Potential for prediction of psychosis and bipolar disorder in Child and Adolescent Mental Health Services: a longitudinal register study of all people born in Finland in 1987

Current strategies to predict psychosis identify only a small proportion of individuals at risk. Additional strategies are needed to increase capacity for pre­diction and prevention of serious mental illness, ideally during childhood and adolescence. One possible approach would be to investigate systems in which psychosis risk factors are concentrated during childhood. One notable such system is represented by Child and Adolescent Mental Health Services (CAMHS). Although psychotic disorders are uncommon in CAMHS, many risk factors for psychosis are highly prevalent in young people who enter this system. We hypothesized, therefore, that youth attending CAMHS would be a high‐risk group for psychosis if followed into adulthood and, furthermore, that CAMHS systems would capture a substantial proportion of future psychosis cases. We constructed a total population cohort study of all Finns born in 1987 (N=55,875), linking together extensive register data on health care contacts from birth through age 28 years. We identified all individuals diagnosed with a psychotic or bipolar disorder by age 28 (N=1,785). The risk of psychosis/bipolar disorder by age 28 years was 1.8% for individuals who had not attended CAMHS during childhood or adolescence, whereas it was 12.8% for those with a history of any outpatient CAMHS contact (odds ratio, OR=7.9, 95% CI: 7.2‐8.7). Furthermore, the risk of psychosis/bipolar disorder by age 28 years was 2.3% for individuals without a history of inpatient CAMHS admission, whereas it was 24.0% for those with a history of inpatient CAMHS admission (OR=13.3, 95% CI: 11.9‐14.9), and 36.5% for those with a history of inpatient CAMHS admission in adolescence (age 13‐17 years) (OR=24.2, 95% CI: 21.2‐27.6). Individuals who attended CAMHS but received no mental disorder diagnosis had an equally high risk of subsequently developing a psychosis/bipolar disorder as individuals who did receive a diagnosis (OR=0.9, 99.5% CI: 0.7‐1.1). Compared to other CAMHS attendees, individuals who developed psychosis or bipolar disorder were more likely to have had an initial CAMHS diagnosis of depressive or other mood disorder (OR=2.3, 99.5% CI: 1.6‐3.0) and disruptive behaviour disorder (OR=1.7, 99.5% CI: 1.2‐2.5). Of all psychosis/bipolar diagnoses by age 28 years, 50.2% occurred in individuals who had, at some point in childhood or adolescence, attended CAMHS, indicating that CAMHS represent not only a high‐risk but also a high‐capacity system for prediction of psychosis/bipolar disorder. These findings suggest an enormous, untapped potential for large‐scale psychosis/bipolar disorder prediction and prevention research within existing specialist CAMHS.     

Effects of antipsychotics,antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia,depression and bipolar disorder

People with severe mental illness have a considerably shorter lifespan than the general population. This excess mortality is mainly due to physical illness. Next to mental illness‐related factors, unhealthy lifestyle, and disparities in health care access and utilization, psychotropic medications can contribute to the risk of physical morbidity and mortality. We systematically reviewed the effects of antipsychotics, antidepressants and mood stabilizers on physical health outcomes in people with schizophrenia, depression and bipolar disorder. Updating and expanding our prior systematic review published in this journal, we searched MEDLINE (November 2009 ‐ November 2014), combining the MeSH terms of major physical disease categories (and/or relevant diseases within these categories) with schizophrenia, major depressive disorder and bipolar disorder, and the three major psychotropic classes which received regulatory approval for these disorders, i.e., antipsychotics, antidepressants and mood stabilizers. We gave precedence to results from (systematic) reviews and meta‐analyses wherever possible. Antipsychotics, and to a more restricted degree antidepressants and mood stabilizers, are associated with an increased risk for several physical diseases, including obesity, dyslipidemia, diabetes mellitus, thyroid disorders, hyponatremia; cardiovascular, respiratory tract, gastrointestinal, haematological, musculoskeletal and renal diseases, as well as movement and seizure disorders. Higher dosages, polypharmacy, and treatment of vulnerable (e.g., old or young) individuals are associated with greater absolute (elderly) and relative (youth) risk for most of these physical diseases. To what degree medication‐specific and patient‐specific risk factors interact, and how adverse outcomes can be minimized, allowing patients to derive maximum benefits from these medications, requires adequate clinical attention and further research.     

Internalizing psychopathology and all‐cause mortality: a comparison of transdiagnostic vs. diagnosis‐based risk prediction

Previous studies have documented the utility of a transdiagnostic internalizing factor in predicting important future outcomes (e.g., subsequent mental disorder diagnoses). To date, however, no study has investigated whether an internalizing factor predicts mortality risk. Also, while pre­vious studies of mortality risk have emphasized its associations with particular internalizing disorders, no study has assessed how the transdiagnostic internalizing factor vs. disorder‐specific variance differently predict that risk. The primary aims of this study were to explore: a) whether the internalizing factor predicts mortality risk, b) whether particular internalizing psychopathologies uniquely predict mortality risk over and beyond the transdiagnostic internalizing factor, and c) whether there is a significant interaction of internalizing with self‐reported health in the prediction of mortality risk. We utilized a large national sample of American adults from the Midlife in the United States (MIDUS), a longitudinal study that examined midlife development of individuals across multiple waves between 1995 and 2015. Data were analyzed for the 6,329 participants who completed the phone interview and self‐administered questionnaire in MIDUS 1 (1995‐1996) and were then followed up until October 31, 2015 or until death. To investigate the association between internalizing and mortality risk, we used the semi‐parametric proportional hazards Cox model, where survival time was regressed on a latent internalizing factor. Overall findings indicate that a transdiagnostic internalizing factor significantly predicts mortality risk over a 20‐year period (hazard ratio, HR=1.12, 95% CI: 1.05‐1.16, p<0.01) and that internalizing outperforms disorder‐specific variance (e.g., depression‐specific variance) in the prediction of that risk. Further, there was a significant interaction between transdiagnostic internalizing and self‐reported health, whereby internalizing psychopathology had a specific association with early death for individuals with excellent self‐reported health condition (HR=1.50, 95% CI: 1.17‐1.84, p<0.05). This highlights the clinical utility of using the transdiagnostic internalizing factor for prediction of an important future outcome, and supports the argument that internalizing psychopathology can be a meaningful liability to explore in public health practice.     

Sedentary behavior and physical activity levels in people with schizophrenia,bipolar disorder and major depressive disorder: a global systematic review and meta‐analysis

People with severe mental illness (schizophrenia, bipolar disorder or major depressive disorder) die up to 15 years prematurely due to chronic somatic comorbidities. Sedentary behavior and low physical activity are independent yet modifiable risk factors for cardiovascular disease and premature mortality in these people. A comprehensive meta‐analysis exploring these risk factors is lacking in this vulnerable population. We conducted a meta‐analysis investigating sedentary behavior and physical activity levels and their correlates in people with severe mental illness. Major electronic databases were searched from inception up to April 2017 for articles measuring sedentary behavior and/or physical activity with a self‐report questionnaire or an objective measure (e.g., accelerometer). Random effects meta‐analyses and meta‐regression analyses were conducted. Sixty‐nine studies were included (N=35,682; 39.5% male; mean age 43.0 years). People with severe mental illness spent on average 476.0 min per day (95% CI: 407.3‐545.4) being sedentary during waking hours, and were significantly more sedentary than age‐ and gender‐matched healthy controls (p=0.003). Their mean amount of moderate or vigorous physical activity was 38.4 min per day (95% CI: 32.0‐44.8), being significantly lower than that of healthy controls (p=0.002 for moderate activity, p<0.001 for vigorous activity). People with severe mental illness were significantly less likely than matched healthy controls to meet physical activity guidelines (odds ratio = 1.5; 95% CI: 1.1‐2.0, p<0.001, I²=95.8). Lower physical activity levels and non‐compliance with physical activity guidelines were associated with male gender, being single, unemployment, fewer years of education, higher body mass index, longer illness duration, antidepressant and antipsychotic medication use, lower cardiorespiratory fitness and a diagnosis of schizophrenia. People with bipolar disorder were the most physically active, yet spent most time being sedentary. Geographical differences were detected, and inpatients were more active than outpatients and those living in the community. Given the established health benefits of physical activity and its low levels in people with severe mental illness, future interventions specifically targeting the prevention of physical inactivity and sedentary behavior are warranted in this population.     

Bipolar‐associated miR‐499‐5p controls neuroplasticity by downregulating the Cav1.2 subunit CACNB2

Bipolar disorder (BD) is a chronic mood disorder characterized by manic and depressive episodes. Dysregulation of neuroplasticity and calcium homeostasis are frequently observed in BD patients, but the underlying molecular mechanisms are largely unknown. Here, we show that miR‐499‐5p regulates dendritogenesis and cognitive function by downregulating the BD risk gene CACNB2. miR‐499‐5p expression is increased in peripheral blood of BD patients, as well as in the hippocampus of rats which underwent juvenile social isolation. In rat hippocampal neurons, miR‐499‐5p impairs dendritogenesis and reduces surface expression and activity of the L‐type calcium channel Cav1.2. We further identified CACNB2, which encodes a regulatory β‐subunit of Cav1.2, as a direct functional target of miR‐499‐5p in neurons. miR‐499‐5p overexpression in the hippocampus in vivo induces short‐term memory impairments selectively in rats haploinsufficient for the Cav1.2 pore forming subunit Cacna1c. In humans, miR‐499‐5p expression is negatively associated with gray matter volumes of the left superior temporal gyrus, a region implicated in auditory and emotional processing. We propose that stress‐induced miR‐499‐5p overexpression contributes to dendritic impairments, deregulated calcium homeostasis, and neurocognitive dysfunction in BD.     

Preventive psychiatry: a blueprint for improving the mental health of young people

Preventive approaches have latterly gained traction for improving mental health in young people. In this paper, we first appraise the conceptual foundations of preventive psychiatry, encompassing the public health, Gordon''s, US Institute of Medicine, World Health Organization, and good mental health frameworks, and neurodevelopmentally‐sensitive clinical staging models. We then review the evidence supporting primary prevention of psychotic, bipolar and common mental disorders and promotion of good mental health as potential transformative strategies to reduce the incidence of these disorders in young people. Within indicated approaches, the clinical high‐risk for psychosis paradigm has received the most empirical validation, while clinical high‐risk states for bipolar and common mental disorders are increasingly becoming a focus of attention. Selective approaches have mostly targeted familial vulnerability and non‐genetic risk exposures. Selective screening and psychological/psychoeducational interventions in vulnerable subgroups may improve anxiety/depressive symptoms, but their efficacy in reducing the incidence of psychotic/bipolar/common mental disorders is unproven. Selective physical exercise may reduce the incidence of anxiety disorders. Universal psychological/psychoeducational interventions may improve anxiety symptoms but not prevent depressive/anxiety disorders, while universal physical exercise may reduce the incidence of anxiety disorders. Universal public health approaches targeting school climate or social determinants (demographic, economic, neighbourhood, environmental, social/cultural) of mental disorders hold the greatest potential for reducing the risk profile of the population as a whole. The approach to promotion of good mental health is currently fragmented. We leverage the knowledge gained from the review to develop a blueprint for future research and practice of preventive psychiatry in young people: integrating universal and targeted frameworks; advancing multivariable, transdiagnostic, multi‐endpoint epidemiological knowledge; synergically preventing common and infrequent mental disorders; preventing physical and mental health burden together; implementing stratified/personalized prognosis; establishing evidence‐based preventive interventions; developing an ethical framework, improving prevention through education/training; consolidating the cost‐effectiveness of preventive psychiatry; and decreasing inequalities. These goals can only be achieved through an urgent individual, societal, and global level response, which promotes a vigorous collaboration across scientific, health care, societal and governmental sectors for implementing preventive psychiatry, as much is at stake for young people with or at risk for emerging mental disorders.     

Body mass and sex,but not breeding condition and season,influence open‐field exploration in the yellow‐necked mouse

Theory predicts that risk taking should be influenced by external (e.g., season) and internal (e.g., breeding condition, sex, and body mass) conditions. We investigated whether these factors are associated with a potentially risky behavior: exploration of a novel environment. We conducted repeated open‐field tests of exploration in a common forest rodent, the yellow‐necked mouse Apodemus flavicollis. Contrary to expectations, the exploration did not vary with the season (spring vs. fall) or the reproductive status of the tested animals. Also unexpectedly, there was an inverted U‐shaped relationship between body mass and exploration: animals with intermediate body mass tended to have the highest exploration tendencies. Males were more exploratory than females. Finally, even after adjusting for the effects of body mass and sex, individuals exhibited consistent, repeatable differences in exploration tendencies (“behavioral types” or “personalities”). The discrepancies between certain broad generalizations and our results suggest that risk taking depends on details of species‐specific biology.     

Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders,bipolar disorder and major depressive disorder: a systematic review and meta‐analysis

Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The primary aim of this systematic review and meta‐analysis was to assess the prevalence of MetS and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder, comparing subjects with different disorders and taking into account demographic variables and psychotropic medication use. The secondary aim was to compare the MetS prevalence in persons with any of the selected disorders versus matched general population controls. The pooled MetS prevalence in people with severe mental illness was 32.6% (95% CI: 30.8%‐34.4%; N = 198; n = 52,678). Relative risk meta‐analyses established that there was no significant difference in MetS prevalence in studies directly comparing schizophrenia versus bipolar disorder, and in those directly comparing bipolar disorder versus major depressive disorder. Only two studies directly compared people with schizophrenia and major depressive disorder, precluding meta‐analytic calculations. Older age and a higher body mass index were significant moderators in the final demographic regression model (z = ?3.6, p = 0.0003, r² = 0.19). People treated with all individual antipsychotic medications had a significantly (p<0.001) higher MetS risk compared to antipsychotic‐naïve participants. MetS risk was significantly higher with clozapine and olanzapine (except vs. clozapine) than other antipsychotics, and significantly lower with aripiprazole than other antipsychotics (except vs. amisulpride). Compared with matched general population controls, people with severe mental illness had a significantly increased risk for MetS (RR = 1.58; 95% CI: 1.35‐1.86; p<0.001) and all its components, except for hypertension (p = 0.07). These data suggest that the risk for MetS is similarly elevated in the diagnostic subgroups of severe mental illness. Routine screening and multidisciplinary management of medical and behavioral conditions is needed in these patients. Risks of individual antipsychotics should be considered when making treatment choices.     

Late-life Onset Bipolar Disorder Presenting as a Case of Pseudo-Dementia: A Case Discussion and Review of Literature

Depression and comorbid cognitive impairment in the elderly can be difficult to distinguish from dementia. Adding to the complex differential is that depression may be part of a bipolar illness rather than a unipolar mood disorder. A diligent workup and close monitoring of patients can inform appropriate treatment and can make the difference between recovery and persistence of symptoms. The present case will illustrate how a comprehensive workup utilizing extensive data gathering, laboratory workup, use of neuropsychological testing, neuroimaging, and timely treatment can lead to successful clinical outcomes that can be sustained for many years.     

Characteristics of Attempted Suicide by Patients with Schizophrenia Compared with Those with Mood Disorders: A Case-Controlled Study in Northern Japan

Recent reports suggest a lifetime suicide risk for schizophrenia patients of approximately 5%. This figure is significantly higher than the general population suicide risk consequently, detection of those at risk is clinically important. This study was undertaken to define the characteristics of suicide attempts by schizophrenia patients compared with attempts by patients with mood disorders. All patients were diagnosed using the ICD-10 criteria. The study population comprised 65 patients with F2 disorders (schizophrenia, schizotypal and delusional disorders), i.e., “the F2 group”, and 94 patients with F3 disorders (mood disorders), i.e., “the F3 group”, who presented in the clinical setting of consultation-liaison psychiatry. The F2 group had a significantly younger mean age and significantly higher ratios of ‘past/present psychiatric treatment’ and ‘more than 3 months interruption of psychiatric treatment’. In contrast, the ratios of ‘physical disorder comorbidity’, ‘alcohol intake at suicide attempt’ and ‘suicide note left behind’ were significantly higher in the F3 group. The F2 group attempted suicide by significantly more serious methods. Furthermore, ‘hallucination-delusion’ was the most prevalent motive in the F2 group and was the only factor that showed a significant association with the seriousness of the method of suicide attempt (OR = 3.36, 95% CI: 1.05–11.33).     

Degrees of compositional shift in tree communities vary along a gradient of temperature change rates over one decade: Application of an individual‐based temporal beta‐diversity concept

Temporal patterns in communities have gained widespread attention recently, to the extent that temporal changes in community composition are now termed “temporal beta‐diversity.” Previous studies of beta‐diversity have made use of two classes of dissimilarity indices: incidence‐based (e.g., Sørensen and Jaccard dissimilarity) and abundance‐based (e.g., Bray–Curtis and Ružička dissimilarity). However, in the context of temporal beta‐diversity, the persistence of identical individuals and turnover among other individuals within the same species over time have not been considered, despite the fact that both will affect compositional changes in communities. To address this issue, I propose new index concepts for beta‐diversity and the relative speed of compositional shifts in relation to individual turnover based on individual identity information. Individual‐based beta‐diversity indices are novel dissimilarity indices that consider individual identity information to quantitatively evaluate temporal change in individual turnover and community composition. I applied these new indices to individually tracked tree monitoring data in deciduous and evergreen broad‐leaved forests across the Japanese archipelago with the objective of quantifying the effect of climate change trends (i.e., rates of change in both annual mean temperature and annual precipitation) on individual turnover and compositional shifts at each site. A new index explored the relative contributions of mortality and recruitment processes to temporal changes in community composition. Clear patterns emerged showing that an increase in the temperature change rate facilitated the relative contribution of mortality components. The relative speed of compositional shift increased with increasing temperature change rates in deciduous forests but decreased with increasing warming rates in evergreen forests. These new concepts provide a way to identify novel and high‐resolution temporal patterns in communities.     

Mood and disruptive behavior disorders and symptoms in the offspring of patients with bipolar I disorder

The study aimed to ascertain the prevalence of mood and disruptive behavior disorders and symptoms in 35 children of 29 adult outpatients with a DSM-IV diagnosis of bipolar I disorder, compared with 33 children of 29 healthy adults, matched with patients on age, socioeconomic status and education. The offspring of bipolar patients had a 9.48 fold higher risk of receiving a psychiatric diagnosis. While only two children of patients with bipolar disorder were diagnosed with a mood disorder, 30.9% displayed mild depressed mood, compared with 8.8% of the controls, a statistically significant difference. The bipolar offspring also scored significantly higher on the hyperactivity and conduct problems subscales as well as the ADHD index of the Conners’ Teacher Rating Scale. The disruptive behavior and mood symptoms observed in early life in the offspring of bipolar patients may indicate the need for early psychosocial intervention.     

Multigenerational exposure to increased temperature reduces metabolic rate but increases boldness in Gambusia affinis

Acute exposure to warming temperatures increases minimum energetic requirements in ectotherms. However, over and within multiple generations, increased temperatures may cause plastic and evolved changes that modify the temperature sensitivity of energy demand and alter individual behaviors. Here, we aimed to test whether populations recently exposed to geothermally elevated temperatures express an altered temperature sensitivity of metabolism and behavior. We expected that long‐term exposure to warming would moderate metabolic rate, reducing the temperature sensitivity of metabolism, with concomitant reductions in boldness and activity. We compared the temperature sensitivity of metabolic rate (acclimation at 20 vs. 30°C) and allometric slopes of routine, standard, and maximum metabolic rates, in addition to boldness and activity behaviors, across eight recently divergent populations of a widespread fish species (Gambusia affinis). Our data reveal that warm‐source populations express a reduced temperature sensitivity of metabolism, with relatively high metabolic rates at cool acclimation temperatures and relatively low metabolic rates at warm acclimation temperatures compared to ambient‐source populations. Allometric scaling of metabolism did not differ with thermal history. Across individuals from all populations combined, higher metabolic rates were associated with higher activity rates at 20°C and bolder behavior at 30°C. However, warm‐source populations displayed relatively bolder behavior at both acclimation temperatures compared to ambient‐source populations, despite their relatively low metabolic rates at warm acclimation temperatures. Overall, our data suggest that in response to warming, multigenerational exposure (e.g., plasticity, adaptation) may not result in trait change directed along a simple “pace‐of‐life syndrome” axis, instead causing relative decreases in metabolism and increases in boldness. Ultimately, our data suggest that multigenerational warming may produce a novel combination of physiological and behavioral traits, with consequences for animal performance in a warming world.     

Mortality in people with schizophrenia: a systematic review and meta‐analysis of relative risk and aggravating or attenuating factors

People with schizophrenia die 15‐20 years prematurely. Understanding mortality risk and aggravating/attenuating factors is essential to reduce this gap. We conducted a systematic review and random‐effects meta‐analysis of prospective and retrospective, nationwide and targeted cohort studies assessing mortality risk in people with schizophrenia versus the general population or groups matched for physical comorbidities or groups with different psychiatric disorders, also assessing moderators. Primary outcome was all‐cause mortality risk ratio (RR); key secondary outcomes were mortality due to suicide and natural causes. Other secondary outcomes included any other specific‐cause mortality. Publication bias, subgroup and meta‐regression analyses, and quality assessment (Newcastle‐Ottawa Scale) were conducted. Across 135 studies spanning from 1957 to 2021 (schizophrenia: N=4,536,447; general population controls: N=1,115,600,059; other psychiatric illness controls: N=3,827,955), all‐cause mortality was increased in people with schizophrenia versus any non‐schizophrenia control group (RR=2.52, 95% CI: 2.38‐2.68, n=79), with the largest risk in first‐episode (RR=7.43, 95% CI: 4.02‐13.75, n=2) and incident (i.e., earlier‐phase) schizophrenia (RR=3.52, 95% CI: 3.09‐4.00, n=7) versus the general population. Specific‐cause mortality was highest for suicide or injury‐poisoning or undetermined non‐natural cause (RR=9.76‐8.42), followed by pneumonia among natural causes (RR=7.00, 95% CI: 6.79‐7.23), decreasing through infectious or endocrine or respiratory or urogenital or diabetes causes (RR=3 to 4), to alcohol or gastrointestinal or renal or nervous system or cardio‐cerebrovascular or all natural causes (RR=2 to 3), and liver or cerebrovascular, or breast or colon or pancreas or any cancer causes (RR=1.33 to 1.96). All‐cause mortality increased slightly but significantly with median study year (beta=0.0009, 95% CI: 0.001‐0.02, p=0.02). Individuals with schizophrenia <40 years of age had increased all‐cause and suicide‐related mortality compared to those ≥40 years old, and a higher percentage of females increased suicide‐related mortality risk in incident schizophrenia samples. All‐cause mortality was higher in incident than prevalent schizophrenia (RR=3.52 vs. 2.86, p=0.009). Comorbid substance use disorder increased all‐cause mortality (RR=1.62, 95% CI: 1.47‐1.80, n=3). Antipsychotics were protective against all‐cause mortality versus no antipsychotic use (RR=0.71, 95% CI: 0.59‐0.84, n=11), with largest effects for second‐generation long‐acting injectable anti­psychotics (SGA‐LAIs) (RR=0.39, 95% CI: 0.27‐0.56, n=3), clozapine (RR=0.43, 95% CI: 0.34‐0.55, n=3), any LAI (RR=0.47, 95% CI: 0.39‐0.58, n=2), and any SGA (RR=0.53, 95% CI: 0.44‐0.63, n=4). Antipsychotics were also protective against natural cause‐related mortality, yet first‐generation antipsychotics (FGAs) were associated with increased mortality due to suicide and natural cause in incident schizophrenia. Higher study quality and number of variables used to adjust the analyses moderated larger natural‐cause mortality risk, and more recent study year moderated larger protective effects of antipsychotics. These results indicate that the excess mortality in schizophrenia is associated with several modifiable factors. Targeting comorbid substance abuse, long‐term maintenance antipsychotic treatment and appropriate/earlier use of SGA‐LAIs and clozapine could reduce this mortality gap.     

Development of Health Equity Indicators in Primary Health Care Organizations Using a Modified Delphi

Objective

The purpose of this study was to develop a core set of indicators that could be used for measuring and monitoring the performance of primary health care organizations'' capacity and strategies for enhancing equity-oriented care.

Methods

Indicators were constructed based on a review of the literature and a thematic analysis of interview data with patients and staff (n = 114) using procedures for qualitatively derived data. We used a modified Delphi process where the indicators were circulated to staff at the Health Centers who served as participants (n = 63) over two rounds. Indicators were considered part of a priority set of health equity indicators if they received an overall importance rating of>8.0, on a scale of 1–9, where a higher score meant more importance.

Results

Seventeen indicators make up the priority set. Items were eliminated because they were rated as low importance (<8.0) in both rounds and were either redundant or more than one participant commented that taking action on the indicator was highly unlikely. In order to achieve health care equity, performance at the organizational level is as important as assessing the performance of staff. Two of the highest rated “treatment” or processes of care indicators reflects the need for culturally safe and trauma and violence-informed care. There are four indicators that can be used to measure outcomes which can be directly attributable to equity responsive primary health care.

Discussion

These indicators and subsequent development of items can be used to measure equity in the domains of treatment and outcomes. These areas represent targets for higher performance in relation to equity for organizations (e.g., funding allocations to ongoing training in equity-oriented care provision) and providers (e.g., reflexive practice, skill in working with the health effects of trauma).     

Why Has the Continuous Decline in German Suicide Rates Stopped in 2007?

Background

Whereas German suicide rates had a clear decreasing tendency between 1991 and 2006, they increased from 2007 to 2010. Deeper analyses of suicide data might help to understand better this change. The aim of this study was to analyze 1) whether recent trends can be related to changes in specific suicide methods and diverge by gender and age; 2) whether the decrease of suicide rates before 2007 as well as the increase from 2007 to 2010 are driven by the same suicide method.

Methods

Analyses were based on suicide data from the Federal Statistical Office of Germany. For 1998–2010, 136.583 suicide cases of men and women with known age and suicide method could be identified. These data were analyzed by joinpoint regression analysis, allowing identification of the best fitting point in time (“joinpoint”) at which the suicide rate significantly changes in magnitude or direction.

Results

The national downward trend between 1998 and 2007 was mainly due to corresponding changes in self-poisoning by other means than drugs (e.g., pesticides) (annual percentage change (APC) ≤ −4.33), drowning (APC ≤ −2.73), hanging (APC ≤ −2.69) and suicides by firearms (APC ≤ −1.46) in both genders. Regarding the overall increase of age-adjusted suicide rates in Germany 2007–2010, mainly the increase of self-poisoning (e.g., by drugs) and “being overrun” (APC ≥ 1.50) contributed to this trend.

Limitations

The true suicide rates might have been underestimated because of errors in the official death certificates.

Conclusions

Increase in suicide rates in Germany since 2007 went along with corresponding changes for “being overrun” and “self-poisoning”. Copycat suicides following the railway suicide of the goalkeeper Robert Enke partly contributed to the results. Thus, prevention of Werther effects and limitation of the availability of high pack sizes for drugs are of special relevance for the reversal of this trend.     

Rewilding with invertebrates and microbes to restore ecosystems: Present trends and future directions

1. Restoration ecology has historically focused on reconstructing communities of highly visible taxa while less visible taxa, such as invertebrates and microbes, are ignored. This is problematic as invertebrates and microbes make up the vast bulk of biodiversity and drive many key ecosystem processes, yet they are rarely actively reintroduced following restoration, potentially limiting ecosystem function and biodiversity in these areas.
2. In this review, we discuss the current (limited) incorporation of invertebrates and microbes in restoration and rewilding projects. We argue that these groups should be actively rewilded during restoration to improve biodiversity, ecosystem function outcomes, and highlight how they can be used to greater effect in the future. For example, invertebrates and microbes are easily manipulated, meaning whole communities can potentially be rewilded through habitat transplants in a practice that we refer to as “whole‐of‐community” rewilding.
3. We provide a framework for whole‐of‐community rewilding and describe empirical case studies as practical applications of this under‐researched restoration tool that land managers can use to improve restoration outcomes.
4. We hope this new perspective on whole‐of‐community restoration will promote applied research into restoration that incorporates all biota, irrespective of size, while also enabling a better understanding of fundamental ecological theory, such as colonization and competition trade‐offs. This may be a necessary consideration as invertebrates that are important in providing ecosystem services are declining globally; targeting invertebrate communities during restoration may be crucial in stemming this decline.

     

Altered Myelination of the Hippocampal Formation in Subjects with Schizophrenia and Bipolar Disorder

Myelination of the frontal and temporal lobes occurs at a similar time period as symptom onset in schizophrenia. To assess this potential relationship, we compared myelination and oligodendrocyte numbers in the hippocampal formation of controls and matched subjects with schizophrenia and bipolar disorder. The levels and distribution of the myelin marker myelin basic protein (MBP) and the oligodendrocyte marker adenomatous polyposis coli (APC) were measured using immunocytochemistry. MBP immunoreactivity (IR) was increased in several hippocampal subregions of control females versus control males. Female subjects with schizophrenia and bipolar disorder exhibited decreased myelination in the hippocampal formation while male subjects with bipolar disorder showed increased MBP levels in the superior medullary lamina. In contrast, the number of APC immunoreactive cells did not differ in any disorder or region. Our results demonstrate an interaction between gender, mental illness, and myelination, and may be related to cognitive deficits seen in schizophrenia and bipolar disorder.     

Many chronological aging clocks can be found throughout the epigenome: Implications for quantifying biological aging

Epigenetic alterations are a hallmark of aging and age‐related diseases. Computational models using DNA methylation data can create “epigenetic clocks” which are proposed to reflect “biological” aging. Thus, it is important to understand the relationship between predictive clock sites and aging biology. To do this, we examined over 450,000 methylation sites from 9,699 samples. We found ~20% of the measured genomic cytosines can be used to make many different epigenetic clocks whose age prediction performance surpasses that of telomere length. Of these predictive sites, the average methylation change over a lifetime was small (~1.5%) and these sites were under‐represented in canonical regions of epigenetic regulation. There was only a weak association between “accelerated” epigenetic aging and disease. We also compare tissue‐specific and pan‐tissue clock performance. This is critical to applying clocks both to new sample sets in basic research, as well as understanding if clinically available tissues will be feasible samples to evaluate “epigenetic aging” in unavailable tissues (e.g., brain). Despite the reproducible and accurate age predictions from DNA methylation data, these findings suggest they may have limited utility as currently designed in understanding the molecular biology of aging and may not be suitable as surrogate endpoints in studies of anti‐aging interventions. Purpose‐built clocks for specific tissues age ranges or phenotypes may perform better for their specific purpose. However, if purpose‐built clocks are necessary for meaningful predictions, then the utility of clocks and their application in the field needs to be considered in that context.