Pre-psychotic Period Research Articles

Temporal and Effort cost Decision-making in Healthy Individuals with Subclinical Psychotic Symptoms

The value people attribute to rewards is influenced both by the time and the effort required to obtain them. Impairments in these computations are described in patients with schizophrenia and appear associated with negative symptom severity. This study investigated whether deficits in temporal and effort cost computations can be observed in individuals with subclinical psychotic symptoms (PS) to determine if this dysfunction is already present in a potentially pre-psychotic period. Sixty participants, divided into three groups based on the severity of PS (high, medium and low), performed two temporal discounting tasks with food and money and a concurrent schedule task, in which the effort to obtain food increased over time. We observed that in high PS participants the discounting rate appeared linear and flatter than that exhibited by participants with medium and low PS, especially with food. In the concurrent task, compared to those with low PS, participants with high PS exerted tendentially less effort to obtain snacks only when the required effort was high. Participants exerting less effort in the higher effort condition were those with higher negative symptoms. These results suggest that aberrant temporal and effort cost computations might be present in individuals with subclinical PS and therefore could represent a vulnerability marker for psychosis.

S33. ETRO - A PROSPECTIVE FOLLOW-UP STUDY OF THE COMBINED TREATMENT APPROACH “ROBIN” FOR ADOLESCENTS WITH HIGH RISK FOR DEVELOPING A PSYCHOTIC DISORDER: THERAPY MODULES ENHANCED BY A SMARTPHONE APPLICATION

BackgroundThe most promising strategy in targeted prevention of psychotic disorders is to treat the at risk-symptoms in the pre-psychotic period. Although high risk-symptoms for psychotic disorder are common in adolescence and associated with a marked reduction in functioning, the evidence base required to guide effective interventions for adolescents at risk and even first-episode psychosis is limited. The clinicians from the early intervention center in Zurich have developed the treatment approach “Robin” (standardized manual and smartphone App) for adolescents with high risk for developing a psychotic disorder. The manual is targeting at risk-symptoms, comorbid disorders, improvement of quality of life and daily functioning. The therapy modules are based on evidence based treatment strategies in adults with a high risk and recommendations for adolescents with first episodes of psychosis. It follows the guidelines on early intervention in clinical psychosis high risk states of the European Association for Psychiatry. The intervention also includes a smartphone application for supporting the patients between sessions. This application targets real-time symptom assessment, medication adherence, and provides coping strategies for dealing with symptoms of psychosis and daily life hurdles.MethodsThe clinical intervention study ETRo is designed as a naturalistic controlled trial. The goal is to compare efficacy of a 16-week intervention in patients with at-risk symptoms (age range 13–18) with an active control group (treatment as usual). Power calculations conducted in collaboration with a statistician determined the recruitment goal of 30 participants in the treatment condition. Participants from a former early recognition study (N=62, Age: 13–18 years, Ø 15.06) are included for the control condition. For the intervention condition, help seeking adolescents with APS-Symptoms, aged 13–18, are being recruited during a three year time period. Within this prospective study, at-risk symptoms and data for comorbid symptoms, functioning, self-efficacy, and quality of life are collected at six time points (baseline, during the treatment period, immediately after intervention and 6, 12 and 24 months later).ResultsSince August 2017, first participants have been included and their treatment has started. In Florence, we will present our first results. This will include implementation of the treatment program and first findings of treatment period.DiscussionEven though young patients with at-risk symptoms may profit best of specialised treatment approaches, little is known about age-appropriate treatment strategies in this vulnerable age group. This is one of the first controlled trials to test the efficacy of a specific treatment program for minor patients with attenuated psychotic symptoms.

Sleep dysfunction and thalamic abnormalities in adolescents at ultra high-risk for psychosis

BackgroundSleep dysfunction is a pervasive, distressing characteristic of psychosis, yet little is known regarding sleep quality prior to illness onset. At present, it is unclear whether sleep dysfunction precedes the emergence of psychotic symptoms, signifying a core feature of the disorder, or if it represents a consequence of prolonged contact with aspects of schizophrenia and its treatment (e.g., medication use or neurotoxicity) or co-morbid symptoms (e.g., depressive and manic symptomatology). The current study examined sleep dysfunction in adolescents at ultra high-risk (UHR) for psychosis, relationships between sleep disturbances and psychosis symptoms, volume of an integral sleep-structure (thalamus), and associations between thalamic abnormalities and sleep impairment in UHR youth. MethodThirty-three UHR youth and 33 healthy controls (HC) participated in a self-assessment of sleep functioning (Pittsburgh Sleep Quality Index; PSQI), self and parent-report clinical interviews, and structural magnetic resonance imaging (MRI). ResultsUHR adolescents displayed increased latency to sleep onset and greater sleep disturbances/disrupted continuity compared to HC youth, over and above concurrent mood symptoms. Among UHR youth, increased sleep dysfunction was associated with greater negative symptom severity but not positive symptoms. Compared to HC adolescents, UHR participants displayed decreased bilateral thalamus volume, which was associated with increased sleep dysfunction. ConclusionsSleep dysfunction occurs during the pre-psychotic period, and may play a role in the etiology and pathophysiology of psychosis. In addition, the relationship of disrupted sleep to psychosis symptoms in UHR youth indicates that prevention and intervention strategies may be improved by targeting sleep stabilization in the pre-psychotic period.

From Eating Disorder to Schizophrenia

The comorbidity of eating disorders with psychosis is less investigated than the other comorbidities. There are some possibilities to explain this comorbidity. At first, disordered eating behaviors may start and because of the weight loss and changed medical conditions psyhotic symptoms may develop. Another explanation, eating disorder symptoms occur during prepsychotic period as antecedent symptoms or eating disorder and schizophrenia exist as different entities. Because of the weight gain as a side effect of antipsychotics, it is a complicated issue to treat these patients who have eating disorders and psychosis together. We present a patient, whose symptoms started as an eating disorder and then was diagnosed as schizophrenia. After the antipsychotic treatment her psychotic symptoms resolved however fear of weight gain and food restriction continued. We will discuss the diagnosis and treatment strategies in clinical pictures where eating disorders exist together with schizophrenia.

Cognitive behavioral therapy in prodromal psychosis.

There is a strong impetus in the psychosis research field to develop interventions that aim to prevent the onset of psychotic disorders. Over the past 15 years there has been a tremendous development in the work aimed at understanding the pre-psychotic period. More recently there has been a focus on developing and testing treatments both pharmacological and psychological that could potentially prevent or delay the onset of psychosis. One of the psychological treatments that has received the most attention is cognitive behavioral therapy (CBT). Relatively few trials have been completed and this paper reviews the existing trials. Implications of these trials for the treatment of this early phase as well as for designing future studies are discussed.

Intervenção precoce na psicose: primeiro episódio psicótico e período crítico.

Besides intervention in prepsychotic period, early intervention in psychosis includes interventions done after the onset of the first-episode psychosis, namely psychopharmacological and psychosocial phase-specific intervention. The main aim is to reduce the duration of untreated psychosis (DUP) and to ensure that besides remission of the symptoms there is also a psychosocial recovery. Many centers set up an assertive and integrated early intervention program, involving an active search of patients with a treatment that includes antipsychotic medication, cognitive behavioral therapy, psychoeducation, family and vocational interventions. The authors of this review explain the concepts and main studies that support this kind of treatment in early psychosis. The results of published data show that is possible to reduce the DUP and improve the clinical and functional outcomes with this intervention. Critical period hypothesis proposes that deterioration occurs aggressively in the first 2 to 5 years of early psychosis, so it is crucial to intervene in this period to ensure a functional recovery. Cost-benefit ratio seems to be favorable to early intervention model, with reduction of in-stay period, which is an important component of the direct costs of psychotic illness. Early intervention service model organization is also reviewed by the authors of this research. The results of many studies show favorable outcomes for the integrative early intervention and so many countries included it in their political mental health directives and attributed funds for early intervention in psychosis.

Early intervention in psychosis: prepsychotic period

Psychotic disorders, namely schizophrenia, are severe illnesses with their onset in adolescence or youth adult age and have a classic limited outcome. In recent years there has been some research about early intervention in psychosis which can be done in prepsychotic period (prodrome) and/or after the onset of full blown psychotic episode. The authors review the literature about the diagnosis, evaluation, and possible interventions in patients in prepsychotic period (prodrome). Identification of patients with ultra high risk of psychosis could identify patients with a risk of development psychosis in 40%. The main interventions, pharmacological and psychosocial treatments, and main published studies are explained. Prospective identification of these patients and their treatment could prevent the development of full blown psychosis, delay the onset or promote the recovery of the disorder. We must remember some ethical issues about this kind of intervention, namely the stigma and false positive individuals. The results from the research in this area are mainly preliminary, but these studies suggest that some interventions are effective and promising. In future we must have trials with more number of patients included and probably a refinement of the criteria of ultra high risk patients.

Cognitive‐behavioral therapy for individuals at high risk of developing psychosis

Early intervention for psychosis has become an established clinical practice. Research is now focusing on identifying individuals in the pre-psychotic period when they appear to be putatively prodromal for psychosis. Criteria have been established for identifying these young people who are at clinical high risk, and there have been some early studies testing both pharmacological and psychological treatments. Cognitive behavioral therapy (CBT) has been tested as a potentially effective intervention in this group. Here, we describe two cases that were treated with CBT.

Randomized Controlled Trial of Interventions for Young People at Ultra-High Risk of Psychosis: Study Design and Baseline Characteristics

Intervention during the pre-psychotic period of illness holds the potential of delaying or even preventing the onset of a full-threshold disorder, or at least of reducing the impact of such a disorder if it does develop. The first step in realizing this aim was achieved more than 10 years ago with the development and validation of criteria for the identification of young people at ultra-high risk (UHR) of psychosis. Results of three clinical trials have been published that provide mixed support for the effectiveness of psychological and pharmacological interventions in preventing the onset of psychotic disorder. The present paper describes a fourth study that has now been undertaken in which young people who met UHR criteria were randomized to one of three treatment groups: cognitive therapy plus risperidone (CogTher + Risp: n = 43); cognitive therapy plus placebo (CogTher + Placebo: n = 44); and supportive counselling + placebo (Supp + Placebo; n = 28). A fourth group of young people who did not agree to randomization were also followed up (monitoring: n = 78). Baseline characteristics of participants are provided. The present study improves on the previous studies because treatment was provided for 12 months and the independent contributions of psychological and pharmacological treatments in preventing transition to psychosis in the UHR cohort and on levels of psychopathology and functioning can be directly compared. Issues associated with recruitment and randomization are discussed.

How people negotiate for success as psychosis emerges

This study focuses on how people try to successfully manage daily life despite emerging but undetected psychosis and explores how those who know them support their success. The findings we report here are part of a larger qualitative study. After a diagnosis of psychosis was made, participants were asked to reflect on the period before their first episode. We categorize and describe how participants actively negotiated for success in activities and social situations during the prepsychotic period. We also explain strategies used by significant others to support this success and how all study subjects portrayed emerging difficulties as normal. We give some examples of how early detection and recovery programmes may modify their current practices as they consider that individuals may have already discovered strategies to actively deal with functional and social decline that was occurring during the prepsychotic period.

From prediction error to psychosis: ketamine as a pharmacological model of delusions

Recent cognitive neuropsychiatric models of psychosis emphasize the role of attentional disturbances and inappropriate incentive learning in the development of delusions. These models highlight a pre-psychotic period in which the patient experiences perceptual and attentional disruptions. Irrelevant details and numerous associations between stimuli, thoughts and percepts are imbued with inappropriate significance and the attempt to rationalize and account for these bizarre experiences results in the formation of delusions. The present paper discusses delusion formation in terms of basic associative learning processes. Such processes are driven by prediction error signals. Prediction error refers to mismatches between an organism's expectation in a given environment and what actually happens and it is signalled by both dopaminergic and glutamatergic mechanisms. Disruption of these neurobiological systems may underlie delusion formation. We review similarities between acute psychosis and the psychotic state induced by the NMDA receptor antagonist drug ketamine, which impacts upon both dopaminergic and glutamatergic function. We conclude by suggesting that ketamine may provide an appropriate model to investigate the formative stages of symptom evolution in schizophrenia, and thereby provide a window into the earliest and otherwise inaccessible aspects of the disease process.

Is the psychopathology of acute and transient psychotic disorder different from schizophrenic and schizoaffective disorders?

Objective. – This study explores psychopathological aspects of acute and transient psychotic disorders (ATPD), a diagnostic category introduced with ICD-10, to elucidate its relationship with schizophrenia and schizoaffective psychoses. Methods. – We recruited all consecutive inpatients fulfilling the ICD-10 criteria of ATPD (F23) during a 5-year period as well as control groups with “positive” schizophrenia (PS) and bipolar schizoaffective disorder (BSAD) matched for gender and age at index episode. For the evaluation of psychopathological parameters during index episode a standardized symptom list was used. Prepsychotic (prodromal) symptoms were also assessed. Results. – During the prepsychotic period few differences between the groups were detected. The most important difference between ATPD and the other two other psychotic disorders regarding phenomenology of the full-blown episodes was a higher frequency of “rapidly changing delusional topics”, “rapidly changing mood” and anxiety in ATPD. Conclusion. – ATPD show a characteristic psychopathological picture consistent with earlier concepts such as cycloid psychoses and bouffée délirante. Nevertheless, psychopathology alone is not enough to establish ATPD as an independent nosological entity.

Hair analysis for cannabinoids and amphetamines in a psychosis incidence study

It remains often uncertain whether the use of illicit substances has contributed to the aetiology of psychosis. Gas chromatography–mass spectrometry can be used to detect them in hair of the head. Given a monthly growth rate between 1.0 and 1.5 cm, one can examine hair segments that originated during the pre-psychotic period. We examined the usefulness of hair analysis to detect the use of cannabinoids or amphetamines during this period. One hundred patients participated in a psychosis incidence study and 64 yielded hair. Refusal was associated with non-Dutch ethnicity, not with a clinical diagnosis of use. A monthly growth rate of 1.5 cm was assumed and 33 specimens were found to be long enough. Cannabinoids or amphetamines were detected in nine specimens. In seven they were not detected, whereas the patients had reported their use. It is likely that their hair grew at a slower rate and that the examined segments belonged to an earlier period of time, during which the substances were not used. Lack of knowledge about the individual hair growth rate is an important limitation to the usefulness of this method.

Ethics and early intervention in psychosis: keeping up the pace and staying in step

The intense clinical and research interest in early psychosis in recent years has highlighted a range of ethical issues which need to be considered carefully. Our perspective is based on 16 years of clinical and research experience with young people at this phase of illness as well as the research contributions of many others. We discuss the ethical dilemmas in relation to the three key foci, which make up the early psychosis paradigm. These are the pre-psychotic or prodromal phase, the period of untreated psychosis and the first psychotic episode and the critical period of recovery, which follows this. Most attention is devoted to the pre-psychotic period, however ethical considerations related to research in the other two clinical foci are briefly covered as well. Our contention is that the ethical issues are essentially identical to those arising in early intervention research in mainstream medicine. This has been concealed by inconsistency and emotion, which has great potential to confuse, politicize and derail rational debate. The legacy of the isolation of psychiatry from medicine and consequent prejudice and stigma in the professional as well as the public mind seems to be fuelling a tendency in some societies to view psychiatric research as qualitatively different from other medical research. Sound clinical research data should be allowed to illuminate the options for potential consumers across all phases of illness. The alternative is research paralysis, which would force clinical practice to expand blindly without an evidence base.

Duration of psychosis and outcome in first-episode schizophrenia.

This study was undertaken to assess the potential effect of duration of untreated illness on outcome in a group of first-episode schizophrenic patients. Seventy patients with schizophrenia diagnosed according to the Research Diagnostic Criteria entered the study and were followed for up to 3 years. All patients received standardized treatment and uniform assessments both during the acute phase of their illness and throughout the follow-up period. Outcome was measured in terms of time to remission of acute psychotic symptoms as well as degree of symptom remission. The mean duration of psychotic symptoms before initial treatment was 52 weeks, preceded by a substantial prepsychotic period. According to survival analysis, duration of illness before treatment was found to be significantly associated with time to remission as well as with level of remission. The effect of duration of illness on outcome remained significant when diagnosis and gender variables, themselves associated with outcome, were controlled in a regression analysis. Duration of illness was not correlated with age at onset, mode of onset, premorbid adjustment, or severity of illness at entry into the study. Duration of psychosis before treatment may be an important predictor of outcome in first-episode schizophrenia. Acute psychotic symptoms could reflect an active morbid process which, if not ameliorated by neuroleptic drug treatment, may result in lasting morbidity. Further implications of these findings are discussed.

About prognostic signs in the initial period of postpartum delusional psychoses

Recently, interest in psychoses in the postpartum period has revived. V. K. Prorokova et al. (1960) rightly point out the syndromic diversity and nosological heterogeneity of mental diseases in the puerperium. In this regard, it is especially important to identify prognostically significant signs of the initial (prepsychotic) period of these mental diseases for the purpose of their early diagnosis and differentiated treatment. The role of various pathogenic factors preceding the development of psychosis should also be clarified.