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Aim: Research in the phenomenological tradition suggests that the schizophrenia spectrum is characterized by disturbance of the 'basic' self, whereas borderline personality disorder involves disturbance of the 'narrative' self. The current study investigated this proposal in an ultra-high risk for psychosis sample., Methods: The sample consisted of 42 ultra-high-risk participants with a mean age of 19.22 years. Basic self-disturbance was measured using the Examination of Anomalous Self-Experience. Borderline personality pathology was measured using the borderline personality disorder items from the structured clinical interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) Axis II Personality Questionnaire., Results: No correlation was found between the measures of basic self-disturbance and borderline personality pathology., Conclusions: The finding is consistent with the proposal that different (although not mutually exclusive) types of self-disturbance characterize the schizophrenia spectrum and borderline personality disorder. Further research should further examine the question of basic self-disturbance in patients with established borderline personality disorder., (© 2013 Wiley Publishing Asia Pty Ltd.)

The results of a recent double-blind, randomized, placebo-controlled trial performed in 81 young patients at ultra-high risk for psychosis indicated that a 12-week intervention of 1.2g/day of ω-3 polyunsaturated fatty acids (PUFA) significantly reduced the risk of transition to psychosis and improved positive, negative and general symptoms as well as functioning. The aim of this post-hoc analysis was to determine at which time point ω-3 PUFAs start to significantly differ from placebo in improving psychopathology and functioning in young people at risk of developing psychosis. Analyses were performed using the mixed model repeated-measures analysis of variance. Compared to placebo, ω-3 PUFAs' significant effects on the amplitude of the reduction in General and Total PANSS scores are evident after the first four weeks of treatment; a reduction of positive symptoms and a lower mean PANSS positive score were apparent after eight weeks, whereas the significant drop in negative symptoms and the significant change and higher mean scores in global functioning occur later at 12weeks. The delay of onset of ω -3 PUFAs seems comparable to that of antipsychotics and antidepressants., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Importance: The ultra high-risk (UHR) criteria were introduced to prospectively identify patients at high risk of psychotic disorder. Although the short-term outcome of UHR patients has been well researched, the long-term outcome is not known., Objective: To assess the rate and baseline predictors of transition to psychotic disorder in UHR patients up to 15 years after study entry., Design: Follow-up study of a cohort of UHR patients recruited to participate in research studies between 1993 and 2006., Setting: The Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service for UHR patients in Melbourne, Australia., Participants: Four hundred sixteen UHR patients previously seen at the PACE clinic., Main Outcomes and Measures: Transition to psychotic disorder, as measured using the Comprehensive Assessment of At-Risk Mental States, Brief Psychiatric Rating Scale/Comprehensive Assessment of Symptoms and History, or state public mental health records., Results: During the time to follow-up (2.4-14.9 years after presentation), 114 of the 416 participants were known to have developed a psychotic disorder. The highest risk for transition was within the first 2 years of entry into the service, but individuals continued to be at risk up to 10 years after initial referral. The overall rate of transition was estimated to be 34.9% over a 10-year period (95% CI, 28.7%-40.6%). Factors associated with transition included year of entry into the clinic, duration of symptoms before clinic entry, baseline functioning, negative symptoms, and disorders of thought content., Conclusions and Relevance: The UHR patients are at long-term risk for psychotic disorder, with the highest risk in the first 2 years. Services should aim to follow up patients for at least this period, with the possibility to return for care after this time. Individuals with a long duration of symptoms and poor functioning at the time of referral may need closer monitoring. Interventions to improve functioning and detect help-seeking UHR patients earlier also may be indicated.

Objective: To investigate whether long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs) improve functioning and psychiatric symptoms in young people with borderline personality disorder (BPD) who also meet ultra-high risk criteria for psychosis., Methods: We conducted a post hoc subgroup analysis of a double-blind, randomized controlled trial. Fifteen adolescents with BPD (mean age 16.2 years, [SD 2.1]) were randomized to either 1.2 g/day n-3 PUFAs or placebo. The intervention period was 12 weeks. Study measures included the Positive and Negative Syndrome Scale, the Montgomery-Åsberg Depression Rating Scale, and the Global Assessment of Functioning. Side effects were documented with the Udvalg for Kliniske Undersøgelser. Fatty acids in erythrocytes were analyzed using capillary gas chromatography., Results: At baseline, erythrocyte n-3 PUFA levels correlated positively with psychosocial functioning and negatively with psychopathology. By the end of the intervention, n-3 PUFAs significantly improved functioning and reduced psychiatric symptoms, compared with placebo. Side effects did not differ between the treatment groups., Conclusions: Long-chain n-3 PUFAs should be further explored as a viable treatment strategy with minimal associated risk in young people with BPD. (, Clinical Trial Registration Number: NCT00396643).

Prospective studies have suggested genetic variation in the neuregulin 1 (NRG1) and D-amino-acid oxidase activator (DAOA) genes may assist in differentiating high-risk individuals who will or will not transition to psychosis. In a prospective cohort (follow-up=2.4-14.9 years) of 225 individuals at ultra-high risk (UHR) for psychosis, we assessed haplotype-tagging single-nucleotide polymorphisms (htSNPs) spanning NRG1 and DAOA for their association with transition to psychosis, using Cox regression analysis. Two NRG1 htSNPs (rs12155594 and rs4281084) predicted transition to psychosis. Carriers of the rs12155594 T/T or T/C genotype had a 2.34 (95% confidence interval (CI)=1.37-4.00) times greater risk of transition compared with C/C carriers. For every rs4281084 A-allele the risk of transition increased by 1.55 (95% CI=1.05-2.27). For every additional rs4281084-A and/or rs12155594-T allele carried the risk increased ∼1.5-fold, with 71.4% of those carrying a combination of 3 of these alleles transitioning to psychosis. None of the assessed DAOA htSNPs were associated with transition. Our findings suggest NRG1 genetic variation may improve our ability to identify UHR individuals at risk for transition to psychosis.

Objective: The ultra-high risk clinical phenotype is associated with substantial distress and functional impairment and confers a greatly enhanced risk for transition to full-threshold psychosis. A range of interventions aimed at relieving current symptoms and functional impairment and reducing the risk of transition to psychosis has shown promising results, but the optimal type and sequence of intervention remain to be established. The aim of this study was to determine which intervention was most effective at preventing transition to psychosis: cognitive therapy plus low-dose risperidone, cognitive therapy plus placebo, or supportive therapy plus placebo., Method: A double-blind, randomized, placebo-controlled 12-month trial of low-dose risperidone, cognitive therapy, or supportive therapy was conducted in a cohort of 115 clients of the Personal Assessment and Crisis Evaluation Clinic, a specialized service for young people at ultra-high risk of psychosis located in Melbourne, Australia. Recruitment commenced in August 2000 and ended in May 2006. The primary outcome measure was transition to full-threshold psychosis, defined a priori as frank psychotic symptoms occurring at least daily for 1 week or more and assessed using the Comprehensive Assessment of At-Risk Mental States. Secondary outcome measures were psychiatric symptoms, psychosocial functioning, and quality of life., Results: The estimated 12-month transition rates were as follows: cognitive therapy + risperidone, 10.7%; cognitive therapy + placebo, 9.6%; and supportive therapy + placebo, 21.8%. While there were no statistically significant differences between the 3 groups in transition rates (log-rank test P = .60), all 3 groups improved substantially during the trial, particularly in terms of negative symptoms and overall functioning., Conclusions: The lower than expected, essentially equivalent transition rates in all 3 groups fail to provide support for the first-line use of antipsychotic medications in patients at ultra-high risk of psychosis, and an initial approach with supportive therapy is likely to be effective and carries fewer risks., (© Copyright 2013 Physicians Postgraduate Press, Inc.)

Recent findings on intervention options in individuals at ultra-high risk (UHR) for psychosis underline the necessity of a screening tool that facilitates early detection in low-threshold, non-specialized settings. The aim of this study was to examine, whether the Community Assessment of Psychic Experience (CAPE) could be used as a screening tool to detect individuals at an increased risk for developing psychosis in a clinical, help-seeking population. The utility of the CAPE was assessed against the Comprehensive Assessment of At-Risk Mental States (CAARMS). The CAPE is a 42-item self-report questionnaire that proved to be stable, reliable and valid for self reported psychotic-like experiences in the general population. 165 individuals between 13 and 24years of age were assessed for being at UHR for developing psychosis. 50.9% individuals were CAARMS-positive and 49.1% were CAARMS-negative. The ROC-analysis provided two cut-off points: The cut-off value of 3.20 in the positive dimension showed a sensitivity of 67%, a specificity of 73%, a positive predictive value of 72% and a negative predictive value of 68%. The cut-off value of 2.80 in the positive dimension showed a higher sensitivity (83%) and a better negative predictive value (74%), but a lower specificity (49%) and a reduced positive predictive value (63%). Our results show promise that the CAPE is a valid, simple and cost-effective instrument for detecting individuals at UHR in a clinical population. It may represent a useful screening tool for calling clinicians' attention to subjects with psychotic-like experiences., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Aim: The study aims to investigate affect recognition in young people at different stages of psychotic illness., Methods: Seventy-nine ultra-high risk patients, 30 first-episode schizophrenia patients and 30 healthy control subjects completed a facial affect labelling test and an affective prosody recognition test. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS)., Results: We observed significant impairments in facial and vocal emotion recognition in both of the clinical groups compared with the control group. These group differences remained significant when age, sex and education were taken into account., Conclusions: The findings suggest that emotion recognition impairments may be independent of the stage of illness in schizophrenia. Deficits in emotion recognition may be present before the full expression of psychotic illness, and may contribute to the social cognition and social functioning deficits apparent in emerging psychotic disorders., (© 2012 Wiley Publishing Asia Pty Ltd.)

Problems in the perception of emotional material, in particular deficits in the recognition of negative stimuli, have been demonstrated in schizophrenia including in first-episode samples. However, it is largely unknown if emotion recognition impairment is present in people with subthreshold psychotic symptoms. Here, we examined the capacity to recognize facially expressed emotion and affective prosody in 79 individuals at ultra high-risk for psychosis, 30 clinically stable individuals with first-episode schizophrenia assessed as outpatients during the early recovery phase of illness, and 30 unaffected healthy control subjects. We compared (1) scores for a combined fear-sadness aggregate index across face and voice modalities, (2) summary scores of specific emotions across modalities, and (3) scores for specific emotions for each sensory modality. Findings supported deficits in recognition of fear and sadness across both modalities for the clinical groups (the ultra high-risk and first-episode group) as compared with the healthy controls. Furthermore, planned contrasts indicated that compared with the healthy control subjects, both clinical groups had a significant deficit for fear and sadness recognition in faces and for anger recognition in voices. Specific impairments in emotion recognition may be apparent in people at clinical high-risk for schizophrenia before the full expression of psychotic illness. The results suggest a trait deficit and an involvement of the amygdala in the pathology of ultra high-risk states.

Objective: Genetic syndromes related to psychosis have become increasingly important for exploring the trajectory that leads to psychosis onset. A very significant opportunity for mapping earlier phases of the trajectory can be found in 22q11.2 deletion syndrome (22q11DS). Comparative studies have shown that schizophrenic disorder in 22q11DS largely resembles schizophrenia in the general population, but only few studies have investigated the features of prodromal symptoms in 22q11DS. The aim of the present study was to investigate differences and similarities between two samples: patients with 22q11DS clinically at risk for psychotic onset (UHR+22q11DS group) and patients at clinical high risk for psychotic onset (UHR group)., Method: The study was conducted on a sample of 30 individuals UHR+22q11DS and 81 individuals at UHR without 22q11DS. The two groups were compared on positive, negative and depressive symptoms, level of general functioning and IQ., Results: There was a significant group difference in negative symptoms, but no significant differences were found for positive, global and total symptoms. The UHR+22q11DS group showed a lower level of general functioning. The clinical profile of the UHR+22q11DS group was clearly more homogeneous., Conclusions: Even if the two UHR groups are comparable in terms of positive symptoms, the UHR+22q11DS have a specific clinical pattern characterized by higher negative symptoms, lower general functioning and an older age of onset of the UHR state. This finding may be of clinical value for the development of specific therapeutic intervention for UHR+22q11DS, and of theoretical value since the two groups may share only some underlying etiopathogenetic mechanisms., (Copyright © 2012 Elsevier B.V. All rights reserved.)

It has recently been shown that treatment with long-chain omega-3 polyunsaturated fatty acids (PUFAs) could decrease the rate of transition to psychosis, and improve psychiatric symptoms and global functioning in people at ultra-high risk (UHR) for psychosis. Previous studies have suggested that resting state brain activity measured with electroencephalography (EEG) may represent an objective biomarker of changes in neural function associated with supplementation with omega-3 PUFAs. It has also been proposed that although resting state EEG cannot, by itself, predict transition to psychosis in UHR individuals, the combination of resting state EEG with negative symptoms may be a valid predictor of transition. The present study investigated whether treatment with omega-3 PUFAs influenced resting state EEG in UHR participants, and whether or not the association of the participants' resting state EEG with their levels of negative symptoms was dependent on their transition status. The brain activity of 73 UHR participants was recorded in the context of a randomized, placebo-controlled trial of the effects of supplementation with omega-3 PUFAs. The UHR participants who subsequently transitioned to psychosis (UHR+) did not differ from those who did not transition (UHR-) in terms of resting state EEG power in any frequency band. However, negative symptom scores were associated with increased delta activity in the frontal region of the UHR+ participants, but not in the UHR- participants. Treatment with omega-3 PUFAs did not induce changes in resting state EEG in either group. The results suggest that decreased frontal delta activity, in combination with high levels of negative symptoms, may be a risk factor for subsequent transition to psychosis in UHR individuals., (Copyright © 2012 Elsevier B.V. All rights reserved.)

It has been suggested that some cases of schizophrenia may be caused by an interaction between physiological risk factors and exposure to certain neurotropic infectious agents such as Herpes Simplex Virus type 1 (HSV1). This study investigated whether HSV1 exposure was associated with structural brain abnormalities in individuals who, because of genetic or other factors, were deemed at ultra high risk (UHR) of developing psychosis. Twenty-five UHR individuals with a history of HSV1 exposure (HSV1+), 33 UHR participants without a history of HSV1 exposure (HSV1-) and 19 healthy controls participated in the study. All participants underwent a T1-weighted structural MRI scan, and HSV1 exposure was determined based on the presence of IgG class antibodies in the blood serum. Voxel based morphometry revealed that the HSV1+ participants exhibited volumetric gray matter reductions in the cuneus, relative to both the HSV1--and healthy control participants (p<0.05, small volume corrected for familywise error). The results of the study suggest that a history of HSV1 infection is associated with volumetric gray matter reductions in individuals at ultra-high risk for developing psychosis, and are consistent with previous studies that have identified structural gray matter abnormalities in HSV1-infected patients with established schizophrenia., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: In recent years there has been increasing interest in functional recovery in the early phase of schizophrenia. Concurrently, new remission criteria have been proposed and several studies have examined their clinical relevance for prediction of functional outcome in first-episode psychosis (FEP). However, the longitudinal interrelationship between full functional recovery (FFR) and symptom remission has not yet been investigated. This study sought to: (1) examine the relationships between FFR and symptom remission in FEP over 7.5 years; (2) test two different models of the interaction between both variables., Method: Altogether, 209 FEP patients treated at a specialized early psychosis service were assessed at baseline, 8 months, 14 months and 7.5 years to determine their remission of positive and negative symptoms and functional recovery. Multivariate logistic regression and path analysis were employed to test the hypothesized relationships between symptom remission and FFR., Results: Remission of both positive and negative symptoms at 8-month follow-up predicted functional recovery at 14-month follow-up, but had limited value for the prediction of FFR at 7.5 years. Functional recovery at 14-month follow-up significantly predicted both FFR and remission of negative symptoms at 7.5 years, irrespective of whether remission criteria were simultaneously met. The association remained significant after controlling for baseline prognostic indicators., Conclusions: These findings provided support for the hypothesis that early functional and vocational recovery plays a pivotal role in preventing the development of chronic negative symptoms and disability. This underlines the need for interventions that specifically address early psychosocial recovery.

Objectives: To investigate if low-dose lithium may counteract the microstructural and metabolic brain changes proposed to occur in individuals at ultra-high risk (UHR) for psychosis., Methods: Hippocampal T2 relaxation time (HT2RT) and proton magnetic resonance spectroscopy ((1)H-MRS) measurements were performed prior to initiation and following three months of treatment in 11 UHR patients receiving low-dose lithium and 10 UHR patients receiving treatment as usual (TAU). HT2RT and (1)H-MRS percentage change scores between scans were compared using repeated measures ANOVA and correlated with behavioural change scores., Results: Low-dose lithium significantly reduced HT2RT compared to TAU (p=0.018). No significant group by time effects was seen for any brain metabolites as measured with (1)H-MRS, although myo-inositol, creatine, choline-containing compounds and NAA increased in the group receiving low-dose lithium and decreased or remained unchanged in subjects receiving TAU., Conclusions: This pilot study suggests that low-dose lithium may protect the microstructure of the hippocampus in UHR states as reflected by significantly decreasing HT2RT. Larger scale replication studies in UHR states using T2 relaxation time as a proxy for emerging brain pathology seem a feasible mean to test neuroprotective strategies such as low-dose lithium as potential treatments to delay or even prevent the progression to full-blown disorder.

Bipolar affective disorder (BD) is a severe, recurrent and disabling disorder with devastating consequences for individuals, families and society. Although these hazards and costs provide a compelling rationale for development of early detection and early intervention strategies in BD, the development of at-risk criteria for first episode mania is still in an early stage of development. In this paper we review the literature with respect to the clinical, neuroantomical and neuropsychological data, which support this goal. We also describe our recently developed bipolar at-risk criteria (BAR). This criteria comprises the peak age range of the first onset of bipolar disorder, genetic risk, presenting with sub-threshold mania, cyclothymic features or depressive symptoms. An initial pilot evaluation of the BAR criteria in 22 subjects indicated conversion rates to proxies of first-episode mania of 23% within 265 days on average, and high specificity and sensitivity of the criteria. If prospective studies confirm the validity of the BAR criteria, then the criteria would have the potential to open up new avenues of research for indicated prevention in BD and might therefore offer opportunities to ameliorate the severity of, or even prevent BD.

The role of polyunsaturated fatty acids and their metabolites for the cause and treatment of psychotic disorders are widely discussed. The efficacy as an augmenting agent in chronic schizophrenia seems to be small or not present, however epidemiological data, as well as some recent controlled studies in emerging psychosis point towards possible preventive effects of long-chain polyunsaturated fatty acids in early and very early stages of psychotic disorders and some potential secondary or tertiary beneficial long-term effects in later, more chronic stages, in particular for metabolic or extra-pyramidal side effects. In this comprehensive review, we describe the physiology and metabolism of polyunsaturated fatty acids, phospholipases, epidemiological evidence and the effect of these fatty acids on the brain and neurodevelopment. Furthermore, we examine the available evidence in indicated prevention in emerging psychosis, monotherapy, add-on therapy and tolerability. The neuroprotective potential of n-3 LC-PUFAs for indicated prevention, i.e. delaying transition to psychosis in high-risk populations needs to be further explored.

Objective: To compare the long-term outcome in individuals with early-onset (before age 18) and adult-onset schizophrenia spectrum disorder who were initially diagnosed and treated in the same clinical center., Method: A prospective follow-up study of 723 consecutive first-episode psychosis patients (age range 14 to 30 years) on average 7.4 years after initial presentation to an early psychosis service, the Early Psychosis Prevention and Intervention Centre in Melbourne, Australia. The outcome measures included the Brief Psychiatric Rating Scale, the Schedule for the Assessment of Negative Symptoms, the Beck Depression Inventory, the Global Assessment of Functioning Scale, the Social and Occupational Functioning Assessment Scale, and the Quality of Life Scale., Results: Follow-up interviews were conducted on 66.9% (484/723) individuals, of whom 75.6% (366/484) received a schizophrenia spectrum disorder diagnosis at baseline. Early-onset schizophrenia spectrum disorder was observed in 11.2% (41/366). At follow-up, individuals with early-onset reported significantly fewer positive symptoms and were characterised by significantly superior functioning on measures assessing global functioning, social-occupational functioning, and community functioning than individuals with adult-onset. The early-onset group also achieved significantly better vocational outcomes and had a more favourable course of illness with fewer psychotic episodes over the last two years prior to follow-up. Finally, when investigated as a continuous variable, younger age at onset significantly correlated with better symptomatic and functional outcomes., Conclusions: These results question the assumption that early-onset schizophrenia typically has a poor outcome. Early detection and specialised treatment for the first psychotic episode appear to be more effective at improving long-term functional outcomes in people with early-onset schizophrenia as in those with adult-onset schizophrenia. This possibility and the reasons for it need further investigation., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Purpose of Review: To provide an update of the recent studies on the age of onset of the major mental illnesses, with a special focus on the prospects for prevention and early intervention., Recent Findings: The studies reviewed here confirm previous reports on the age of onset of the major mental disorders. While the behaviour disorders, and certain anxiety disorders, emerge during childhood, most of the high prevalence disorders (anxiety, mood and substance use) emerge during adolescence and early adulthood, as do the psychotic disorders. Early age of onset has been shown to be associated with a longer duration of untreated illness and poorer clinical and functional outcomes., Summary: Although the onset of most mental disorders usually occurs during the first three decades of life, effective treatment is typically not initiated until a number of years later. Although there is increasing evidence to suggest that intervention during the early stages of a disorder may help reduce the severity and/or the persistence of the initial or primary disorder and prevent secondary disorders, additional research is needed into appropriate treatment for early stage cases as well as the long-term effects of early intervention, and to appropriate service design for those in the early stages of a mental illness. This will mean not only the strengthening and re-engineering of existing systems but also, crucially, the construction of new streams of care for young people in transition to adulthood.

Objective: Cognitive therapy and/or low-dose antipsychotic administered during the prodromal phase of schizophrenia may prevent or delay the onset of full-blown illness. However, it is unclear which of these treatments are most effective, how long treatment should be given, and whether effects will be sustained over a prolonged period., Method: In order to examine these issues, we conducted a randomized controlled trial of cognitive therapy + risperidone; cognitive therapy + placebo; and supportive therapy + placebo in young people at ultra high risk for developing a psychotic disorder (that is, putatively prodromal). The main outcome was transition to psychotic disorder, with level of symptoms and functioning the secondary outcomes. This article reports the interim 6-month follow-up results. The study was conducted from August 2000 to May 2007., Results: Of a possible 464 eligible ultra high risk individuals, 115 were recruited to the randomized controlled trial (cognitive therapy + risperidone, n = 43; cognitive therapy + placebo, n = 44; and supportive therapy + placebo, n = 28). An additional 78 individuals agreed to follow-up assessments but not to randomization ("monitoring group," n = 78). At 6 months, 8 of the 115 participants (7.0%) and 4 of the monitoring group (5.1%) had developed psychotic disorder. There were no significant differences between the 3 randomized groups (log rank test, P = .92) or between all 4 groups (log rank test, P = .93). There was also no difference between the 4 groups in secondary measures, with all groups showing a reduction in symptoms and increased functioning., Conclusions: Rates of transition to psychosis were lower than expected, particularly in the control supportive therapy + placebo group. This may have accounted for the negative finding, as the sample was therefore underpowered to find any difference between groups. Alternatively, it may be that all treatments were equally effective or equally ineffective at 6 months., Trial Registration: http://www.anzctr.org.au Identifier: ACTRN012605000247673., (© Copyright 2011 Physicians Postgraduate Press, Inc.)

Background: Around 20% of patients who suffer from psychosis will experience a single psychotic episode (SPE), but relatively little is known about the characteristics and predictors for this group of patients. This study sought to: 1) characterise the subgroup of first-episode psychosis (FEP) patients who experienced a SPE over a 7.5-year follow-up; and 2) to identify significant predictors for this subgroup independent of potential confounders., Methods: A representative sample of 413 FEP patients treated at a specialist early psychosis service were assessed at baseline and followed-up for 7.5 years. Binary logistic regression models were employed to investigate univariate and adjusted associations between baseline predictors and experiencing a SPE. Results were adjusted for the influence of known prognostic factors for psychosis., Results: Follow-up data was available for 274 participants. Forty-six (16.5%) achieved clinical remission and experienced no recurrence over the follow-up period. Duration of untreated psychosis (DUP) shorter than 60 days (OR=3.89, p=0.007), more rapid response to antipsychotic treatment (OR=0.33, p=0.019) and no parental loss (OR=5.25, p=0.045) significantly predicted a SPE. The association remained significant after controlling for potential confounders., Conclusions: Early treatment (within two months of onset of psychotic symptoms) and social support significantly reduce vulnerability to subsequent psychotic episodes. Future studies need to investigate the interplay between biological factors (i.e. sensitized dopaminergic system), environmental variables (i.e. exposure to trauma, stigma and discrimination), and psychological attributes (i.e. cognitive schemata) in order to elucidate the processes underlying the vulnerability to recurrent psychotic episodes., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Introduction: We have developed ultra-high risk criteria for bipolar affective disorder (bipolar at-risk - BAR) which include general criteria such as being in the peak age range of the onset of the disorder and a combination of specific criteria including sub-threshold mania, depressive symptoms, cyclothymic features and genetic risk. In the current study, the predictive validity of these criteria were tested in help-seeking adolescents and young adults., Method: This medical file-audit study was conducted at ORYGEN Youth Health (OYH), a public mental health program for young people aged between 15 and 24years and living in metropolitan Melbourne, Australia. BAR criteria were applied to the intake assessments of all non-psychotic patients who were being treated in OYH on 31 January, 2008. All entries were then checked for conversion criteria. Hypomania/mania related additions or alterations to existing treatments or initiation of new treatment by the treating psychiatrist served as conversion criteria to mania., Results: The BAR criteria were applied to 173 intake assessments. Of these, 22 patients (12.7%) met BAR criteria. The follow-up period of the sample was 265.5days on average (SD 214.7). There were significantly more cases in the BAR group (22.7%, n=5) than in the non-BAR group (0.7%, n=1) who met conversion criteria (p<.001)., Conclusions: These findings support the notion that people who develop a first episode of mania can be identified during the prodromal phase. The proposed criteria need further evaluation in prospective clinical trials., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: To describe the longer-term clinical and functional outcome of a large, epidemiologic representative cohort of individuals experiencing a first episode of psychosis., Method: A naturalistic, prospective follow-up of an epidemiologic sample of 723 consecutive first-episode psychosis patients, followed between January 1998 and April 2005, at a median of 7.4 years after initial presentation to the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne, Australia. EPPIC is a frontline public mental health early psychosis program, servicing a geographically defined catchment area with a population of about 800,000 people. The main outcome measures included the Brief Psychiatric Rating Scale, the Schedule for the Assessment of Negative Symptoms, the Beck Depression Inventory, the Global Assessment of Functioning Scale, the Social and Occupational Functioning Assessment Scale, the Quality of Life Scale, and the remission criteria developed by the Remission in Schizophrenia Working Group., Results: Follow-up information was collected on up to 90.0% (n = 651) of the baseline cohort of 723 participants, with 66.9% (n = 484) interviewed. In the last 2 years, 57% of individuals with schizophrenia/schizophreniform, 54% with schizoaffective disorder, 62% with affective psychosis, and 68% with other psychotic disorders reported some paid employment. Depending upon the criteria applied, symptomatic remission at follow-up was observed in 37%-59% of the cohort. Social/vocational recovery was observed in 31% of the cohort. Approximately a quarter achieved both symptomatic remission and social/vocational recovery., Conclusion: The relatively positive outcomes are consistent with a beneficial effect of specialized early intervention programs; however it is premature to draw firm conclusions. There was no control group and there are many differences between the relevant comparison studies and the present one. Although difficult to conduct, large scale controlled health services research trials are required to definitively determine the impact and optimal duration of specialized early psychosis programs., (2010 Physicians Postgraduate Press, Inc.)

Objective: We aimed to replicate a recent finding of high prevalence of trauma history in patients at 'ultra-high risk' (UHR) of psychotic disorder and to investigate whether trauma predicts conversion to psychosis in this population., Method: A consecutive sample of UHR patients was assessed. History of trauma was accessed with the General Trauma Questionnaire. Cox regression models were used to explore relationship between conversion to psychosis and trauma., Results: Of 92 UHR patients nearly 70% had experienced a traumatic event and 21.7% developed psychosis during follow-up (mean 615 days). Patients who had experienced a sexual trauma (36%) were significantly more likely to convert to first-episode psychosis (OR 2.96) after controlling for meeting multiple UHR intake groups., Conclusion: UHR patients have a high prevalence of history of trauma. Previous sexual trauma may be a predictor of onset of psychotic disorder in this population.

Context: The use of antipsychotic medication for the prevention of psychotic disorders is controversial. Long-chain omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) may be beneficial in a range of psychiatric conditions, including schizophrenia. Given that omega-3 PUFAs are generally beneficial to health and without clinically relevant adverse effects, their preventive use in psychosis merits investigation., Objective: To determine whether omega-3 PUFAs reduce the rate of progression to first-episode psychotic disorder in adolescents and young adults aged 13 to 25 years with subthreshold psychosis., Design: Randomized, double-blind, placebo-controlled trial conducted between 2004 and 2007., Setting: Psychosis detection unit of a large public hospital in Vienna, Austria., Participants: Eighty-one individuals at ultra-high risk of psychotic disorder., Interventions: A 12-week intervention period of 1.2-g/d omega-3 PUFA or placebo was followed by a 40-week monitoring period; the total study period was 12 months., Main Outcome Measures: The primary outcome measure was transition to psychotic disorder. Secondary outcomes included symptomatic and functional changes. The ratio of omega-6 to omega-3 fatty acids in erythrocytes was used to index pretreatment vs posttreatment fatty acid composition., Results: Seventy-six of 81 participants (93.8%) completed the intervention. By study's end (12 months), 2 of 41 individuals (4.9%) in the omega-3 group and 11 of 40 (27.5%) in the placebo group had transitioned to psychotic disorder (P = .007). The difference between the groups in the cumulative risk of progression to full-threshold psychosis was 22.6% (95% confidence interval, 4.8-40.4). omega-3 Polyunsaturated fatty acids also significantly reduced positive symptoms (P = .01), negative symptoms (P = .02), and general symptoms (P = .01) and improved functioning (P = .002) compared with placebo. The incidence of adverse effects did not differ between the treatment groups., Conclusions: Long-chain omega-3 PUFAs reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states. Trial Registration clinicaltrials.gov Identifier: NCT00396643.

Objective: Over the last 15 years, a focus on early intervention in psychotic disorders has emerged. Initially, the early psychosis movement focused on timely recognition and phase-specific treatment of first-episode psychosis. However, early psychosis researchers suspected that pushing the point of intervention even further back to the prodromal phase of psychotic disorders may result in even better outcomes. This article reviews intervention research in the ultra-high-risk phase of psychotic disorders., Data Sources: A literature search of intervention trials with ultra-high-risk cohorts published after 1980 was conducted on PubMed with the search terms prodrome and intervention., Study Selection: All published intervention trials with ultra-high-risk cohorts., Data Synthesis: The first generation of intervention trials indicated that both pharmacologic and psychological intervention strategies may be of value in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder., Conclusions: Further controlled intervention trials with larger sample sizes are required in order to confirm and extend these findings. We argue that the clinical staging model provides a framework for the rationale and design of such studies, with simpler, safer, and more benign interventions being better candidates for first-line treatment, while more complex and potentially harmful treatments should be reserved for those cases in which response has failed to occur. Recent evidence indicates that neuroprotective agents, such as essential fatty acids, may be a suitable form of intervention for the ultra-high-risk phase of psychotic disorders, with a positive risk-benefit balance. Ethical aspects have become more salient given the recently observed declining transition rate in ultra-high-risk samples. We outline the key questions for the next generation of ultra-high-risk intervention trials., (Copyright 2009 Physicians Postgraduate Press, Inc.)

Aim: Although the different approaches to psychosis research have made significant advances in their own fields, integration between the approaches is often lacking. This paper attempts to integrate a strand of cognitive research in psychotic disorders (specifically, social cognition research) with phenomenological accounts of schizophrenia and other psychotic disorders., Method: The paper is a critical investigation of phenomenological models of disturbed selfhood in schizophrenia in relation to cognitive theories of social cognition in psychotic disorders., Results: We argue that disturbance of the basic sense of self, as articulated in the phenomenological literature, may underlie the social cognition difficulties present in psychotic disorders. This argument is based on phenomenological thinking about self-presence ('ipseity') being the primary or most basic ground for the intentionality of consciousness - that is, the directedness of consciousness towards others and the world. A disruption in this basic ground of conscious life has a reverberating effect through other areas of cognitive and social functioning. We propose three routes whereby self-disturbance may compromise social cognition, including dissimilarity, disruption of lived body and disturbed mental coherence., Conclusions: If this model is supported, then social cognition difficulties may be thought of as a secondary index or marker of the more primary disturbance of self in psychotic disorders. Further empirical work examining the relationship between cognitive and phenomenological variables may be of value in identifying risk markers for psychosis onset, thus contributing to early intervention efforts, as well as in clarifying the essential psychopathological features of schizophrenia and other psychotic disorders., (© 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Asia Pty Ltd.)

Ethyl-eicosapentaenoic acid (E-EPA) is an omega-3 fatty acid that has been used in a range of neuropsychiatric conditions with some benefits. However, its mechanism of action is unknown. Here, we investigate its effects on in vivo brain metabolism in first-episode psychosis (FEP). Proton magnetic resonance spectroscopy at 3 T was performed in the temporal lobes of 24 FEP patients before and after 12 weeks of treatment in the context of a larger double-blind, placebo-controlled E-EPA augmentation study. Treatment group effects for glutathione (F1,12=6.1, p=0.03), and a hemisphere-by-group interaction for glutamine/glutamate (F1,20=4.4, p=0.049) were found. Glutathione increased bilaterally and glutamate/glutamine increased in the left hemisphere following E-EPA administration. Improvement in negative symptoms correlated with metabolic brain changes, particularly glutathione (r=-0.57). These results suggest that E-EPA augmentation alters glutathione availability and modulates the glutamine/glutamate cycle in early psychosis, with some of the metabolic brain changes being correlated with negative symptom improvement. Larger confirmatory studies of these postulated metabolic brain effects of E-EPA are warranted.

Objective: To investigate if ethyl-eicosapentaenoic acid (E-EPA) augmentation improves antipsychotic efficacy and tolerability in first-episode psychosis (FEP)., Method: We performed a 12-week, randomized, double-blind, placebo-controlled trial of 2-g E-EPA augmentation in 80 FEP patients. Sixty-nine patients were eligible for analysis; a post hoc analysis was computed for a subgroup of nonaffective FEP patients (N = 53). The first participant was included in November 2000 and the last participant completed the trial in August 2003. Primary outcome measures were symptom change scores and time to first response, while tolerability measures and cumulative antipsychotic dose were secondary outcome measures., Results: Analysis of covariance controlling for baseline symptoms found no significant mean difference between E-EPA and placebo at week 12 for symptom change scores. Cox regression analysis revealed a significant treatment by diagnosis interaction (p = .024) for time to first response favoring E-EPA in nonaffective psychosis. Post hoc analysis for cumulative response rates further confirmed a higher response rate at week 6 (42.9% [15/35] vs. 17.6% [6/34] for all participants, p = .036; 54.2% [13/24] vs. 17.2% [5/29] for the nonaffective psychosis subset, p = .008); however, the difference at week 12 was no longer significant. Analysis of secondary outcome measures revealed that E-EPA-augmented participants needed 20% less antipsychotic medication between weeks 4 through 6 (p = .03), had less extrapyramidal side effects in the initial 9 weeks (p < .05 for all participants and for all timepoints), and reported less constipation (p = .011) and fewer sexual side effects (p = .016) than those treated with antipsychotic medication alone., Conclusion: The findings suggest that E-EPA may accelerate treatment response and improve the tolerability of antipsychotic medications. However, it was not possible to demonstrate a sustained symptomatic benefit of E-EPA in early psychosis, possibly due to a ceiling effect, since a high proportion of first-episode patients already achieve symptomatic remission with antipsychotic medication alone. Further controlled trials in nonaffective early psychosis seem warranted., Trial Registration: Australian Clinical Trials Registry identifier 12605000267651 (http://actr.org.au).

Intervention in the prodromal phase of schizophrenia and related psychotic disorders may prevent or delay the onset of these disorders, or reduce the severity of the psychosis. Identifying the schizophrenia prodrome is difficult, however, because of its non-specific symptoms and the wide symptom variability between individuals. Over the past 15 years, we have investigated the schizophrenia prodrome and developed criteria for detecting people suspected of experiencing a prodromal phase (ie, they are thought to be at imminent risk of onset of a psychotic disorder). About 35% of those meeting our criteria have developed a psychotic disorder within 12 months. We have established a clinical service, the PACE (Personal Assessment and Crisis Evaluation) Clinic, for people with suspected incipient psychosis, and trialled interventions aimed at preventing or delaying the onset of psychotic disorders. Our results and studies in other countries seem to indicate that psychological and psychosocial interventions, either alone or in combination with pharmacotherapy, may be effective in at least delaying, if not preventing, the onset of a psychotic disorder.

Background: While there is evidence that some cases of schizophrenia may be associated with microbial infections, the role of microbial agents has not been investigated in people with emerging psychosis., Methods: Participants were 105 help seeking ultra-high risk individuals. Psychiatric measures included the Brief Psychiatric Rating Scale and the Scale for the Assessment of Negative Symptoms. Serum IgG antibodies against human herpesviruses and Toxoplasma gondii were determined using immunoassay methods. Multiple linear regression with adjustment for age and sex was applied to test associations between serum antibodies and psychiatric measures., Results: Higher levels of serum IgG antibodies against Toxoplasma gondii in Toxoplasma-positive individuals were significantly associated with more severe positive psychotic symptoms. No significant association was observed between antibody levels and psychiatric measures in individuals positive for human herpesviruses., Conclusions: In some individuals infection with Toxoplasma gondii may be an environmental factor contributing to the manifestation of positive psychotic symptoms.

Background: There is increasing evidence that fatty acid deficiencies or imbalances may contribute to childhood neurodevelopmental disorders., Methods: We conducted a randomized, double-blind, placebo-controlled 6-week pilot trial investigating the effects of 1.5 g/d of omega-3 fatty acids (.84 g/d eicosapentaenoic acid, .7 g/d docosahexaenoic acid) supplementation in 13 children (aged 5 to 17 years) with autistic disorders accompanied by severe tantrums, aggression, or self-injurious behavior. The outcome measure was the Aberrant Behavior Checklist (ABC) at 6 weeks., Results: We observed an advantage of omega-3 fatty acids compared with placebo for hyperactivity and stereotypy, each with a large effect size. Repeated-measures ANOVA indicated a trend toward superiority of omega-3 fatty acids over placebo for hyperactivity. No clinically relevant adverse effects were elicited in either group., Conclusions: The results of this study provide preliminary evidence that omega-3 fatty acids may be an effective treatment for children with autism.

Aim: This paper reports the rationale, methodology and baseline characteristics of a large long-term follow-up study of first-episode psychosis from a geographically defined catchment area., Method: A total of 723 first-episode psychosis patients were recruited from a specialized early psychosis service between 1989 and 2001 and prospectively followed up at a median of 7.4 years after initial presentation. Participants' baseline demographic, clinical and functional characteristics are described. Sampling bias at study recruitment was assessed by comparison with a more complete sample of Early Psychosis Prevention and Intervention Centre (EPPIC) cases rated directly from the medical records., Results:   At baseline, 57% of the sample were diagnosed with schizophrenia or schizophreniform disorder, whereas the full range of psychotic disorders was represented. Statistical analysis confirmed that the sample recruited was representative of total EPPIC-treated incident cases., Conclusions: The EPPIC long-term follow-up study is a large and epidemiologically representative first-episode psychosis cohort that has been subsequently prospectively followed up over a long period. Such a sample provides a rare opportunity to study the course and outcome of psychotic disorders.

Unlabelled: Over the last decade there has been considerable interest in early intervention in schizophrenia and other psychotic disorders, driven by observations that early intervention might favorably alter the course of illness. New clinical and research programs have been established around the globe aiming to reduce treatment delays in psychosis and, more recently, to identify and possibly treat individuals in the pre-psychotic phase who are at imminent risk of developing psychosis. Since May 2004, a service for individuals at high risk (HR) for psychosis has been established at Vienna General Hospital. Individuals are offered comprehensive assessment and treatment which includes participation in a RCT investigating the effects of Omega-3 fatty acids versus placebo in addition to standard care. The aim of this article is to describe (1) classification of psychotic symptoms in incipient psychosis and (2) findings of the screening process as well as baseline characteristics in individuals with and without transition to psychosis., Inclusion Criteria: 1. Age 13 to 24 years 2. High Risk (HR) as classified by Yung et al. (1998) HR criteria: one or more of following characteristics occurred within the last 12 months: 1. Frank psychotic symptoms < 1 week 2. Attenuated psychotic symptoms > 1 week, several times per week 3. Drop in GAF of > 30% (>1 months) plus family history of psychosis or individual has schizotypal personality disorder Other psychiatric measures: SCID for DSM-IV, PANSS, MADRS, and the UKU side effect rating scale. Between May 2004 and June 2005, 140 individuals were referred to our service for suspected psychosis. 69 individuals (49,3%) met HR criteria, 21 (15%) were detected with first-episode psychosis at initial presentation; 50 (35,7%) individuals did not meet criteria for HR or DSM-IV psychotic disorder. 42 (60,9%) of 69 individuals with HR agreed to participate in the proposed EPA/DHA treatment trial. Co-morbidity of axis-I disorders was high in the HR group: 54,3% affective disorders, 40% anxiety/obsessive-compulsive disorders, 14,3 substance related disorders, 11,4% eating disorders and 2,9% somatoform disorders. To date 6 (14,3%) individuals have made a transition to psychotic disorder. These subjects scored significantly higher at the negative and at the general psychopathology scale ofPANSS and at the MADRS at time of randomization. Early detection and intervention in psychotic disorders seems to be a feasible goal which can be achieved in an outpatient setting. Individuals with HR can be detected and already show a substantial loss of functioning. In the process of screening for individuals with HR a high number of undiscovered cases of psychosis can be found. Given their high prevalence, treatment of comorbid axis-I conditions should be carefully addressed in HR and studied in relation to the risk of progression to psychosis. In contrast to antipsychotics, Omega-3 fatty acids have a high acceptance among youth and parents. At this stage the role of Omega-3 fatty acids remains unclear because the trial is not finished yet.

Objective: To identify the treated incidence of psychosis in catchment of the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia., Method: Cases were aged 15-29 years with a first episode of a psychotic disorder accepted into EPPIC between 1997 and 2000. Age- and sex-specific incidence rates per 10,000 person-years were calculated in 5 year age bands. Rate ratios were used for age group comparisons., Results: The age-specific treated incidence of first-episode psychosis in 15-29-year old individuals was 16.7 per 10,000 person-years in males, and 8.1 per 10,000 person-years in females. The incidence was highest in 20-24-year-old males and in 15-19-year-old females. For both sexes, incidence rates were significantly lower in the 25-29-year age group., Conclusions: The incidence of psychosis in the catchment of EPPIC was higher than previously reported, especially in female teenagers. Peak rates in 15-24 year olds suggest a youth model approach to early psychosis may be indicated.

Objective: We examined if age of onset of psychiatric symptoms and/or sex predict conversion to non-affective or affective psychosis in individuals considered to be at ultra-high risk for schizophrenia., Method: Participants (n=86) were offered treatment and monthly follow-up until transition to psychosis, or for 12 months if they did not meet exit criteria for psychotic disorder. Individuals without transition to psychosis at 12-month were reassessed approximately 3 years after the end of the treatment phase. Ultra-high risk was defined by the presence of subthreshold and/or self-limiting psychotic symptoms and/or having a family history of psychotic disorder combined with functional decline. Cox regressions after adjustment for treatment interventions were applied to investigate associations between age of onset, sex, and other baseline measures with progression to psychotic outcomes., Results: Early age of onset of psychiatric symptoms, in particular onset before age 18 was the only tested variable that significantly predicted non-affective psychosis. Independent significant predictors of affective psychosis were poor functioning, female sex and the presence of a combination of intake criteria (family history of psychosis plus drop in functioning, and attenuated and/or brief limited psychotic symptoms) at baseline., Conclusions: Age of onset of psychiatric symptoms is the single most important factor associated with conversion to non-affective psychosis in ultra-high risk individuals.

Bioactive lipids, in particular arachidonic acid (AA), are vital for monoaminergic neurotransmission, brain development and synaptic plasticity. Phospholipases A2 (PLA2) are key-enzymes in AA metabolism and are activated during monoaminergic neurotransmission. Reduced membrane AA levels, and an altered activity of PLA2 have been found in peripheral membranes of drug-naïve patients with schizophrenia with some conflicting results in more chronic patient populations. Furthermore, in vivo brain phosphorus-31 magnetic resonance spectroscopy suggests reduced lipid membrane precursors (phosphomonoesters) and increased membrane breakdown products (phosphodiesters) in drug-naïve or early treated first-episode schizophrenia patients compared to age-matched controls or chronic populations and these changes were correlated with peripheral red blood cell membrane AA levels. We postulate that processes modulating membrane lipid metabolism are associated with psychotic illnesses and might partially explain the mechanism of action of antipsychotic agents, as well as experimental agents such as purified ethyl-eicosapentaenoic acid (E-EPA). Recent supplementation trials suggest that E-EPA is a modestly effective augmentation treatment resulting in reduced doses of antipsychotic medication in acutely ill patients with schizophrenia (but not in residual-type schizophrenia). This review investigates the role of bioactive lipids in schizophrenia and its treatment, as well as its potential use in prevention.

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.

Cognitive impairment is an important clinical feature in many individuals with schizophrenia. Factors associated with cognitive deficit are not well established. Duration of untreated psychosis (DUP) has recently gained interest as a prognostic factor in schizophrenia. This study reports on the association between DUP and cognitive function. Subjects comprised 42 individuals (30 males, 12 females) who experienced a first-episode of DSM-III-R schizophrenia or schizophreniform disorder. Cognitive function was determined at clinical stabilization using the WAIS-R. An estimate of cognitive deterioration was based on the WAIS-R subtest profile. Longer DUP, male gender, higher premorbid IQ and younger age at admission independently predicted cognitive deterioration. Poorer performance on Digit Symbol and Comprehension subtests was associated with longer DUP. The findings suggest that untreated psychosis compromises some aspects of cognitive function. Studies investigating the association between DUP and outcome should control for potentially confounding variables. Early treatment of psychosis could help to reduce the prominent cognitive deficit in first-episode schizophrenia.

Objective: Performance IQ (PIQ) is often lower than verbal IQ (VIQ) in schizophrenic patients. Whether PIQ < VIQ precedes psychotic symptoms in schizophrenia remains uncertain., Method: We investigated premorbid IQ scores in 63 subjects assessed at a child and adolescent psychiatric unit (mean age 13.1 years, SD 3.2), who at follow-up in adulthood (mean age 30.9 years, SD 3.9) received a lifetime RDC diagnosis of schizophrenia-related psychosis, affective disorder, or no psychiatric disorder., Results: Premorbid PIQ < VIQ significantly differentiated the groups with schizophrenia-related psychosis and no psychiatric disorder. Subjects with schizophrenia-related psychosis had a significantly lower mean value for premorbid PIQ, but not VIQ, compared to subjects who developed affective disorder or subjects without psychiatric disorder., Conclusion: Our results emphasize premorbid intellectual deficits in schizophrenia. Those deficits might largely be in consequence of an impairment on the PIQ scale.

The relationship between childhood behavioral disturbance and comorbidity for adult psychiatric disorders has not been sufficiently investigated. Subjects of this report (N = 185) were offspring of parents with schizophrenia or affective disorder and of normal parents from the New York High-Risk Project. Data on childhood behavior at the mean age of 9.5 years were obtained in a parent interview at initial assessment in 1971-72. Adulthood outcomes were assessed through standardized interviews, and lifetime axis I diagnoses were based on Research Diagnostic Criteria. Subjects with comorbidity for axis I disorders exhibited significantly more behavioral problems as children, compared with those who developed either one or no psychiatric disorder in adulthood. This association was not biased by gender or parental diagnosis of psychiatric disorder. The findings emphasize that psychiatric comorbidity can be traced back to childhood and underline the importance of longitudinal observations in psychiatric research.

Objective: An association between childhood behavioral disturbance and adulthood schizophrenia has been seen previously in retrospective or follow-back studies and in prospective studies. The authors examined the relationship between childhood behavioral problems and adulthood schizophrenia-related psychoses. Because a high rate of childhood behavioral problems is known to be associated with adult substance abuse, these analyses controlled for substance abuse., Method: The subjects of this investigation (N = 185) were offspring of parents with schizophrenia or affective disorder and of normal parents from the New York High-Risk Project (sample A). Data on childhood behavioral problems were obtained in a parent interview at initial assessment in 1971-1972. Adulthood outcomes (schizophrenia-related psychoses, affective disorders, anxiety disorders, substance abuse) were based on lifetime axis I diagnoses according to the Research Diagnostic Criteria., Results: Substance abuse had a significant interaction with the clinical outcome groups. In subjects without substance abuse, those with schizophrenia-related psychoses had exhibited significantly more behavioral problems as children than had adult offspring with affective or anxiety disorder or with substance abuse only or no disorder., Conclusions: These results support the view that schizophrenia-related psychoses can be followed back to early behavioral disturbances. The confounding effects of substance abuse should be statistically controlled in studies of longitudinal associations between childhood behavioral disturbance and axis I outcomes.

Unlabelled: Social deficits, as well as low performance on intelligence tests, are known early symptoms of schizophrenia. We studied whether impairment of social intelligence can be detected before the outbreak of the disorder. In the New York High-Risk Project, children at risk for schizophrenia (HRSz) or affective disorder (HRAff) and a normal control group (NC) were studied over the past 26 years. The children are now in mid-adulthood, with known psychiatric outcomes. Developmental and clinical data from childhood can now be related to adulthood diagnoses. We compared mean WISC (or WISC-R) and WAIS (or WAIS-R) scores from childhood and adolescence, and change of IQ, between the risk groups, as well as between the adulthood outcomes. We were specifically interested in the development of social intelligence (the Picture Arrangement and Comprehension subtests). We used logistic regression analyses to generate a model predicting adulthood schizophrenia., Results: IQ at age 9,7 was lower in children with HRSz than with HRAff. Adulthood schizophrenia, compared with major depressive disorder and no psychiatric diagnosis could not be related conclusively to low IQ. This may be a result of the study design, since children with IQ below 70 or behavioral problems were not eligible as study subjects. There was no evidence of lower scores or more decline in social intelligence related to age or group membership (risk or outcome). Subtest-Scatter, a nondirectional measure of the differences between all subtests and Vocabulary, reflecting a lesser difference between crystallized and fluid intelligence, was identified as a significant predictor of adulthood schizophrenia, in the whole group as well as in the HRSz group alone.

The impact of premorbid social and intellectual functioning in childhood and early adolescence on the developmental course of schizophrenia is not sufficiently understood. In a retrospective case study (93 consecutive in-patients, 43 males and 50 females) of first-episode psychosis occurring in adolescence, the relationship between premorbid adjustment and short-term therapeutic outcome under treatment conditions was examined. All of the patients had a DSM-III-R diagnosis of schizophrenia (n = 56) or schizo-affective disorder (n = 37). The mean age of the patients at the time of the study was 15.8 (SD = 1.0). Premorbid functioning during childhood and early adolescence was assessed by using the Cannon-Spoor et al. Premorbid Adjustment Scale (PAS) and studied with respect to its prognostic relevance for short-term therapeutic outcome (eight weeks) under neuroleptic treatment (350-700 mg Chlorpromazin dose equivalent). Criteria for clinical outcome were obtained from the study by Pearlson et al. (1989) which defines three grades (complete remission, partial remission and no response), according to the degree of positive symptomatology. Statistical analysis was based on nonparametric variance analysis. Patients with complete remission of positive symptoms after eight weeks of therapy had experienced far better premorbid adjustment in early adolescence and in childhood. Diagnosis and gender did not bias this result. Our data suggest that premorbid social functioning is a crucial variable with regard to therapeutic outcome in first-episode psychosis. Previous studies have reported a relation between poor premorbid functioning and negative symptoms. We found premorbid adjustment related to the course of positive symptoms.

The positive (perceptual-cognitive) and negative (social-interpersonal) dimensions of schizotypal personality traits were examined in biological relatives of individuals with Axis I disorder. The subjects were young adult offspring from three contrasting parental groups, including schizophrenic disorder, affective disorder, and normal controls. Cognitive correlates, including digit span (presumed to assess working memory) and P3 amplitudes, were also examined. Preliminary results showed that positive and negative dimensions were distinguished by different prevalence patterns in the offspring subjects, and by a different pattern of correlations with cognitive measures. Negative dimensions were more frequent in offspring from the schizophrenic parental group than in the offspring from affective disorder and normal control parental groups. Digits forward and backward, and P3 amplitude decrements, characterized a subset of offspring with negative features from the schizophrenic parental group. Positive dimensions did not differ between the psychiatric parental groups, and did not covary with digit span or P3 amplitude assessments. These results support the view that positive and negative dimensions may reflect separable pathophysiologic processes.