The psychosis high-risk state: a comprehensive state-of-the-art review

Context During the past 2 decades, a major transition in the clinical characterization of psychotic disorders has occurred. The construct of a clinical high-risk (HR) state for psychosis has evolved to capture the prepsychotic phase, describing people presenting with potentially prodromal symptoms. The importance of this HR state has been increasingly recognized to such an extent that a new syndrome is being considered as a diagnostic category in the DSM-5. Objective To reframe the HR state in a comprehensive state-of-the-art review on the progress that has been made while also recognizing the challenges that remain. Data Sources Available HR research of the past 20 years from PubMed, books, meetings, abstracts, and international conferences. Study Selection and Data Extraction Critical review of HR studies addressing historical development, inclusion criteria, epidemiologic research, transition criteria, outcomes, clinical and functional characteristics, neurocognition, neuroimaging, predictors of psychosis development, treatment trials, socioeconomic aspects, nosography, and future challenges in the field. Data Synthesis Relevant articles retrieved in the literature search were discussed by a large group of leading worldwide experts in the field. The core results are presented after consensus and are summarized in illustrative tables and figures. Conclusions The relatively new field of HR research in psychosis is exciting. It has the potential to shed light on the development of major psychotic disorders and to alter their course. It also provides a rationale for service provision to those in need of help who could not previously access it and the possibility of changing trajectories for those with vulnerability to psychotic illnesses.

Integrated psychological therapy (IPT) for schizophrenia: is it effective?

Against the background of evidence-based treatments for schizophrenia, nowadays the implementation of specific cognitive and behavioral interventions becomes more important in the standard care of these patients. Over the past 25 years, research groups in 9 countries have carried out 30 independent evaluations of Integrated Psychological Therapy (IPT), a group program that combines neurocognitive and social cognitive interventions with social skills approaches for schizophrenic patients. The aim of the present study was to evaluate the effectiveness of IPT under varying treatment and research conditions in academic and nonacademic sites. In a first step, all 30 published IPT studies with the participation of 1393 schizophrenic patients were included in the meta-analysis. In a second step, only high-quality studies (HQS) (7 studies including 362 patients) were selected and analyzed to check whether they confirmed the results of the first step. Positive mean effect sizes favoring IPT over control groups (placebo-attention conditions, standard care) were found for all dependent variables, including symptoms, psychosocial functioning, and neurocognition. Moreover, the superiority of IPT continued to increase during an average follow-up period of 8.1 months. IPT obtained similarly favorable effects across the different outcome domains, assessment formats (expert ratings, self-reports, and psychological tests), settings (inpatient vs outpatient and academic vs nonacademic), and phases of treatment (acute vs chronic). The HQS confirmed the results of the complete sample. The analysis indicates that IPT is an effective rehabilitation approach for schizophrenia that is robust across a wide range of patients and treatment conditions.

[Effectiveness of Integrated Psychological Therapy for schizophrenia patients : A meta-analysis including 28 independent studies.]

Over the past 24 years, research groups in eight different countries have conducted 28 independent evaluation studies on Integrated Psychological Therapy (IPT) including 1,329 schizophrenia patients. The present study examines the effectiveness of IPT under different treatment conditions by means of a meta-analytic review. The most salient results indicate favourable mean effect sizes for IPT in comparison to control groups (placebo-attention conditions, standard care). Moreover, the superiority of IPT continues to increase during an average catamnestic phase of 8.1 months. The method obtains similarly favourable effects in different functional areas (neurocognition, social behaviour, psychopathology) and different assessment formats (expert ratings, self-reports, psychological tests). The comparison of different settings of IPT and control groups shows the superiority of IPT in any given therapy or site condition. The analysis of subsamples of inpatients, outpatients, and patients in varying rehabilitation phases reveals similarly favourable effects. Comparing only high-quality studies yields comparable results. In summary, the present meta-analysis corroborates evidence that IPT is an 'empirically validated treatment' according to American Psychiatric Association guidelines.

Identifying mechanisms of treatment effects and recovery in rehabilitation of schizophrenia: longitudinal analytic methods

The longitudinal dimension of schizophrenia and related severe mental illness is a key component of theoretical models of recovery. However, empirical longitudinal investigations have been underrepresented in the psychopathology of schizophrenia. Similarly, traditional approaches to longitudinal analysis of psychopathological data have had serious limitations. The utilization of modern longitudinal methods is necessary to capture the complexity of biopsychosocial models of treatment and recovery in schizophrenia. The present paper summarizes empirical data from traditional longitudinal research investigating recovery in symptoms, neurocognition, and social functioning. Studies conducted under treatment as usual conditions are compared to psychosocial intervention studies and potential treatment mechanisms of psychosocial interventions are discussed. Investigations of rehabilitation for schizophrenia using the longitudinal analytic strategies of growth curve and time series analysis are demonstrated. The respective advantages and disadvantages of these modern methods are highlighted. Their potential use for future research of treatment effects and recovery in schizophrenia is also discussed.

What do we mean by Female and Male in Neurocognitive Experiments on Language?

For several years now, neuroscientific research has been striving towards fundamental answers to questions about the relevance of sex/gender to language processing in the brain. This research has been effected through the search for sex/gender differences in the neurobiology of language processing. Thus, the main aim has ever been to focus on the differentiation of the sexes/genders, failing to define what sex, what gender, what female or male is in neurolingustic research. In other words, although neuroscientific findings have provided key insights into the brain functioning of women and men, neuropsychology has rarely questioned the complexity of the sex/gender variable beyond biology. What does “female” or “male” mean in human neurocognition; how are operationalisations implemented along the axes of “femaleness” or “maleness”; or what biological evidence is used to register the variables sex and/or gender? In the neurosciences as well as in neurocognitive research, questions such as these have so far not been studied in detail, even if they are highly significant for the scientific process. Instead, the variable of sex/gender has always been thought as solely dichotomous (as either female or male), oppositional and exclusionary of each other. Here, this theoretical contribution sets in. Based on findings in neuroscience and concepts in gender theory, this poster is dedicated to the reflection about what sex/gender is in the neuroscience of language processing. Following this aim, two levels of interest will be addressed. First: How do we define sex/gender at the level of participants? And second: How do we define sex/gender at the level of the experimental task? For the first, a multifactorial registration (work in progress) of the variable sex/gender will be presented, i.e. a tool that records sex/gender in terms of biology and social issues as well as on a spectrum between femaleness and maleness. For the second, the compulsory dichotomy of a gendered task when neurolinguistically approaching our cognitions of sex/gender will be explored.

Significance of social cognitive remediation therapy within a comprehensive treatment concept

Objectives: The final goal in the successful treatment of schizophrenia patients is defined in improved functional recovery. Thus the integration of social cognitive tasks within a comprehensive treatment concept should offer significant advantages in generalization and transfer of therapy effects. Recent therapy outcome research supports these advantages. Empirical modeling identified social cognition as a mediating factor between neurocognition and functional recovery. Regarding this, we first developed the Integrated Psychological Therapy Program (IPT). It consists of 5 subprograms and combines interventions on neurocognition, social cognition, and social competence. As a further development of the cognitive part of IPT we developed the Integrated Neurocognitive Therapy (INT), which focuses on all social and neurocognitive domains defined by MATRICS. Methods: The aim was to investigate whether the application of the complete IPT is superior in comparison to the use of single IPT subprograms. Data were based on 37 independent IPT studies including a total sample of 1692 schizophrenia patients. Additionally, the proximal outcome in cognitive domains as well as in more distal outcome areas was investigated in an international RCT on INT including 169 schizophrenia outpatients. Results: All IPT subprogram variations obtained significant effects in proximal outcome. Each subprogram domain reached the largest effects in the targeted area. With regard to distal outcomes, combinations of subprograms showed a significant reduction of negative symptoms and an improvement in not targeted areas of functioning. This strongly supports vertical generalization effects to other functional domains. Regarding INT, results support efficacy compared to TAU in various cognitive domains, in psychosocial functioning and symptoms after therapy and at 1-year-follow-up. Conclusion: Results support evidence for the efficacy of longer lasting integrated therapy. The success of these treatment concepts is strongly based on successful therapy of social cognitive functions.

State of the art of integrated therapy approaches in the treatment of schizophrenia: empirical evidence and clinical relevance

Objective: Integrated behavior therapy approaches are defined by the combination of behavioral and or cognitive interventions targeting neurocognition combined with other goal-oriented treatment targets such as social cognition, social skills, or educational issues. The Integrated Psychological Therapy Program (IPT) represents one of the very first behavior therapy approaches combining interventions of neurocognition, social cognition, and social competence. This comprehensive group-based bottom-up and top-down approach consists of five subprograms, each with incremental steps. IPT has been successfully implemented in several countries in Europe, America, Australia and in Asia. IPT worked as a model for some other approaches designed in the USA. IPT was undergone two further developments: based on the social competence part of IPT, the three specific therapy programs focusing residential, occupational or recreational topics were developed. Recently, the cognitive part of INT was rigorously expanded into the Integrated Neurocognitive Therapy (INT) designed exclusively for outpatient treatment: INT includes interventions targeting all neurocognitive and social cognitive domains defined by the NIMH-MATRICS initiative. These group and partially PC-based exercises are structured into four therapy modules, each starting with exercises on neurocognitive domains followed by social cognitive targets. Efficacy: The evidence of integrated therapy approaches and its advantage compared to of one-track interventions was becoming a discussion tool in therapy research as well as in mental health systems. Results of meta-analyses support superiority of integrated approaches compared to one-track interventions in more distal outcome areas such as social functioning. These results are in line with the large body of 37 independent IPT studies in 12 countries. Moreover, IPT research indicates the maintenance of therapy effects after the end of therapy and some evidence generalization effects. Additionally, the international randomized multi-center study on INT with 169 outpatients strongly supports the successful therapy of integrated therapy in proximal and distal outcome such as significant effects in cognition, functioning and negative symptoms. Clinical implication: therapy research as well as expert’s clinical experience recommends integrated therapy approaches such as IPT to be successful agents within multimodal psychiatric treatment concepts. Finally, integrated group therapy based on cognitive remediation seems to motivate and stimulate schizophrenia inpatients and outpatients to more successful and independent life also demanded by the recovery movement.

Cognitive remediation therapy: Does it generalize to significant outcome areas?

Objective: Cognitive remediation therapy (CRT) approaches have demonstrated to be effective in improving cognitive functions in schizophrenia. However, there is a lack of integrated CR approaches that target multiple neuro- and social-cognitive domains with a special focus on the generalization of therapy effects to functional outcome and negative symptoms. Method: This 8-site randomized controlled trial evaluated the efficacy of a novel cognitive-behavioral group therapy approach called integrated neurocognitive therapy (INT). INT includes manual-based exercises to improve all neuro- and social-cognitive domains as defined by the Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative by compensation and restitution. One hundred and fifty-six outpatients with a diagnosis of schizophrenia or schizoaffective disorder accord- ing to DSM-IV-TR were randomly assigned to receive 15 weeks of INT or treatment as usual (TAU). INT patients received 30 bi-weekly therapy sessions. Each session lasted 90min. Mixed models were applied to assess changes in neurocognition, social cognition, symptoms, and functional outcome at post-treatment and at 9-month follow-up. Results: Compared to TAU, INT patients showed significant improvements on multiple neuro- and social-cognitive domains, negative symptoms, and functional outcome after therapy and at 9-month follow-up. Number-needed-to-treat analyses indicate that only five INT patients are necessary to produce durable and meaningful improvements in functional outcome. Conclusions: Integrated interventions on neurocognition and social cognition have the potential to improve not only cognitive performance but also functional outcome and negative symptoms. These findings are important as treatment guidelines for schizophrenia have criticized CRT for their poor generalization effects.

The Impact of Marijuana Use on Memory in Patients with HIV/AIDS

The most robust neurocognitive effect of marijuana use is memory impairment. Memory deficits are also high among persons living with HIV/AIDS, and marijuana use among this population is disproportionately common. Yet research examining neurocognitive outcomes resulting from co-occurring marijuana and HIV is virtually non-existent. The primary aim of this case-controlled study was to identify patterns of neurocognitive impairment among HIV patients who used marijuana compared to HIV patients who did not use drugs by comparing the groups on domain T-scores. Participants included 32 current marijuana users and 37 non-drug users. A comprehensive battery assessed substance use and neurocognitive functioning. Among the full sample, marijuana users performed significantly worse on verbal memory tasks compared to non-drug users and significantly better on attention/working memory tasks. A secondary aim of this study was to test whether the effect of marijuana use on memory was moderated by HIV disease progression, but these models were not significant. This study also examined whether the effect of marijuana use was differentially affected by marijuana use characteristics, finding that earlier age of initiation was associated with worse memory performance. These findings have important clinical implications, particularly given increased legalization of this drug to manage HIV infection.

Social Cognition, Negative Symptoms and Psychosocial Functioning in Schizophrenia.

Although functional recovery could be advocated as an achievable treatment goal, many effective interventions for the treatment of psychotic symptoms, such as antipsychotic drugs, may not improve functioning. The last two decades of cognitive and clinical research on schizophrenia were a turning point for the firm acknowledgment of how relevant social cognitive deficits and negative symptoms could be in predicting psychosocial functioning. The relevance of social cognition dysfunction in schizophrenia patients’ daily living is now unabated. In fact, social cognition deficits could be the most significant predictor of functionality in patients with schizophrenia, non-redundantly with neurocognition. Emerging evidence suggests that negative symptoms appear to play an indirect role, mediating the relationship between neurocognition and social cognition with functional outcomes. Further explorations of this mediating role of negative symptoms have revealed that motivational deficits appear to be particularly important in explaining the relationship between both neurocognitive and social cognitive dysfunction and functional outcomes in schizophrenia. In this paper we will address the relative contribution of two key constructs—social cognitive deficits and negative symptoms, namely how intertwined they could be in daily life functioning of patients with schizophrenia.

A systematic review of the psychobiological burden of informal caregiving for patients with dementia: focus on cognitive and biological markers of chronic stress

As the physiological impact of chronic stress is difficult to study in humans, naturalistic stressors are invaluable sources of information in this area. This review systematically evaluates the research literature examining biomarkers of chronic stress, including neurocognition, in informal dementia caregivers. We identified 151 papers for inclusion in the final review, including papers examining differences between caregivers and controls as well as interventions aimed at counteracting the biological burden of chronic caregiving stress. Results indicate that cortisol was increased in caregivers in a majority of studies examining this biomarker. There was mixed evidence for differences in epinephrine, norepinephrine and other cardiovascular markers. There was a high level of heterogeneity in immune system measures. Caregivers performed more poorly on attention and executive functioning tests. There was mixed evidence for memory performance. Interventions to reduce stress improved cognition but had mixed effects on cortisol. Risk of bias was generally low to moderate. Given the rising need for family caregivers worldwide, the implications of these findings can no longer be neglected.