Detecting incipient schizophrenia: a validation of the Azima battery in first episode psychosis

Early psychosis intervention aims to accurately detect adolescents and young adults at risk for major mental disorders, particularly schizophrenia, yet early biomedical diagnostic accuracy remains poor. However, phenomenological approaches focusing on eliciting and understanding the subjective experience of help-seeking youth better detect incipient schizophrenia. The Azima Battery is an occupational therapy projective assessment that uses expressive media in a standard setup, in order to phenomenologically elicit and describe the activity performance and narratives of individuals at risk of, or on, the psychotic-spectrum.The purpose of this study was to estimate the predictive validity of the Azima Battery with youth seeking help for a first episode of psychosis, and identify patterns of performance distinctive of a diagnosis of schizophrenia 1-year later. A mixed methods phenomenological approach was used to calculate the predictive validity of the Azima Battery in detecting incipient schizophrenia, and to qualitatively identify patterns of performance. Study results demonstrate that the diagnostic accuracy of the Azima Battery is greater than psychiatric interviewing for a future diagnosis of schizophrenia (N = 62: 88.7 % vs 42 %). Performance elements and patterns statistically distinctive of schizophrenia are described, and relate to the structure of the created objects. Therefore, the Azima Battery is a valid measure for clinical use by occupational therapists working in early intervention for psychosis as a complement to traditional psychiatric interviewing.     

Fine motor function and neuropsychological deficits in individuals at risk for schizophrenia

Deficits in fine motor function and neuropsychological performance have been described as risk factors for schizophrenia. In the Basel FEPSY study (Früherkennung von Psychosen; English: Early Detection of Psychosis) individuals at risk for psychosis were identified in a screening procedure (Riecher–Rössler et al. 2005). As a part of the multilevel assessment, 40 individuals at risk for psychosis and 42 healthy controls matched for age, sex and handedness were investigated with a fine motor function test battery and a neuropsychological test battery. Individuals at risk showed lower performances in all subtests of the fine motor function tests, predominantly in dexterity and velocity (wrist/fingers and arm/hand). In the neuropsychological test battery, individuals at risk performed less well compared to healthy controls regarding sustained attention, working memory and perseveration. The combined evaluation of the two test batteries (neuropsychological and fine motor function) separates the two groups into individuals at risk and healthy controls better than each test battery alone. A multilevel approach might therefore be a valuable contribution to detecting beginning schizophrenia.     

The prevention of schizophrenia

Preventive strategies can be divided into universal, selective and indicated prevention and early intervention. Universal interventions are directed to the general population. Selective approaches are targeted at people who have risk factors for an illness, but who do not show any current signs. Indicated approaches target high risk individuals with minimal signs or symptoms foreshadowing mental disorder, but who do not meet diagnostic levels at the current time. Early intervention involves treating those with already diagnosable disorder in a timely and optimal manner aiming to decrease the severity of the illness, and reduce secondary morbidity. Although universal and selective interventions are not yet viable strategies, indicated prevention and early intervention are now realistic possibilities in schizophrenia. Development of methods to identify those at risk of psychosis continues to evolve. Promising results in the prevention and delay of transition to psychotic disorder from high risk state have been found. Early intervention in schizophrenia, including promotion of early help-seeking, has been shown to reduce the duration of untreated psychosis, which is known to be associated with poor outcome in schizophrenia. Early intervention programmes which optimise the care of the first episode have been shown to produce better outcomes than routine management.     

The prevention of schizophrenia

Preventive strategies can be divided into universal, selective and indicated prevention and early intervention. Universal interventions are directed to the general population. Selective approaches are targeted at people who have risk factors for an illness, but who do not show any current signs. Indicated approaches target high risk individuals with minimal signs or symptoms foreshadowing mental disorder, but who do not meet diagnostic levels at the current time. Early intervention involves treating those with already diagnosable disorder in a timely and optimal manner aiming to decrease the severity of the illness, and reduce secondary morbidity. Although universal and selective interventions are not yet viable strategies, indicated prevention and early intervention are now realistic possibilities in schizophrenia. Development of methods to identify those at risk of psychosis continues to evolve. Promising results in the prevention and delay of transition to psychotic disorder from high risk state have been found. Early intervention in schizophrenia, including promotion of early help-seeking, has been shown to reduce the duration of untreated psychosis, which is known to be associated with poor outcome in schizophrenia. Early intervention programmes which optimise the care of the first episode have been shown to produce better outcomes than routine management.     

Risk of suicide and suicidal ideation in psychosis: Results from an Italian multi-modal pilot program on early intervention in psychosis

Suicidality is high in schizophrenia, particularly in first-episode patients. Little is known about patients with prodromal symptoms of psychosis or otherwise high-risk persons.In a sample enrolled in an early intervention program implemented in Milan (Italy), a history of attempted suicide before enrollment was found in 6 first-episode schizophrenia (out of 87, 6.9%), and 7 high-risk of psychosis (out of 81, 8.6%) patients.In the first-episode group, a history of suicide attempts was related to a shorter duration of untreated psychosis. In the high-risk group, a family psychiatric history in first/second degree relatives of patients and a personal history of substance abuse were both associated with an enhanced risk of attempted suicide before enrollment.During the first year of treatment, 3 new attempted suicides were recorded among 57 (5.3%) high-risk patients, and none among first-episode patients (n = 58) (no dropout in the sample). The levels of suicide ideation on the BPRS did not differ by group at assessment, and significantly declined from assessment at entry to 1-year follow-up, except in seven HRP patients who become positive for core symptoms of schizophrenia, as measured on the BPRS.At enrollment, patients at high risk of psychosis had the same prevalence of past suicide attempts than first-episode schizophrenia patients: since suicide attempt is the most important predictor of a future suicidal attempt, the assessment of suicide risk should be given a privileged role in patients at high risk of psychosis as well.     

Age of onset of schizophrenia: perspectives from structural neuroimaging studies

Many of the major neuropsychiatric illnesses, including schizophrenia, have a typical age of onset in late adolescence. Late adolescence may reflect a critical period in brain development making it particularly vulnerable for the onset of psychopathology. Neuroimaging studies that focus on this age range may provide unique insights into the onset and course of psychosis. In this review, we examine the evidence from 2 unique longitudinal cohorts that span the ages from early childhood through young adulthood; a study of childhood-onset schizophrenia where patients and siblings are followed from ages 6 through to their early twenties, and an ultra-high risk study where subjects (mean age of 19 years) are studied before and after the onset of psychosis. From the available evidence, we make an argument that subtle, regionally specific, and genetically influenced alterations during developmental age windows influence the course of psychosis and the resultant brain phenotype. The importance of examining trajectories of development and the need for future combined approaches, using multimodal imaging together with molecular studies is discussed.     

Assessment and Intervention for the Suicidal Patient with Schizophrenia

The risk for suicidal behavior in schizophrenia is high with 10–15% committing suicide and 20–40% making suicide attempts. Due to the chronicity and complexity of schizophrenia and the multi-determined nature of suicidal behavior, the clinician must utilize a biopsychosocial approach to assessment and intervention. Clinical factors such as psychosis, depression and substance abuse increase the risk for suicidal behavior in schizophrenia. Social factors such as social adjustment and social supports also play a critical role. Ongoing assessment and intervention of suicidal behavior, clinical symptomatology, social environment and treatment issues are essential. Prediction and prevention of suicidal behavior are not always possible however. Treatment focused on the reduction of symptomatology and maintenance of an effective social environment may attenuate the risk for suicidal behavior in schizophrenia.     

Dilemma of early drug intervention in prepsychotic illnesses of adolescence

It will be largely supposed that early intervention in schizophrenia improves the outcome of the illness. The paper summarizes the up today significant knowledge about the early recognition and treatment of schizophrenic psychosis in the adolescence. It will be pointed at the diagnostic difficulties and peculiarities in this age group. A comprehensive repeated assessment is necessary if prodromal symptoms of schizophrenia respectively psychotic states have to be taken in account. It will be pleaded for a early low dosis therapy with atypical neuroleptics to prevent the "psychotic catastrophe", that means the full outbreak of the disease. The pharmacotherapy should be a part of an intensive multimodal treatment program. The longstanding continuity of the relations to one and the same treatment setting and therapist responsible for it seems to influence the outcome positively.     

A.E. Bennett Research Award. Prenatal rubella, premorbid abnormalities, and adult schizophrenia.

BACKGROUND: Premorbid neurocognitive, neuromotor, and behavioral function tends to be disturbed in schizophrenia. We previously demonstrated that a birth cohort clinically and serologically documented with prenatal rubella evidenced a marked increase in risk of nonaffective psychosis. In our study, we examined whether rubella-exposed subjects destined to develop schizophrenia and other schizophrenia spectrum disorders (SSD), compared with exposed control subjects, had greater impairment in several premorbid functions. METHODS: Subjects were interviewed using a direct, comprehensive research assessment and diagnosed by consensus. We compared the degree of IQ decline, as well as premorbid neuromotor and behavioral dysfunction, between rubella-exposed subjects who developed schizophrenia spectrum psychosis (SSP) and exposed control subjects from the cohort. We also compared the gestational timing of rubella infection between the cases and control subjects. RESULTS: This rubella-exposed birth cohort evidenced a markedly increased risk of SSD (20.4% or 11/53). Rubella-exposed SSP cases, compared with rubella-exposed control subjects, demonstrated a decline in IQ from childhood to adolescence, and increased premorbid neuromotor and behavioral abnormalities. Moreover, it appears that early gestational rubella exposure may represent a period of increased vulnerability for SSD. CONCLUSIONS: These findings link a known prenatal exposure, a deviant neurodevelopmental trajectory in childhood and adolescence, and SSP in adulthood within the same individuals.     

Is cannabis use a contributory cause of psychosis?

OBJECTIVE: To assess whether cannabis use in adolescence and young adulthood is a contributory cause of schizophreniform psychosis in that it may precipitate psychosis in vulnerable individuals. METHOD: We reviewed longitudinal studies of adolescents and young adults that examined the relations between self-reported cannabis use and the risk of diagnosis with a psychosis or of reporting psychotic symptoms. We also reviewed studies that controlled for potential confounders, such as other forms of drug use and personal characteristics that predict an increased risk of psychosis. We assessed evidence for the biological plausibility of a contributory causal relation. RESULTS: Evidence from 6 longitudinal studies in 5 countries shows that regular cannabis use predicts an increased risk of a schizophrenia diagnosis or of reporting symptoms of psychosis. These relations persisted after controlling for confounding variables, such as personal characteristics and other drug use. The relation did not seem to be a result of cannabis use to self-medicate symptoms of psychosis. A contributory causal relation is biologically plausible because psychotic disorders involve disturbances in the dopamine neurotransmitter systems with which the cannabinoid system interacts, as demonstrated by animal studies and one human provocation study. CONCLUSION: It is most plausible that cannabis use precipitates schizophrenia in individuals who are vulnerable because of a personal or family history of schizophrenia.     

Pharmacological intervention in the initial prodromal phase of psychosis.

Early identification and treatment of schizophrenia may alleviate the symptoms, delay the onset and improve the outcome of psychosis. Thus, detection of individuals at risk during the prodromal phase is an important task. Universal approaches to screen the general population or healthy subjects at risk have not proven possible to-date. However, clinical criteria for detecting ultra-high risk individuals have been developed for specialized settings, with their implementation in interventional studies. This article examines the rationale for early detection and intervention of psychosis, along with a review of some of the current studies. These target prevention using psychological and/or pharmacological intervention strategies have demonstrated promising results in high risk individuals. The German Research Network on Schizophrenia (GRNS) is conducting two multicenter early intervention studies; one with early psychological intervention in subjects who manifest early prodromal symptoms; with the second trial applying clinical management and pharmacological early intervention in subjects experiencing late prodromal symptoms (high risk subjects). Despite the promising results, many of the current studies have small sample sizes with study durations of a short period. The full benefits of early detection and intervention should be revealed once larger and longer studies are conducted.     

Interpreting the association between cannabis use and increased risk for schizophrenia

Recent longitudinal studies from Sweden, the Netherlands, New Zealand, and Israel report that cannabis use during childhood and adolescence doubles the risk of later appearance of psychosis or schizophrenia. These data have been interpreted as indicating that cannabis has a causal effect along the pathway to psychosis. In this paper, we will offer an alternative explanation of these data. Recent investigations of patients with schizophrenia found increased density of cannabinoid receptors in the dorso-lateral prefrontal cortex and the anterior cingulate cortex. Others reported higher levels of endogenous cannabinoids in the blood and cerebrospinal fluid of patients; these findings were independent of possible cannabis use. Several genetic studies have reported an association between genes encoding the cannabinoid receptor and schizophrenia. Thus, an alternative explanation of the association between cannabis use and schizophrenia might be that pathology of the cannabinoid system in schizophrenia patients is associated with both increased rates of cannabis use and increased risk for schizophrenia, without cannabis being a causal factor for schizophrenia.     

Thought Disorder in Offspring of Schizophrenic Parents: Findings From the New York High-Risk Project

The goal of the present analyses was to examine the hypothesis that mild forms of thought disorder (TD) may serve as an indicator of genetic liability for schizophrenia. A subset of 232 subjects drawn from the New York High-Risk Project was used to compare individuals at high risk for schizophrenia (ie, offspring of parents with schizophrenia; n = 63) with 2 groups of individuals at low risk for schizophrenia (ie, offspring of parents with affective disorder [n = 52] and offspring of psychiatrically normal parents [n = 117]). Subjects were administered the Rorschach Inkblot Test, and their responses were assessed according to the Thought Disorder Index (TDI). The high-risk offspring displayed significantly more TD than the other 2 groups, as shown by significantly higher TDI scores. Moreover, they had more deviant verbalizations, according to their significantly higher scores on a composite Idiosyncratic Verbalizations score. As expected, the offspring who developed psychosis produced more TD in adolescence than those who did not develop psychosis. In the sample as a whole, TD scores during late adolescence/early adulthood were positively associated with schizotypal features during mid-adulthood. These findings support the assertion that the presence of TD serves as an endophenotypic marker of a schizophrenia diathesis.     

The Italian guidelines for early intervention in schizophrenia: development and conclusions

Aim: The effectiveness of early intervention in schizophrenia is still under discussion. The guidelines described in the present paper were aimed at contributing to the current debate by providing Italian practitioners, families, patients and health managers with evidence‐based information on early intervention. They also examined the diagnostic tools that are currently available for assessing different stages of psychotic disorders. Methods: A multidisciplinary panel of experts (the Guidelines Development Group) used a set of key‐questions to develop an explicit search strategy to conduct a systematic review of the literature published from January 2000 to June 2006. Trained personnel then selected papers from those yielded by the literature search. The Guidelines Development Group's final recommendations were scaled according to the Italian National Guidelines System grading system. Results: The evidence available up to the time of the literature search does not allow for recommendation of early intervention targeting prodromal or at‐risk patients to prevent progression from the prodromal phase to acute, full‐blown psychosis, nor to improve prognosis. Conversely, identification and timely treatment of first‐episode psychotic patients through specific early intervention programmes are highly recommended. Conclusions: The Italian Guidelines on early intervention in schizophrenia are based on a comprehensive assessment of an updated, large‐scale body of literature. They draw specific, evidence‐based conclusions to assist clinicians and stakeholders in the planning and implementation of appropriate intervention programmes. Further research is needed to ascertain the effectiveness of early intervention in delaying or preventing the conversion to psychosis and improving prognosis in prodromal or at‐risk patients. Further investigation is also required for first‐episode and critical period patients.     

Evaluating and treating the prodromal stage of schizophrenia

Identification of a person in the prodromal stage of schizophrenia, before the onset of the first episode of psychosis, provides an opportunity for early, potentially preventative, interventions. Recent attempts to develop at risk or prodromal syndrome diagnostic criteria have proved to be successful at identifying individuals at high risk for psychosis. Preliminary investigations find that pharmacologic and psychotherapeutic interventions may reduce the risk of psychosis in at risk individuals, but until more is known, current treatment guidelines recommend close monitoring, therapeutic interventions that address identified problems, including supportive or cognitive therapies to reduce the functional consequences of the presenting symptoms, family interventions to reduce family distress and improve coping, and intervention with schools to decrease likelihood of school failure. Pharmacologic intervention targeting the prodromal symptoms is not recommended, given the uncertain risk to benefit ratio.     

Neurocognitive deficits in the (putative) prodrome and first episode of psychosis

OBJECTIVE: International research programs have contributed to the creation of operationally defined criteria to identify individuals at risk for schizophrenia. Although there has been substantial progress in the prospective study of the schizophrenia prodrome, the utility of current diagnostic criteria remains questionable because of the relatively low base rates of incident psychoses, the high false-positive rate and ethical concerns regarding the treatment of individuals at risk. The identification of brain based neurocognitive vulnerability markers for schizophrenia may contribute to the development of an at risk algorithm with greater predictive accuracy. METHODS: Forty subjects at risk (AR) for schizophrenia, 15 in their first episode (FE) of schizophrenia, and 36 healthy comparison (HC) subjects were administered a neurocognitive battery that assessed the domains of processing speed, working memory, verbal episodic memory, executive functioning and general intelligence. RESULTS: At baseline, AR subjects showed neurocognitive deficits across all domains compared to HC subjects that were less severe than those observed in the FE sample. In preliminary analyses, AR subjects who later converted to psychosis (N=5) had greater neurocognitive impairment at baseline evaluation compared to those individuals who remained "at risk" at follow-up. CONCLUSIONS: Neurocognitive deficits may be important in the pathogenesis of early psychosis and could help to define individuals at greatest risk for schizophrenia. Continued research in larger cohorts is needed to test the validity of this neurocognitive profile and its utility as a vulnerability marker.     

Self-disturbances as a possible premorbid indicator of schizophrenia risk: A neurodevelopmental perspective

Self-disturbances (SDs) are increasingly identified in schizophrenia and are theorized to confer vulnerability to psychosis. Neuroimaging research has shed some light on the neural correlates of SDs in schizophrenia. But, the onset and trajectory of the neural alterations underlying SDs in schizophrenia remain incompletely understood. We hypothesize that the aberrant structure and function of brain areas (e.g., prefrontal, lateral temporal, and parietal cortical structures) comprising the “neural circuitry of self” may represent an early, premorbid (i.e., pre-prodromal) indicator of schizophrenia risk. Consistent with neurodevelopmental models, we argue that “early” (i.e., perinatal) dysmaturational processes (e.g., abnormal cortical neural cell migration and mini-columnar formation) affecting key prefrontal (e.g., medial prefrontal cortex), lateral temporal cortical (e.g., superior temporal sulcus), and parietal (e.g., inferior parietal lobule) structures involved in self-processing may lead to subtle disruptions of “self” during childhood in persons at risk for schizophrenia. During adolescence, progressive neurodevelopmental alterations (e.g., aberrant synaptic pruning) affecting the neural circuitry of self may contribute to worsening of SDs. This could result in the emergence of prodromal symptoms and, eventually, full-blown psychosis. To highlight why adolescence may be a period of heightened risk for SDs, we first summarize the literature regarding the neural correlates of self in typically developing children. Next, we present evidence from neuroimaging studies in genetic high-risk youth suggesting that fronto-temporal–parietal structures mediating self-reflection may be abnormal in the premorbid period. Our goal is that the ideas presented here might provide future directions for research into the neurobiology of SDs during the pre-psychosis development of youth at risk for schizophrenia.     

Early recognition and intervention for schizophrenia

Studies dealing with the prodromal stage of schizophrenia point to the possibility of early detection and early intervention. Major socioeconomic and social consequences are associated with this disorder. The duration of untreated psychosis seems to play an important role in the course of the disease; i.e. a prolonged duration until adequate treatment is obtained correlates to poorer prognosis. Social, cognitive, affective, and structural brain variations appear in the early prodromal stage. Recent early intervention studies show the possibility of reducing transition rates by preventive treatment of patients at a higher risk of psychosis and already manifesting impaired function. In this review, prodromal signs and possibilities for early detection and intervention in schizophrenia are presented.     

The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. I. Study rationale and design

The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome. This identifies them as being at high risk for developing psychosis in the near future. The study aims include prevention of psychosis onset and disability, as well as palliation of ongoing symptomatology.This report presents the study rationale and design. Recent studies will be reviewed that have advanced our knowledge about the early course of schizophrenia and our ability to predict onset prospectively, advances that have rendered prodromal intervention research feasible and ethical. The study design has many novel features. It tests for prevention versus delay in psychosis onset, as well as for efficacy and safety in a newly defined clinical population. This has required the development of innovative clinical research assessment instruments and a new operational definition of psychosis onset. The integration of these novel elements into an otherwise typical clinical trial design is detailed. The companion report will address sample recruitment and the clinical phenomenology at baseline of this putative "prodromal" entity.