Longitudinal inference of multiscale markers in psychosis: from hippocampal centrality to functional outcome.

Multiscale neuroscience conceptualizes mental illness as arising from aberrant interactions across and within multiple biopsychosocial scales. We leverage this framework to propose a multiscale disease progression model of psychosis, in which hippocampal-cortical dysconnectivity precedes impairments in episodic memory and social cognition, which lead to more severe negative symptoms and lower functional outcome. As psychosis represents a heterogeneous collection of biological and behavioral alterations that evolve over time, we further predict this disease progression for a subtype of the patient sample, with other patients showing normal-range performance on all variables. We sampled data from two cross-sectional datasets of first- and multi-episode psychosis, resulting in a sample of 163 patients and 119 non-clinical controls. To address our proposed disease progression model and evaluate potential heterogeneity, we applied a machine-learning algorithm, SuStaIn, to the patient data. SuStaIn uniquely integrates clustering and disease progression modeling and identified three patient subtypes. Subtype 0 showed normal-range performance on all variables. In comparison, Subtype 1 showed lower episodic memory, social cognition, functional outcome, and higher negative symptoms, while Subtype 2 showed lower hippocampal-cortical connectivity and episodic memory. Subtype 1 deteriorated from episodic memory to social cognition, negative symptoms, functional outcome to bilateral hippocampal-cortical dysconnectivity, while Subtype 2 deteriorated from bilateral hippocampal-cortical dysconnectivity to episodic memory and social cognition, functional outcome to negative symptoms. This first application of SuStaIn in a multiscale psychiatric model provides distinct disease trajectories of hippocampal-cortical connectivity, which might underlie the heterogeneous behavioral manifestations of psychosis.

Investigation of the neural correlates of mentalizing through the Dynamic Inference Task, a new naturalistic task of social cognition.

Understanding others' intentions requires both the identification of social cues (e.g., emotional facial expressions, gaze direction) and the attribution of a mental state to another. The neural substrates of these processes have often been studied separately, and results are heterogeneous, in part attributable to the variety of paradigms used. The aim of the present study was to explore the neural regions underlying these sociocognitive processes, using a novel naturalistic task in which participants engage with human protagonists featured in videos. A total of 51 right-handed volunteers underwent functional magnetic resonance imaging while performing the Dynamic Inference Task (DIT), manipulating the degree of inference (high vs. low), the presence of emotion (emotional vs. nonemotional), and gaze direction (direct vs. averted). High nonemotional inference elicited neural activation in temporal regions encompassing the right posterior superior temporal sulcus. The presence (vs. absence) of emotion in the high-inference condition elicited a bilateral pattern of activation in internal temporal areas around the amygdala and orbitofrontal structures, as well as activation in the right dorsomedial part of the superior frontal gyrus and the left precuneus. On account of its dynamic, naturalistic approach, the DIT seems a suitable task for exploring social interactions and the way we interact with others, both in nonclinical and clinical populations.

Fibromyalgia patients make scarce reference to pain in self-defining memories.

OBJECTIVE: Self-defining memories (SDMs) are vivid, emotionally intense and well-rehearsed autobiographical memories that provide fundamental information about one's cognitive affective motivational representation of self. Exploring SDMs in fibromyalgia (FM) is of interest for understanding the psychopathology of this disorder and improving clinical interventions. Our aim was to compare patients and healthy controls (HC) on SDM characteristics. METHOD: We included 25 patients with FM and 24 HC matched for age, sex and education level. Each participant described five SDMs, which were coded for content, specificity, integration, tension, redemption, contamination, affective response, date, and reference to pain. We statistically controlled our results for the most plausible confounding factors related to FM that could affect SDM recall, namely depression, anxiety, cognitive inhibition, pain severity and medication. RESULTS: Compared with HC, patients retrieved less specific SDMs with a more negative emotional valence but less tension. They reported more relationship-related memories, and fewer redemptive ones, with less meaning-making. The number of memories referring to physical or psychological pain did not differ between groups. None of the confounding factors we analysed could explain (either alone or in combination) the statistical differences between groups for SDMs characteristics. CONCLUSION: We discuss functional avoidance and alexithymia as two main factors for poor reference to pain in patients' SDMs that further reveal affective dysregulation in FM. In clinical practice, remediating the way in which pain is integrated into SDMs in FM may help to mitigate its negative impact on everyday life.

Modulation of the N400 component in relation to hypomanic personality traits in a word meaning ambiguity resolution task.

AIM: High levels of hypomanic personality traits have been associated with an increased risk of developing bipolar disorder (BD). Changes in semantic content, impaired verbal associations, abnormal prosody, and abnormal speed of language are core features of BD, and are thought to be related to semantic processing abnormalities. In the present study, we used event-related potentials to investigate the relation between semantic processing (N400 component) and hypomanic personality traits. METHODS: We assessed 65 healthy young adults on the Hypomanic Personality Scale (HPS). Event-related potentials were recorded during a semantic ambiguity resolution task exploring semantic ambiguity (polysemous word ending a sentence) and congruency (target word semantically related to the sentence). RESULTS: As expected, semantic ambiguity and congruency both elicited an N400 effect across our sample. Correlation analyses showed a significant positive relationship between the Social Vitality subscore of the HPS and N400 modulation in the frontal region of interest in the incongruent unambiguous condition, and in the frontocentral region of interest in the incongruent ambiguous condition. CONCLUSION: We found differences in semantic processing (i.e., detection of incongruence and semantic inhibition) in individuals with higher Social Vitality subscores. In the light of the literature, we discuss the notion that a semantic processing impairment could be a potential marker of vulnerability to BD, and one that needs to be explored further in this clinical population.

Transdiagnostic cognitive biases in psychiatric disorders: A systematic review and network meta-analysis.

Psychiatric disorders are characterized by cognitive deficits, which have been proposed as a transdiagnostic feature of psychopathology ("C" factor). Similarly, cognitive biases (e.g., in attention, memory, and interpretation) represent common tendencies in information processing that are often associated with psychiatric symptoms. However, the question remains whether cognitive biases are also transdiagnostic or are specific to certain psychiatric disorders/symptoms. The current systematic review sought to address whether the proposed "C" factor of transdiagnostic cognitive dysfunction in psychopathology can be extended to cognitive biases. Overall, 31 studies comprising 4401 participants (2536 patients, 1865 non-clinical controls) met inclusion criteria, assessing 19 cognitive biases across 20 diagnostic categories, with most studies focusing on interpretation (k = 22) and attention (k = 11) biases and only 2 assessing memory biases. Traditional meta-analyses found a moderate effect size (g = 0.32) for more severe cognitive biases in all patients relative to non-clinical controls, as well as small but significant associations between interpretation biases and transdiagnostic symptom categories (general psychopathology: r = 0.20, emotion dysfunction: r = 0.17, psychotic symptoms: r = 0.25). Network meta-analyses revealed significant patient versus non-clinical control differences on attention and interpretation biases across diagnoses, as well as significant differences between diagnoses, with highest severity in panic disorder for attention biases and obsessive-compulsive disorder for interpretation biases. The current findings extend the big "C" interpretation of transdiagnostic cognitive dysfunction in psychiatric disorders to cognitive biases and transdiagnostic symptom dimensions. Results also suggest that while the presence of cognitive biases is transdiagnostic, bias severity differs across diagnoses, as in traditional neurocognitive deficits.

Impact of hypomanic personality traits on brain functional connectivity during a dynamic theory-of-mind task.

Hypomanic personality traits are present in the general population and represent a risk factor for developing bipolar disorder. This personality style, notably its social component, is linked to difficulties in theory of mind (i.e., ability to infer mental states). Exploring the neural correlates of mental states' inference in individuals with these personality traits can provide meaningful insights into the development of bipolar disorder. The aim of the present study was therefore to investigate the potential impact of hypomanic traits on brain activation and task-based connectivity strength during a dynamic theory of mind task in a nonclinical population. A total of 52 nonclinical participants were recruited, and hypomanic traits were assessed with the Hypomanic Personality Scale. The severity of hypomanic traits was positively associated with right middle and inferior frontal gyri activations (in high vs. low inference in nonemotional condition and emotion vs. no emotion in high inference, respectively). It was also associated with stronger connectivity between the salience network (i.e., bilateral putamen and pallidum) and bilateral superior temporal gyri (high inference in nonemotional condition), and between cerebellar and temporal areas (high inference in emotional condition). These changes may either reflect adaptations or differential processing, and further studies are therefore mandatory.

Episodic Memory and Schizophrenia: From Characterization of Relational Memory Impairments to Neuroimaging Biomarkers.

Episodic memory research in schizophrenia has a long history already which has clearly established significant impairments and strong associations with brain measures and functional outcome. The purpose of this chapter is not to make an exhaustive review of the recent literature but to highlight some relatively recent developments in the cognitive neuroscience field of episodic memory and schizophrenia. Hence, we present a contemporary view focusing specifically of relational memory which represents a form of episodic memory that refers to associations or binding among items or elements presented together. We describe the major tasks used and illustrate how their combination with brain imaging has: (1) favored the use of experimental memory tasks to isolate specific processes with specific neural correlates, (2) led to a distributed view of the neural correlates of memory impairments in schizophrenia where multiple regions are contributing, and (3) made possible the identification of fMRI biomarkers specific to episodic memory. We then briefly propose what we see as the next steps for memory research in schizophrenia so that the impact of this work can be maximized.

Disentangling the Relationships Between the Clinical Symptoms of Schizophrenia Spectrum Disorders and Theory of Mind: A Meta-analysis.

BACKGROUND AND HYPOTHESIS: Previous studies have suggested links between clinical symptoms and theory of mind (ToM) impairments in schizophrenia spectrum disorders (SSD), but it remains unclear whether some symptoms are more strongly linked to ToM than others. STUDY DESIGN: A meta-analysis (Prospero; CRD42021259723) was conducted to quantify and compare the strength of the associations between ToM and the clinical symptoms of SSD (Positive, Negative, Cognitive/Disorganization, Depression/Anxiety, Excitability/Hostility). Studies (N = 130, 137 samples) including people with SSD and reporting a correlation between clinical symptoms and ToM were retrieved from Pubmed, PsycNet, Embase, Cochrane Library, Science Direct, Proquest, WorldCat, and Open Gray. Correlations for each dimension and each symptom were entered into a random-effect model using a Fisher's r-to-z transformation and were compared using focused-tests. Publication bias was assessed with the Rosenthal failsafe and by inspecting the funnel plot and the standardized residual histogram. STUDY RESULTS: The Cognitive/Disorganization (Zr = 0.28) and Negative (Zr = 0.24) dimensions revealed a small to moderate association with ToM, which was significantly stronger than the other dimensions. Within the Cognitive/Disorganization dimension, Difficulty in abstract thinking (Zr = 0.36) and Conceptual disorganization (Zr = 0.39) showed the strongest associations with ToM. The association with the Positive dimension (Zr = 0.16) was small and significantly stronger than the relationship with Depression/Anxiety (Zr = 0.09). Stronger associations were observed between ToM and clinical symptoms in younger patients, those with an earlier age at onset of illness and for tasks assessing a combination of different mental states. CONCLUSIONS: The relationships between Cognitive/Disorganization, Negative symptoms, and ToM should be considered in treating individuals with SSD.

Activation of the left medial temporal gyrus and adjacent brain areas during affective theory of mind processing correlates with trait schizotypy in a nonclinical population.

Schizophrenia, a severe psychiatric disorder, is associated with abnormal brain activation during theory of mind (ToM) processing. Researchers recently suggested that there is a continuum running from subclinical schizotypal personality traits to fully expressed schizophrenia symptoms. Nevertheless, it remains unclear whether schizotypal personality traits in a nonclinical population are associated with atypical brain activation during ToM tasks. Our aim was to investigate correlations between fMRI brain activation during affective ToM (ToMA) and cognitive ToM (ToMC) tasks and scores on the Schizotypal Personality Questionnaire (SPQ) and the Basic Empathy Scale in 39 healthy individuals. The total SPQ score positively correlated with brain activation during ToMA processing in clusters extending from the left medial temporal gyrus (MTG), lingual gyrus and fusiform gyrus to the parahippocampal gyrus (Brodmann area: 19). During ToMA processing, the right inferior occipital gyrus, right MTG, precuneus and posterior cingulate cortex negatively correlated with the emotional disconnection subscore and the total score of self-reported empathy. These posterior brain regions are known to be involved in memory and language, as well as in creative reasoning, in nonclinical individuals. Our findings highlight changes in brain processing associated with trait schizotypy in nonclinical individuals during ToMA but not ToMC processing.

Cerebral blood flow in schizophrenia: A systematic review and meta-analysis of MRI-based studies.

INTRODUCTION: Schizophrenia-spectrum disorders (SSD) represent one of the leading causes of disability worldwide and are usually underpinned by neurodevelopmental brain abnormalities observed on a structural and functional level. Nuclear medicine imaging studies of cerebral blood flow (CBF) have already provided insights into the pathophysiology of these disorders. Recent developments in non-invasive MRI techniques such as arterial spin labeling (ASL) have allowed broader examination of CBF across SSD prompting us to conduct an updated literature review of MRI-based perfusion studies. In addition, we conducted a focused meta-analysis of whole brain studies to provide a complete picture of the literature on the topic. METHODS: A systematic OVID search was performed in Embase, MEDLINEOvid, and PsycINFO. Studies eligible for inclusion in the review involved: 1) individuals with SSD, first-episode psychosis or clinical-high risk for psychosis, or; 2) had healthy controls for comparison; 3) involved MRI-based perfusion imaging methods; and 4) reported CBF findings. No time span was specified for the database queries (last search: 08/2022). Information related to participants, MRI techniques, CBF analyses, and results were systematically extracted. Whole-brain studies were then selected for the meta-analysis procedure. The methodological quality of each included studies was assessed. RESULTS: For the systematic review, the initial Ovid search yielded 648 publications of which 42 articles were included, representing 3480 SSD patients and controls. The most consistent finding was that negative symptoms were linked to cortical fronto-limbic hypoperfusion while positive symptoms seemed to be associated with hyperperfusion, notably in subcortical structures. The meta-analysis integrated results from 13 whole-brain studies, across 426 patients and 401 controls, and confirmed the robustness of the hypoperfusion in the left superior and middle frontal gyri and right middle occipital gyrus while hyperperfusion was found in the left putamen. CONCLUSION: This updated review of the literature supports the implication of hemodynamic correlates in the pathophysiology of psychosis symptoms and disorders. A more systematic exploration of brain perfusion could complete the search of a multimodal biomarker of SSD.

Facial emotion recognition processes according to schizotypal personality traits: An eye-tracking study.

Facial emotion recognition has been shown to be impaired among patients with schizophrenia and, to a lesser extent, among individuals with high levels of schizotypal personality traits. However, aspects of gaze behavior during facial emotion recognition among the latter are still unclear. This study therefore investigated the relations between eye movements and facial emotion recognition among nonclinical individuals with schizotypal personality traits. A total of 83 nonclinical participants completed the Schizotypal Personality Questionnaire (SPQ) and performed a facial emotion recognition task. Their gaze behavior was recorded by an eye-tracker. Self-report questionnaires measuring anxiety, depressive symptoms, and alexithymia were administered. At the behavioral level, correlation analyses showed that higher SPQ scores were associated with lower surprise recognition accuracy scores. Eye-tracking data revealed that higher SPQ scores were associated with shorter dwell time on relevant facial features during sadness recognition. Regression analyses revealed that the total SPQ score was the only significant predictor of eye movements during sadness recognition, and depressive symptoms were the only significant predictor of surprise recognition accuracy. Furthermore, dwell time predicted response times for sadness recognition in that shorter dwell time on relevant facial features was associated with longer response times. Schizotypal traits may be associated with decreased attentional engagement in relevant facial features during sadness recognition and impede participants' response times. Slower processing and altered gaze patterns during the processing of sad faces could lead to difficulties in everyday social situations in which information must be rapidly processed to enable the successful interpretation of other people's behavior.

Exploring the Relationship Between Suicidality and Persistent Negative Symptoms Following a First Episode of Psychosis.

BACKGROUND AND HYPOTHESIS: Suicide is a leading cause of death in first-episode psychosis (FEP), with an elevated risk during the first year following illness onset. The association between negative symptoms and suicidality remains contentious. Some studies suggest that negative symptoms may be associated with lower suicidality, while others fail to find an association between the two. No previous studies have specifically investigated suicidality in Persistent Negative Symptoms (PNS) and its associated subgroups. STUDY DESIGN: In a large cohort of FEP patients (n = 515) from an early intervention service, we investigated suicidality in those with PNS, secondary PNS (ie, sPNS; PNS with clinical-level positive, depressive, or extrapyramidal symptoms), and non-PNS (all other patients) over 24 months. Patients were categorized into PNS groups based on symptoms from month 6 to month 12, and suicidality was evaluated using the Brief Psychiatric Rating Scale (BPRS). STUDY RESULTS: Covarying for age and sex, we found that sPNS had higher suicidality relative to PNS and non-PNS throughout the 24-month period, but PNS and non-PNS did not differ. These differences were maintained after adjusting for depressive symptoms. CONCLUSION: We observed that PNS did not significantly differ from non-PNS. However, we identified sPNS as a group with elevated suicidality above and beyond depression, suggesting that sPNS would benefit from targeted intervention and that PNS categorization identifies a subgroup for whom negative symptoms are not associated with lower suicidality.

Impact of switching or initiating antipsychotic treatment on body weight during a 6-month follow-up in a cohort of patients with schizophrenia.

OBJECTIVE: Although weight gain is one of the most widely studied adverse effects of second-generation antipsychotics, only relatively few studies have specifically evaluated the long-term effect of switching antipsychotic medication on body weight. We aimed to evaluate the impact of switching antipsychotics on body mass index (BMI) during a 6-month follow-up period in a large cohort of patients with schizophrenia. METHOD: Data came from a 6-month prospective naturalistic survey in 6007 patients with schizophrenia. RESULTS: We prospectively studied the effect on BMI of initiating or switching antipsychotic medication after 6 months of treatment among 3801 patients with schizophrenia in a real-life setting. Patients who were being treated with clozapine or olanzapine at baseline were more likely to experience a decrease in BMI during the follow-up period than the patients who were being treated with a conventional antipsychotic (odds ratio, 2.25 and 1.68, respectively). Patients treated with aripiprazole and, to a lesser extent, those treated with risperidone were more likely to experience a decrease in BMI during follow-up than patients treated with conventional antipsychotics (odds ratio, 2.96 and 2.06, respectively). CONCLUSIONS: Our findings suggest that switching antipsychotics could be an effective strategy for reducing or preventing weight gain.

Depression, anxiety and personality dimensions in female first-degree relatives of alcohol-dependent probands.

A total of 136 with or without first-degree relatives with alcohol dependence were compared according to lifetime prevalence of psychiatric disorders and personality dimensions. Family history positive women showed significant higher prevalence rates of depression and agoraphobia, and exhibited lower scores on Reward Dependence, Self-Directedness and Cooperativeness dimensions.

Altered Surface Area Covariance in the Mentalizing Network in Schizophrenia: Insight Into Theory of Mind Processing.

BACKGROUND: Theory of mind (ToM), the cognitive capacity to attribute mental states to self and others, is robustly affected in schizophrenia. The neural substrates of ToM impairment have been largely studied with functional imaging, but little is known about structural abnormalities. We compared structural covariance (between-subjects correlations of brain regional measures) of magnetic resonance imaging-based cortical surface area between patients with schizophrenia and healthy control subjects and between schizophrenia subgroups based on the patients' ToM ability to examine ToM-specific effects on structural covariance in schizophrenia. METHODS: T1-weighted structural images were acquired on a 3T magnetic resonance imaging scanner, and ToM was assessed with the Hinting Task for 104 patients with schizophrenia and 69 healthy control subjects. The sum of surface area was computed for 12 regions of interest selected and compared between groups to examine structural covariance within the often reported mentalizing network: rostral and caudal middle frontal gyrus, inferior parietal lobule, precuneus, and middle and superior temporal gyrus. High and low ToM groups were defined using a median split on the Hinting Task. RESULTS: Cortical surface contraction was observed in the schizophrenia group, predominantly in temporoparietal regions. Patients with schizophrenia also exhibited significantly stronger covariance between the right rostral middle frontal gyrus and the right superior temporal gyrus than control subjects (r = 4.015; p < .001). Direct comparisons between high and low ToM subgroups revealed stronger contralateral frontotemporal covariances in the low ToM group. CONCLUSIONS: Our results provide evidence for structural changes underlying ToM impairments in schizophrenia that need to be confirmed to develop new therapeutic perspectives.

Faux Pas Recognition and Executive Processes in Patients with Alcohol Use Disorder: Toward an Investigation of Interindividual Heterogeneity.

OBJECTIVE: Impairment of executive functions (EF) has been documented for decades in patients with alcohol use disorders (AUD), while more recent studies have also reported impaired theory of mind. Both have been associated with negative outcomes, particularly a high risk of relapse. However, the interrelatedness of EF and theory of mind impairments remains subject to debate. METHOD: About 19 AUD outpatients and 20 healthy controls (HC) were asked to complete measures of motor inhibition, mental flexibility, and updating to assess EF, and the faux pas test to assess theory of mind. RESULTS: As expected, patients' mean performances on EF and faux pas measures were poorer than those of HC. Correlational analyses revealed that executive processes were differentially related to faux pas subscores. Additional single-case analyses corroborated the strong association between EF and faux pas interpretation, as patients with AUD mostly had congruent performances (i.e., both EF and faux pas impaired or both EF and faux pas preserved). CONCLUSIONS: This study highlights the interrelatedness of EF and faux pas performances in AUD, but also emphasizes the incomplete overlap of the cognitive processes involved in these tasks, with heterogeneous patterns of association. Based on these findings, tailored cognitive rehabilitation programs that simultaneously target EF and faux pas recognition could be developed to favor patients' social inclusion and reduce the risk of relapse. Results also argue in favor of systematic screening for EF and theory of mind impairments among AUD patients.

Dynamic Interplay Between Insight and Persistent Negative Symptoms in First Episode of Psychosis: A Longitudinal Study.

Persistent negative symptoms (PNS) are an important factor of first episode of psychosis (FEP) that present early on in the course of illness and have a major impact on long-term functional outcome. Lack of clinical insight is consistently associated with negative symptoms during the course of schizophrenia, yet only a few studies have explored its evolution in FEP. We sought to explore clinical insight change over a 24-month time period in relation to PNS in a large sample of FEP patients. Clinical insight was assessed in 515 FEP patients using the Scale to assess Unawareness of Mental Disorder. Data on awareness of illness, belief in response to medication, and belief in need for medication were analyzed. Patients were divided into 3 groups based on the presence of negative symptoms: idiopathic (PNS; n = 135), secondary (sPNS; n = 98), or absence (non-PNS; n = 282). Secondary PNS were those with PNS but also had clinically relevant levels of positive, depressive, or extrapyramidal symptoms. Our results revealed that insight improved during the first 2 months for all groups. Patients with PNS and sPNS displayed poorer insight across the 24-month period compared to the non-PNS group, but these 2 groups did not significantly differ. This large longitudinal study supported the strong relationship known to exist between poor insight and negative symptoms early in the course of the disorder and probes into potential factors that transcend the distinction between idiopathic and secondary negative symptoms.

Structural brain correlates of cognitive function in schizophrenia: A meta-analysis.

Schizophrenia is characterized by cognitive impairments and widespread structural brain abnormalities. Brain structure-cognition associations have been extensively studied in schizophrenia, typically involving individual cognitive domains or brain regions of interest. Findings in overlapping and diffuse brain regions may point to structural alterations in large-scale brain networks. We performed a systematic review and meta-analysis examining whether brain structure-cognition associations can be explained in terms of biologically meaningful brain networks. Of 7,261 screened articles, 88 were included in a series of meta-analyses assessing publication bias, heterogeneity, and study quality. Significant associations were found between overall brain structure and eight MATRICS-inspired cognitive domains. Brain structure mapped onto the seven Yeo functionally defined networks and extraneous structures (amygdala, hippocampus, and cerebellum) typically showed associations with conceptually related cognitive domains, with higher-level domains (e.g., executive function, social cognition) associated with more networks. These findings synthesize the extensive literature on brain structure and cognition in schizophrenia from a contemporary network neuroscience perspective and suggest that brain structure-cognition associations in schizophrenia may follow functional network architecture.

Subtyping negative symptoms in first-episode psychosis: Contrasting persistent negative symptoms with a data-driven approach.

Persistent negative symptoms (PNS) are linked to poor functional outcomes and may be primary or caused by secondary factors. Although several studies have examined PNS in first-episode psychosis (FEP), a comparison with a data-driven approach is lacking. Here, we compared clinically defined PNS subgroups with class trajectories identified through latent growth modeling (LGM). Patients admitted to an early intervention service (N = 392) were classified as PNS (n = 105), secondary PNS (sPNS; n = 74), or non-PNS (n = 213) based on longitudinal data collected six to twelve months after admission. LGM was used to stratify patients based on similar negative symptom course over the same time period. Using multiple linear regression, we assessed the utility of both approaches in predicting Social and Occupational Functioning Assessment Scale (SOFAS) scores at two-year follow-up. Three negative symptom trajectories were identified: low and remitting (LR; n = 158), moderate and improving (MI; n = 163) and delayed partial response (DR; n = 71). Most non-PNS patients followed the LR trajectory, while patients with PNS or sPNS were generally divided between MI and DR. Both PNS classification and trajectory membership were significant predictors of two-year functional outcomes; the DR and MI trajectories predicted greater increases in SOFAS scores (DR: b = -19.14; MI: b = -11.54) than either sPNS (b = -9.19) or PNS (b = -6.46). These findings demonstrate that combining PNS and symptom-based stratification can predict functional outcomes more accurately than either taxonomy alone. Such a combined approach could yield significant advances in developing more targeted interventions for patients at risk for poor functional outcomes.

Normal-range verbal memory in the first-episode of psychosis: Clinical and functional outcomes across 24 months and impact of estimated verbal memory decrement.

Verbal memory (VM) dysfunction is prevalent in first-episode psychosis (FEP) and has major impacts on long-term functional and clinical outcomes. Nevertheless, a substantial proportion of FEP patients have VM performance in the norm, called normal-range (NR) VM, and only a few studies have explored its relation to outcomes. Moreover, probable decrements between estimated premorbid and current cognitive performance could confuse the relationship between VM and clinical or functional outcomes in FEP patients. These potential interactions have not yet been considered in FEP, thus, we examined 1) the longitudinal relationship between VM performance (NR vs. below NR (BNR)) in FEP and clinical and functional outcomes over 24 months following admission to treatment, and 2) compared the clinical and functional status of NR patients with and without cognitive decrement at baseline and 12 months. A total of 271 patients (BNR = 114, NR = 157; 81 out of 105 NR with decrement) completed measures of psychosocial functioning and clinical symptoms at baseline, month 12, and month 24. Generalized Estimating Equations and unpaired t-tests were used to address the first and second aim, respectively. NR demonstrated better functioning and fewer negative symptoms when compared to BNR. Interestingly, NR patients with decrement reported significantly more negative symptoms at baseline compared to their counterparts without decrement. These findings document that a large proportion (57.9 %) of FEP patients have NR VM that appear to be functionally advantageous but that NR VM is nuanced by the presence or absence of a potential decrement early in the developmental course of the disorder.