The influence of illness‐related variables,personal resources and context‐related factors on real‐life functioning of people with schizophrenia

In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real‐life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real‐life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness‐related variables, personal resources and context‐related factors. Some of these variables were never investigated before in relationship with real‐life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real‐life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real‐life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real‐life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real‐life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia.     

Social defeat and the culture of chronicity: or,why schizophrenia does so well over there and so badly here

The history of the way schizophrenia has been conceptualized in American psychiatry has led us to be hesitant to explore the role of social causation in schizophrenia. But there is now good evidence for social impact on the course, outcome, and even origin of schizophrenia, most notably in the better prognosis for schizophrenia in developing countries and in the higher rates of schizophrenia for dark-skinned immigrants to England and the Netherlands. This article proposes that “social defeat” may be one of the social factors that may impact illness experience and uses original ethnographic research to argue that social defeat is a common feature of the social context in which many people diagnosed with schizophrenia in America live today.     

The cortical serotonin2A receptor and the pathology of schizophrenia: a likely accomplice

A large body of evidence shows that there is a change in the density of cortical serotonin2A receptors (5HT2AR) in post-mortem CNS from subjects with schizophrenia. Furthermore, some antipsychotic drugs have also been shown to cause a decrease in the density of 5HT2AR in the rat CNS. Thus, it appeared possible that changes in this receptor in human post-mortem CNS simply reflected an antipsychotic drug effect. However, a great deal of research on the 5HT2AR and schizophrenia now suggests that the changes in this receptor are complex and may be involved in both the pathology of the disorder and the effects of some antipsychotic drugs. Moreover, recent advances in basic research on the role of the 5HT2AR in the CNS add further support to the hypothesis that the receptor could be involved in the pathology of the illness. In particular, an argument will be developed that the changes in the 5HT2AR in schizophrenia are reflective of a real or perceived change in serotonergic tone and that this forms an important part of the pathology of the illness.     

Personal stigma in schizophrenia spectrum disorders: a systematic review of prevalence rates,correlates, impact and interventions

A systematic electronic PubMed, Medline and Web of Science database search was conducted regarding the prevalence, correlates, and effects of personal stigma (i.e., perceived and experienced stigmatization and self‐stigma) in patients with schizophrenia spectrum disorders. Of 54 studies (n=5,871), published from 1994 to 2011, 23 (42.6%) reported on prevalence rates, and 44 (81.5%) reported on correlates and/or consequences of perceived or experienced stigmatization or self‐stigma. Only two specific personal stigma intervention studies were found. On average, 64.5% (range: 45.0–80.0%) of patients perceived stigma, 55.9% (range: 22.5–96.0%) actually experienced stigma, and 49.2% (range: 27.9–77.0%) reported alienation (shame) as the most common aspect of self‐stigma. While socio‐demographic variables were only marginally associated with stigma, psychosocial variables, especially lower quality of life, showed overall significant correlations, and illness‐related factors showed heterogeneous associations, except for social anxiety that was unequivocally associated with personal stigma. The prevalence and impact of personal stigma on individual outcomes among schizophrenia spectrum disorder patients are well characterized, yet measures and methods differ significantly. By contrast, research regarding the evolution of personal stigma through the illness course and, particularly, specific intervention studies, which should be conducted utilizing standardized methods and outcomes, are sorely lacking.     

The interplay among psychopathology,personal resources,context‐related factors and real‐life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non‐recovered patients

Improving real‐life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness‐related variables, personal resources, context‐related factors and real‐life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4‐year follow‐up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow‐up. In addition, we compared the network structure of patients who were classified as recovered at follow‐up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow‐up study. The network structure did not change significantly from baseline to follow‐up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow‐up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non‐recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self‐reinforcing networks of symptoms and dysfunctions in people with schizophrenia.     

Relegating Psychosis: Blood Work and “Routine Connection” in the Clozapine Clinic

This paper attends to the sociality available in the clozapine clinic regimen and suggests that the social dimensions of clozapine treatment may be as important as the biochemical efficacy of clozapine. The clozapine clinic is where people diagnosed with chronic schizophrenia who take the antipsychotic clozapine go for routine monitoring of clozapine side effects, particularly haematological effects. Psychopharmaceutical treatments are often criticized for being reductionistic and dehumanizing, but clozapine clinics offer increased clinical contact in the age of deinstitutionalization. The inadvertent social benefits of biomedically reductive treatments have not previously been ethnographically attended to in the clozapine-only context. Drawing on 18 months of ethnographic fieldwork with 43 clozapine clients and 16 clinical caregivers in two clozapine clinics in the United Kingdom in Australia, I argue that routine clinical attachments in the clozapine clinic can serve a therapeutic role in terms of providing opportunities for clients’ health agency, social competence and accountability. This socio-therapeutic quality appeared to be available because the clinical emphasis was not on psychotic illness. It depended, however, on reliable and familiar social exchanges inside the clinic and on the predictability of clinical activity. The importance of unemotional but unfailing relationships and rhythms in the clozapine clinic context echoes cross-cultural findings about how schizophrenia is managed more productively in environments that invite more neutral and equal social exchanges.

     

Predicting phenology by integrating ecology,evolution and climate science

Forecasting how species and ecosystems will respond to climate change has been a major aim of ecology in recent years. Much of this research has focused on phenology – the timing of life‐history events. Phenology has well‐demonstrated links to climate, from genetic to landscape scales; yet our ability to explain and predict variation in phenology across species, habitats and time remains poor. Here, we outline how merging approaches from ecology, climate science and evolutionary biology can advance research on phenological responses to climate variability. Using insight into seasonal and interannual climate variability combined with niche theory and community phylogenetics, we develop a predictive approach for species’ reponses to changing climate. Our approach predicts that species occupying higher latitudes or the early growing season should be most sensitive to climate and have the most phylogenetically conserved phenologies. We further predict that temperate species will respond to climate change by shifting in time, while tropical species will respond by shifting space, or by evolving. Although we focus here on plant phenology, our approach is broadly applicable to ecological research of plant responses to climate variability.     

Oxytocin,testosterone, and human social cognition

I describe an integrative social‐evolutionary model for the adaptive significance of the human oxytocinergic system. The model is based on a role for this hormone in the generation and maintenance of social familiarity and affiliation across five homologous, functionally similar, and sequentially co‐opted contexts: mothers with offspring, female and male mates, kin groups, individuals with reciprocity partners, and individuals within cooperating and competing social groups defined by culture. In each situation, oxytocin motivates, mediates and rewards the cognitive and behavioural processes that underlie the formation and dynamics of a more or less stable social group, and promotes a relationship between two or more individuals. Such relationships may be positive (eliciting neurological reward, reducing anxiety and thus indicating fitness‐enhancing effects), or negative (increasing anxiety and distress, and thus motivating attempts to alleviate a problematic, fitness‐reducing social situation). I also present evidence that testosterone exhibits opposite effects from oxytocin on diverse aspects of cognition and behaviour, most generally by favouring self‐oriented, asocial and antisocial behaviours. I apply this model for effects of oxytocin and testosterone to understanding human psychological disorders centrally involving social behaviour. Reduced oxytocin and higher testosterone levels have been associated with under‐developed social cognition, especially in autism. By contrast, some combination of oxytocin increased above normal levels, and lower testosterone, has been reported in a notable number of studies of schizophrenia, bipolar disorder and depression, and, in some cases, higher oxytocin involves maladaptively ‘hyper‐developed’ social cognition in these conditions. This pattern of findings suggests that human social cognition and behaviour are structured, in part, by joint and opposing effects of oxytocin and testosterone, and that extremes of such joint effects partially mediate risks and phenotypes of autism and psychotic‐affective conditions. These considerations have direct implications for the development of therapies for alleviating disorders of social cognition, and for understanding how such disorders are associated with the evolution of human cognitive‐affective architecture.     

Urbanicity,social adversity and psychosis

In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual‐ and area‐level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non‐affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area‐level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date.     

The Role of OXT,OXTR, AVP,and AVPR1a Gene Expression in the Course of Schizophrenia

Schizophrenia is a serious and chronic mental illness, the symptoms of which usually appear for the first time in late adolescence or early adulthood. To date, much research has been conducted on the etiology of schizophrenia; however, it is still not fully understood. Oxytocin and vasopressin as neuromodulators that regulate social and emotional behavior are promising candidates for determining the vulnerability to schizophrenia. The aim of this study was to evaluate the expression of OXT, OXTR, AVP, and AVPR1a genes at the mRNA and protein levels in patients with schizophrenia. Due to the neurodegenerative nature of schizophrenia, the study group was divided into two subgroups, namely, G1 with a diagnosis that was made between 10 and 15 years after the onset of the illness, and G2 with a diagnosis made up to two years after the onset of the illness. Moreover, the relationship between the examined genes and the severity of schizophrenia symptoms, assessed using PANSS (Positive and Negative Syndrome Scale) and CDSS scales (Clinical Depression Scale for Schizophrenia) was evaluated. The analysis of the expression of the studied genes at the mRNA and protein levels showed statistically significant differences in the expression of all the investigated genes. OXT and AVPR1a gene expression at both the mRNA and protein levels were significantly lower in the schizophrenia group, and OXTR and AVP gene expression at both the mRNA and protein levels was higher in the schizophrenia subjects than in the controls. Furthermore, a significant correlation of OXT gene expression at the mRNA and protein levels with the severity of depressive symptoms in schizophrenia as assessed by CDSS was found.     

Reduced connectivity in the self-processing network of schizophrenia patients with poor insight

Lack of insight (unawareness of illness) is a common and clinically relevant feature of schizophrenia. Reduced levels of self-referential processing have been proposed as a mechanism underlying poor insight. The default mode network (DMN) has been implicated as a key node in the circuit for self-referential processing. We hypothesized that during resting state the DMN network would show decreased connectivity in schizophrenia patients with poor insight compared to patients with good insight. Patients with schizophrenia were recruited from mental health care centers in the north of the Netherlands and categorized in groups having good insight (n = 25) or poor insight (n = 19). All subjects underwent a resting state fMRI scan. A healthy control group (n = 30) was used as a reference. Functional connectivity of the anterior and posterior part of the DMN, identified using Independent Component Analysis, was compared between groups. Patients with poor insight showed lower connectivity of the ACC within the anterior DMN component and precuneus within the posterior DMN component compared to patients with good insight. Connectivity between the anterior and posterior part of the DMN was lower in patients than controls, and qualitatively different between the good and poor insight patient groups. As predicted, subjects with poor insight in psychosis showed decreased connectivity in DMN regions implicated in self-referential processing, although this concerned only part of the network. This finding is compatible with theories implying a role of reduced self-referential processing as a mechanism contributing to poor insight.     

Correlation of cognitive functions with some aspects of illness, treatment and social functioning in recurrently hospitalized schizophrenic patients

Cognitive deficits are found to be contributors to poorer psychosocial functioning, rehabilitation outcome and lack of treatment success in schizophrenia. Aim of the study was to examine correlation of cognitive functions with some aspects of illness, treatment and social functioning in a group of recurrently hospitalized schizophrenic patients (N=60). Deficient results on psychomotor processing speed, verbal fluency and verbal learning correlated with the longer duration of illness, higher number of hospitalizations and shorter duration of regular antipsychotic treatment. Deficient results on verbal fluency correlated with the younger age of onset, poor functional autonomy and organizational skills, whereas deficient results on psychomotor processing and verbal learning correlated with poor organizational skills alone. Score on verbal fluency was predictive of social skills impairment, whereas score on psychomotor processing was predictive of functional autonomy and organizational skills impairment. Functioning of different cognitive domains could be predictive of functioning in different social domains. Interplay of specific cognitive deficit and social functioning could be responsible for recurrent hospitalizations and unfavorable treatment choices.     

A meta‐review of “lifestyle psychiatry”: the role of exercise,smoking, diet and sleep in the prevention and treatment of mental disorders

There is increasing academic and clinical interest in how “lifestyle factors” traditionally associated with physical health may also relate to mental health and psychological well‐being. In response, international and national health bodies are producing guidelines to address health behaviors in the prevention and treatment of mental illness. However, the current evidence for the causal role of lifestyle factors in the onset and prognosis of mental disorders is unclear. We performed a systematic meta‐review of the top‐tier evidence examining how physical activity, sleep, dietary patterns and tobacco smoking impact on the risk and treatment outcomes across a range of mental disorders. Results from 29 meta‐analyses of prospective/cohort studies, 12 Mendelian randomization studies, two meta‐reviews, and two meta‐analyses of randomized controlled trials were synthesized to generate overviews of the evidence for targeting each of the specific lifestyle factors in the prevention and treatment of depression, anxiety and stress‐related disorders, schizophrenia, bipolar disorder, and attention‐deficit/hyperactivity disorder. Standout findings include: a) convergent evidence indicating the use of physical activity in primary prevention and clinical treatment across a spectrum of mental disorders; b) emerging evidence implicating tobacco smoking as a causal factor in onset of both common and severe mental illness; c) the need to clearly establish causal relations between dietary patterns and risk of mental illness, and how diet should be best addressed within mental health care; and d) poor sleep as a risk factor for mental illness, although with further research required to understand the complex, bidirectional relations and the benefits of non‐pharmacological sleep‐focused interventions. The potentially shared neurobiological pathways between multiple lifestyle factors and mental health are discussed, along with directions for future research, and recommendations for the implementation of these findings at public health and clinical service levels.     

Schizophrenia and family

Family represents an important supportive social network for most patients with schizophrenia. In order to provide safe and low-stress environment, necessary for the successful long-term treatment of schizophrenia the family must be helped. Family members suffer both emotionally and financially. Their burden is high and quality of life is low. Relatives change their life values and preferences when a severe mental illness occurs in the family and are ready to cooperate. Family interventions constitute an integral part of complex schizophrenia treatment. To be successful interventions must take into account relatives beliefs, perspectives and issues of concern. The goal of this paper is to 1) overview studies on family burden, 2) provide theoretical background for family interventions, 3) describe a family psychoeducational approach as an optimal treatment modification.     

Recurrent sublethal warming reduces embryonic survival,inhibits juvenile growth,and alters species distribution projections under climate change

The capacity to tolerate climate change often varies across ontogeny in organisms with complex life cycles. Recently developed species distribution models incorporate traits across life stages; however, these life‐cycle models primarily evaluate effects of lethal change. Here, we examine impacts of recurrent sublethal warming on development and survival in ecological projections of climate change. We reared lizard embryos in the laboratory under temperature cycles that simulated contemporary conditions and warming scenarios. We also artificially warmed natural nests to mimic laboratory treatments. In both cases, recurrent sublethal warming decreased embryonic survival and hatchling sizes. Incorporating survivorship results into a mechanistic species distribution model reduced annual survival by up to 24% compared to models that did not incorporate sublethal warming. Contrary to models without sublethal effects, our model suggests that modest increases in developmental temperatures influence species ranges due to effects on survivorship.     

Theory of mind and the social brain: implications for understanding the genetic basis of schizophrenia

Genome‐wide association studies in schizophrenia have recently made significant progress in our understanding of the complex genetic architecture of this disorder. Many genetic loci have been identified and now require functional investigation. One approach involves studying their correlation with neuroimaging and neurocognitive endophenotypes. Theory of Mind (ToM) deficits are well established in schizophrenia and they appear to fulfill criteria for being considered an endophenotype. We aim to review the behavioral and neuroimaging‐based studies of ToM in schizophrenia, assess its suitability as an endophenotype, discuss current findings, and propose future research directions. Suitable research articles were sourced from a comprehensive literature search and from references identified through other studies. ToM deficits are repeatable, stable, and heritable: First‐episode patients, those in remission and unaffected relatives all show deficits. Activation and structural differences in brain regions believed important for ToM are also consistently reported in schizophrenia patients at all stages of illness, although no research to date has examined unaffected relatives. Studies using ToM as an endophenotype are providing interesting genetic associations with both single nucleotide polymorphisms (SNPs) and specific copy number variations (CNVs) such as the 22q11.2 deletion syndrome. We conclude that ToM is an important cognitive endophenotype for consideration in future studies addressing the complex genetic architecture of schizophrenia, and may help identify more homogeneous clinical sub‐types for further study     

The impacts of increasing drought on forest dynamics,structure, and biodiversity in the United States

We synthesize insights from current understanding of drought impacts at stand‐to‐biogeographic scales, including management options, and we identify challenges to be addressed with new research. Large stand‐level shifts underway in western forests already are showing the importance of interactions involving drought, insects, and fire. Diebacks, changes in composition and structure, and shifting range limits are widely observed. In the eastern US, the effects of increasing drought are becoming better understood at the level of individual trees, but this knowledge cannot yet be confidently translated to predictions of changing structure and diversity of forest stands. While eastern forests have not experienced the types of changes seen in western forests in recent decades, they too are vulnerable to drought and could experience significant changes with increased severity, frequency, or duration in drought. Throughout the continental United States, the combination of projected large climate‐induced shifts in suitable habitat from modeling studies and limited potential for the rapid migration of tree populations suggests that changing tree and forest biogeography could substantially lag habitat shifts already underway. Forest management practices can partially ameliorate drought impacts through reductions in stand density, selection of drought‐tolerant species and genotypes, artificial regeneration, and the development of multistructured stands. However, silvicultural treatments also could exacerbate drought impacts unless implemented with careful attention to site and stand characteristics. Gaps in our understanding should motivate new research on the effects of interactions involving climate and other species at the stand scale and how interactions and multiple responses are represented in models. This assessment indicates that, without a stronger empirical basis for drought impacts at the stand scale, more complex models may provide limited guidance.     

Sex determination,longevity, and the birth and death of reptilian species

Vertebrate sex‐determining mechanisms (SDMs) are triggered by the genotype (GSD), by temperature (TSD), or occasionally, by both. The causes and consequences of SDM diversity remain enigmatic. Theory predicts SDM effects on species diversification, and life‐span effects on SDM evolutionary turnover. Yet, evidence is conflicting in clades with labile SDMs, such as reptiles. Here, we investigate whether SDM is associated with diversification in turtles and lizards, and whether alterative factors, such as lifespan's effect on transition rates, could explain the relative prevalence of SDMs in turtles and lizards (including and excluding snakes). We assembled a comprehensive dataset of SDM states for squamates and turtles and leveraged large phylogenies for these two groups. We found no evidence that SDMs affect turtle, squamate, or lizard diversification. However, SDM transition rates differ between groups. In lizards TSD‐to‐GSD surpass GSD‐to‐TSD transitions, explaining the predominance of GSD lizards in nature. SDM transitions are fewer in turtles and the rates are similar to each other (TSD‐to‐GSD equals GSD‐to‐TSD), which, coupled with TSD ancestry, could explain TSD's predominance in turtles. These contrasting patterns can be explained by differences in life history. Namely, our data support the notion that in general, shorter lizard lifespan renders TSD detrimental favoring GSD evolution in squamates, whereas turtle longevity permits TSD retention. Thus, based on the macro‐evolutionary evidence we uncovered, we hypothesize that turtles and lizards followed different evolutionary trajectories with respect to SDM, likely mediated by differences in lifespan. Combined, our findings revealed a complex evolutionary interplay between SDMs and life histories that warrants further research that should make use of expanded datasets on unexamined taxa to enable more conclusive analyses.     

Dopamine and glutamate in schizophrenia: biology,symptoms and treatment

Glutamate and dopamine systems play distinct roles in terms of neuronal signalling, yet both have been proposed to contribute significantly to the pathophysiology of schizophrenia. In this paper we assess research that has implicated both systems in the aetiology of this disorder. We examine evidence from post‐mortem, preclinical, pharmacological and in vivo neuroimaging studies. Pharmacological and preclinical studies implicate both systems, and in vivo imaging of the dopamine system has consistently identified elevated striatal dopamine synthesis and release capacity in schizophrenia. Imaging of the glutamate system and other aspects of research on the dopamine system have produced less consistent findings, potentially due to methodological limitations and the heterogeneity of the disorder. Converging evidence indicates that genetic and environmental risk factors for schizophrenia underlie disruption of glutamatergic and dopaminergic function. However, while genetic influences may directly underlie glutamatergic dysfunction, few genetic risk variants directly implicate the dopamine system, indicating that aberrant dopamine signalling is likely to be predominantly due to other factors. We discuss the neural circuits through which the two systems interact, and how their disruption may cause psychotic symptoms. We also discuss mechanisms through which existing treatments operate, and how recent research has highlighted opportunities for the development of novel pharmacological therapies. Finally, we consider outstanding questions for the field, including what remains unknown regarding the nature of glutamate and dopamine function in schizophrenia, and what needs to be achieved to make progress in developing new treatments.     

Alternative reality and art: the creative world of Walter Inglis Anderson

Both mental illness and creativity run in families. This observation suggests the possibility of genetic predisposition; in light of the known dynamic interrelationships among the environment, the personality, and the brain, however, it does not diminish the possibility of significant environmental influence on personal development. An examination of the biological, psychological, and social forces impacting the life of Walter Inglis Anderson (1903-1965), the South's most important artist, serves as a case in point. Anderson's upbringing, including his mother's determination that her sons become artists and her beliefs about the shamanistic role of artists in society, might have played a large part in establishing an unusual and indelible frame of reference in a family whose history insinuated the possibility of untoward outcomes.Walter Anderson's life as an artist--one who lived at times in an alternative reality--raises questions about how a different set of circumstances might have affected his mental state as well as his talent. This essay discusses some of the important relationships, events, and circumstances in Walter Anderson's life from a biopsychosocial perspective, with emphasis on psychodynamic implications of his illness and its questionable diagnosis as schizophrenia.