunctive therapies targeting specific cognitive domains or impairments may require more extensive testing of the domains targeted to maximize sensitivity for detecting specific predicted cognitive outcomes. (JINS, 2008, 14, 209–221.)Presented in part at the annual International Neuropsychology Society meeting in Portland, OR, February 2007; and the 2007 International Congress for Schizophrenia Research in Colorado Springs, CO.