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Results of a co-morbid insomnia and depression study of eszopiclone and fluoxetine demonstrated that co-therapy produced greater improvements in sleep and depression than fluoxetine monotherapy. To determine if changes in the HAMD17 were due to sleep, individual HAMD17 items were evaluated.
Patients met DSM-IV criteria for MDD and insomnia, with screening HAMD17 >14. All patients received fluoxetine QAM for 10 weeks, and randomly received double-blind eszopiclone 3mg or placebo QHS for 8 weeks, followed by a single-blind placebo 2-week run-out. HAMD17 was completed at Weeks 4, 8, and 10. Individual items were compared with ANCOVA using an LOCF approach.
Mean baseline HAMD17 scores were 22 for each group. At Week 4, differences were noted between treatment groups in the total score, and the individual items of insight, the three insomnia items (p<0.02 vs monotherapy), with a trend for guilt (p=0.07). At Week 8, significant differences between groups were noted in total score (p=0.0005), in the clinician-administered Bech subscale (p<0.001), in the three insomnia items (p<0.001), guilt, work/activities, and anxiety psychic (p<0.05). At Week 10, the total score, guilt, the three insomnia items, work/activities, retardation, agitation, anxiety psychic, general somatic symptoms, and hypochondriasis demonstrated significant improvements (p<0.05 vs monotherapy) despite discontinuation of eszopiclone.
Eszopiclone/fluoxetine co-therapy resulted in significant improvements in the insomnia items of the HAMD17. In addition, several items related to core depressive symptoms were also improved with co-therapy compared with monotherapy.
Schizophrenia is associated with altered neural development. We assessed neurological soft signs (NSS) and dermatoglyphic anomalies (total a–b ridge count (TABRC) and total finger ridge count) in 15 pairs of twins concordant and discordant for schizophrenia. Within-pair differences in both NSS and TABRC scores were significantly greater in discordant compared to concordant monozygotic pairs. There was no significant difference in NSS and TABRC scores between subjects with schizophrenia and their co-twins without the illness. However, monozygotic discordant twins with schizophrenia had higher ABRCs on their right hands compared to their co-twins without the illness. These findings suggest that an unidentified environmental event acting between weeks 6 and 15 of gestation affects the development of monozygotic twins who go on to develop schizophrenia but does not have a corresponding effect on their co-twins who do not develop the illness. The effect of such an event on dermatoglyphic profiles appears lateralised to the right hand in affected twins.
This study investigated the attitudes of medical students towards psychiatry, both as a subject on the medical curriculum and as a career choice. Three separate questionnaires previously validated on medical student populations were administered prior to and immediately following an 8-week clinical training programme. The results indicate that the perception of psychiatry was positive prior to clerkship and became even more so on completion of training. On completion of the clerkship, there was a rise in the proportion of students who indicated that they might choose a career in psychiatry. Attitudes toward psychiatry correlated positively with the psychiatry examination results. Those that intended to specialise in psychiatry achieved significantly higher examination scores in the psychiatry examination.
Although genetic and environmental factors operating before or around the time of birth have been demonstrated to be relevant to the aetiology of the major psychoses, a seasonal variation in the rates of admission of such patients has long been recognised. Few studies have compared first and readmissions. This study examined for seasonal variation of admission in the major psychoses, and compared diagnostic categories by admission status. Patients admitted to Irish psychiatric inpatient facilities between 1989 and 1994 with an ICD-9/10 diagnosis of schizophrenia or affective disorder were identified from the National Psychiatric Inpatient Reporting System (NPIRS). The data were analysed using a hierarchical log linear model, the chi-square test, a Kolmogorov-Smirnov (KS) type statistic, and the method of Walter and Elwood. The hierarchical log linear model demonstrated significant interactions between the month of admission and admission order (change in scaled deviance 28.77, df = 11, P < 0.003). Both first admissions with mania, and readmissions with bipolar affective disorder exhibited significant seasonality. In contrast, only first admissions with schizophrenia showed significant seasonal effects. Although first admissions with mania and readmissions with bipolar disorder both show seasonality, seasonal influences appear to be more relevant to onset of schizophrenia than subsequent relapse.
P300 wave anomalies correlate with genetic risk for schizophrenia and constitute a plausible endophenotype for the disease. The COMT gene is thought to influence cognitive performance and to be a susceptibility gene for schizophrenia. Unlike two previous studies, we found no significant influence of the COMT gene on P300 amplitude or latency in 189 individuals examined. The well-supported role of the COMT gene both in dopamine catabolism as well as in prefrontal cognition makes a strong theoretical case for the influence of COMT Val158Met polymorphism on P300 endophenotypes. However, the available neurophysiologic evidence suggests that any such association, if present, must be very subtle.
We study numerically the region of convergence of the normal form transformation for the case of the Charney–Hasagawa–Mima (CHM) equation to investigate whether certain finite amplitude effects can be described in normal form coordinates. Specifically, we consider a Galerkin truncation of the CHM equation to four Fourier modes, and ask: Can the finite amplitude phenomenon known as precession resonance (Bustamante et al., Phys. Rev. Lett., vol. 113, 2014, 084502) be described by the normal form variables of wave turbulence theory? The answer is no, due to the failure of convergence of the normal form transformation at the wave amplitudes required for precession resonance. We show this by first characterising precession resonance in the original system, then, searching for this resonance in the normal form equations of motion. We find a large discrepancy between the dynamics of the original system and the transformed normal form system. This prompts an investigation into the convergence of the transformation in the state space of wave amplitudes. We find that the numerically calculated region of convergence is a region of finite wave amplitudes, well beyond the usual limit of weak nonlinearity. However, the amplitudes at the boundary of this region of convergence (i.e. the amplitudes at which the normal form transformation begins to diverge) match closely with the amplitudes at which precession resonance occurs in the original system. We conclude that the precession resonance mechanism cannot be explained by the usual methods of normal forms in wave turbulence theory, so a more general theory for intermediate nonlinearity is required.
A central component of primates’ social ontogeny is play with conspecifics. Play is constrained by ecological factors, especially food abundance, and social play is most likely limited by partner availability, which in turn can be related to ecology. However, how much social and ecological factors collectively influence social play rates has not yet been investigated. We used a multivariate approach to test to what degree fruit and partner availability affected social play rates of wild immature chimpanzees in Taï National Park. As fruit abundance and partner availability increased, infant and juvenile play rates rose, with juvenile play being affected more by fruit abundance than infant play. Partner availability predicted infant play rates better during the low than the high fruit availability season, which was not the case for juvenile play. Our results indicate that young chimpanzees face a trade-off in allocating time or energy to foraging and social play, with foraging becoming increasingly dominant with age. This joint analysis of social and ecological factors suggests that food abundance modulates the effect of partner availability on social play rates in young chimpanzees.
The association between incarceration and psychiatric disorders has been noted. Yet, existing studies are cross-sectional or examine the risk of recidivism, which has limited the predictive validity of psychiatric disorders as a risk factor for incarceration. To overcome this limitation, this study used a prospective cohort to examine whether psychiatric diagnoses in early adulthood predicted incarceration throughout a 30-year follow-up. It tested the association between psychiatric diagnoses with future incarcerations, their number and durations, controlling for education and ethnic status.
This study merged data from three sources in Israel: a prospective 10-year birth cohort study of young adults aged 25–34, conducted in the 1980s (N = 4914) that included a psychiatric interview; data from the Prison Service, including the cause, number and duration of incarcerations; and from the Vital Statistics Registry on death records.
Multivariate analysis showed that substance-use disorders, antisocial personality and lower levels of education predicted future incarceration, their number and maximum duration. The remainder diagnoses were not significantly associated with future incarceration.
Results limited the prediction of future incarcerations to persons diagnosed with substance use and antisocial personality, and do not support an independent predictive association between additional psychiatric diagnoses and future incarceration.
Childhood adversity (CA) increases the risk of subsequent mental health problems. Adolescent social support (from family and/or friends) reduces the risk of mental health problems after CA. However, the mechanisms of this effect remain unclear, and we speculate that they are manifested on neurodevelopmental levels. Therefore, we investigated whether family and/or friendship support at ages 14 and 17 function as intermediate variables for the relationship between CA before age 11 and affective or neural responses to social rejection feedback at age 18. We studied 55 adolescents with normative mental health at age 18 (26 with CA and therefore considered “resilient”), from a longitudinal cohort. Participants underwent a Social Feedback Task in the magnetic resonance imaging scanner. Social rejection feedback activated the dorsal anterior cingulate cortex and the left anterior insula. CA did not predict affective or neural responses to social rejection at age 18. Yet, CA predicted better friendships at age 14 and age 18, when adolescents with and without CA had comparable mood levels. Thus, adolescents with CA and normative mood levels have more adolescent friendship support and seem to have normal mood and neural responses to social rejection.
Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TGs) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations.
Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models.
Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51–2.77, I2 = 45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies.
Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
Recent cases of acute kidney injury due to Seoul hantavirus infection from exposure to wild or pet fancy rats suggest this infection is increasing in prevalence in the UK. We conducted a seroprevalence study in England to estimate cumulative exposure in at-risk groups with contact with domesticated and wild rats to assess risk and inform public health advice. From October 2013 to June 2014, 844 individual blood samples were collected. Hantavirus seroprevalence amongst the pet fancy rat owner group was 34.1% (95% CI 23·9–45·7%) compared with 3·3% (95% CI 1·6–6·0) in a baseline control group, 2·4% in those with occupational exposure to pet fancy rats (95% CI 0·6–5·9) and 1·7% with occupational exposure to wild rats (95% CI 0·2–5·9). Variation in seroprevalence across groups with different exposure suggests that occupational exposure to pet and wild rats carries a very low risk, if any. However incidence of hantavirus infection among pet fancy rat owners/breeders, whether asymptomatic, undiagnosed mild viral illness or more severe disease may be very common and public health advice needs to be targeted to this at-risk group.
Functional neurological disorders (FNDs), also known as conversion disorder, are unexplained neurological symptoms unrelated to a neurological cause. The disorder is common, yet poorly understood. The symptoms are experienced as involuntary but have similarities to voluntary processes. Here we studied intention awareness in FND.
A total of 26 FND patients and 25 healthy volunteers participated in this functional magnetic resonance study using Libet's clock.
FND is characterized by delayed awareness of the intention to move relative to the movement itself. The reporting of intention was more precise, suggesting that these findings are reliable and unrelated to non-specific attentional deficits. That these findings were more prominent with aberrant positive functional movement symptoms rather than negative symptoms may be relevant to impairments in timing for an inhibitory veto process. Attention towards intention relative to movement was associated with lower right inferior parietal cortex activity in FND, a region early in the processing of intention. During rest, aberrant functional connectivity was observed with the right inferior parietal cortex and other motor intention regions.
The results converge with observations of low inferior parietal activity comparing involuntary with voluntary movement in FND, emphasizing core deficiencies in intention. Heightened precision of this impaired intention is consistent with Bayesian theories of impaired top-down priors that might influence the sense of involuntariness. A primary impairment in voluntary motor intention at an early processing stage might explain clinical observations of slowed effortful voluntary movement, heightened self-directed attention and underlie functional movements. These findings further suggest novel therapeutic targets.