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.

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.

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.

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.

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.

Cognitive functioning in a group of adolescents at risk for psychosis.

Cognitive deficits are a core feature of schizophrenia, and impairments are present in groups at-risk for psychosis. Most at-risk studies include young adults and not younger age-groups, such as adolescents. Participants are usually help-seeking individuals, even though risk factors may also be present in non-help seeking adolescents. We aim to explore cognitive functions in a group of non-help-seeking 15-year-old adolescents at risk for psychosis compared to age- and gender matched controls, including particular focus on specific cognitive domains. Hundred participants (mean age = 15.3) were invited after completing the 14-year-old survey distributed by the Norwegian Mother-, Father- and Child Study. At-risk adolescents were selected based on high scores on 19 items assessing both psychotic experiences and anomalous self-experiences. Matched controls were selected from the same sample. Cognitive functioning was assessed using the MATRICS Consensus Cognitive Battery and IQ using Wechsler's Abbreviated Test of Intelligence. We found that the adolescents at-risk for psychosis had significantly poorer scores than controls on the composite score of the MCCB. IQ scores were also significantly lower in the at-risk group. The results highlight general cognitive deficits as central in a group of non-help-seeking adolescents at-risk for psychosis. Results indicate that the development of cognitive impairments starts early in life in at-risk groups. It is still unclear whether specific cognitive domains, such as verbal learning, are related to psychotic symptoms or may be specifically vulnerable to symptoms of depression and anxiety.

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.

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.

Childhood trauma, social cognition and schizophrenia: Specific association between physical neglect and cognitive theory of mind in homicide offenders.

Schizophrenia is associated with a small, but increased risk of violent behavior, including homicide. Violent individuals with schizophrenia have elevated rates of childhood trauma and substantial social cognitive impairments. The aim of this study was to examine if childhood trauma is related to social cognition in homicide offenders with schizophrenia. We recruited 26 individuals with schizophrenia sentenced to compulsory mental care for homicide/attempted homicide and 28 non-violent schizophrenia controls. They filled out the Childhood Trauma Questionnaire (CTQ), providing scores for physical abuse, sexual abuse, emotional abuse, physical neglect and emotional neglect. Social cognition was assessed with two measures of emotion processing (Emotion in Biological Motion, Pictures of Facial Affect) and two theory of mind (ToM) tests (Hinting Task, Movie for the Assessment of Social Cognition: MASC). Spearman's rho correlation coefficients were computed, and significant results followed up with partial correlation analyses controlling for IQ. Three associations were statistically significant, all in the homicide group; between CTQ physical neglect and cognitive ToM assessed with Hinting Task and with MASC, and between CTQ emotional neglect and Hinting Task. Only the first remained significant after controlling for IQ, indicating a specific association between physical neglect and cognitive ToM in homicide offenders with schizophrenia.

Negative Symptom Domains Are Associated With Verbal Learning in Adolescents With Early Onset Psychosis.

Background: Early-onset psychosis (EOP) is among the leading causes of disease burden in adolescents. Negative symptoms and cognitive deficits predicts poorer functional outcome. A better understanding of the association between negative symptoms and cognitive impairment may inform theories on underlying mechanisms and elucidate targets for development of new treatments. Two domains of negative symptoms have been described in adult patients with schizophrenia: apathy and diminished expression, however, the factorial structure of negative symptoms has not been investigated in EOP. We aimed to explore the factorial structure of negative symptoms and investigate associations between cognitive performance and negative symptom domains in adolescents with EOP. We hypothesized that (1) two negative symptom factors would be identifiable, and that (2) diminished expression would be more strongly associated with cognitive performance, similar to adult psychosis patients. Methods: Adolescent patients with non-affective EOP (n = 169) were included from three cohorts: Youth-TOP, Norway (n = 45), Early-Onset Study, Norway (n = 27) and Adolescent Schizophrenia Study, Mexico (n = 97). An exploratory factor analysis was performed to investigate the underlying structure of negative symptoms (measured with the Positive and Negative Syndrome Scale (PANSS)). Factor-models were further assessed using confirmatory factor analyses. Associations between negative symptom domains and six cognitive domains were assessed using multiple linear regression models controlling for age, sex and cohort. The neurocognitive domains from the MATRICS Consensus Cognitive Battery included: speed of processing, attention, working memory, verbal learning, visual learning, and reasoning and problem solving. Results: The exploratory factor analysis of PANSS negative symptoms suggested retaining only a single factor, but a forced two factor solution corroborated previously described factors of apathy and diminished expression in adult-onset schizophrenia. Results from confirmatory factor analysis indicated a better fit for the two-factor model than for the one-factor model. For both negative symptom domains, negative symptom scores were inversely associated with verbal learning scores. Conclusion: The results support the presence of two domains of negative symptoms in EOP; apathy and diminished expression. Future studies on negative symptoms in EOP should examine putative differential effects of these symptom domains. For both domains, negative symptom scores were significantly inversely associated with verbal learning.

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.

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.

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.

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.

Early Substance Use Cessation Improves Cognition-10 Years Outcome in First-Episode Psychosis Patients.

Background: Cognitive impairment may be a risk factor for, as well as a consequence of, psychosis. Non-remitting symptoms, premorbid functioning, level of education, and socioeconomic background are known correlates. A possible confounder of these associations is substance use, which is common among patients with psychosis and linked to worse clinical outcomes. Studies however show mixed results for the effect of substance use on cognitive outcomes. In this study, the long-term associations of substance use with cognition in a representative sample of first-episode psychosis patients were examined. Methods: The sample consisted of 195 patients. They were assessed for symptom levels, function, and neurocognition at 1, 2, 5, and 10 years after first treatment. Test scores were grouped into factor analysis-based indices: motor speed, verbal learning, visuomotor processing, verbal fluency, and executive functioning. A standardized composite score of all tests was also used. Patients were divided into four groups based on substance-use patterns during the first 2 years of treatment: persistent users, episodic users, stop-users, and nonusers. Data were analyzed using linear mixed effects modeling. Results: Gender, premorbid academic functioning, and previous education were the strongest predictors of cognitive trajectories. However, on motor speed and verbal learning indices, patients who stopped using substances within the first 2 years of follow-up improved over time, whereas the other groups did not. For verbal fluency, the longitudinal course was parallel for all four groups, while patients who stopped using substances demonstrated superior performances compared with nonusers. Persistent users demonstrated impaired visuomotor processing speed compared with nonusers. Within the stop- and episodic use groups, patients with narrow schizophrenia diagnoses performed worse compared with patients with other diagnoses on verbal learning and on the overall composite neurocognitive index. Discussion: This study is one of very few long-term studies on cognitive impairments in first-episode psychosis focusing explicitly on substance use. Early cessation of substance use was associated with less cognitive impairment and some improvement over time on some cognitive measures, indicating a milder illness course and superior cognitive reserves to draw from in recovering from psychosis.

Neurognitive function and symptom remission 2 years after ECT in major depressive disorders.

BACKGROUND: There is a lack of knowledge of possible cognitive side effects of electroconvulsive therapy (ECT) beyond the first few months after treatment. We aim to describe cognitive effects and symptom remission 2 years after ECT in major depressive disorders. METHOD: Twenty-seven depression patients were assessed with the MATRICS Consensus Cognitive Battery (MCCB) and the Everyday Memory Questionnaire (EMQ) before and 2 years after ECT. Their scores were compared with those of healthy matches. Depression and remission status were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). Main statistical analyses were ANOVAs and linear mixed model tests. RESULTS: At baseline, the patient group was significantly impaired on 7 of 10 cognitive tests compared to the control group. Two years later, this gap was reduced to impairment on 5 of 10 tests. Within the patient group, neurocognitive function either increased significantly from baseline to follow-up, or there was no change. Two years after ECT, 62.9% of the patients were in remission. Those in remission reported better subjective memory function, but displayed no different neuropsychological test results, compared to the non-remitters. LIMITATIONS: Major limitations were low sample size and lack of uniform ECT procedure. CONCLUSIONS: We found improved neurocognitive function 2 years after ECT. This effect occurred regardless of remission status, suggesting that ECT induces unique cognitive boosting processes.

Healthy Adolescent Performance With Standardized Scoring Tables for the MATRICS Consensus Cognitive Battery: A Multisite Study.

OBJECTIVE: The aim of this study was to develop standardized scores and scoring tables for test performance in healthy adolescents for the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for each year from 11 to 19 years of age, by sex, with T scores and percentile ranks. METHODS: A total of 502 healthy participants (aged 11-19 years) from 7 cohorts from Ireland, Norway, Sweden, and United States, were included in this multisite study. Regression-predicted means for the MCCB tests, except the social cognition subtest, were calculated using the MCCB test scores as outcome variables and age, age2, sex, age × sex as predictors. The regression-predicted means for each combination of age and sex were added with the residuals from the entire cohort to yield the expected distribution of that group. Age effects were examined using regression models with age and age2 as predictors. Sex differences were examined using Student's t-tests. RESULTS: Significant positive age effects were found for all tests, except for the Brief Visuospatial Memory Test, revised (BVMT-R; measure of visual learning). Females performed significantly better than males on BACS Symbol coding (measure of speed of processing) and BVMT-R, while males performed significantly better than females on NAB Mazes (measure of reasoning and problem solving). Based on the regression-predicted distributions of scores, 19 standardized scoring tables for each test and domain were created. CONCLUSIONS: With the results from this study, we have developed an accessible standardized data set of healthy adolescent test performance for the MCCB.

Large social cognitive impairments characterize homicide offenders with schizophrenia.

Schizophrenia is associated with an increased violence risk, particularly homicide. One possible, but scarcely explored, contributor to the increased violence risk is social cognitive impairment. Individuals with schizophrenia show impairments in social cognition that are associated with poor functional outcome. This study examined social cognition among homicide offenders with schizophrenia (HOS), applying validated measures of emotion perception and theory of mind (ToM). Two groups of individuals with schizophrenia were compared, one had committed homicide (HOS, n = 26), and the other had no violence history (non-HOS, n = 28). Healthy controls (HC, n = 71) were included as reference group for one measure. Emotion perception was indexed by the Emotion in Biological Motion (Emotion) and Pictures of Facial Affect (PFA) tests. ToM was assessed with the Hinting Task and Movie for the Assessment of Social Cognition (MASC). The results showed that HOS participants had significantly poorer performance than non-HOS in both emotion perception and ToM. For the MASC test, HOS participants showed large deficits compared to HC (-4 standard deviations). Particularly, HOS participants made a substantial number of undermentalizing errors. The results suggest that emotion perception deficits and a tendency to undermentalize may be important for understanding homicide in schizophrenia.

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.