Lower Premorbid IQ Research Articles

Associations of psychotic symptom dimensions with clinical and developmental variables in twin and general clinical samples.

Positive, negative and disorganised psychotic symptom dimensions are associated with clinical and developmental variables, but differing definitions complicate interpretation. Additionally, some variables have had little investigation. To investigate associations of psychotic symptom dimensions with clinical and developmental variables, and familial aggregation of symptom dimensions, in multiple samples employing the same definitions. We investigated associations between lifetime symptom dimensions and clinical and developmental variables in two twin and two general psychosis samples. Dimension symptom scores and most other variables were from the Operational Criteria Checklist. We used logistic regression in generalised linear mixed models for combined sample analysis (n = 875 probands). We also investigated correlations of dimensions within monozygotic (MZ) twin pairs concordant for psychosis (n = 96 pairs). Higher symptom scores on all three dimensions were associated with poor premorbid social adjustment, never marrying/cohabiting and earlier age at onset, and with a chronic course, most strongly for the negative dimension. The positive dimension was also associated with Black and minority ethnicity and lifetime cannabis use; the negative dimension with male gender; and the disorganised dimension with gradual onset, lower premorbid IQ and substantial within twin-pair correlation. In secondary analysis, disorganised symptoms in MZ twin probands were associated with lower premorbid IQ in their co-twins. These results confirm associations that dimensions share in common and strengthen the evidence for distinct associations of co-occurring positive symptoms with ethnic minority status, negative symptoms with male gender and disorganised symptoms with substantial familial influences, which may overlap with influences on premorbid IQ.

Social exclusion as a major outcome domain of psychotic disorders: early predictors, and associations with non-recovery and clinical staging 21years after a first episode of psychosis.

People with psychotic disorders have high levels of social exclusion; however, little is known about its early predictors. We present a long-term observational cohort study aimed at examining early risk factors for later social exclusion. A total of 243 subjects were assessed at their first psychotic episode for early risk factors including sociodemographic variables, familial risk of major mental disorders, perinatal complications, childhood factors, and adolescent factors and re-assessed after a mean follow-up of 21years for 12 social exclusion domains: leisure activities, housing, work, income, neighborhood deprivation, educational attainment, physical and mental health, family and social support, legal competence, and discrimination. The ability of risk factors to predict social exclusion was examined using hierarchical linear regression. Overall social exclusion was independently predicted by low parental socio-economic status, length of follow-up, familial risk of schizophrenia, obstetric complications, neurodevelopmental delay, poor childhood adjustment, childhood adversity, poor adolescent social networks, poor adolescent adjustment, and low premorbid IQ. The model explained 58.2% of the variance in total social exclusion score. Each social exclusion domain was predicted by a different set of variables, which explained between 17.8 and 57.0% of their variance, although low socio-economic status, familial risk of schizophrenia, obstetric complications, childhood adversity, and poor social networks predicted most of the social exclusion domains. Early risk factors strongly predicted later social exclusion. A multifaceted approach to preventing later social exclusion is crucial in people with a first episode of psychosis and early risk factors of social exclusion.

73 Identification of 24-Month Cognitive Trajectories Among Clinical High Risk for Psychosis (CHR-P) Using Latent Class Mixture Modeling

Objective:Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits.Participants and Methods:Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning & problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (>5%).Results:A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2).Conclusions:Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes.

Long-term resting EEG correlates of repetitive mild traumatic brain injury and loss of consciousness: alterations in alpha-beta power.

Long-term changes to EEG spectra after mild traumatic brain injury (mTBI, i.e., concussion) have been reported; however, the role of injury characteristics in long-term EEG changes is unclear. It is also unclear how any chronic EEG changes may underlie either subjective or objective cognitive difficulties, which might help explain the variability in recovery after mTBI. This study included resting-state high-density electroencephalography (EEG) and mTBI injury data from 340 service members and veterans collected on average 11 years after injury as well as measures of objective and subjective cognitive functioning. The average absolute power within standard bands was computed across 11 spatial regions of the scalp. To determine how variation in brain function was accounted for by injury characteristics and aspects of cognition, we used regression analyses to investigate how EEG power was predicted by mTBI history characteristics [number, number with post-traumatic amnesia and witnessed loss of consciousness (PTA + LOC), context of injury (combat or non-combat), potentially concussive blast exposures], subjective complaints (TBIQOL General Cognitive and Executive Function Concerns), and cognitive performance (NIH Toolbox Fluid Intelligence and premorbid IQ). Post-traumatic amnesia (PTA) and loss of consciousness (LOC), poorer cognitive performance, and combat experience were associated with reduced power in beta frequencies. Executive function complaints, lower premorbid IQ, poorer cognitive performance, and higher psychological distress symptoms were associated with greater power of delta frequencies. Multiple regression confirmed the relationship between PTA + LOC, poor cognitive performance, cognitive complaints, and reduced power in beta frequencies and revealed that repetitive mTBI was associated with a higher power in alpha and beta frequencies. By contrast, neither dichotomous classification of the presence and absence of mTBI history nor blast exposures showed a relationship with EEG power variables. Long-term alterations in resting EEG spectra measures of brain function do not appear to reflect any lasting effect of a history of mTBI or blast exposures. However, power in higher frequencies reflects both injury characteristics and subjective and objective cognitive difficulties, while power in lower frequencies is related to cognitive functions and psychological distress associated with poor long-term outcomes after mTBI.

Associations of Peak-Width Skeletonized Mean Diffusivity and Post-Stroke Cognition.

Post-stroke cognitive impairment is common and can have major impact on life after stroke. Peak-width of Skeletonized Mean Diffusivity (PSMD) is a diffusion imaging marker of white matter microstructure and is also associated with cognition. Here, we examined associations between PSMD and post-stroke global cognition in an ongoing study of mild ischemic stroke patients. We studied cross-sectional associations between PSMD and cognition at both 3-months (N = 229) and 1-year (N = 173) post-stroke, adjusted for premorbid IQ, sex, age, stroke severity and disability, as well as the association between baseline PSMD and 1-year cognition. At baseline, (mean age = 65.9 years (SD = 11.1); 34% female), lower Montreal Cognitive Assessment (MoCA) scores were associated with older age, lower premorbid IQ and higher stroke severity, but not with PSMD (βstandardized = −0.116, 95% CI −0.241, 0.009; p = 0.069). At 1-year, premorbid IQ, older age, higher stroke severity and higher PSMD (βstandardized = −0.301, 95% CI −0.434, −0.168; p < 0.001) were associated with lower MoCA. Higher baseline PSMD was associated with lower 1-year MoCA (βstandardized = −0.182, 95% CI −0.308, −0.056; p = 0.005). PSMD becomes more associated with global cognition at 1-year post-stroke, possibly once acute effects have settled. Additionally, PSMD in the subacute phase after a mild stroke could help predict long-term cognitive impairment.

Neuromotor dysfunction as a major outcome domain of psychotic disorders: A 21-year follow-up study

BackgroundThe long-term stability of neuromotor domains assessed at the first episode of psychosis (FEP) and their ability for predicting a number of outcomes remains largely unknown, and this study addressed these issues. MethodsThis was a longitudinal study of 243 participants with FEP who were assessed at baseline for background variables and parkinsonism, dyskinesia, neurological soft signs (NSS) and catatonia, and reassessed 21 years later for the same neuromotor variables, psychopathology, functioning, personal recovery, cognitive performance and medical comorbidity. Stability of neuromotor ratings was assessed using the intraclass correlations coefficient and associations between the predictors and outcomes were examined using univariate and multivariate statistics. ResultsBaseline dyskinesia and NSS ratings showed excellent stability over time whereas that for parkinsonism and catatonia was relatively low. Neuromotor dysfunction at follow-up was independently predicted by a family history of schizophrenia, obstetric complications, neurodevelopmental delay, low premorbid IQ and baseline ratings of dyskinesia and NSS. Moreover, baseline dyskinesia and NSS ratings independently predicted more positive and negative symptoms, poor functioning and less personal recovery; catatonia predicted less personal recovery and more medical comorbidity. Baseline neuromotor ratings explained between 4% (for medical comorbidity) and 34% (for neuromotor dysfunction) of the variance in the outcomes. Lastly, neuromotor dysfunction at baseline highly predicted clinical staging at follow-up. ConclusionBaseline neuromotor domains show variable stability over time and relate distinctively to very long-term outcomes. Both baseline dyskinesia and NSS are trait markers of the disease process and robust predictors of the outcomes.

Acceptability of cognitive remediation for schizophrenia: a systematic review and meta-analysis of randomized controlled trials.

Acceptability is an important factor for predicting intervention use and potential treatment outcomes in psychosocial interventions. Cognitive remediation (CR) improves cognition and functioning in people with a diagnosis of schizophrenia, but its acceptability, and the impact of participants and treatment characteristics, remain to be investigated. Few studies provide a direct measure of acceptability, but treatment drop-out rates are often available and represent a valid surrogate. The systematic search conducted for the most comprehensive CR outcomes database for schizophrenia was updated in December 2020. Eligible studies were randomized clinical trials comparing CR with any other control condition in patients diagnosed with schizophrenia spectrum disorders and that also reported drop-out in treatment and control arms separately. Acceptability was measured as odd-ratios (OR) of drop-out. Of 2119 identified reports, 151 studies, reporting 169 comparisons between CR and control interventions with 10 477 participants were included in the analyses. The overall rate of drop-out was 16.58% for CR programs and 15.21% for control conditions. In the meta-analysis, no difference emerged between CR interventions and controls [OR 1.10, 95% confidence interval (CI) 0.96-1.25, p = 0.177]. Factors improving acceptability were: inpatient only recruitment, participants with fewer years of education and lower premorbid IQ, the presence of all CR core elements, and the presence of techniques to transfer cognitive gains into real-world functioning. CR for people diagnosed with schizophrenia is effective and has a good acceptability profile, similar to that of other evidence-based psychosocial interventions.

Effectiveness, Core Elements, and Moderators of Response of Cognitive Remediation for Schizophrenia

Cognitive impairment is a core feature of schizophrenia, with negative consequences on functional outcomes. Although cognitive remediation (CR) is effective and mentioned in treatment guidance for schizophrenia, its active ingredients and ideal candidates are still debated. To provide a comprehensive update on CR effectiveness for cognition and functioning in schizophrenia and analyze the core ingredients of efficacy and role of patient characteristics. The reference list of the last comprehensive meta-analysis in 2011 was screened against eligibility criteria. Then, electronic databases (PubMed, Scopus, and PsycInfo) were systematically searched for articles published from January 2011 to February 2020. Reference lists of included articles and relevant reviews were hand searched, and Google Scholar was manually inspected. Eligible studies were randomized clinical trials comparing CR with any other control condition in patients diagnosed with schizophrenia spectrum disorders (with an unrestricted clinical status). Screening was performed by at least 2 independent reviewers. The PRISMA guidelines were followed. Study data were independently extracted and pooled using random-effect models. Cohen d was used to measure outcomes. Trial methodological quality was evaluated with the Clinical Trials Assessment Measure. Primary outcomes were changes in global cognition and overall functioning from baseline to after treatment, subsequently investigated through metaregressions, subgroup, and sensitivity analyses based on prespecified hypotheses, to identify potential moderators of response associated with treatment modality and patient characteristics. Of 1815 identified reports, 358 full texts were assessed and 194 reports on 130 studies were included. Based on 130 studies with 8851 participants, CR was effective on cognition (d, 0.29 [95% CI, 0.24-0.34]) and functioning (d, 0.22 [95% CI, 0.16-0.29]). An active and trained therapist (cognition: χ21, 4.14; P = .04; functioning: χ21, 4.26; P = .04), structured development of cognitive strategies (cognition: χ21, 9.34; P = .002; functioning: χ21, 8.12; P = .004), and integration with psychosocial rehabilitation (cognition: χ21, 5.66; functioning: χ21, 12.08) were crucial ingredients of efficacy. Patients with fewer years of education (global cognition: coefficient, -0.055 [95% CI, -0.103 to -0.006]; P = .03; global functioning: coefficient, -0.061 [95% CI, -0.112 to -0.011]; P = .02), lower premorbid IQ (global functioning: coefficient, -0.013 [-0.025 to -0.001]; P = .04), and higher baseline symptom severity (global cognition: coefficient, 0.006 [95% CI, 0.002 to 0.010]; P = .005) emerged as optimal candidates. These findings show that CR is an evidence-based intervention that should be included consistently into clinical guidelines for the treatment of individuals with schizophrenia and implemented more widely in clinical practice.

Rethinking the course of psychotic disorders: modelling long-term symptom trajectories.

The clinical course of psychotic disorders is highly variable. Typically, researchers have captured different course types using broad pre-defined categories. However, whether these adequately capture symptom trajectories of psychotic disorders has not been fully assessed. Using data from AESOP-10, we sought to identify classes of individuals with specific symptom trajectories over a 10-year follow-up using a data-driven approach. AESOP-10 is a follow-up, at 10 years, of 532 incident cases with a first episode of psychosis initially identified in south-east London and Nottingham, UK. Using extensive information on fluctuations in the presence of psychotic symptoms, we fitted growth mixture models to identify latent trajectory classes that accounted for heterogeneity in the patterns of change in psychotic symptoms over time. We had sufficient data on psychotic symptoms during the follow-up on 326 incident patients. A four-class quadratic growth mixture model identified four trajectories of psychotic symptoms: (1) remitting-improving (58.5%); (2) late decline (5.6%); (3) late improvement (5.4%); (4) persistent (30.6%). A persistent trajectory, compared with remitting-improving, was associated with gender (more men), black Caribbean ethnicity, low baseline education and high disadvantage, low premorbid IQ, a baseline diagnosis of non-affective psychosis and long DUP. Numbers were small, but there were indications that those with a late decline trajectory more closely resembled those with a persistent trajectory. Our current approach to categorising the course of psychotic disorders may misclassify patients. This may confound efforts to elucidate the predictors of long-term course and related biomarkers.

Cognitive subgroups in first episode bipolar I disorder: Relation to clinical and brain volumetric variables.

Distinct cognitive subgroups are seen in patients with long duration bipolar I disorder (BDI), possibly reflective of underlying pathophysiological differences. It is unknown whether such cognitive heterogeneity is present at illness onset. We applied latent class analysis (LCA) to cognitive test scores in first episode BDI patients. Exploratory analysis elucidated whether impaired subgroups were characterized by 'early neurodevelopmental' (low premorbid IQ and intracranial volume) versus 'later neurodevelopmental' (decline from premorbid to current IQ, changes in relative grey (GM)/white (WM) matter volumes) pathology. Recently recovered first manic episode BDI patients (n=91) and healthy controls (HC, n=63) comprised the study sample. LCA identified subgroups based on processing speed, verbal memory, non-verbal memory, executive functioning, attention and working memory scores. Subgroups were compared amongst each other and HC on premorbid/current IQ, intracranial (ICV), total brain and regional volumes. Three cognitive subgroups emerged: (i) globally impaired (GI, n=31), scoring 0.5-1 SD below demographically corrected norms across domains, (ii) selectively impaired (SI, n=47), with predominant processing speed deficits and (iii) high performing (HP, n=13), with above-average cognitive performance. GI patients showed a 'later neurodevelopmental' pattern, with normal ICV, significant decline from premorbid to current IQ, higher total GM and lower total WM (with respect to total brain volume) versus SI and HC (p=0.003). GI patients had higher left frontal pole GM versus HC (p<0.05, FWE corrected). A globally impaired patient subgroup is identifiable in first episode BDI, possibly characterized by unique neurodevelopmental pathologic processes proximal to illness onset.

Predictors of cognitive impairment in treatment-resistant depression

BackgroundCognitive impairment is a well-recognized symptom of major depressive disorder; however, contributing factors are not fully characterized. The present study examined the neurocognitive profiles and predictors of cognitive impairment in patients with treatment-resistant depression (TRD). MethodsModerate to severely depressed TRD patients were compared to matched healthy volunteers (HV) in verbal learning and recall and executive functions. Based on cognitive scores, cluster analysis was performed to identify subsets within the TRD sample. Predictors of cognitive impairment were also investigated. ResultsTRD patients showed worse performance in tests assessing verbal memory, executive attentional shifting, and inhibitory control. The cluster analysis revealed two groups: a cognitively impaired (CI) group that showed a generalized deficit across cognitive domains, and a relatively cognitively intact group that performed better than CI in all domains except attentional shifting. A logistic binomial regression of the two groups revealed three significant contributing risk factors for CI: 1) older age, 2) lower premorbid IQ, and 3) benzodiazepine use. Cognitive impairment and benzodiazepine use were associated with worse functioning. ConclusionsSignificant cognitive impairment is present in TRD and is associated with worse functioning. Age, lower premorbid IQ, and benzodiazepine use increased the likelihood of generalized cognitive impairment in TRD patients. The detrimental effect of benzodiazepine on cognitive impairment is independent of anxiety symptoms. Further research is needed to characterize the timeline of cognitive impairment in depression.

M123. EPISODIC VERBAL MEMORY DEFICIT IN SCHIZOPHRENIA: A MARKER OF PROGRESSION OF DISEASE OR DIFFERENT NEURODEVELOPMENTAL PATHWAYS FROM THE ONSET?

BackgroundEpisodic verbal memory primarily indicates acquisition or registration of memory for verbally presented information, being one of the main neuropsychological impaired functions in individuals with schizophrenia. Furthermore, it appears to be more susceptible than other memory systems to early neuronal dysfunction, supporting hypotheses about a neuroprogressive course of schizophrenia (SZ). On the other hand, it is unclear if such memory dysfunction in schizophrenia could not only be associated with illness progression, but also with neurodevelopment markers such as premorbid crystallized intellectual functioning (IQ). Therefore, we aimed to better understand the relationship between years of illness (YOI), IQ and episodic verbal memory in individuals with SZ.MethodsWe included 218 individuals with confirmed diagnosis of SZ from 3 separate centers (Hospital de Clínicas de Porto Alegre, Brazil; Hospital de Clínicas da Universidade Federal do Paraná, Brazil, and Hospital Clínic de Barcelona, Spain). All participants were informed about study procedures and signed consent before assessment. Participants underwent cognitive assessment with Hopkins Verbal Learning Test (HVLT) for episodic memory and Wechsler Abbreviated Scale of Intelligence for estimated crystallized premorbid IQ. We conducted a mediational analysis to estimate the effect sizes of years of illness in predicting memory deficits considering the indirect effect of IQ as a mediator, as well as age and sex as covariates.ResultsThere was a significant indirect effect of years of illness on HVLT immediate recall through IQ, ab=-.119 CI 95% [-.248, -.013]. The mediator could account for more than a third of the total effect, PM=.39. The direct effect of years of illness on immediate recall was only a trend (c: -.09, p= .068), while the total effect counting IQ was significant (c’=-.15, p=.007).DiscussionThe effect sizes of IQ were greater than the direct effect of years of illness on memory deficits in our sample. This finding implicates that neurodevelopment markers such as IQ may be as important as disease progression itself in predicting cognitive outcomes in SZ. While patients with lower premorbid IQ appears to be more prone to memory deficits, those with better early intellectual development appears to count on a protective effect. Neuroprogression in schizophrenia would be an addition of neurodevelopment and disease progression. These results help to give new lights on the heterogeneity in the course of schizophrenia, different trajectories and the need of more personalized approach. Further prospective studies are mandatory.

Emotional processing subtypes in bipolar disorder: A cluster analysis

BackgroundEvidence regarding the performance of Bipolar Disorder patients (BD) on Emotional Processing (EP) is conflicting, suggesting that heterogeneity within this population may exist. It is not completely understood if this impacts on clinical presentation and functional outcomes. MethodsA total of 212 BD patients were recruited. Patients underwent MATRICS Consensus Cognitive Battery as well as a clinical evaluation to detect premorbid traits, comorbidities and clinical features. Performance on each basic emotion on the Emotional Recognition Task (ERT) and Reading the Mind in the Eyes Test were entered into hierarchical cluster analyses in order to determine the number of clusters and to assign subjects to specific clusters. We then compared subgroups on clinical factors and real-world community functioning. ResultsNo differences between BD patients as a group and controls were found in EP performance. Two clusters of BD patients were found, one with “intact” performance (71.2%) that performed as healthy controls (HC) and other with “impaired” performance (28.8%) performing worse than HC and schizophrenic patients on basic emotion recognition. Patients in the “impaired group” presented higher rates of childhood trauma, schizotypal traits, lower premorbid IQ and education, poor psychosocial functioning and cognitive performance. LimitationsCross-sectional data which limits our ability to infer directionality of our findings. ConclusionThese results suggest the presence of two subgroups regarding EP performance with unique clinical and neurodevelopmental profiles associated. Next steps will include using these data to identify a homogeneous group of patients to target these disabling symptoms with treatment.

Patterns of recovery course in early intervention for FIRST episode non-affective psychosis patients: The role of timing

BackgroundPrevention of symptom relapse and promotion of functional recovery are the two main goals of early intervention following a first episode of non-affective psychosis (FEP). The identification of patterns of recovery is important in developing and implementing recovery focused interventions at set time interval. MethodPatterns of recovery course, in terms of symptomatic and functional remission, were explored at 1 and 3-year follow-up in a sample of 373 consecutive FEP patients. Relapses during this period were considered. ResultsFour patterns of recovery course were defined: good stable (26%), good unstable (21%), poor unstable (10%), poor stable (43%). Those who met criteria for good stable recovery were more likely have less severe baseline negative symptoms (OR = 2.092; 95% CI = 0.99–4.419) and to not be diagnosed with schizophrenia (OR = 2.242; 95% CI = 1.015–4.954). Short DUP (OR = 2.152; 95% CI = 0.879–5.27) and low premorbid IQ (OR = 2.281; 95% CI = 0.954–5.457) increased the likelihood of good unstable recovery. Less severe baseline negative symptoms (OR = 3.851; 95% CI = 1.422–10.435) and single status (OR = 4.307; 95% CI = 1.014–18.293) increased the likelihood of a poor unstable recovery. Poor unstable pattern was significantly associated with a high relapse rate (73%). ConclusionsOur results shed light on identifying different recovery patterns in FEP. Despite evidence for early intervention effectiveness, we should explore ways to prevent relapse and improve long-term recovery, particularly in reference to the role of timing in the design of interventions.

Machine learning for predicting psychotic relapse at 2 years in schizophrenia in the national FACE-SZ cohort

BackgroundPredicting psychotic relapse is one of the major challenges in the daily care of schizophrenia. ObjectivesTo determine the predictors of psychotic relapse and follow-up withdrawal in a non-selected national sample of stabilized community-dwelling SZ subjects with a machine learning approach. MethodsParticipants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical and cognitive assessment, including recording of current treatment. Relapse was defined by at least one acute psychotic episode of at least 7 days, reported by the patient, her/his relatives or by the treating psychiatrist, within the 2-year follow-up. A classification and regression tree (CART) was used to construct a predictive decision tree of relapse and follow-up withdrawal. ResultsOverall, 549 patients were evaluated in the expert centers at baseline and 315 (57.4%) (mean age = 32.6 years, 24% female gender) were followed-up at 2 years.On the 315 patients who received a visit at 2 years, 125(39.7%) patients had experienced psychotic relapse at least once within the 2 years of follow-up. High anger (Buss&Perry subscore), high physical aggressiveness (Buss&Perry scale subscore), high lifetime number of hospitalization in psychiatry, low education level, and high positive symptomatology at baseline (PANSS positive subscore) were found to be the best predictors of relapse at 2 years, with a percentage of correct prediction of 63.8%, sensitivity 71.0% and specificity 44.8%.High PANSS excited score, illness duration <2 years, low Buss&Perry hostility score, high CTQ score, low premorbid IQ and low medication adherence (BARS) score were found to be the best predictors of follow-up withdrawal with a percentage of correct prediction of 52.4%, sensitivity 62%, specificity 38.7%. ConclusionMachine learning can help constructing predictive score. In the present sample, aggressiveness appears to be a good early warning sign of psychotic relapse and follow-up withdrawal and should be systematically assessed in SZ subjects. The other above-mentioned clinical variables may help clinicians to improve the prediction of psychotic relapse at 2 years.

Systemic inflammation and intelligence in early adulthood and subsequent risk of schizophrenia and other non-affective psychoses: a longitudinal cohort and co-relative study

Schizophrenia is associated with impaired neurodevelopment as indexed by lower premorbid IQ. We examined associations between erythrocyte sedimentation rate (ESR), a marker of low-grade systemic inflammation, IQ, and subsequent schizophrenia and other non-affective psychoses (ONAP) to elucidate the role of neurodevelopment and inflammation in the pathogenesis of psychosis. Population-based data on ESR and IQ from 638 213 Swedish men assessed during military conscription between 1969 and 1983 were linked to National Hospital Discharge Register for hospitalisation with schizophrenia and ONAP. The associations of ESR with IQ (cross-sectional) and psychoses (longitudinal) were investigated using linear and Cox-regression. The co-relative analysis was used to examine effects of shared familial confounding. We examined mediation and moderation of effect between ESR and IQ on psychosis risk. Baseline IQ was associated with subsequent risk of schizophrenia (adjusted HR per 1-point increase in IQ = 0.961; 95% confidence interval (CI) 0.960-0.963) and ONAP (adjusted HR = 0.973; 95% CI 0.971-0.975). Higher ESR was associated with lower IQ in a dose-response fashion. High ESR was associated with increased risk for schizophrenia (adjusted HR = 1.14; 95% CI 1.01-1.28) and decreased risk for ONAP (adjusted HR = 0.85; 95% CI 0.74-0.96), although these effects were specific to one ESR band (7-10 mm/hr). Familial confounding explained ESR-IQ but not ESR-psychoses associations. IQ partly mediated the ESR-psychosis relationships. Lower IQ is associated with low-grade systemic inflammation and with an increased risk of schizophrenia and ONAP in adulthood. Low-grade inflammation may influence schizophrenia risk by affecting neurodevelopment. Future studies should explore the differential effects of inflammation on different types of psychosis.

T68. DIFFERENT INFLUENCES OF INTELLECTUAL FUNCTIONING AND COGNITIVE PERFORMANCE TO FUNCTIONAL OUTCOMES IN SCHIZOPHRENIA AND HEALTHY CONTROLS

BackgroundIndividuals with schizophrenia (SZ) have marked functional impairments in wide range of domains, such as employment, independent living and interpersonal relationships. Several clinical, cognitive and psychological factors have been shown to predict functional outcomes. However, current pharmacological and psychosocial treatments have failed to rehabilitate patients, which indicates that the mechanisms of functional outcomes are not completely clear. Therefore, we aimed to better understand the relationship between intellectual and cognitive performance to functional outcome of subjects with SZ compared to unaffected individuals. Considering the neurodevelopmental course of SZ, our hypothesis was that premorbid crystallized IQ would interact with cognition to influence functionality.MethodsWe included 188 individuals with confirmed diagnosis of SZ and 268 unaffected subjects (HC) from two separate multisite studies conducted by the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS) consortium. We used the following variables for the analysis: a) Estimated crystallized premorbid intellectual functioning (IQ): Wechsler Test of Adult Reading (WTAR); b) Cognitive performance: Dot Probe Expectancy task (DPX) and Relational and Item-Specific Encoding task (RISE) from CNTRACS; c) Functional capacity: UCSD Performance-based Skills Assessment – Brief (UPSA-B). We conducted linear regressions to predict functional outcome considering demographic, intellectual, and cognitive variables, as well as the interaction between cognition and IQ in participants with SZ and HC separately.ResultsParticipants with SZ had worse cognitive performance and premorbid IQ, and poorer functional outcome compared to HC. For the prediction of UPSA-B, the regression model that included cognition and IQ as predictors and age and parental SES as covariates was significant in SZ (F(4, 124) = 8.473, p < .001, Adj. R2 = .189), with the both variables showing significant main effects: IQ (β = .311, t = 3.324, p = .001) and cognition (β = .216, t = 2.630, p = .0010). When we included the IQ x cognition interaction (F(5, 123) = 7.035, p < .001, Adjusted R2 = .191), it did not significantly improve the model (F = 1.224, p = 0.27), and the interaction was not significant (β = -.11, t = -1.106, p = .27). In HC, the regression model with only main effects was similar to what was seen in SZ (F(4,313) = 27.62, p < .001, Adj. R2 = .25), with main effects of IQ (β = .239, t = 4.418, p < .001) and cognition (β = .349, t = 6.891, p < .001) (Figure 1). However, when we included the IQ x cognition interaction (F(5,312) = 24.15, p < .001, Adjusted R2 = .27), the interaction was significant (β = -.139, t = -2.801, p = .005) and accounted for a significant increase in variance over and above the other main effects (F = 7.8452, p = .005).DiscussionIn SZ, both higher IQ and better cognitive performance were independent predictors of better functioning. However, in HC, functionality was predicted by the interaction between IQ and cognition, with the form of the interaction suggesting that for HC participants with higher IQ, there was less effect of cognition on predicting better functioning. Conversely, in HC with lower premorbid IQ, better cognitive performance has a stronger effect in predicting better functioning. The fact that both IQ and cognition had independent relationships to functional outcome in SZ could help explain the limited clinically significant results found in previous studies of cognitive remediation and psychosocial interventions that did not also consider the impact of premorbid IQ. Future studies could focus on early interventions to prevent functional impairments through the stimulation of early intellectual development.

Association of Childhood Infection With IQ and Adult Nonaffective Psychosis in Swedish Men

Associations between childhood infection, IQ, and adult nonaffective psychosis (NAP) are well established. However, examination of sensitive periods for exposure, effect of familial confounding, and whether IQ provides a link between childhood infection and adult NAP may elucidate pathogenesis of psychosis further. To test the association of childhood infection with IQ and adult NAP, to find whether shared familial confounding explains the infection-NAP and IQ-NAP associations, and to examine whether IQ mediates and/or moderates the childhood infection-NAP association. Population-based longitudinal cohort study using linkage of Swedish national registers. The risk set included all Swedish men born between 1973 and 1992 and conscripted into the military until the end of 2010 (n = 771 698). We included 647 515 participants in the analysis. Hospitalization with any infection from birth to age 13 years. Hospitalization with an International Classification of Diseases diagnosis of NAP until the end of 2011. At conscription around age 18 years, IQ was assessed for all participants. At the end of follow-up, the mean (SD) age of participants was 30.73 (5.3) years. Exposure to infections, particularly in early childhood, was associated with lower IQ (adjusted mean difference for infection at birth to age 1 year: -1.61; 95% CI, -1.74 to -1.47) and with increased risk of adult NAP (adjusted hazard ratio for infection at birth to age 1 year: 1.19; 95% CI, 1.06 to 1.33). There was a linear association between lower premorbid IQ and adult NAP, which persisted after excluding prodromal cases (adjusted hazard ratio per 1-point increase in IQ: 0.976; 95% CI, 0.974 to 0.978). The infection-NAP and IQ-NAP associations were similar in the general population and in full-sibling pairs discordant for exposure. The association between infection and NAP was both moderated (multiplicative, β = .006; SE = 0.002; P = .02 and additive, β = .008; SE = 0.002; P = .001) and mediated (β = .028; SE = 0.002; P < .001) by IQ. Childhood infection had a greater association with NAP risk in the lower, compared with higher, IQ range. Early childhood is a sensitive period for the effects of infection on IQ and NAP. The associations of adult NAP with early-childhood infection and adolescent IQ are not fully explained by shared familial factors and may be causal. Lower premorbid IQ in individuals with psychosis arises from unique environmental factors, such as early-childhood infection. Early-childhood infections may increase the risk of NAP by affecting neurodevelopment and by exaggerating the association of cognitive vulnerability with psychosis.

Effect of GHB-use and GHB-induced comas on dorsolateral prefrontal cortex functioning in humans.

BackgroundGamma-hydroxybutyric acid (GHB) is a recreational drug associated with increasing numbers of GHB-dependent patients and emergency attendances often related to GHB-induced comas. Working memory (WM) deficits have been reported in association with GHB use, and animal studies have shown that GHB induces oxidative stress in vulnerable WM-related brain areas such as the dorsolateral prefrontal cortex (DLPFC). However, the effects of chronic GHB use and multiple GHB-induced comas on WM-related brain function in humans remains unknown.MethodsWe recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users who never experienced GHB-induced coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants performed an n-back WM task during functional magnetic resonance imaging (fMRI) to probe DLPFC functioning.ResultsThe GHB-Coma group had lower premorbid IQ (p = .006) than the GHB-NoComa group despite comparable age and education level. There were also group differences in the use of other drugs than GHB. Therefore, all group comparisons were adjusted for IQ and drug use other than GHB. Compared with the GHB-NoComa and the No-GHB groups, the GHB-Coma group showed increased activity in the right DLPFC (pSVC = 0.028) and increased functional connectivity of the right DLPFC with a cluster comprising the left anterior cingulate and medial frontal gyrus (pFWE = 0.003). No significant fMRI differences were observed between the GHB-NoComa and No-GHB groups. Due to technical problems, no behavioural data were collected.DiscussionThese results suggest that multiple GHB-induced comas, but not GHB-use per se, are associated with alterations in WM-related brain function. Public awareness campaigns are required to minimize the potential adverse effects induced by GHB recreational use, and especially GHB-induced comas, even if no immediate side effects are experienced.

Premorbid IQ subgroups in first episode non affective psychosis patients: Long-term sex differences in function and neurocognition

BackgroundLow IQ has been associated with schizophrenia, even to the point of being posited as a possible causal factor for psychosis. However, individuals with normal and high IQ also develop psychotic illnesses. The aim of this study was to characterize premorbid IQ subgroups at first episode of psychosis (FEP). MethodsThe study sample comes from a large epidemiological, 3-year longitudinal, intervention program on psychosis containing individuals living in a catchment area in Spain. Estimated premorbid IQ (epIQ) scores were used to build low (<90), normal (90–110) and high (>110) epIQ subgroups in samples of FEP patients (N=292) and healthy controls (N=199). The epIQ subgroups were compared in sociodemographic, neuropsychological, clinical and premorbid characteristics. Long-term functional and cognitive outcome, with a focus on sex differences, were also explored. ResultsLow-epIQ was more frequently found in FEP patients (28.8%) than in healthy controls (14.6%). Low-epIQ patients were more likely to have worse premorbid adjustment, belong to low socioeconomic status families, have less years of education, and to be single, unemployed, and younger. They presented more severe impairments in processing speed, executive and global cognitive function. Female patients with low-epIQ showed better baseline function and more stable outcome than males. ConclusionsOur results indicate that low premorbid IQ is a morbid manifestation, easily detected in a subgroup of FEP patients that predicts poorer outcome particularly in males. This perspective provides important information for the tailoring of subgroup-specific early intervention programs for psychosis.