Intervention, causal reasoning, and the neurobiology of mental disorders: Pharmacological drugs as experimental instruments

In psychiatry, pharmacological drugs play an important experimental role in attempts to identify the neurobiological causes of mental disorders. Besides being developed in applied contexts as potential treatments for patients with mental disorders, pharmacological drugs play a crucial role in research contexts as experimental instruments that facilitate the formulation and revision of neurobiological theories of psychopathology. This paper examines the various epistemic functions that pharmacological drugs serve in the discovery, refinement, testing, and elaboration of neurobiological theories of mental disorders. I articulate this thesis with reference to the history of antipsychotic drugs and the evolution of the dopamine hypothesis of schizophrenia in the second half of the twentieth century. I argue that interventions with psychiatric patients through the medium of antipsychotic drugs provide researchers with information and evidence about the neurobiological causes of schizophrenia. This analysis highlights the importance of pharmacological drugs as research tools in the generation of psychiatric knowledge and the dynamic relationship between practical and theoretical contexts in psychiatry.     

The financial situation before and after first-time psychiatric in-patient diagnosis of schizophrenia spectrum,bipolar, and major depressive disorder

Schizophrenia spectrum, bipolar, and major depressive disorders are severe mental illnesses (SMIs) that not only entail great suffering for those affected but also major societal costs. In this study, I use administrative register data to provide a detailed picture of the financial situation of people with SMI in Sweden during a period of $\pm$10 years around first-time psychiatric in-patient diagnosis of schizophrenia spectrum, bipolar, and major depressive disorders. Receiving a diagnosis was associated with a considerable drop in earnings, which was largely compensated for by social transfers: mainly sickness and disability insurance. However, there were also large and increasing pre-diagnosis earnings gaps, relative to matched comparison groups, especially among those with schizophrenia spectrum disorders. These gaps were to a lesser extent compensated for by social transfers. Consequently, there were permanent and increasing – due to lost earnings growth – income differentials. Hence, findings in previous studies are confirmed: even in an advanced welfare state, people with SMI – especially those with schizophrenia – have an extremely weak position on the labour market and an equally difficult financial situation.     

The role of trust in global health research collaborations

Collaborations in global health research are on the rise because they enhance productivity, facilitate capacity building, accelerate output and make tackling big, multifactorial research questions possible. In this paper, I examine the concepts of trust and reliance in scientific collaborations in general, but also in the particular context of collaborations in global health research between high‐income countries and low‐and‐middle income countries (LMIC). I propose and defend the argument that given the particular characteristics of collaborations and demands of trust relationships, reliance is a better relational mode for successful collaborations. Although reliance can be difficult to establish in situations where asymmetry of power exists, trust should not be the only relational mode available to LMIC researchers because of the type of vulnerability it introduces to the relationship. I conclude that the promotion of good collaborations requires addressing the power imbalances between partners, and establishing an even playing field in global health research.     

Psychiatric morbidity of a long stay hospital population with chronic schizophrenia and implications for future community care.

In the United Kingdom there are plans to close most mental hospitals over the next 10 years. There is continuing uncertainty about the effectiveness of community psychiatric services that will be expected to cope with mental hospital inpatients after discharge, most of whom have schizophrenia. A survey was conducted to assess the severity of illness among such patients and implications for their future care. All 222 patients in non-psychogeriatric long stay wards of a mental hospital who met research diagnostic criteria for schizophrenia were interviewed by two psychiatrists with the comprehensive psychopathological rating scale to establish the prevalence of psychiatric symptomatology. A complete interview was not possible for 28 patients, mainly for reasons related to their schizophrenia. Despite energetic pharmacological and social treatments almost half of the 194 patients interviewed had enduring florid psychotic symptoms that presented as one or more delusions or auditory hallucinations, or both, and a sizable proportion showed behaviour that would set them apart in a community setting. The results illustrate a problem that is still imperfectly understood by policy makers and administrators in central and local government and in health authorities who are responsible for planning and implementing services for psychiatric care in the community.     

Issues for cross-cultural psychiatric research in South Africa

South Africa's heterogenous society offers many opportunities for cross-cultural psychiatric research, but researchers in the country are subject to a number of restraints. Apart from legally enforced segregation, there are strict censorship laws and restricted access to certain types of information. The issues surrounding categorization of cultures and factors affecting publishing research from South Africa have important implications for the type of work that is done. It is a central argument of this article that the issues affecting research in South Africa are relevant to other countries as well, and parallels between the local and international context are drawn. The South African experience suggests that analysis of the research enterprise itself is a useful part of the business of cross-cultural psychiatric research.I am grateful to Beverley Jo Dickman, Terry Dowdall, Ronith Elk, Alan Flisher, Don Foster, Jane Steere and Sally Swartz for their comments on this article. Emile Boonzaaier provided a useful critique on an earlier draft. The arguments presented in this article are, however, my responsibility alone.     

The outcome of targeting community mental health services: evidence from the West Lambeth schizophrenia cohort.

OBJECTIVES--To report outcome of targeting community mental health services to people with schizophrenia in an inner London district who had been shown, one year after discharge, to have high levels of psychotic symptomatology and social disability but very low levels of supported housing and structured day activity. DESIGN--Repeat interview survey of symptoms, disability, and receipt of care four years after index discharge. SETTING--Inner London health district with considerable social deprivation and a mental hospital in the process of closure. SUBJECTS--51 patients originally aged 20-65 years who satisfied the research diagnostic criteria for schizophrenia. MAIN OUTCOME MEASURES--Contact with services during the three months before interview, levels of symptoms (from present state examination), global social disability rating. RESULTS--65% (33/51) of the study group had been readmitted at least once in the three years between surveys. Recent contacts with community psychiatric nurses and rates of hospital admission increased (8 at one year v 24 at four years, p < 0.01; 5 v 13, p < 0.06). Conversely, fewer patients were in contact with social workers (17 v 7, p < 0.03). Proportions in supported housing, day care, or sheltered work did not change. Unemployment rates remained very high. A considerable reduction (almost a halving) in psychiatric symptoms was observed, but there was no significant change in mean levels of social disability. CONCLUSIONS--The policy of targeting the long term mentally ill resulted in significant increases in professional psychiatric input to the cohort but failed to improve access to social workers or suitable accommodation. Improvements in social functioning did not follow from reductions in the proportions of patients with psychotic mental states. Social interventions are likely to be crucial to achieving the Health of the Nation target of improving social functioning for the seriously mentally ill, as improving mental state seems in itself to be insufficient.     

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 nature of psychiatric disorders

A foundational question for the discipline of psychiatry is the nature of psychiatric disorders. What kinds of things are they? In this paper, I review and critique three major relevant theories: realism, pragmatism and constructivism. Realism assumes that the content of science is real and independent of human activities. I distinguish two “flavors” of realism: chemistry‐based, for which the paradigmatic example is elements of the periodic table, and biology‐based, for which the paradigm is species. The latter is a much better fit for psychiatry. Pragmatism articulates a sensible approach to psychiatric disorders just seeking categories that perform well in the world. But it makes no claim about the reality of those disorders. This is problematic, because we have a duty to advocate for our profession and our patients against other physicians who never doubt the reality of the disorders they treat. Constructivism has been associated with anti‐psychiatry activists, but we should admit that social forces play a role in the creation of our diagnoses, as they do in many sciences. However, truly socially constructed psychiatric disorders are rare. I then describe powerful arguments against a realist theory of psychiatric disorders. Because so many prior psychiatric diagnoses have been proposed and then abandoned, can we really claim that our current nosologies have it right? Much of our current nosology arose from a series of historical figures and events which could have gone differently. If we re‐run the tape of history over and over again, the DSM and ICD would not likely have the same categories on every iteration. Therefore, we should argue more confidently for the reality of broader constructs of psychiatric illness rather than our current diagnostic categories, which remain tentative. Finally, instead of thinking that our disorders are true because they correspond to clear entities in the world, we should consider a coherence theory of truth by which disorders become more true when they fit better into what else we know about the world. In our ongoing project to study and justify the nature of psychiatric disorders, we ought to be broadly pragmatic but not lose sight of an underlying commitment, despite the associated difficulties, to the reality of psychiatric illness.     

Prioritising African perspectives in psychiatric genomics research: Issues of translation and informed consent

Psychiatric genomics research with African populations comes with a range of practical challenges around translation of psychiatric genomics research concepts, procedures, and nosology. These challenges raise deep ethical issues particularly around legitimacy of informed consent, a core foundation of research ethics. Through a consideration of the constitutive function of language, the paper problematises like‐for‐like, designative translations which often involve the ‘indigenization’ of English terms or use of metaphors which misrepresent the risks and benefits of research. This paper argues that effective translation of psychiatric genomics research terminology in African contexts demands substantive engagement with African conceptual schemas and values. In developing attenuated forms of translational thinking, researchers may recognise the deeper motivational reasons behind participation in research, highlighting the possibility that such reasons may depart from the original meaning implied within informed consent forms. These translational issues might be ameliorated with a critical re‐examination of how researchers develop and present protocols to institutional ethics review boards.     

Social Defeat in Recovery-Oriented Supported Housing: Moral Experience, Stigma, and Ideological Resistance

Drawing from ethnographic observations and interview data gathered during 6?months working as a home caregiver at the Pinewood Apartments, a recovery-oriented supported housing community in Texas, I demonstrate how stigma and social defeat were moral and social processes that pervaded life for all involved, including service providers. Yet, because of the extreme power differentials that characterized tenant-staff relationships, the assault of stigma and social defeat was much more frequent, existentially intense, and morally and materially consequential for certain tenants, whose attempts at ideological resistance were delegitimized by service providers, including myself, who were backed by the authority of dominant psychiatric and moralistic discourses concerning the inherent irrationality and irresponsibility of people with severe mental illness. Nevertheless, due to the indeterminate and at times inharmonious nature of moral experience, it is not my intention to portray tenants as wholly defeated. Rather, individual tenants often exhibited defeat and resistance simultaneously.     

My Neighbor: Children's Perception of Agency in Interaction with an Imaginary Agent

Children may treat an invisible entity as a live and thinking entity, known as an imaginary companion (IC). Some researchers suggest that this is simply pretend play, but it is possible that children experience agency in their interactions with ICs. Given the literature on cognitive science and social brain research, we hypothesize that young children may have an agent-perception system that responds to an invisible agent by which they may experience realistic agency in their interactions with ICs. In this study, children were introduced to an invisible agent and an invisible stone. However, they assigned biological and psychological properties to the agent but not the stone. The tendency of assigning such properties was stronger in children with ICs than in those without ICs. These results contribute to our understanding of cognitive and neural development in typical and atypical children.     

On the Alleged Right to Participate in High‐Risk Research

Reigning regulatory frameworks for biomedical research impose on researchers and research ethics committees an obligation to protect research participants from risks that are unnecessary, disproportionate to potential research benefits, and non‐minimized. Where the research has no potential to produce results of direct benefit to the subjects and the subjects are unable to give consent, these requirements are strengthened by an additional condition, that risks should not exceed a certain minimal threshold. In this article, I address the question of whether there should be limits of permissible risks in non‐therapeutic research involving competent and healthy subjects. Some commentators argue that competent and informed individuals should have a right to participate even in extremely risky research and that research ethics committees should never reject studies because they are too dangerous. To use David Shaw's expression, competent volunteers should have ‘a right to participate in high‐risk research’. I argue that this idea is ill‐founded, as it does not take into account the social mission and complex collaborative nature of research practice as well as the inequity of power between researchers and subjects. Imposition of limits on permissible risks for healthy volunteers is justified by the need to protect research enterprise and the need to protect the weaker party, namely the subjects. Also, I suggest that the best way to set boundaries on research risks is to leave the judgment of risk acceptability to research ethics committees.     

La psychothérapie individuelle de la schizophrénie: mise en perspective de son histoire, de ses développements récents et de ses orientations nouvelles

Empirical study of long-term outcomes for persons with schizophrenia suggests that recovery is often possible. This literature also emphasizes that recovery may involve different kinds of experiences for different people with the same psychiatric condition. For some, recovery may mean symptom remission while for others it may be reflected by the achievement of psychosocial milestones. For yet others, however, to recover can involve subjective changes in how those persons experience themselves as meaningful agents in the world. For some, to recover could be to reclaim a full sense of self, a sense of self that permits to engage in relationship with others and the rigors of daily life. In this chapter, we review the potential of individual psychotherapy to address the more subjective aspects of recovery related to sense of self. We first review literature on the effectiveness of psychotherapy for persons with schizophrenia. We then discuss literature on the larger issue of how decrement in personal narrative metacognition may underpin some of the disturbance in sense of self observed in schizophrenia. Finally, we focus on how psychotherapy could be conceptualized and adapted to help enrich self-experience by addressing narrative and metacognition. Directions for future research are discussed.     

Culture and Disability Behavior

A substantial amount of literature suggests that illness behavior in the United States is a product of a patient''s core culture; equally credible findings do not support this contention. Most students and graduates in the health care professions believe that illness and disability behavior are affected by a patient''s culture, but they are hard put to find convincing examples of that relationship. In experience with medical students studying the social and cultural bases of illness behavior, with patients who are disabled and with persons who claim disability in the absence of physical disease or disabling psychopathology, I observed no deviant disability behavior that was typical for the members of any cultural group, and no behavior was displayed by the members of one cultural group that was not seen in members of other cultural groups. No cultural stereotypes were upheld. I did find evidence that disability behavior is influenced by personality factors, social situations and the gains derived from the disability status. Evolving concepts of “entitlement,” which are closely related to socioeconomic status, also have a significant influence. The impact of feedback from others in a person''s many social and medical subcultures is a more crucial determinant of illness and disability behavior, except in those for whom illness and disability behavior is determined by the limitations imposed by the disease or by a personality structure resistant to cultural expectations and social feedback.     

La schizophr��nie et les troubles de l��exp��rience en premi��re personne: convergence et divergence de six points de vue

Contemporary researchers have tended to present psychosocial dysfunction in schizophrenia as a result of biological and social forces. While this has greatly advanced the knowledge base, we are still without a full account of the illness??s first-person dimensions. As such, there is a risk of failing to grasp that schizophrenia is a disorder that interrupts the lives of people, making them struggle to find and create security and meaning. While literature from a range of sources has explored self-experience in schizophrenia, one barrier to the creation of a larger synthesis and application of this work is that it remains unclear whether, and to what degree, these differing views of self-experience are compatible. To address this issue, this paper reviews six different accounts of self-experience, a fundamental, first-person dimension of schizophrenia. They are early psychiatry, existential psychiatry, psychoanalysis, phenomenology, psychosocial rehabilitation, and dialogical psychology. After comparing and contrasting the six, we conclude that there is a wide ranging, in general consensus, which suggests that many suffering from schizophrenia experience themselves as diminished relative to their former selves??that is, after onset, they experience themselves as less able to engage the world effectively, which intensifies their anxieties in the face of everyday interactions. However, significant disagreement exists regarding the emergence and natural course of these difficulties. Do they predate the illness? Is recovery possible and if so, under what conditions? In the end, we suggest a program of research to create a richer account of first-person experience of schizophrenia.     

Certificates of confidentiality in research: rationale and usage

Certificates of confidentiality (COCs) are a tool to protect researchers from being compelled to release identifying information about their subjects. Whereas institutional review board (IRB) review and informed consent procedures are mandatory tools to protect human subjects, COCs are voluntary. There are limited data about who procures COCs and why, and whether they are useful. Three Institutes of the National Institutes of Health (NIH) provided data on 114 research projects that had received COCs. Eighty-three researchers had procured a single COC and 11 researchers had procured 31 COCs. One hundred and four (91%) of the COCs were obtained by researchers at academic sites, and 17 institutions collectively accounted for 82 COCs. The most commonly cited sources of information about COCs came from colleagues (n = 18, 35%) and previous experience (n = 17, 33%). The most common reasons for procuring a COC were that the research involved genetics (n = 28, 54%), the research could lead to social stigmatization or discrimination (n = 22, 42%), or the research could damage an individual's financial standing, employability, or reputation (n = 21, 40%). These findings show that COCs are often congregated within institutions and by particular individuals. This may be because others are unaware of COCs or because others do not believe they are necessary or useful.     

Opening the Black Box of Developmental Experiments: Behavioural Mechanisms Underlying Long‐Term Effects of Early Social Experience

Typically, animals spend a considerable portion of their time with social interactions involving mates, offspring, competitors and group members. The social performance during these interactions can strongly depend on the social environment individuals have experienced early in life. Despite a considerable number of experiments investigating long‐term effects of the early social environment, our understanding of the behavioural mechanisms mediating these effects is still limited, mainly for two reasons. (1) Only in few experimental studies have researchers actually observed and quantified the behaviour of their study animals during the social treatment. (2) Even if differences in social interactions between social rearing treatments are reported, these differences might not be causally linked to any observed long‐term effects later in life. The aim of this review was to investigate whether behavioural records of animals during the experimental manipulation of their social environment can help (1) identifying behavioural mechanisms involved in a long‐term effect and (2) obtaining a better understanding of the long‐term consequences of early manipulations. First, I review studies that manipulated the social environment at an early stage of the ontogeny, observed the social interactions and behaviour during the social experience phase and subsequently tested the performance in social and non‐social behavioural tasks at a later life stage. In all reviewed studies, treatment differences were reported both in social interactions during the social experience phase and in social and/or non‐social behaviours later in life. Second, I discuss four classes of behavioural mechanisms that can cause the reported long‐term effects of social experience, namely learning by experience, social learning, sensory stimulation and social cueing. I conclude that social interactions during the social experience phase should always be recorded for at least two reasons. Knowledge about how the social interactions differ between rearing treatments (1) permits researchers to formulate hypotheses about candidate mechanisms causing long‐term effects on behaviour and (2) can help to interpret unexpected outcomes of developmental experiments. Finally, I propose that as a crucial ultimate step towards understanding effects of the early social environment, we should develop targeted experiments testing for the causality of identified candidate mechanism.     

Impact of obesity on health-related quality of life in schizophrenia and bipolar disorder

Objective: Studies have reported that up to 60% of individuals with schizophrenia and 68% of those with bipolar disorder are overweight/obese. This paper explores the health‐related quality of life (HRQOL) of individuals with schizophrenia or bipolar disorder as a function of obesity status. Methods and Procedures: Two hundred and eleven participants were recruited from four psychiatric programs (outpatient, day treatment, case management, and psychosocial rehabilitation). HRQOL was assessed using both a general measure (Medical Outcomes Study Short‐Form‐36 (SF‐36)) and a weight‐related measure (Impact of Weight on Quality of Life‐Lite (IWQOL‐Lite)). To interpret HRQOL scores obtained by the obese group, we compared scores to those obtained by reference groups from the weight‐loss literature. Results: Sixty‐three percent of participants with schizophrenia and 68% of those with bipolar disorder were obese. Obese participants were more likely to be women, on mood stabilizers, taking a greater number of psychiatric medications, and to have poorer weight‐related and general HRQOL. Weight‐related HRQOL in the obese psychiatric sample was more impaired than in outpatient and day treatment samples seeking weight loss but less impaired than in gastric‐bypass patients. Several of the physical domains of general HRQOL were more impaired for the obese psychiatric sample than for the outpatient weight‐loss sample. However, physical functioning was less impaired for the obese psychiatric sample than for gastric‐bypass patients. Discussion: The presence of obesity among individuals with schizophrenia or bipolar disorder is associated with decreased HRQOL. These results have implications for prevention and management of weight gain in individuals with schizophrenia or bipolar disorder.     

Incidence of psychotic illness in London: comparison of ethnic groups.

OBJECTIVE--To compare annual incidences of psychosis in people from different ethnic groups as defined in the 1991 census. SETTING--Catchment area of district psychiatric hospital. DESIGN--All people aged 16 to 54 years who made contact with a wide range of community and hospital services between 1 July 1991 and 30 June 1992 were screened for psychotic symptoms. Patients with such symptoms were interviewed face to face to collect information on demography, ethnic group, psychiatric history and symptoms, drug use, and how care had been sought. A key informant, usually a close relative, was also interviewed. MAIN OUTCOME MEASURES--Age standardised incidence of schizophrenia and non-affective psychosis according to the ninth edition of the International Classification of Diseases in each ethnic group. RESULTS--Ninety three patients took part, of whom 38 were assigned a certain or very likely diagnosis of schizophrenia (15 in white population, 14 in black, seven in Asian, and two in others). The age standardised annual incidence of schizophrenia was 2.2 (95% confidence interval 1.5 to 2.9) per 10,000 of the population. The incidence ratio for schizophrenia in all ethnic minority groups compared with the white population was 3.6 (1.9 to 7.1); the corresponding figure for non-affective psychosis was 3.7 (2.2 to 6.2). CONCLUSIONS--Raised incidences of schizophrenia were not specific to the African Caribbeans, which suggests that the current focus on schizophrenia in this population is misleading. Members of all ethnic minority groups were more likely to develop a psychosis but not necessarily schizophrenia. The personal and social pressures of belonging to any ethnic minority group in Britain are important determinants in the excess of psychotic disorders found.