Secondary psychoses: an update

Psychotic disorders due to a known medical illness or substance use are collectively termed secondary psychoses. In this paper, we first review the historic evolution of the concept of secondary versus primary psychosis and how this distinction supplanted the earlier misleading classification of psychoses into organic and functional. We then outline the clinical features and approach to the diagnosis of secondary psychotic disorders. Features such as atypical presentation, temporal relation to detectable medical cause, evidence of direct physiological causal relationship to the etiological agent, and the absence of evidence of a primary psychotic illness that may better explain the presentation suggest consideration of a secondary psychosis. Finally, we discuss how careful studies of secondary psychotic disorders can help elucidate the pathophysiology of primary, or idiopathic, psychotic disorders such as schizophrenia. We illustrate this issue through a discussion of three secondary psychotic disorders — psychoses associated with temporal lobe epilepsy, velocardiofacial syndrome, and N‐methyl D‐aspartate (NMDA) receptor encephalitis — that can, respectively, provide neuroanatomical, genetic, and neurochemical models of schizophrenia pathogenesis.     

Existentialism and Present-Day Psychiatry Abroad

The criticism and overcoming of various idealist distortions of the nature of mental diseases and of the scientific method in psychiatry certainly constitute most important prerequisites for the scientific materialist study of psychoses. Such a critique is impossible without determining the influence exercised by various trends in Western idealist philosophy and the reflection of this influence upon the views and directions of contemporary psychiatry abroad. Because of its specific features, psychiatry as a science has proved to be central to the ever more exacerbated struggle between materialism and materialist scholarship, on the one hand, and various idealist trends, open or concealed, on the other. Soviet psychiatrists are the authors of a number of works of critical analysis of the ideological and philosophical sources of various idealist trends in modern psychiatry abroad (1, and others). When, in this article, we return once again to the question of modern "existentialist psychiatry," it is for the following reasons.     

Early intervention in psychosis: concepts,evidence and future directions

The rise of the early intervention paradigm in psychotic disorders represents a maturing of the therapeutic approach in psychiatry, as it embraces practical preventive strategies which are firmly established in mainstream health care. Early intervention means better access and systematic early delivery of existing and incremental improvements in knowledge rather than necessarily requiring dramatic and elusive breakthroughs. A clinical staging model has proven useful and may have wider utility in psychiatry. The earliest clinical stages of psychotic disorder are non-specific and multidimensional and overlap phenotypically with the initial stages of other disorders. This implies that treatment should proceed in a stepwise fashion depending upon safety, response and progression. Withholding treatment until severe and less reversible symptomatic and functional impairment have become entrenched represents a failure of care. While early intervention in psychosis has developed strongly in recent years, many countries have made no progress at all, and others have achieved only sparse coverage. The reform process has been substantially evidence-based, arguably more so than other system reforms in mental health. However, while evidence is necessary, it is insufficient. It is also a by-product as well as a catalyst of reform. In early psychosis, we have also seen the evidence-based paradigm misused to frustrate overdue reform. Mental disorders are the chronic diseases of the young, with their onset and maximum impact in late adolescence and early adult life. A broader focus for early intervention would solve many of the second order issues raised by the early psychosis reform process, such as diagnostic uncertainty despite a clear-cut need for care, stigma and engagement, and should be more effective in mobilizing community support. Early intervention represents a vital and challenging project for early adopters in global psychiatry to consider.     

Community Psychiatry and the Population Explosion

Although excessive population has long been a dilemma in certain areas of the world, current rates of growth present a global threat to all nations. Arguments based on economics, world peace, individual freedom, humanism and the preservation of life''s amenities all point to the urgent need for programs to control birth rates. This applies to the United States also, although we have the advantage of a relatively high cultural and economic level from which to attack the problem.Modern psychiatry is increasingly committed to the Community Mental Health concept, which in part implies greater involvement with the element of the population that is socially and economically at a disadvantage. Effective treatment cannot ignore the effects on the patient of intolerable reality situations, often produced by successive unwanted pregnancies. In addition, a positive approach to family planning by psychiatrists and social workers will provide the structure needed for truly preventive psychiatry; as our knowledge of the determinants of psychosis, delinquency and mental retardation expands, selective counseling can do much to prevent these family and social tragedies.Both as world citizens and as practitioners of a profession, psychiatrists cannot afford to delay pledging their resources to the solution of so compelling a problem.     

Schizophrenia and Violence: Systematic Review and Meta-Analysis

Background

Although expert opinion has asserted that there is an increased risk of violence in individuals with schizophrenia and other psychoses, there is substantial heterogeneity between studies reporting risk of violence, and uncertainty over the causes of this heterogeneity. We undertook a systematic review of studies that report on associations between violence and schizophrenia and other psychoses. In addition, we conducted a systematic review of investigations that reported on risk of homicide in individuals with schizophrenia and other psychoses.

Methods and Findings

Bibliographic databases and reference lists were searched from 1970 to February 2009 for studies that reported on risks of interpersonal violence and/or violent criminality in individuals with schizophrenia and other psychoses compared with general population samples. These data were meta-analysed and odds ratios (ORs) were pooled using random-effects models. Ten demographic and clinical variables were extracted from each study to test for any observed heterogeneity in the risk estimates. We identified 20 individual studies reporting data from 18,423 individuals with schizophrenia and other psychoses. In men, ORs for the comparison of violence in those with schizophrenia and other psychoses with those without mental disorders varied from 1 to 7 with substantial heterogeneity (I ² = 86%). In women, ORs ranged from 4 to 29 with substantial heterogeneity (I ² = 85%). The effect of comorbid substance abuse was marked with the random-effects ORs of 2.1 (95% confidence interval [CI] 1.7–2.7) without comorbidity, and an OR of 8.9 (95% CI 5.4–14.7) with comorbidity (p<0.001 on metaregression). Risk estimates of violence in individuals with substance abuse (but without psychosis) were similar to those in individuals with psychosis with substance abuse comorbidity, and higher than all studies with psychosis irrespective of comorbidity. Choice of outcome measure, whether the sample was diagnosed with schizophrenia or with nonschizophrenic psychoses, study location, or study period were not significantly associated with risk estimates on subgroup or metaregression analysis. Further research is necessary to establish whether longitudinal designs were associated with lower risk estimates. The risk for homicide was increased in individuals with psychosis (with and without comorbid substance abuse) compared with general population controls (random-effects OR = 19.5, 95% CI 14.7–25.8).

Conclusions

Schizophrenia and other psychoses are associated with violence and violent offending, particularly homicide. However, most of the excess risk appears to be mediated by substance abuse comorbidity. The risk in these patients with comorbidity is similar to that for substance abuse without psychosis. Public health strategies for violence reduction could consider focusing on the primary and secondary prevention of substance abuse. Please see later in the article for Editors'' Summary     

Pediatric psychopharmacology: too much or too little?

This paper provides a selective overview of the past, present and future of pediatric psychopharmacology. The acceptance of medication use in child psychiatry was based on the results of double‐blind, placebo‐controlled trials documenting the efficacy of drug treatments for attention‐deficit/hyperactivity disorder, enuresis, depression, anxiety disorders, obsessive‐compulsive disorder and psychoses. This period of success was followed by a series of challenges, including a growing awareness of the long‐term adverse effects of medications and of the inadequacy of long‐term drug surveillance. There is great concern today that children are being overtreated with medication, especially in the US. Further advances in pediatric psychopharmacology may come from examination of large medical data sets including both pharmacological and psychiatric information, which could lead to drug repurposing, as well as from preclinical translational studies such as those using human induced pluripotent stem cells.     

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.     

Rational Love,Relational Medicine: Psychiatry and the Accumulation of Precarious Kinship

In north Indian psychiatry, clinical attentions to women’s symptoms often involve scrutiny of emotions related to marriage and its breakdown. In pharmaceutically oriented practice, relations are used to evaluate biologies, and drugs produce the truth about relations at the same time that they produce the truth about bodies. In the process, clinical practice often involves unmaking relations, generating loss, in certain instances, as a dire result. In this, a particular kind of clinical knowing emerges, engaging broad cultural and historical connections between love and madness more than definitions of right and wrong unions. In asking how disciplinary and relational modes of biomedicine converge, I argue that in north Indian psychiatry’s attentions to women, rather than enforcing normative configurations of “the family,” biomedicine grapples with the gendered fallout of kinship.     

Traitement pharmacologique du premier épisode psychotique

Pharmacological treatment has a central role in the treatment of a first episode psychosis. However, drug therapy must be viewed as within a framework of a global approach, whose aim is to facilitate the participation of the patient in the treatment regime. As the initial symptoms of psychotic disorders may often be atypical and complicated by co-morbidity, this can make both the early diagnosis and the choice of an appropriate treatment difficult. In a more dimensional approach to diagnosis rather than a categorical approach, it is important to identify the presence of affective symptoms (depressive or manic) which may necessitate the addition of either an antidepressant or a mood stabilizer. The indication for using atypical antipsychotic drugs as first choice in treatment has been firmly established in the current literature. These novel antipsychotic drugs are less prone to inducing undesirable side-effects, such as cognitive impairment and dysphoria, and appear to have a more favourable effect than conventional neuroleptics on the course of both depressive symptoms as well as hostile and aggressive behaviours. Furthermore, they seem to have a mood stabilizing effect, and are more easily accepted by the patients. Even though there is a reduced risk of acute extrapyramidal side-effects and late onset dyskinesia, the risk of weight gain as well as cardiovascular and endocrinological complications is considerable. This review article focuses on problems related to pharmacological treatment of first episode psychosis. It is the result of an extensive review of the current literature available on this field. The results have been discussed and organised in the form of clinical guidelines for the treatment of both non-affective and affective first episode psychoses.     

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.     

Are psychiatrists an endangered species? Observations on internal and external challenges to the profession

Based on recently voiced concerns about a crisis in psychiatry, six challenges to our profession are identified and discussed. As we approach the revisions of ICD-10 and DSM-IV, the validity of psychiatry’s diagnostic definitions and classification systems is increasingly questioned also from inside psychiatry. In addition, confidence in the results of therapeutic intervention studies is waning. A further challenge is the existence of de facto subgroups with opposing ideologies, a situation which is responsible for an unclear role profile of the psychiatrist. Challenges from outside include mounting patient and carer criticism, intrusion of other professions into psychiatry’s traditional field of competence, and psychiatry’s low status within medicine and in society in general. Studies suggest that the decline of the recruitment into psychiatry, as it is observed in many countries, might be related to problems arising from these challenges. It is unclear whether psychiatry will survive as a unitary medical discipline or whether those segments which are more rewarding, both financially and in status, will break away, leaving the unattractive tasks to carry out by what remains of psychiatry. The demise of the generalist and the rise of the specialist in modern society may contribute to this development. Attempts are underway by professional bodies to define the profile of a “general psychiatrist”. Such discussions should be complemented by an analysis of the incentives which contribute to the centrifugal tendencies in psychiatry.     

Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring

Previous studies have shown that maternal antibodies to Toxoplasma measured during pregnancy are associated with an increased risk of schizophrenia and other psychoses in adult offspring. Recently, it has been recognized that different genotypes of Toxoplasma have distinct neuropathogenic potential. The objective of this study was to investigate whether parasite genotype is a contributing factor to disease risk. We have developed an enzyme-linked immunosorbent assay (ELISA) that uses polymorphic polypeptides specific to the three clonal parasite lineages and derived from three dense granule antigens, GRA5, GRA6 and GRA7. We used this assay to measure type-specific antibodies in the sera from 219 pregnant women whose children developed schizophrenia and affective psychotic illnesses in adult life, and 618 matched unaffected control mothers from three cohorts of the Collaborative Perinatal Project. We found that the offspring of mothers with a serological pattern consistent with Toxoplasma type І infection were at significantly increased risk for the development of psychoses as compared with the matched unaffected control mothers (odds ratio = 1.94; 95% confidence interval = 1.08–3.46; p = 0.03). The risk was particularly elevated for affective psychoses (OR = 5.24; 95% CI = 1.67–16.5; p = 0.005). In contrast, we did not find an association between maternal antibodies to other genotypes and risk of psychoses in the offspring. These findings suggest an influence of the parasite genotype on increased risk of psychosis and provide further support for a substantive role of Toxoplasma in the etiology of psychosis.     

Studies of higher nervous activity in functional phychoses.

Psychiatric illnesses can be conceived of as experiments of nature, providing a variety of pathopsychological mechanisms which may elucidate normal psychological processes. Clinically the reactive psychoses are predominantly psychogenic reaction types. They present disturbances of higher nervous activity, similar to those of the neuroses. The unconditional reflex activity is practically as in normal controls, and the most outstanding finding was the large effect of psychodynamic complex structures. This is a physiological parallel to the clinical manifestations with great concern over experienced mental trauma. In the manic-depressive psychoses the most characteristic feature is a marked disturbance of unconditional reflex activity. This factor may be an important physiological mechanism underlying the more biological than psychodynamic reaction type and partly explain the changes of mood and associated interferences with sleep, body weight, sexual activity, aggression and other instinctual and vegetative functions. Schizophrenic psychoses also present changes of unconditional reflex activity, predominantly in the direction of inhibition of response. In addition there are severe dissociations within and between the three levels of unconditional reflexes and the two signaling systems. It is suggested that schizophrenia represents a functional maladaptation, which can be explained from the principles of autokinesis and schizokinesis established by Gantt in animal experiments. Prognostic models based on experimentally established impairment of performances were shown to predict long-term risks of schizophrenic defects just as well as models based on constellations of clinical symptoms. I would predict that psychophysiology and experimental psychology will become increasingly more important for establishing diagnosis and prognosis in the functional psychoses. The data of this article point toward a basis for a prophylactic psychiatry.     

Cannabis use and the risk of developing a psychotic disorder

We briefly review the evidence that cannabis use in adolescence and young adulthood is a contributory cause of schizophreniform psychoses, by summarising longitudinal studies that: a) have examined relationships between cannabis use and the risk of psychosis or psychotic symptoms; and b) have controlled for potential confounders, such as other forms of drug use and personal characteristics that predict an increased risk of psychosis. There is now reasonable evidence from longitudinal studies that regular cannabis use predicts an increased risk of schizophrenia and of reporting psychotic symptoms. These relationships have persisted after controlling for confounding variables such as personal characteristics and other drug use. The relationships did not seem to be explained by cannabis being used to self-medicate symptoms of psychosis. A contributory causal relationship is biologically plausible because psychotic disorders involve disturbances in the dopamine neurotransmitter system with which the cannabinoid system interacts, as has been shown by animal studies and a human provocation study. We briefly explore the clinical and public health implications of the most plausible hypothesis, that cannabis use precipitates schizophrenia in persons who are vulnerable because of a personal or family history of schizophrenia.     

Atypical antipsychotics in the elderly

Central criteria for the definition of atypical antipsychotics are antipsychotic efficacy and minimal or none extrapyramidal symptoms (EPS). This last criterium is of importance in the differentiation with the traditional antipsychotics. Of the four atypical antipsychotics which are discussed here, clozapine is the most atypical. The best proof is its good efficacy in the treatment of Parkinson psychosis with minimal adverse effects on motor function. Clozapine is the best choice for this indication. At this moment there is not enough evidence available concerning quetiapine. Risperidon and olanzapine give more Dopamine2-occupancy with higher doses and can evoke EPS, but this is still less compared to the traditional antipsychotics. All four atypical drugs cause less tardive dyskinesia. Atypical antipsychotics are not well studied in the treatment of elderly patients with functional psychosis. However the available information and the literature on the treatment of young adults makes it probable that the atypical antipsychotics are at least as effective in the elderly as the traditional antipsychotics. The median daily doses are lower for elderly than for younger patients. Risperidon has been proven effective in the treatment of agressive behaviour in dementia. Atypical antipsychotics have their 'own' adverse effects. Those which have the most impact in the elderly are discussed.     

Course and Outcome in Involutional Paranoid States

The problem of presenile psychoses — this "perhaps the most unclarified area in all psychiatry" (Kraepelin) - is still unresolved. Specifically, opinions differ very widely on the nosological independence of involutional paranoid states. Some writers classify them with advanced schizophrenia (1, 2), others regard them as schizophrenia or organic psychoses (3), yet others regard them as nosologically independent, pointing to the significance in their development of constitutional features of personality (4) or regard them as "paranoid reactions in pathological brain function, wholly acquired." (5)     

The rise of counselling and the return of alienism.

Current services for those with mental disorders show two trends. Psychiatric services are becoming concentrated on the care of those with "severe mental illness," largely (but unjustifiably) synonymous with chronic psychosis. The retreat of psychiatry from the care of those with non-psychotic mental disorders has helped the growth of counselling services for these patients. However, there is no evidence that non-directive counselling is effective for such disorders, in contrast to the evidence for the effectiveness of other treatments that are usually delivered by psychologists or community psychiatric nurses. By retreating from the concerns of general practice and general medicine, psychiatry is returning to the days of alienism: in Victorian terms, the care of "the mad." Possible consequences include increasing expectations of psychiatric services that cannot be met, a loss of skills within psychiatry, and increased demoralisation in the mental health services.     

Transdiagnostic dimensions of psychosis in the Bipolar‐Schizophrenia Network on Intermediate Phenotypes (B‐SNIP)

The validity of the classification of non‐affective and affective psychoses as distinct entities has been disputed, but, despite calls for alternative approaches to defining psychosis syndromes, there is a dearth of empirical efforts to identify transdiagnostic phenotypes of psychosis. We aimed to investigate the validity and utility of general and specific symptom dimensions of psychosis cutting across schizophrenia, schizoaffective disorder and bipolar I disorder with psychosis. Multidimensional item‐response modeling was conducted on symptom ratings of the Positive and Negative Syndrome Scale, Young Mania Rating Scale, and Montgomery‐Åsberg Depression Rating Scale in the multicentre Bipolar‐Schizophrenia Network on Intermediate Phenotypes (B‐SNIP) consortium, which included 933 patients with a diagnosis of schizophrenia (N=397), schizoaffective disorder (N=224), or bipolar I disorder with psychosis (N=312). A bifactor model with one general symptom dimension, two distinct dimensions of non‐affective and affective psychosis, and five specific symptom dimensions of positive, negative, disorganized, manic and depressive symptoms provided the best model fit. There was further evidence on the utility of symptom dimensions for predicting B‐SNIP psychosis biotypes with greater accuracy than categorical DSM diagnoses. General, positive, negative and disorganized symptom dimension scores were higher in African American vs. Caucasian patients. Symptom dimensions accurately classified patients into categorical DSM diagnoses. This study provides evidence on the validity and utility of transdiagnostic symptom dimensions of psychosis that transcend traditional diagnostic boundaries of psychotic disorders. Findings further show promising avenues for research at the interface of dimensional psychopathological phenotypes and basic neurobiological dimensions of psychopathology.     

Failures of metacognition and lack of insight in neuropsychiatric disorders

Lack of insight or unawareness of illness are the hallmarks of many psychiatric disorders, especially schizophrenia (SCZ) and other psychoses and could be conceived of as a failure in metacognition. Research in this area in the mental health field h as burgeoned with the development and widespread use of standard assessment instruments and the mapping out of the clinical and neuropsychological correlates of insight and its loss. There has been a growing appreciation of the multi-faceted nature of the concept and of the different 'objects' of insight, such as the general awareness that one is ill, to more specific metacognitive awareness of individual symptoms, impairments and performance. This in turn has led to the notion that insight may show modularity and may fractionate across different domains and disorders, supported by work that directly compares metacognition of memory deficits and illness awareness in patients with SCZ, Alzheimer's disease and brain injury. The focus of this paper will be on the varieties of metacognitive failure in psychiatry, particularly the psychoses. We explore cognitive models based on self-reflectiveness and their possible social and neurological bases, including data from structural and functional MRI. The medial frontal cortex appears to play an important role in self-appraisal in health and disease.