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The effects of long-term antipsychotic medication on cognition in schizophrenia are unclear (Husa A.P. et al., Schizophr. Res. 2014).
Understanding how long-term antipsychotic treatment affects cognition is crucial for the development of safe, evidence-based treatment of schizophrenia.
To analyse the association between cumulative lifetime antipsychotic dose and cognition in schizophrenia at age 43 years in a general population sample.
Sixty (33 males) schizophrenia spectrum subjects from the Northern Finland Birth Cohort 1966 were assessed at age 43 years by California Verbal Learning Test, Visual Object Learning Test, Abstraction Inhibition and Working Memory task, Verbal fluency, Visual series, Vocabulary, Digit Span and Matrix reasoning. Cumulative lifetime antipsychotic dose-years were collected from treatment records and interviews. A factor analysis based on the cognitive tests resulted in one cognitive factor. The association between this cognitive composite score and antipsychotic dose-years was analysed by linear regression.
Higher lifetime antipsychotic dose-years were statistically significantly associated with poorer cognitive composite score at age 43 years (B=-0.32, p>0.001), also when adjusted for gender, onset age, remission and number of hospital treatment days (B=-0.42, p=0.008).
To our knowledge, this is the first report of an association between cumulative lifetime antipsychotic dose and cognition in midlife in schizophrenia. Based on this data, the use of high antipsychotic doses may relate to poorer cognitive functioning in schizophrenia after twenty years of illness. These results do not support the view that antipsychotics prevent cognitive decline or promote cognitive recovery in schizophrenia.
Cognitive deficits, such as verbal memory dysfunction, are a core feature of schizophrenia. Yet the longitudinal course and associations of cognitive deficits with antipsychotic medication remain unclear.
Our aim was to analyze how lifetime antipsychotic dosage associates with the change of verbal learning and memory in individuals with schizophrenia during a 9-year follow-up.
Forty-two subjects with schizophrenic psychoses (22 males) from the Northern Finland 1966 Birth Cohort went through diagnostic interviews and cognitive assessment including California Verbal Learning Test (CVLT) at the ages of 34 and 43 years. Data of the subjects’ lifetime antipsychotic doses in chlorpromazine equivalents were collected from patient history records, interviews and national registers. The association between verbal learning and memory (immediate free recall of trials 1-5 and free recall after long delay) and dose-years of antipsychotics was analyzed by logistic regression model.
Higher dose-years of any and typical antipsychotics, but not atypical antipsychotics, associated statistically significantly to worse verbal learning and memory in cross-sectional analyses at age 34 years, even when onset age, sex, and severity of symptoms were controlled for. However, there was no statistically significant association between lifetime antipsychotic use and verbal learning and memory change between ages 34 and 43 years.
High lifetime antipsychotic dose did not associate to decrease in verbal learning and memory in schizophrenia in 9 years of follow-up. To our knowledge, this is a first report on association between cumulative lifetime antipsychotic use and change in cognition in a long-term naturalistic follow-up.
Higher lifetime antipsychotic exposure has been associated with poorer cognition in schizophrenia. The cognitive effects of adjunctive psychiatric medications and lifetime trends of antipsychotic use remain largely unclear. We aimed to study how lifetime and current benzodiazepine and antidepressant medications, lifetime trends of antipsychotic use and antipsychotic polypharmacy are associated with cognitive performance in midlife schizophrenia.
Sixty participants with DSM-IV schizophrenia from the Northern Finland Birth Cohort 1966 were examined at 43 years of age with an extensive cognitive test battery. Cumulative lifetime and current use of psychiatric medications were collected from medical records and interviews. The associations between medication and principal component analysis-based cognitive composite score were analysed using linear regression.
Lifetime cumulative DDD years of benzodiazepine and antidepressant medications were not significantly associated with global cognition. Being without antipsychotic medication (for minimum 11 months) before the cognitive examination was associated with better cognitive performance (P = 0.007) and higher lifetime cumulative DDD years of antipsychotics with poorer cognition (P = 0.020), when adjusted for gender, onset age and lifetime hospital treatment days. Other lifetime trends of antipsychotic use, such as a long antipsychotic-free period earlier in the treatment history, and antipsychotic polypharmacy, were not significantly associated with cognition.
Based on these naturalistic data, low exposure to adjunctive benzodiazepine and antidepressant medications does not seem to affect cognition nor explain the possible negative effects of high dose long-term antipsychotic medication on cognition in schizophrenia.
Recurrent affective problems are predictive of cognitive impairment, but
the timing and directionality, and the nature of the cognitive
impairment, are unclear.
To test prospective associations between life-course affective symptoms
and cognitive function in late middle age.
A total of 1668 men and women were drawn from the Medical Research
Council National Survey of Health and Development (the British 1946 birth
cohort). Longitudinal affective symptoms spanning age 13–53 years served
as predictors; outcomes consisted of self-reported memory problems at
60–64 years and decline in memory and information processing from age 53
to 60–64 years.
Regression analyses revealed no clear pattern of association between
longitudinal affective symptoms and decline in cognitive test scores,
after adjusting for gender, childhood cognitive ability, education and
midlife socioeconomic status. In contrast, affective symptoms were
strongly, diffusely and independently associated with self-reported
Affective symptoms are more clearly associated with self-reported memory
problems in late midlife than with objectively measured cognitive
Large scale, international clinical trials are formidable challenges, but they are the most effective means of answering important clinical questions in a definitive, generalizable manner. They require adequate funding and must be rigorously conducted. Much can be gleaned from such studies, which address the important research questions and provide answers to related questions. Such trials are enormously rewarding and are worth the expense and effort.
The aim of this study was to estimate the amount of childhood hepatitis B virus transmission in children born in the UK, a very low-prevalence country, that is preventable only by universal hepatitis B immunization of infants. Oral fluid specimens were collected from schoolchildren aged 7–11 years in four inner city multi-ethnic areas and tested for the presence of antibody to hepatitis B core antigen (anti-HBc). Those found positive or indeterminate were followed up with testing on serum to confirm their hepatitis B status. The overall prevalence of anti-HBc in children was low [0·26%, 95% confidence interval (CI) 0·14–0·44]. The estimated average annual incidence of hepatitis B was estimated to be 29·26/100 000 children (95% CI 16·00–49·08). The total incidence that is preventable only by a universal infant immunization programme in the UK was estimated to be between 5·00 and 12·49/100 000. The study demonstrates that the extent of horizontal childhood hepatitis B virus transmission is low in children born in the UK and suggests that schools in the UK are an uncommon setting for the transmission of the virus. Targeted hepatitis B testing and immunization of migrants from intermediate- and high-prevalence countries is likely to be a more effective measure to reduce childhood transmission than a universal infant immunization programme.
Some personality characteristics have previously been associated with an increased risk for psychiatric disorder. Longitudinal studies are required in order to tease apart temporary (state) and enduring (trait) differences in personality among individuals with bipolar disorder (BD). This study aimed to determine whether there is a characteristic personality profile in BD, and whether associations between BD and personality are best explained by state or trait effects.
A total of 2247 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder study completed the NEO Five-Factor Inventory administered at study entry, and at 1 and 2 years.
Personality in BD was characterized by high neuroticism (N) and openness (O), and low agreeableness (A), conscientiousness (C) and extraversion (E). This profile was replicated in two independent samples, and openness was found to distinguish BD from major depressive disorder. Latent growth modeling demonstrated that manic symptoms were associated with increased E and decreased A, and depressed symptoms with higher N and lower E, A, C and O. During euthymic phases, high N and low E scores predicted a future depression-prone course.
While there are clear state effects of mood on self-reported personality, personality variables during euthymia predict future course of illness. Personality disturbances in extraversion, neuroticism and openness may be enduring characteristics of patients with BD.
We have demonstrated a uniform, robust interface for high-k deposition with significant improvements in device electrical performance compared to conventional surface preparation techniques. The interface was a thin thermal oxide that was grown and then etched back in a controlled manner to the desired thickness. Utilizing this approach, an equivalent oxide thickness (EOT) as low as 0.87 nm has been demonstrated on high-k gate stacks having improved electrical characteristics as compared to more conventionally prepared starting surfaces.
Several studies have indicated that additional genes in the major histocompatibility complex
(MHC) region, other than the class II genes HLA-DQB1 and -DRB1 (the IDDM1 locus), may
contribute to susceptibility and resistance to type 1 diabetes. The relative magnitude of these non-
DR/DQ effects is uncertain and their map location is unknown owing to the extraordinary linkage
disequilibrium that extends over the 3.5 Mb of the MHC. The homozygous parent test has been
proposed as a method for detection of additional risk factors conditional on HLA-DQB1 and -DRB1.
However, this method is inefficient since it uses only parents homozygous for the primary disease
locus, the DQB1-DRB1 haplotype. To overcome this limitation, Conditional ETDT was used in the
present report to test for association conditional on the DQB1-DRB1 haplotype, thereby allowing all
parents to be included in the analysis. First, we confirm in UK and Sardinian type 1 diabetic families
that allelic variation at HLA-DRB1 has a very significant effect on the association of DQB1 and vice
versa. The Conditional ETDT was then applied to the HLA TNF (tumour necrosis factor) region and
microsatellite marker D6S273 region, both of which have been reported to contribute to IDDM1
independent of the HLA-DQB1-DRB1 genes. We found no evidence for a major role for either of these
two regions in IDDM1.
Microwave remote plasma oxidation were used to study the oxidation of Si and SiGe samples at a lower temperature. C–V measurements were performed to investigate the trap density, and the corresponding bonding structures of thin oxide were revealed by FTIR analysis. SIMS depth profiles were used to reveal the extent of the Ge segregation in SiGe samples. The system can grow ultra thin SiO2 with lower effective trap density. And Ge segregation can be largely suppressed by atomic oxygen oxidation at a lower temperature.
The implantation of Au into A1203 followed by thermal annealing at 1100°C leads to dramatic changes in the optical properties. The linear and nonlinear optical properties are correlated to the presence of small Au precipitates which form during annealing.
Titanium nitride films were prepared by reactive ion beam assisted deposition (RIBAD) with Ar+/Ti ratios ranging from 1.0 to 2.3. The compositions, phases and textures of these films were studied by AES and XRD as a function of Ar+/Ti ratio and nitrogen partial pressure. The results indicate that the IBAD titanium nitride films deposited at high Ar+/Ti ratio and low nitrogen partial pressure may have reduced nitrogen concentration, (200) preferred orientation, and possibly contain the Ti2N phase.
GaAs films grown on silicon substrates suffer from a high density of threading dislocations. One technique to reduce these dislocations is the use of strained layered superlattices (SLS) InGaAs-GaAsP as buffer. We found that the effectiveness and interactions of the SLS with the threading dislocations strongly depend on the dislocation type and the strain field of the superlattices. Because of the high dislocation density in GaAs/Si, the SLS acts as a medium for dislocation interactions and annihilations. Highly strained SLS (∼ 2%) is required to bend the dislocations and keep them bent at the strained interfaces. We found that the combination between annealing and a highly strained superlattice coupled with selective epitaxy is an effective approach to reduce the threading dislocations in GaAs grown on Si. Transmission electron microscopy is used to study these effects.
Picosecond ultrasonics have been used to measure the sound velocity and index of refraction in a thin film of AlAs. The AlAs layer was grown by molecular-beam epitaxy on a buffer layer of GaAs which was deposited on a semi-insulating GaAs wafer. The AlAs film was capped by a thin layer of GaAs, and a very thin film of InSb. To generate a sound wave effectively a picosecond light pulse was absorbed in the InSb film. As the sound wave propagates through the microstructure it changes the optical properties in the various films, and this produces a change in the optical reflectivity, which is measured. From the round trip time of the acoustic wave we have determined the sound velocity in the AlAs film.
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