Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study.

INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool. METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables. RESULTS: Compared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges' g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses. CONCLUSION: EOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

Childhood trauma, antipsychotic medication, and symptom remission in first-episode psychosis.

BACKGROUND: To what extent psychotic symptoms in first-episode psychosis (FEP) with a history of childhood interpersonal trauma (CIT) are less responsive to antipsychotic medication is not known. In this longitudinal study, we compare symptom trajectories and remission over the first 2 years of treatment in FEP with and without CIT and examine if differences are linked to the use of antipsychotics. METHODS: FEP (N = 191) were recruited from in- and outpatient services 1997-2000, and assessed at baseline, 3 months, 1 and 2 years. Inclusion criteria were 15-65 years, actively psychotic with a DSM-IV diagnosis of psychotic disorder and no previous adequate treatment for psychosis. Antipsychotic medication is reported as defined daily dosage (DDD). CIT (<18) was assessed with the Brief Betrayal Trauma Survey, and symptomatic remission based on scores from the Positive and Negative Syndrome Scale. RESULTS: CIT (n = 63, 33%) was not associated with symptomatic remission at 2 years follow-up (71% in remission, 14% in relapse), or time to first remission (CIT 12/ no-CIT 9 weeks, p = 0.51). Those with CIT had significantly more severe positive, depressive, and excited symptoms. FEP with physical (N = 39, 20%) or emotional abuse (N = 22, 14, 7%) had higher DDD at 1 year (p < 0.05). Mean DDD did not excerpt a significant between-group effect on symptom trajectories of positive symptoms. CONCLUSION: Results indicate that antipsychotic medication is equally beneficial in the achievement of symptomatic remission in FEP after 2 years independent of CIT. Still, FEP patients with CIT had more severe positive, depressive, and excited symptoms throughout.

The "zipper model of empathy" applied to violence in schizophrenia: A search for social cognitive underpinnings of lack of empathic behavior.

BACKGROUND: The "zipper model of empathy" has been proposed for psychopathy. It postulates that empathic behavior may fail to arise due to impaired facial emotion recognition. In this study, we examined if the model may be of relevance for schizophrenia. METHODS: In a sample of participants with schizophrenia and a history of severe interpersonal violence, associations between measures of social cognition (emotion recognition, theory of mind) and aspects of psychopathy (lack of empathy, lack of remorse) were investigated. A non-violent sample experiencing schizophrenia served as a control group. RESULTS: Correlation analyses revealed a specific and statistically significant association between facial emotion recognition and lack of empathy in the violent sample. Follow-up analyses identified that neutral emotions were of particular importance. Logistic regression analyses confirmed that impairments in facial emotion recognition predicted levels of empathy in the violent sample experiencing schizophrenia. CONCLUSIONS: Our results suggest that the "zipper model of empathy" may be relevant for schizophrenia. The findings further point to the potential benefit of including social cognitive training in the treatment of persons with schizophrenia and a history of interpersonal aggression.

Anomalous self-experiences and neurocognitive functioning in adolescents at risk for psychosis: Still no significant associations found between these two vulnerability markers.

BACKGROUND: Anomalous self-experiences (ASEs) and neurocognitive impairments are considered essential domains of vulnerability for developing psychotic disorders. However, little research exists of possible associations between ASEs and neurocognitive functions in individuals at-risk for psychosis. The interconnections between ASEs and neurocognitive impairments should therefore be clarified as much as possible, especially in young individuals at risk. No previous studies have investigated these two fundamental domains in non-help-seeking adolescents at risk for developing psychosis. METHODS: This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). Adolescents (N = 48, 94% females, mean age = 15.3) were invited to participate after completing a 14-year-old survey distributed by MoBA. At-risk adolescents were selected based on the 0.4% highest scores on 19 items assessing both psychotic-like experiences and ASEs. Five specifically selected and formulated items measuring ASEs were computed to an ASEs total score. Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery. RESULTS: Regression analyses revealed no significant relationships between ASEs and any neurocognitive domain. CONCLUSIONS: We did not find any significant associations between ASEs and neurocognitive functions in non-help-seeking adolescents at risk for psychotic disorders, which is in line with reports from other types of cohorts. Thus, ASEs and neurocognitive functions may be understood as two relatively separate domains that co-exist in at-risk states. These results underline the need for a wider scope when making predictions about future trajectories, e.g. the development of psychotic disorders. Including both ASEs and neurocognitive functioning in at-risk populations may increase the specificity of vulnerability criteria in this population and enhance our understanding of early psychosis psychopathology.

Intracranial and subcortical volumes in adolescents with early-onset psychosis: A multisite mega-analysis from the ENIGMA consortium.

Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.

Perinatal complications and executive dysfunction in early-onset schizophrenia.

BACKGROUND: The present study examined the association between perinatal obstetric complications and executive dysfunction in early-onset schizophrenia (EOS), compared to healthy controls. Higher incidences of obstetric complications and more severe executive dysfunctions characterize EOS. Research shows extensive brain maturation in newborns, suggesting them to be particularly vulnerable for perinatal insults. Executive function is mainly mediated by the prefrontal cortex, an area that matures last during pregnancy. Thus, exposure to perinatal complications may influence executive dysfunction in EOS. METHODS: The participants were 19 EOS patients and 54 healthy controls. Executive function was assessed with the D-KEFS Color Word Interference Test and the Wisconsin Card Sorting Test. Information on perinatal obstetric complications and Apgar 5-min scores were obtained from the Norwegian Medical Birth Registry. Associations between perinatal conditions and executive function were studied using stepwise regression analyses. RESULTS: Perinatal complications, and especially shorter gestational lengths, were significantly associated with significant executive dysfunctions in EOS. Perinatal complications did not affect executive function among healthy controls. A significant relationship between lower Apgar 5-min scores and executive dysfunction was found among both EOS patients and healthy controls. CONCLUSIONS: Exposure to perinatal complications, and particularly a shorter gestational length, was associated with increased executive dysfunction in EOS. Exposed healthy controls did not exhibit similar executive difficulties, suggesting that the EOS patients seemed especially vulnerable for executive deficits due to perinatal insults. The findings indicate that EOS youths learn more slowly and experience more difficulty with problem-solving, which carry important implications for clinical practice. Lower Apgar 5-min scores were associated with executive dysfunction in both groups. Low Apgar score at 5 min may therefore be an important early indicator of executive difficulties among adolescents, independent of diagnosis.

Similar impairments shown on a neuropsychological test battery in adolescents with high-functioning autism and early onset schizophrenia: a two-year follow-up study.

Introduction: Cognitive impairments are common in both Autism Spectrum Disorders (ASD) and schizophrenia, but it is unclear whether the pattern of difficulties is similar or different in the two disorders. This cross-sectional and longitudinal study compared the neuropsychological functioning in adolescents with ASD with adolescents with Early Onset Schizophrenia (EOS).Methods: At baseline and at two-year follow-up, participants were assessed with a brief neuropsychological test battery measuring executive functions, visual and verbal learning, delayed recall and recognition and psychomotor speed.Results: We found similar levels of neuropsychological impairment across groups and over time in the adolescents with ASD or EOS. Adolescents in both groups did not improve significantly on verbal learning, verbal delayed recall, visual learning, visual delayed recall or visual delayed recognition, and both groups performed poorer on verbal recognition. Both groups improved on measures of psychomotor processing and executive functions.Conclusion: The findings suggest that it may be difficult to differentiate adolescents with EOS and ASD based on neuropsychological task performance. An implication of the results is that adolescents with either disorder may benefit from a similar approach to the treatment of cognitive impairment in the disorders.

Negative and disorganized symptoms mediate the relationship between verbal learning and global functioning in adolescents with early-onset psychosis.

Neurocognitive deficits are associated with impaired global functioning and psychotic symptoms. However, whether symptoms can mediate the relationship between neurocognition and global functioning in adolescent psychosis is unclear. Here, we investigated if symptoms assessed with the Positive And Negative Syndrome Scale (PANSS), mediated the relationship between neurocognitive performance and global functioning in adolescents with non-affective early-onset psychotic disorders (EOP). Sixty-one adolescent EOP patients (age 12-18 years) from 2 Norwegian clinical cohorts were included. Linear regression models were applied to investigate associations between neurocognitive domains from the MATRICS Consensus Cognitive Battery (MCCB) and global functioning. PANSS symptoms were analyzed using the Wallwork/Fortgang five-factor model. Using the INDIRECT macro for SPSS, mediation effects were tested using bootstrapping with 95% bias corrected confidence intervals. Verbal learning was positively associated with global functioning (P < 0.001) and negatively associated with the disorganized symptom factor (P = 0.002), controlling for age, sex and cohort. Testing of indirect effects, controlling for age, sex and cohort, showed that the Negative (point estimate = 1.56, 95% CI 0.22, 3.47) and Disorganized (point estimate = 1.24, 95% CI 0.05, 3.69) symptom factors significantly mediated the relationship between verbal learning and global functioning. We found that verbal learning, negative and disorganized symptoms influenced global functioning in adolescents with EOP, while reality-distorted positive symptoms did not. These results suggest that assessing these domains in EOP is helpful for planning treatment and rehabilitation programs focusing on functional outcome.

Increased prevalence of psychopathy and childhood trauma in homicide offenders with schizophrenia compared to nonviolent individuals with schizophrenia.

Purpose: Schizophrenia is associated with an increased homicide risk. Personality pathology, particularly antisocial personality disorder and psychopathic traits, has been associated with increased violence risk in schizophrenia. Childhood trauma, more specifically physical abuse, has been associated with violence risk in healthy populations and in individuals with mental illness. It is, however, unclear how childhood trauma relates to homicide in schizophrenia. This is, to our knowledge, the first study to concurrently examine personality pathology and childhood trauma in a group consisting solely of homicide offenders with schizophrenia (HOS). HOS is compared to nonviolent participants with the same diagnosis (non-HOS). Additionally, currently assessed demographical and clinical characteristics of a Norwegian sample of HOS are reported. Materials and methods: Two groups of participants with schizophrenia were recruited in collaboration with in and outpatient clinics across Norway, HOS (n= 26) and non-HOS (n= 28). Assessments of personality pathology and childhood trauma were conducted, and information about clinical and demographical characteristics was registered. Results: HOS participants had significantly higher psychopathy scores, and more frequently reported moderate to severe childhood physical abuse than non-HOS participants. When simultaneously added to a logistic regression model, only psychopathy uniquely contributed to explaining group membership. Conclusions: Psychopathy and physical abuse was more prevalent among HOS participants compared to non-HOS, but only psychopathy independently predicted homicidal status. These results confirm the importance of including an evaluation of psychopathic traits in violence risk assessments of individuals with schizophrenia.

Do clinical characteristics predict the cognitive course in early-onset schizophrenia-spectrum disorders?

BACKGROUND: Being in a period with extensive brain maturation, adolescents with early-onset schizophrenia-spectrum disorders (EOS) provide unique neurodevelopmental data that may contribute to a better understanding of schizophrenia at all ages. Cognitive dysfunction is a central feature of schizophrenia and is more pronounced in EOS than in later onset illness. However, there is limited research on both the long-term course of global cognition in EOS, and how cognition over time is influenced by clinical characteristics during the early illness period. METHODS: Thirty-one EOS patients and 73 controls (age 12-18) were assessed on clinical variables at baseline (PANSS, duration of untreated psychosis [DUP], hospitalizations, suicide attempts, and remission). Neuropsychological assessments with the MATRICS Consensus Cognitive Battery (MCCB) were conducted at baseline and after both 1 and 2 years, and composite scores of total performances were calculated. The analyses were performed with a linear mixed model. RESULTS: The present study found that global cognition followed a stable course over the first years of the disease in EOS, though at a significantly lower level in EOS compared with the controls. We did not detect a relationship between DUP, remission, positive/negative symptoms, and hospitalizations on one hand, and long-term cognition on the other hand, but PANSS-general and suicide attempt history at baseline were identified as risk factors of longitudinal cognitive function. CONCLUSIONS: Though at different levels, the EOS group and the controls had a similar cognitive course over 2 years. Some baseline characteristics (psychotic symptoms, DUP, remission, and hospitalization) had no influence on cognition within the first 2 years of illness. In contrast, general symptoms and a history of suicide attempts at baseline were more potent risk factors of the cognitive course than the psychotic-specific symptoms, and should, therefore, be subject to specific attention in the evaluation and treatment of patients with early-onset psychosis.

Impaired neuropsychological profile in homicide offenders with schizophrenia.

BACKGROUND: Our ability to predict and prevent homicides committed by individuals with schizophrenia is limited. Cognitive impairments are associated with poorer functional outcome in schizophrenia, possibly also homicide. The aim of the current study was to investigate global and specific cognition among homicide offenders with schizophrenia (HOS). METHODS: Twenty-six HOS were compared to 28 individuals with schizophrenia and no history of violence (non-HOS), and a group of healthy controls (HC, n = 151). HOS and non-HOS participants were recruited from in- and outpatient units across Norway. An extensive neuropsychological test battery was administered. RESULTS: HOS participants performed significantly weaker than HC in all cognitive domains. Further, statistically significant differences between HOS and non-HOS participants were found for IQ (d = 0.52) and verbal learning (d = 0.82), with larger impairments in the HOS compared to the non-HOS group. CONCLUSIONS: Our results indicate that HOS participants show clinically significant impairments in global and specific cognition.

Depression and functioning are important to subjective quality of life after a first episode psychosis.

BACKGROUND: Subjective quality of life (S-QoL) is an important outcome measure in first-episode psychosis, but its associations with clinical predictors may vary across the illness course. In this study we examine the association pattern, including both direct and indirect effects, between specific predefined clinical predictors (insight, depression, positive psychotic symptoms and global functioning) and S-QoL the first ten years after a first-episode psychosis. METHODS: Three hundred and one patients with a first-episode psychosis were included at first treatment, and reassessed at 3 months, 1 year, 2 years, 5 years and 10 years after inclusion. At 10-year follow-up 186 participated. S-QoL was assessed with Lehman's Quality of Life Interview. Applying a structural equation model, we investigated cross-sectional association patterns at all assessments between the predefined clinical predictors and S-QoL. RESULTS: At baseline, only depression was significantly associated with S-QoL. At all follow-up assessments, depression and functioning showed significant associations with S-QoL. Insight was not associated with S-QoL at any of the assessments. Better insight, less depressive symptoms and less positive psychotic symptoms were all associated with higher functioning at all assessments. Functioning seems to mediate a smaller indirect inverse association between positive psychotic symptoms and S-QoL. The association pattern was stable across all follow-up assessments. CONCLUSIONS: Together with depression, functioning seems to be important for S-QoL. Functioning seems to be a mediating factor between positive symptoms and S-QoL. A focus on functional outcome continues to be important.

A review of factors associated with severe violence in schizophrenia.

BACKGROUND: There is a modest but consistent association between violence and schizophrenia. The consequences of serious violence could be catastrophic for the victims, as well as the patients themselves and the community. Any knowledge that would help to prevent acts of serious violence would be of considerable value for the individual and the society. AIM: To identify external and clinical risk factors for serious violence in schizophrenia, in addition to considering the strength of the association between the factors assessed and severe violence. METHODS: This was accomplished by a literature survey. One-hundred and two relevant papers were identified that were published during the past 20 years. Forty-four papers were assessed for eligibility. In all, 27 studies including clinical or cognitive variables were reviewed systematically. An effect size was reported where an odds ratio (OR) could be identified or calculated from available data. Five external factors and six clinical domains were evaluated. RESULTS: Substance abuse is robustly linking schizophrenia and violence. Among the clinical factors, insight, impulsivity, psychopathy, motor speed and a global measure of cognition are the factors with the strongest empirical evidence for an association with severe violence. CONCLUSION: This is the first systematic review of risk factors for severe violence in schizophrenia, in which a great number of clinical and external factors have been evaluated. Most of the clinical factors have been compared on effect size. The identified factors that represent an increased risk of violence in patients with schizophrenia should be included in risk assessments.

The research evidence for schizophrenia as a neurodevelopmental disorder.

Schizophrenia is a neurodevelopmental disorder that starts very early. In this review we describe the empirical evidence for the neurodevelopmental model. First, by outlining the roots of psychological research that laid the foundation of the model. Thereafter, describing cognitive dysfunction observed in schizophrenia, and the course of cognitive functioning in the illness. Then, research findings that speak for and studies that speak against the view that schizophrenia is a degenerative process is discussed. We find that there is ample evidence that cognitive disturbance is a core element in schizophrenia. However, we have limited understanding of what initiates the abnormal development. This the paper ends with pointing out some of the factors that may trigger the deviant neurocognitive development in schizophrenia.

Neurocognitive profile in major depressive disorders: relationship to symptom level and subjective memory complaints.

BACKGROUND: The MATRICS Consensus Cognitive Battery (MCCB) was developed for schizophrenia patients, but is also being used to assess neurocognitive function in bipolar disorder. This study aims to describe neurocognitive differences in major depressive disorder patients and healthy controls with the MCCB, and to describe the relationship between depression symptom severity, subjective cognitive complaints, and objective cognitive test performance. METHODS: Thirty-three patients with major depressive disorder and 33 pairwise matched healthy controls were assessed with the MCCB. The patients were also assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Everyday Memory Questionnaire (EMQ). RESULTS: On all neurocognitive domains, the depression patients scored significantly lower than the controls. The level of impairment ranged from 21.0% (Working Memory) to 58.0% (Speed of Processing). There were significant associations between neurocognitive test performance and depression symptom severity, but not with subjective cognitive complaints. CONCLUSIONS: The MCCB was applicable in this study of major depressive disorder, and revealed significant neurocognitive dysfunction in this group. At least one fifth of the patients were impaired on all cognitive domains, with Speed of Processing and Reasoning/Problem Solving being most strongly affected. The objective test scores were significantly related to depression severity, but not to subjective cognitive complaints.

Is there an optimal factor structure of the Positive and Negative Syndrome Scale in patients with first-episode psychosis?

The Positive and Negative Syndrome Scale (PANSS) is the most widely used scale to assess a variety of symptoms in patients with schizophrenia and other psychoses. The factor structure of the PANSS has been examined with confirmatory factor analyses in several studies, but not in a well-defined first-episode psychosis sample. The aim of this paper is to examine the statistical fit of five different PANSS models in a first-episode, non-affective psychosis sample. Confirmatory factor analyses were performed on PANSS data (n = 588). A main criterion for best fit was defined as the Expected Cross Validation Index (ECVI). No tested model revealed an optimally satisfactory model fit index. The Wallwork/Fortgang five-factor model demonstrated the most optimal psychometric properties. The corresponding subscales of all evaluated five-factor models were strongly intercorrelated. The Wallwork/Fortgang five-factor model was found to be statistically and clinically ideal among patients with first-episode psychosis. Therefore, we recommend this model in forthcoming studies among patients with first-episode psychosis. However, to prevent the loss of clinically valuable information on an item level, we do not recommend removing any items from the original form. Our study also implies that the specific choice of model will not have a substantial effect on outcome results in studies on the course and outcome in first-episode psychosis.

Association between early suicidal trajectories in first-episode psychosis and 10-year follow-up: TIPS registry-linked study.

BACKGROUND: Although the risk of suicidality is high in first-episode psychosis, patterns and individual variability in suicidal thoughts and behaviours over time are under-researched. We aimed to identify early trajectories of suicidality over a 2-year follow-up, assess their baseline predictors, and explore associations between those trajectories and later suicidality. METHODS: This longitudinal follow-up study was a part of the Early Treatment and Intervention in Psychosis (TIPS)study. Participants, linked to Norwegian and Danish death registries, were recruited from four catchment areas (665 000 inhabitants) in Norway and Denmark (both inpatient and outpatient). We included participants aged 15-65 years, with an intelligence quotient of more than 70, willing to give informed consent, and with a first episode of active psychotic symptoms. Individuals with comorbid neurological or endocrinal disorders, or those with contraindications to antipsychotics, were excluded. Growth mixture modelling was used to identify trajectories of suicidal thoughts and behaviours over the first 2 years. Multinomial logistic regression was applied to examine the baseline predictors of those trajectories and their associations with suicidality at 10-year follow-up. FINDINGS: A total of 301 participants were recruited from Jan 1, 1997, to Dec 31, 2000. Of the 299 with completed suicidality data at baseline, 271 participated in 1-year follow-up, 250 in 2-year follow-up, 201 in 5-year follow-up, and 186 at 10-year follow-up. At baseline, 176 (58%) were male, 125 (42%) were female. The mean age was 27·80 years (SD 9·64; range 15-63). 280 (93%) participants were of Scandinavian origin. Four trajectories over 2 years were identified: stable non-suicidal (217 [72%]), stable suicidal ideation (45 [15%]), decreasing suicidal thoughts and behaviours (21 [7%]), and worsening suicidal thoughts and behaviours (18 [6%]). A longer duration of untreated psychosis (odds ratio [OR] 1·24, 95% CI 1·02-1·50, p=0·033), poorer premorbid childhood social adjustment (1·33, 1·01-1·73, p=0·039), more severe depression (1·10, 1·02-1·20, p=0·016), and substance use (2·33, 1·21-4·46, p=0·011) at baseline predicted a stable suicidal ideation trajectory. Individuals in the stable suicidal ideation trajectory tended to have suicidal thoughts and behaviours at 10-year follow-up (3·12, 1·33-7·25, p=0·008). Individuals with a worsening suicidal trajectory were at a higher risk of death by suicide between 2 and 10 years (7·58, 1·53-37·62, p=0·013). INTERPRETATION: Distinct suicidal trajectories in first-episode psychosis were associated with specific predictors at baseline and distinct patterns of suicidality over time. Our findings call for early and targeted interventions for at-risk individuals with persistent suicidal ideation or deteriorating patterns of suicidal thoughts and behaviours, or both. FUNDING: Health West, Norway; the Norwegian National Research Council; the Norwegian Department of Health and Social Affairs; the National Council for Mental Health and Health and Rehabilitation; the Theodore and Vada Stanley Foundation; the Regional Health Research Foundation for Eastern Region, Denmark; Roskilde County, Helsefonden, Lundbeck Pharma; Eli Lilly; Janssen-Cilag Pharmaceuticals, Denmark; a National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award and The National Institute of Mental Health grant; a National Alliance for Research on Schizophrenia & Depression Young Investigator Award from The Brain & Behavior Research Foundation; Health South East; Health West; and the Regional Centre for Clinical Research in Psychosis.

Patient satisfaction with treatment in first-episode psychosis.

PURPOSE: To examine first-episode psychotic patients' satisfaction with elements of a comprehensive 2-year treatment program. SUBJECTS AND METHOD: The TIPS (Early Treatment and Intervention in Psychosis) project provided a 2-year treatment program consisting of milieu therapy (inpatient), individual psychotherapy, family intervention and medication. Of 140 patients at baseline, 112 were included at 2-year follow-up. Eighty-four participants were interviewed using a questionnaire eliciting levels of satisfaction with different treatment elements at two of the four sites. RESULTS: Participants and non-participants did not differ on demographic or clinical data at baseline. Of those participating, 75% were satisfied with treatment in general. Individual and milieu therapy received higher rating than medication or family intervention. No predictors of general satisfaction with treatment were found, but continuously psychotic patients were the least satisfied with medication treatment. DISCUSSION: As in most patient satisfaction studies within mental health treatment networks, there was high level of general satisfaction with the total package of treatment but considerable variation in satisfaction for specific interventions. In this sample of first-episode psychosis patients, there was general satisfaction with treatments based on one-to-one relationships while multi-family group intervention was consistently valued less enthusiastically.

Executive function tests in early-onset psychosis: which one to choose?

People with schizophrenia exhibit executive functioning deficits, an area well investigated in the adult onset schizophrenia (AOS) group, but far less so in early-onset schizophrenia (EOS). Since EOS in general seems to exhibit poorer cognitive functions and is clinically more compromised than AOS, choice of efficient and sensitive assessment measures is not necessarily the same within the two groups. The MATRICS Consensus Cognitive Battery was developed for adults when studying treatment effects and uses Mazes (Neuropsychological Assessment Battery [NAB]) to assess executive functioning. We tested 31 adolescents with schizophrenia spectrum disorders and 66 healthy controls in order to examine how Mazes compares to two other commonly used tests to measure executive functioning, D-KEFS Color Word Interference Test (Stroop) and the Wisconsin Card Sorting Test (WCST). Significant discriminating power was found for all three measures. Patients performed 0.8-1.5 SD below controls with Stroop as the most sensitive measure, followed by Mazes and WCST. Mazes was selected by the MATRICS to assess treatment effects in AOS and is shown to be able. We find the instrument also able to separate adolescent patients from controls and thus, it appears a sensible choice in clinical settings. If a more elaborated neuropsychological evaluation of the executive functioning domain is needed, Stroop should be considered a complementary test.

A systematic review of premorbid cognitive functioning and its timing of onset in schizophrenia spectrum disorders.

Cognitive impairments are core features of established schizophrenia spectrum disorders (SSD). However, it remains unclear whether specific cognitive functions are differentially impaired pre-onset and at what age these impairments can be detected. The purpose of this review was to elucidate these issues through a systematic summary of results from longitudinal studies investigating impairment in specific cognitive domains as antecedents of SSD. Relevant studies were identified by electronic and manual literature searches and included any original study of cognitive domains any time pre-onset of SSDs that included a control group. Effect sizes were calculated by domain for studies comparing high-risk participants who developed SSD with those who did not. The strongest evidence for impairment pre-onset was for mental processing speed, verbal learning and memory, executive function, and social cognition. Some verbal impairments, like language abilities at age 3 and verbal learning and memory at age 7, may develop as static deficits. Conversely, some non-verbal impairments, like mental processing speed, visuospatial abilities, and visual working memory manifest as developmental lag and become significant later in life. Most effect sizes were small to moderate, except for verbal fluency (d' = 0,85), implying this impairment as central in high-risk participants who develop SSD. The present review documents extensive cognitive impairments pre-onset of SSD, and that these impairments start early in life, in line with the neurodevelopmental hypothesis of schizophrenia. Increased knowledge about cognitive impairments preonset can provide a better basis for understanding the complex pathogenesis of SSD as well as informing cognitive remediation programs.