Pre-psychotic Phase Research Articles

Basic self-disturbance in adolescents at risk of psychosis: temporal stability investigated by the experience sampling method in a mixed method study.

Basic self-disturbance (BSD), also called anomalous self-experiences (ASEs), are core phenotypic markers for schizophrenia spectrum disorders and a prepsychotic vulnerability marker considered to be temporally stable (trait-phenomenon). Studies of BSD in children and adolescents are lacking. To be clinically useful, we need to know more about the characteristics and temporal development of BSD in prepsychotic phases. This study used a smartphone application measuring the occurrence and subjective intensity of ASEs in the daily life of 27 help-seeking adolescents (12-18 years) repeatedly over a period of 6 months. A total of 5223 unique application-reports based on individually selected and verbatim descriptions of personal core ASEs were analysed by mixed methods. The intensity of ASEs, within subjects and between subjects and irrespective of time intervals or baseline scores obtained by the Examination of Anomalous Self-Experience (EASE) were relatively stable with a mean variability of 1.25 (0.4) SD. Participants with low EASE total scores at baseline had a significantly lower score on ASE intensity than those with high baseline EASE total scores at baseline (mean 2.42 vs 3.42, p=0.046). In this study, ASEs were not reported as essentially fluctuating experiences but as almost constantly present, demonstrating BSD as a mainly trait phenomenon in prepsychotic phases in persons under the age of 18. Considering the continuous experience of BSD and its predictive value for psychosis development, ASEs should be targeted and monitored to the same extent as other prepsychotic features.

Certain Aspects of Immunopychiatry.

Immunopsychiatry is based on the assumption that schizophrenia, bipolar disorders, and major depressive disorders are related with atypical immune reactions or inflammatory processes. It has also been suggested that the neurotoxic effects of COVID-19 due to the perverted autoimmune reaction could offer fresh acumens into psychotic process. Even acute psychotic symptoms have a subtle pre-psychotic phase and unless treatments are aimed at this preceding phase, newer therapies are not going to achieve their targets. Identifying biosignatures of psychotic disorders lead to better understanding of the etiological mechanism involved in such disorders and aid early diagnostic assays. Interestingly, the search for biomarkers also stimulates new experimental treatment strategies as evidenced by the experiments of newer immunological therapies for psychotic disorders. Characterizing biosignatures are thought to play a significant role in the early detection, treatment, and implementation of preventive strategies in psychotic disorders. The search for identifying biosignatures should go hand in hand with newer experimental therapies for psychotic disorders for the benefit of introducing treatments at an early stage of psychosis development. The identification of biomarkers may lead to a shift from symptom based diagnostic category into subtypes based on immunological alterations and brain biology and such a change might have an advantage to make more precise diagnosis aiding better treatment. The field of immunopsychiatry requires more research to put their findings in context.

Schizophrenia, Temporality, and Affection

Temporal experience and its radical alteration in schizophrenia have been one of the central objects of investigation in phenomenological psychopathology. Various phenomenologically oriented researchers have argued that the change in the mode of temporal experience present in schizophrenia can foreground its psychotic symptoms of delusion. This paper aims to further the development of such a phenomenological investigation by highlighting a much-neglected aspect of schizophrenic temporal experience, i.e., its non-emotional affective characteristic. In this paper, it denotes the type of an experience wherein an afflicted individual experiences a pervasive pull or attraction coming from the past, present, and future. By employing Husserl’s account of affection, I argue that such an affectively prominent temporal experience is not yet another abnormality that happens to be present in schizophrenia. Instead, it is indicative of the core disturbance that underpins the schizophrenic temporal mode of experience. I identify such a disturbance as ‘affective modification dysfunction’ and employ it as a core concept with which I synthesize and organise heterogeneous components of schizophrenic temporal experience in their conceptual unity. For the sake of clear description, I organise those components into the following categories: 1.) Time Stop 2.) Ante-festum 3.) Déjà vu/vécu and 4.) Time Fragmentation. I conclude by demonstrating how approaching schizophrenic temporal experience from its affective dimension can further help us better understand its pre-psychotic phase known to precipitate schizophrenic primary delusion, i.e., delusional mood.

The neurobiology of transition to psychosis: clearing the cache.

The prepsychotic phase of schizophrenia is not only important for indicated prevention strategies, but also crucial for developing mechanistic models of the emergence of frank psychosis (transition). This commentary highlights the work of Dukart and colleagues, published in this issue of the Journal of Psychiatry and Neurosicence, who sought to identify MRI-based anatomic endophenotypes of psychosis in a well-characterized sample of patients with at-risk mental state (ARMS) and first-episode psychosis (FEP). Conceptual and translational challenges in clarifying the neurobiology of transitional prepsychotic states are discussed. A role of intracortical myelin in the neurobiology of transition is proposed. Transition may not be an outcome of "progressive structural deficits"; it may occur due to inadequate compensatory responses in the predisposed. The need to revise our current "deficit-oriented" models of neurobiology of psychosis in the wake of burgeoning evidence indicating a dynamic process of cortical reorganization is emphasized.

Identifying children and adolescents at ultra high risk of psychosis in Italian neuropsychiatry services: a feasibility study.

The past 20 years have seen the evolution of the construct of a clinical high-risk (hereafter, HR) state for psychosis. This construct is designed to capture the pre-psychotic phase. Some aspects of this approach, such as its feasibility in children and adolescents, are still under investigation. In the present study, we address the feasibility of implementing prodrome clinics for HR individuals within the framework of Italy's national child and adolescent neuropsychiatry services and the clinical relevance of a HR diagnosis in this population. Using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to identify help-seeking patients meeting at least one HR criterion at baseline (HR+), we recruited 50 subjects for a feasibility study. The results obtained show that the Italian version of the CAARMS is easily administrable, causing patients no substantial discomfort. The prevalence of HR+ in our cohort was 44 %, which increased by an additional 18 % when negative symptoms were considered as an experimental inclusion criterion (HRNeg). The HR+ subjects were significantly more impaired in their social and occupational functioning than their HR- peers (subjects not at HR). The cumulative 1-year transition risk of psychosis of the HR+ group was 26.7 %. When the HRNeg group was added, the 1-year transition risk was 17.3 %. We suggest that administration of the CAARMS to children and adolescents with putative prodromal psychosis is feasible and that this assessment can easily be integrated into existing Italian neuropsychiatry services although clinicians should interpret results with caution as results in this age group still have to be replicated.

Predisposition to Schizophrenia: An Update of Current Understanding.

Within the field of mental health, the concept of predisposition or that of being "at risk" has been properly addressed by Mrazek and Haggarty. This period prior to clear diagnosis of psychosis has been referred by several names like 'premorbid' phase, at-risk individuals, predisposed individuals, prodromal phase, etc. The premorbid phase is perhaps the most debated term in this list because this term suggests that the morbidity arises only in the overt illness phase. However, evidences arising from several different lines of observations suggest that this may not be the case. In spite of the fact that it has been generally accepted that the prodromal phase precedes the clinical phase, identification of this phase remains a challenge. The real challenge in identifying the onset of the prepsychotic phase is the differentiation of 'normal' experiences from these 'abnormal' experiences. Much fewer studies have been conducted for the assessment of cognitive functions in prodromal phase or predisposed phases of schizophrenia. Cognitive deficits, particularly in memory and attentional functions, are among the most extensively documented aspects of psychosis. Regarding the somatosensory abnormalities in the high-risk individuals, so far there has been only one study conducted which involved somatosensory evoked potentials in these patients.

Substance use in clinical high risk for psychosis: a review of the literature.

In the literature, there is evidence suggesting an association between substance use and psychosis. However, little is known about substance use in those who may be in the pre-psychotic phase, that is, those who are putatively prodromal are considered to be at clinical high risk (CHR) of developing psychosis. We conducted a review of publications measuring patterns and rates of substance use in CHR for psychosis individuals and the effects on the transition to psychosis. Of 5527 potentially relevant research papers, 10 met inclusion criteria of CHR subjects and specifically mentioned substance use in the sample. The results of these studies varied. Cannabis, alcohol and tobacco/nicotine were reported as the most commonly used substances. There was limited information on the changes in patterns of use over time. Two out of the ten studies found a significant association between the use of substances and subsequent transition to psychosis. In one of these studies, substance abuse was a predictor of psychosis when included as a variable in a prediction algorithm. In the other study, the abuse of cannabis and nicotine was associated with transition to psychosis. We found limited evidence to suggest that increased rates of substance use may be associated with transition to psychosis. However, further prospective research examining the association between substance use and transition to psychosis is required before any firm conclusions can be made.

Assay of screening and prevention issues for high risk populations with prodromes of severe mental illness

Before the appearance of specific psychotic symptoms, most individuals experience a period of prodromal symptoms associated with severe mental illness. Early intervention during this pre-psychotic phase may improve treatment outcomes, alter the natural course of disease, and prevent or delay mental disease onset. This paper aimed to synthesize four screening strategies (genetic high-risk populations selected by family history with mental illness, finding ultra-high-risk population, the close-in strategy, and the pre-psychotic phase by assessing basic symptoms); two intervention dimensions (psychosocial interventions and antipsychotic medicine); discussions of ethnic issues; and three Taiwanese nurses' roles (the role of assessment for screening, the role of development for screening tools, and the role of preventive intervention providers) to attain early diagnoses and prevention of mental illness. This article provides more information to advanced Taiwanese mental health nurses responsible to promote /s enhance the health of patients with prodromes of severe mental illness.

Research in young people at ultra-high risk for psychosis: a review of the current evidence.

The past 15 years have seen a growing interest in early intervention and detection of psychosis before the onset of the first episode. Recent proposals to include a psychosis risk syndrome (PRS) in DSM 5 have focused attention on the evidence base achieved to date in this field. Aims This article aims to (1) review the underlying principles of early identification and intervention during the pre-psychotic phase, (2) summarise the naturalistic follow-up studies conducted to date in this 'at-risk' population, (3) discuss the identified clinical risk factors for transition to psychosis, (4) summarise the interventional studies both psychological and pharmacological completed to date and (5) briefly discuss the controversy around the proposed inclusion of the PRS in DSM 5. Electronic databases EmBase, MedLine and PsychInfo were searched using the keywords ultra-high risk/at-risk mental state/risk syndrome/pre-psychotic/prodrome/prodromal and psychosis/schizophrenia. The evidence suggests that it is possible to identify individuals who may be at risk of developing psychosis. Results from intervention studies, mostly involving second-generation antipsychotics and cognitive behavioural therapy, are currently insufficient to make treatment recommendations for this group. The emerging research with regard to possible neuroprotective factors such as omega fatty acids is promising, but will require replication in larger cohorts before it can be recommended.

The Psychosis High-Risk State

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. 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. Available HR research of the past 20 years from PubMed, books, meetings, abstracts, and international conferences. 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. 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. 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.

Neurophysiological Alterations in the Prepsychotic Phases

Electroencephalography and Magnetoencephalography have provided valuable information about the brain functioning in psychosis. In the last few years, authors have demonstrated that there are neurophysiological alterations already in the prodromal period, before the development of psychosis. This makes them promising tools for predicting a future transition to psychosis. In this paper we review the latest studies using event-related potentials (ERP) in subjects clinically at high-risk of developing psychosis. We particularly focus in the P300, Mismatch-Negativity (MMN) and P50 paradigms, discussing the main findings, but also the limitations and challenges in electrophysiological studies in this population.

P03-330 - Cannabis use disorders and age at onset of psychosis in 606 patients with first episode psychosis

BackgroundAge at onset of psychosis (AAO) may be younger in patients with cannabis use disorders (CUD) compared to those without CUD (NCUD). Most previous studies did not control for potential confounders, did not report effect sizes and included mostly adult patients from non-representative samples.MethodsControlling for relevant confounders, differences in AAO between patients with and without lifetime CUD were analysed in a large epidemiologically based cohort of 606 first-episode psychosis (FEP) patients (age 14 to 29 years) admitted within three years to the Melbourne Early Psychosis Prevention and Intervention Centre. Data were collected from medical files using a standardized scale.ResultsOverall, AAO was not significantly different in CUD (n = 449; 74.1%) compared to NCUD, neither univariate nor when controlling for gender and premorbid functioning. However, AAO was younger in those with early CUD (starting before age 14) compared to NCUD (F(1) = 11.3; p = 0.001; partial η2 = 0.042). When considering the subgroups of early versus late onset psychosis, AAO was even later in early onset psychosis patients with CUD compared to those with NCUD (F(1) = 8.4; p = 0.004; partial η2 = 0.072). These findings were consistent for patients with non-affective psychoses, in those with CUD without other substance use disorders and in those with CUD explicitly starting in the pre-psychotic phase. Notably, 89.1% started cannabis before the onset of psychotic symptoms.ConclusionsCUD starting before age 14 was associated with an earlier AAO at a small effect size, but only in adult onset FEP patients.

S21-04 - Fatty acid metabolism and the onset of psychotic disorder

IntroductionPotentially chronic diseases often have a critical point in their course beyond which treatment becomes less effective. In support of this, early treatment in schizophrenia and other psychoses has been linked to better outcome.ObjectivesThe emergence of simultaneous brain volume changes in those ultra-high-risk individuals who develop psychosis indicate an active biological process, and underline the importance of pre-onset treatment. However, pre-psychotic intervention has also been questioned as, using current criteria, only 20–50% of individuals classified as prodromal develop a psychotic disorder within a 1–2 years period.AimsTreatment agents in the pre-psychotic phase should, therefore, not have major side effects. Bioactive lipids are molecules that have both intra- and intercellular roles, including mediation, modulation and control of neurobiological processes, such as ion channel and receptor activity, neurotransmitter release, synaptic plasticity, second messenger pathways and neuronal gene expression.MethodsLong-chain omega-3 polyunsaturated fatty acids (PUFAs) have been shown effective for both, mood and psychotic symptoms, and they have neuroprotective properties. Because of the controversy concerned with the extent to which an intervention may produce harm which outweighs its benefits, omega-3 PUFAs are prime candidates for evaluation in putatively prodromal individuals.ResultsWe report on the first randomized, placebo-controlled trial on the preventive use of omega-3 fatty acids in 81 ultra-high-risk individuals.ConclusionsSupplementation with long-chain omega-3 PUFAs reduces the risk of progression to psychotic disorder, and offers a safe and efficacious strategy for indicated prevention in individuals at ultra-high-risk of developing a psychotic illness.

A randomized controlled trial of cognitive behavioral therapy for individuals at clinical high risk of psychosis

Background There has been increasing interest in early detection during the prodromal phase of a psychotic disorder. To date a few treatment studies have been published with some promising results for both pharmacological treatments, using second generation antipsychotics, and psychological interventions, mainly cognitive behavioral therapy. The purpose of this study was to determine first if cognitive behavioral therapy (CBT) was more effective in reducing the rates of conversion compared to a supportive therapy and secondly whether those who received CBT had improved symptoms compared to those who received supportive therapy. Method Fifty-one individuals at clinical high risk of developing psychosis were randomized to CBT or a supportive therapy for up to 6 months. The sample was assessed at 6, 12 and 18 months post baseline on attenuated positive symptoms, negative symptoms, depression, anxiety and social functioning. Results Conversions to psychosis only occurred in the group who received supportive therapy although the difference was not significant. Both groups improved in attenuated positive symptoms, depression and anxiety and neither improved in social functioning and negative symptoms. There were no differences between the two treatment groups. However, the improvement in attenuated positive symptoms was more rapid for the CBT group. Conclusions There are limitations of this trial and potential explanations for the lack of differences. However, both the results of this study and the possible explanations have significant implications for early detection and intervention in the pre-psychotic phase and for designing future treatments.

Spatial working memory in individuals at high risk for psychosis: Longitudinal fMRI study

Background Neurocognitive impairments in executive and mnemonic domains are already evident in the pre-psychotic phases. The longitudinal dynamic course of the neurofunctional abnormalities underlying liability to psychosis and their relation to clinical outcomes is unknown. Methods In this study we used functional magnetic resonance imaging (fMRI) in a cohort of subjects at ultra high clinical risk for psychosis (with an “At Risk Mental State”, ARMS) and in healthy controls. Images were acquired at baseline and again after one year on a 1.5 Tesla Signa, while patients were performing a visuospatial working memory task. Psychopathological assessment of the prodromal symptoms was conducted at the same time points by using the CAARMS and the PANSS instruments. Results There were no significant differences between the ARMS and control groups with respect to age or IQ. Although both groups performed the PAL task with a high degree of accuracy, the ARMS showed an increased latency in answers during the most demanding level of the task. At baseline, such cognitive impairment was associated with reduced activation in the left precuneus, left superior parietal lobule, right middle temporal gyrus in the ARMS as compared to controls. In addition, the ARMS failed to activate parietal areas with increasing difficulty of the task. Between presentation and follow-up the overall clinical status of the ARMS sample improved, despite 2 out of the 15 subjects having developed a full-blown psychosis: the CAARMS (perceptual disorder and thought disorder subscales) and the PANNS general scores decreased, while the GAF score increased. Such clinical amelioration was associated with a longitudinal compensatory increase in occipitoparietal regions. Conclusions The prodromal phase of psychosis is associated with functional alterations in parietal and temporal networks subserving visuospatial working memory which are more evident under high cognitive loads. The clinical improvement at one year is associated with a compensatory increase in occipitoparietal regions.

Social dysfunction predicts two years clinical outcome in people at ultra high risk for psychosis

The experience of a first psychotic episode is associated with a marked impairment in psychosocial functioning. However, the decline may be already evident in the pre-psychotic phases and play a significant role in the etiopathology of the disease onset. A sample of subjects at ultra high clinical risk for psychosis (“At Risk Mental State”, ARMS, n = 152) was compared with a demographically-matched general population ( n = 98,072) on different measures of psychosocial functioning. The proportion of subjects with an ARMS living in communal establishments or living at home with their parents was significantly higher than that of the local population ( p < 0.001). Subjects with an ARMS showed also higher rates of unemployment as compared to the general population ( p < 0.001). GAF scores at baseline were significantly lower in unemployed ARMS as compared to students and employed ARMS ( p = 0.002). ARMS subjects living in communal establishments presented higher rates of co-morbid psychiatric conditions ( p = 0.007) and lower GAF scores at baseline ( p = 0.017). Finally, baseline unemployment and living in a communal establishment were associated with an increased risk of developing a psychotic episode within the following two years ( p < 0.05). We concluded that the “At Risk Mental State” is a clinical condition which is characterized by marked psychosocial impairment and by an increased vulnerability to psychosis. Unemployment at the first contact with the prodromal service may be a risk factor for the development of a psychotic episode.

Lack of Association Between Neuropsychological Performance and Level of Psychosis-Proneness in an Adolescent Psychiatric Sample

Studies of the prodromal stage of schizophrenia show that the late prepsychotic phase is associated with mild neuropsychological deficits that parallel those of schizophrenia. However, it is still unclear whether this association is present across the whole range of symptoms of psychosis-proneness, or specific to the extreme groups. In this study, the linear associations between dimensions of psychosis-proneness (as measured by the 92-item Prodromal Questionnaire) and performance on 20 neuropsychological measures were assessed in a group of 71 nonpsychotic adolescent psychiatric patients. A structure of positive, negative and disorganized prodromal symptom dimensions was found, replicating earlier findings. No symptom dimension was significantly associated with neuropsychological performance, even when corrected for nonspecific psychological distress. These findings suggest that the association between symptoms and neuropsychological performance is specific to high levels of symptoms or to the truly prodromal subpopulation. The results also highlight the importance of simultaneous assessment of affective state.

Basic symptoms in the general population and in psychotic and non-psychotic psychiatric adolescents

Objective Cognitive–perceptive ‘basic symptoms’ are used complementary to ultra-high-risk criteria in order to predict onset of psychosis in the pre-psychotic phase. The aim was to investigate the prevalence of a broad selection of ‘basic symptoms’ in a representative general adolescent population sample (GPS; N = 96) and to compare it with adolescents first admitted for early onset psychosis (EOP; N = 87) or non-psychotic psychiatric disorders (NP; N = 137). Methods Subjects were assessed with the Bonn Scale for the Assessment of Basic Symptoms (BSABS). Prevalence of at least one ‘basic symptom’ and mean numbers were compared across the three groups. Logistic regression was used to predict group membership by BSABS subscales; risk ratios were calculated to identify ‘basic symptoms’ which best discriminated between groups. Results The prevalence of at least any one ‘basic symptom’ was 30.2% in GPS compared to 81% in NP and 96.5% in EOP. Correct classification of EOP when compared to GPS was high (94.0%) and lower when compared to NP (78.6%). Cognitive symptoms discriminated best between EOP and NP. Conclusion Alike other prodromal- and psychotic-like experiences, ‘basic symptoms’ are prevalent in the general adolescent population, yet at a lower rate compared to EOP and NP. The usage of ‘at least one basic symptom’ as a screening criterion for youth at risk of developing a psychotic disorder is not recommended in the general population or in unselected psychiatrically ill adolescents. However, particularly cognitive ‘basic symptoms’ may be a valuable criteria to be included in future ‘at risk’ studies in adolescents.

Duration of untreated prodromal symptoms and 12-month functional outcome of individuals at risk of psychosis

Individuals seeking help from prodromal services may have been experiencing attenuated psychotic features and psychosocial impairments for a long period prior to referral. The effect of an extended duration of these untreated ;at risk' symptoms on patients' long-term functional outcome was assessed in a 12-month longitudinal observational study (n=49). A longer duration of untreated ;at risk' symptoms was correlated with a reduced improvement in Global Assessment of Functioning scores after 12 months (beta=-0.375, P=0.008). This effect was independent of age and gender and may have implications for the improvement of treatment strategies in pre-psychotic phases.

Psychoeducation with patients at-risk for schizophrenia—An exploratory pilot study

Objective To introduce a psychoeducational program for patients of at-risk mental state and its preliminary evaluation. Methods The psychoeducational program was designed as a purely informative intervention and consisted of seven 1-h sessions. Sixteen at-risk mental state patients (mean age 26 ± 4.9 years, 12 males/4 females, mean score on prodromal psychopathology (Bonn Scale for Assessment of predictive Basis Symptoms [BSABS-P] 18.6 ± 13.3) were investigated. Results Comparisons of means before and after psychoeducation showed a significant reduction in psychopathology and fatalistic LoC as well as an improvement in knowledge, global functioning and various areas of QoL. A qualitative evaluation of the psychoeducational program also showed advantages from patients’ perspectives. Conclusions This study provides empirical evidence for benefits of psychoeducation with patients of at-risk mental state for schizophrenia but is exploratory and has some limitations, e.g. the small sample size. Therefore the results have to be replicated in a randomized controlled trial in order to be able to demonstrate conclusively the effectiveness of psychoeducation in the pre-psychotic phase. Practice implications Results from this preliminary study suggest that psychoeducation is a promising intervention for patients of at-risk mental state for schizophrenia, and therefore worthy of more investigations.