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Background Studies that examined sex differences in first-episode patients consistently show that males compared to females have poor premorbid adjustment, earlier age of onset, worse clinical characteristics, and poorer outcomes. However, little is known about potential mediators that could explain these sex differences. Methods Our sample consisted of 137 individuals with first episode schizophrenia (males, n = 105; 77%) with a mean age of 22.1(s.d. = 4.1) years and mean education of 12.5(s.d. = 1.7) years. At entry, patients were within 2 years of their first psychotic episode onset. Baseline assessments were conducted for premorbid adjustment, symptoms, cognitive functioning, insight, and at 6-months for role and social functioning. Results Males as compared to females had poorer premorbid adjustment across several key developmental periods (p < 0.01), an earlier age of onset [M = 20.3(3.3) v. 22.8(5.6), p = 0.002], more negative symptoms (p = 0.044), poorer insight (p = 0.031), and poorer baseline and 6-month role (p = 0.002) and social functioning (p = 0.034). Several of these variables in which males showed impairment were significant predictors of 6-month role and social functioning. Premorbid adjustment and insight mediated the relationship between sex and role and social functioning at 6-months, but not negative symptoms. Discussion Males compared to females were at lower levels across several key premorbid and clinical domains which are strongly associated with functional outcome supporting the hypothesis that males might have a more disabling form of schizophrenia. The relationship between sex with role and social functioning was mediated through premorbid adjustment and insight suggesting pathways for understanding why females might have a less disabling form of schizophrenia.

Background Cognitive training (CT) and aerobic exercise both show promising moderate impact on cognition and everyday functioning in schizophrenia. Aerobic exercise is hypothesized to increase brain-derived neurotrophic factor (BDNF) and thereby synaptic plasticity, leading to increased learning capacity. Systematic CT should take advantage of increased learning capacity and be more effective when combined with aerobic exercise. Methods We examined the impact of a 6-month program of cognitive training & exercise (CT&E) compared to cognitive training alone (CT) in 47 first-episode schizophrenia outpatients. All participants were provided the same Posit Science computerized CT, 4 h/week, using BrainHQ and SocialVille programs. The CT&E group also participated in total body circuit training exercises to enhance aerobic conditioning. Clinic and home-based exercise were combined for a target of 150 min per week. Results The MATRICS Consensus Cognitive Battery Overall Composite improved significantly more with CT&E than with CT alone (p = 0.04), particularly in the first 3 months (6.5 v. 2.2 T-score points, p < 0.02). Work/school functioning improved substantially more with CT&E than with CT alone by 6 months (p < 0.001). BDNF gain tended to predict the amount of cognitive gain but did not reach significance. The cognitive gain by 3 months predicted the amount of work/school functioning improvement at 6 months. The amount of exercise completed was strongly associated with the degree of cognitive and work/school functioning improvement. Conclusions Aerobic exercise significantly enhances the impact of CT on cognition and functional outcome in first-episode schizophrenia, apparently driven by the amount of exercise completed.

Studies demonstrate that dynamic assessment (i.e., learning potential) improves the prediction of response to rehabilitation over static measures in individuals with schizophrenia. Learning potential is most commonly assessed using neuropsychological tests under a test-train-test paradigm to examine change in performance. Novel learning potential approaches using social cognitive tasks may have added value, particularly for the prediction of social functioning, but this area is unexplored. The present study is the first to investigate whether patients with schizophrenia demonstrate social cognitive learning potential across phase of illness. This study included 43 participants at clinical high risk (CHR), 63 first-episode, and 36 chronic schizophrenia patients. Assessment of learning potential involved test-train-test versions of the Wisconsin Card Sorting Test (non-social cognitive learning potential) and the Facial Emotion Identification Test (social cognitive learning potential). Non-social and social cognition pre-training scores (static scores) uniquely predicted concurrent community functioning in patients with schizophrenia, but not in CHR participants. Learning potential showed no incremental explanation of variance beyond static scores. First-episode patients showed larger non-social cognitive learning potential than CHR participants and were similar to chronic patients; chronic patients and CHR participants were similar. Group differences across phase of illness were not observed for social cognitive learning potential. Subsequent research could explore whether non-social and social cognitive learning potential relate differentially to non-social versus social types of training and rehabilitation.

BackgroundThis study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling.MethodsIndividual Placement and Support (IPS) was adapted to meet the goals of individuals whose goals might involve either employment or schooling. IPS was combined with a Workplace Fundamentals Module (WFM) for an enhanced, outpatient, vocational intervention. Random assignment to the enhanced integrated rehabilitation program (N = 46) was contrasted with equally intensive clinical treatment at UCLA, including social skills training groups, and conventional vocational rehabilitation by state agencies (N = 23). All patients were provided case management and psychiatric services by the same clinical team and received oral atypical antipsychotic medication.ResultsThe IPS–WFM combination led to 83% of patients participating in competitive employment or school in the first 6 months of intensive treatment, compared with 41% in the comparison group (p < 0.005). During the subsequent year, IPS–WFM continued to yield higher rates of schooling/employment (92% v. 60%, p < 0.03). Cumulative number of weeks of schooling and/or employment was also substantially greater with the IPS–WFM intervention (45 v. 26 weeks, p < 0.004).ConclusionsThe results clearly support the efficacy of an enhanced intervention focused on recovery of participation in normative work and school settings in the initial phase of schizophrenia, suggesting potential for prevention of disability.

BACKGROUND: Meta-analyses have reported that the effects of cognitive remediation might go beyond improvement in cognition to include unexpected benefits for schizophrenia patients such as negative symptom reduction and improvements in functioning. In addition, some evidence indicated that these potentially beneficial effects are also present in the initial course of schizophrenia, but work in this area is still developing. METHOD: A RCT compared Cognitive Remediation (CR) to Healthy Behaviors Training (HBT) in 80 patients (78% male) with a mean age of 21.9 years and mean education of 12.3 years who had a first psychotic episode within two years of study entry. Participants were trained using CR programs or received HBT involving 50 sessions over 6 months and then booster sessions over the next 6 months. The SANS and BPRS were used to assess symptoms. The UCLA Social Attainment Survey assessed social functioning. RESULTS: Using GLMM, improvements over 12 months were found favoring CR for SANS Expressive Symptoms (p

This cross-sectional study examines the differences in cortical volume and gray-to-white matter contrast (GWC) in first episode schizophrenia patients (SCZ) compared to healthy control participants (HC) and in SCZ patients as a function of exposure to second generation antipsychotic medication. We hypothesize 1) SCZ exhibit regionally lower cortical volumes relative to HCs, 2) cortical volume will be greater with longer exposure to second generation antipsychotics prior to the MRI scan, and 3) lower GWC with longer exposure to second generation antipsychotics prior to the MRI scan, suggesting more blurring from greater intracortical myelin. To accomplish this, MRI scans from 71 male SCZ patients treated with second generation oral risperidone and 42 male HCs were examined. 3D T1-weighted MPRAGE images collected at 1.5T were used to estimate cortical volume and GWC by sampling signal intensity at 30% within the cortical ribbon. Average cortical volume and GWC were calculated and compared between SCZ and HC. Cortical volume and GWC in SCZ patients were correlated with duration of medication exposure for the time period prior to the scan. First-episode SCZ patients had significantly lower cortical volume compared to HCs in bilateral temporal, superior and rostral frontal, postcentral gyral, and parahippocampal regions. In SCZ patients, greater cortical volume was associated with (log-transformed) duration of second-generation antipsychotic medication exposure in bilateral precuneus, right lingual, and right superior parietal regions. Lower GWC was correlated with longer duration of medication exposure bilaterally in the superior frontal lobes. In summary, second generation antipsychotics may increase cortical volume and decrease GWC in first episode SCZ patients.

Introduction Elevated levels of pro-inflammatory cytokines have been reported in meta-analyses of multi-episode schizophrenia patients when compared to controls. However, little is known about whether these same relationships are present in the early course of schizophrenia. Objective To assess first episode schizophrenia patients for depression and to assay blood samples collected at baseline and at 6 months for interleukin-6 (IL-6). Materials and methods Trained raters used the Brief Psychiatric Rating Scale to assess depressive symptoms and a standard lab assay kit to assess for IL-6 levels in plasma. Conclusions Decreases in pro-inflammatory IL-6 levels were significantly related to decreases in depressive symptoms. Within a subset of patients in a 6-month aerobic exercise protocol, the number of exercise sessions completed was significantly correlated with the amount of decrease in IL-6. The reductions observed in IL-6 with aerobic exercise suggest exercise is a promising intervention to reduce brain inflammation effects in schizophrenia patients.

Cortical thinning in frontal and temporal regions has been reported in individuals diagnosed with schizophrenia and, less consistently, among their unaffected first-degree relatives. Likewise, first-degree relatives demonstrate attenuated differences in neurocognitive performance relative to healthy controls, indicating that neurocognitive performance may be an important endophenotype of the disorder. Less is known about how cortical thickness relates to neurocognitive performance in these individuals. Given the robust nature of temporal structural abnormalities in schizophrenia, this study aimed to identify how temporal lobe cortical thickness might relate to verbal memory in first-degree relatives. Unaffected parents and siblings of individuals with adult-onset schizophrenia (N=62) and individuals in healthy control families (N=70) participating in the UCLA Family Study received a structural MRI and completed a battery of neurocognitive tests. Cortical thickness was estimated across the cortex and thickness measures of all regions in the temporal lobe were summed, averaged, and residualized for age and sex to produce a variable. A verbal learning factor was derived from two common tests of verbal learning and memory, the CVLT-II and Logical Memory of the WMS-III. Results demonstrated a significant interaction between group and verbal learning in relationship to temporal lobe thickness. Post-hoc analyses revealed significant correlations between verbal learning and cortical thickness in the relatives of schizophrenia patients which were driven by immediate recall scores on the CVLT-II and Logical Memory. These findings indicate that cortical thickness in the temporal cortex may represent a structural correlate for encoding verbal information in unaffected relatives of individuals with schizophrenia.

Although patients with schizophrenia exhibit impaired suppression of the P50 event-related brain potential in response to the second of two identical auditory stimuli during a paired-stimulus paradigm, uncertainty remains over whether this deficit in inhibitory gating of auditory sensory processes has relevance for patients' clinical symptoms or cognitive performance. The authors examined associations between P50 suppression deficits and several core features of schizophrenia to address this gap.P50 was recorded from 52 patients with schizophrenia and 41 healthy comparison subjects during a standard auditory paired-stimulus task. Clinical symptoms were assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. The MATRICS Consensus Cognitive Battery was utilized to measure cognitive performance in a subsample of 39 patients. Correlation and regression analyses were conducted to examine P50 suppression in relation to clinical symptom and cognitive performance measures.Schizophrenia patients demonstrated a deficit in P50 suppression when compared with healthy subjects, replicating prior research. Within the patient sample, impaired P50 suppression covaried reliably with greater difficulties in attention, poorer working memory, and reduced processing speed.Impaired suppression of auditory stimuli was associated with core pathological features of schizophrenia, increasing confidence that P50 inhibitory processing can inform the development of interventions that target cognitive impairments in this chronic and debilitating mental illness.

Although a number of studies examined recollection and familiarity memory in schizophrenia, most of studies have focused on nonsocial episodic memory. Little is known about how schizophrenia patients remember social information in everyday life and whether social episodic memory changes over the course of illness. This study aims to examine episodic memory for dynamic social interaction with multimodal social stimuli in schizophrenia across phase of illness. Within each phase of illness, probands and demographically matched controls participated: 51 probands at clinical high risk (CHR) for psychosis and 36 controls, 80 first-episode schizophrenia patients and 49 controls, and 50 chronic schizophrenia patients and 39 controls. The participants completed the Social Remember-Know Paradigm that assessed overall social episodic memory, social recollection and familiarity memory, and social context memory, in addition to social cognitive measures and measures on community functioning. Probands showed impairment for recollection but not in familiarity memory and this pattern was similar across phase of illness. In contrast, impaired social context memory was observed in the first-episode and chronic schizophrenia samples, but not in CHR samples. Social context memory was associated with community functioning only in the chronic sample. These findings suggest that an impaired recollection could be a vulnerability marker for schizophrenia whereas impaired social context memory could be a disease-related marker. Further, a pattern of impaired recollection with intact familiarity memory for social stimuli suggests that schizophrenia patients may have a different pattern of impaired episodic memory for social vs nonsocial stimuli.

Background Increasing evidence supports the benefits of regular aerobic exercise for cognition and functioning in schizophrenia. The extent to which these gains are dependent on the amount of aerobic exercise completed remains unclear, although variability in adherence to intended exercise regiments is evident. Furthermore, strategies for encouraging regular exercise sessions in schizophrenia are only starting to be explored. Methods In a randomized controlled trial with 47 first-episode patients with schizophrenia, we contrasted six months of Cognitive Training & Exercise (CT&E) with Cognitive Training (CT) alone. The computerized cognitive training using PositScience BrainHQ and SocialVille programs was provided to all participants, four hours/week at the UCLA clinic for six months. The CT&E group also participated in total body circuit training exercises, with a goal of completing 150 minutes/week. Two of the aerobic exercise sessions were held at the clinic, while the other two were to be completed at home. Intensity of exercise was titrated individually with a heart rate monitor, targeting 60–80% of heart rate reserve. Several incentive strategies to encourage regular exercise were incorporated. Cognitive gain was measured by the MATRICS Consensus Cognitive Battery (MCCB), while the Global Assessment Scale: Role was used to index work/school functioning gain. Results Both groups showed cognitive and work/school functioning gains, but the improvements were three times as large when aerobic exercise was added to cognitive training (for MCCB Overall Composite, Mixed Model F = 7.19, p Discussion The addition of systematic aerobic exercise to cognitive training resulted in substantially more cognitive and functional gain than cognitive training alone. The magnitude of cognitive improvement was clearly related to the amount of regular exercise completed. Several strategies were employed to boost the frequency of exercise, particularly the number of exercise sessions completed outside of clinic group exercise sessions. Development of systematic incentive strategies to encourage regular aerobic exercise will be critical to successful dissemination of exercise programs as part of the treatment of schizophrenia.

Studies indicate that people with schizophrenia experience deficits in their ability to accurately detect emotions, both through facial expressions and voice intonation (i.e., prosody), and that functioning and symptoms are associated with these deficits. This study aimed to examine how facial emotion and affective prosody recognition are related to functioning and symptoms in a first-episode schizophrenia sample. Further, in light of research suggesting variable emotion-specific performance in people with schizophrenia, this study explored emotion-specific performance. Participants were 49 people with a recent first episode of schizophrenia taking part in a larger RCT. Results revealed that affective prosody recognition was significantly correlated with both role and social functioning. Regarding associations with psychiatric symptoms, facial emotion recognition was significantly, negatively associated with all three positive symptom scales, whereas affective prosody recognition was significantly, negatively associated with disorganization only. Emotion-specific analyses revealed that for affective prosody, participants were most accurate in recognizing anger and least accurate for disgust. For facial emotion recognition, participants were most accurate in recognizing happiness and least accurate for fear. Taken together, results suggest that affective prosody recognition is important for social and role functioning in people with first-episode schizophrenia. Results also suggest that this group may struggle more to identify negative emotions, though additional work is needed to clarify this pattern in affective prosody and determine real-world impact on social interactions. Keywords: First-episode schizophrenia, Prosody, Social cognition, Emotion recognition, Schizophrenia-spectrum

AIM: Individual Placement and Support (IPS) improves vocational outcomes in first-episode psychosis patients, but policy makers need information on costs (and personnel time required) to conduct effective IPS. METHODS: Using chart records of 42 clients in a first-episode psychosis study, we examined service time for specific activities over 18 months. RESULTS: The IPS specialist averaged 92(SD=62) minutes per client per week: 39% of time was spent in direct client contact, 9% in meetings without the client, 14% in meetings with the treatment team, 14% in supervision and 24% on travel time. Time required was significantly higher when participants were seeking work/school placements, decreased over duration of enrollment, and was similar for those using work versus school support. CONCLUSIONS: IPS service time covers numerous activities, is reduced when not seeking work/school placements and required less time over enrollment duration. Financing structures should support the full range of IPS services.

Schizophrenia (SZ) is associated with impaired adaptive functioning, including difficulties managing the demands of independent living, work, school, and interpersonal relationships. Prior studies have linked the physiological stress response with less effective coping in daily life. Differences in stress-response tendencies may also support heterogeneity in daily functioning in SZ. The present study examined two established measures of the stress response in patients with first-episode SZ. Salivary cortisol was included as an index of hypothalamic-pituitary-adrenal response. Vagal suppression (VS), a measure of stress-related reduction in heart rate variability, was used to assess parasympathetic flexibility. Greater cortisol response and VS to social-evaluative stress were predicted to be associated with better functioning in SZ over and above relationships with social cognition and neurocognition, two well-established predictors of functional outcome. Thirty-eight first-episode SZ outpatients and 29 healthy comparison subjects (HC) provided social cognitive, neurocognitive, and physiological measurements before and after the Trier Social Stress Test (TSST). Although SZ and HC did not differ on VS to the TSST, patients exhibited significant associations between VS and functioning across all four domains of the Role Functioning Scale. Furthermore, greater VS predicted more effective functioning with friends, beyond the contributions associated with social cognition and neurocognition, and strengthened the positive effects of higher levels of social cognition on independent living/self-care. VS elicited by social-evaluative stress in the laboratory may reflect stress-response tendencies in daily life that are relevant for daily functioning in first-episode SZ.

BACKGROUND: Strong empirical evidence has indicated that the severity of cognitive deficits predicts functional outcome in the early course of schizophrenia, while equally strong evidence has shown that supported employment and supported education can substantially increase the proportion of first-episode psychosis patients who return to school or work. How do these influences on the early course of work/school outcome interface? METHODS: Within a randomized controlled trial of Individual Placement and Support (IPS) and a Workplace Fundamentals Module (IPS-WFM) vs. conventional vocational rehabilitation plus social skills training with 69 individuals with a recent first episode of schizophrenia, we examined both supported employment/education and cognitive deficits in relationship to work/school outcome. A cognitive battery was administered at baseline and after 6 months of randomization to IPS vs. conventional vocational rehabilitation. To examine whether cognitive deficit level at baseline predicted work/school recovery in the context of these treatment conditions, we used as summary scores the first principal component as an overall index of cognitive deficit and the first rotated principal component, a processing-speed/attention factor. We also examined individual cognitive test scores to determine whether IPS-WFM impacted cognitive deficit level. RESULTS: Within 6 months after randomization, 83% of patients in the IPS-WFM intervention participated in competitive employment or school, compared to 41% in the conventional vocational rehabilitation group (p < .005), indicating a strong impact of supported employment/education. Overall level of baseline cognitive deficit significantly predicted participation in competitive work or school by 6 months in the entire sample (r=0.45, p

BACKGROUND: Leptin is derived in adipose tissue and circulates in the body to play a key role in metabolism and energy regulation. In non-psychiatric populations, there is evidence that leptin levels are associated with neurocognitive performance. The production of its circulating soluble binding receptor increases during exercise, which has been associated with neuroplasticity and memory enhancement. The soluble leptin receptor (SLR) is the main leptin binding protein in blood in humans, which serves as an antagonist of the transport of leptin to the brain. Cognitive deficits are well established in schizophrenia, even early in the course of the disorder. However, the question as to whether leptin plays a role in the well-observed cognitive deficits in schizophrenia is unanswered. We examined the relationship between soluble leptin receptor levels and cognitive deficits assessed with the MATRICS Consensus Cognitive Battery (MCCB) prior to participation in a longitudinal study of a combined cognitive training and aerobic exercise program intended to improve cognition and functional outcomes in these young-adult schizophrenia patients. METHODS: The participants were 48 first-episode adult-onset schizophrenia patients treated at the UCLA Aftercare Research Program. Plasma soluble leptin R levels were measured by solid phase sandwich ELISA (D0BR00, R&D Systems) using a Molecular Devices SpectraMax M2 plate reader, and concentrations calculated using a 5-Parameter Logistic Nonlinear Regression Model (SoftMax Pro software). The MATRICS Consensus Cognitive Battery (MCCB) was administered contemporaneously with the plasma blood draw during study baseline, prior to the randomized treatment conditions. RESULTS: Higher plasma soluble leptin receptor levels were significantly correlated in cross-sectional analyses with lower MCCB overall composite cognitive index scores (r= -.33, P=.03). Post-hoc analyses of the individual MCCB domains found 4 of the 7 to be significantly correlated with leptin levels (Speed of Processing (r = -34, P=.02), Attention/Vigilance (r = -34, P=.02), Verbal Learning and Memory (r = -30, P=.04), and Social Cognition (r = -30, P=.04). Soluble leptin receptor levels were not, however, significantly associated Working Memory (r = -19, P=.20), Visual Learning and Memory (r = -.21, P=.15), or Reasoning and Problem Solving (r = -07, P=.63). DISCUSSION: These results indicate certain cognitive deficits after onset of schizophrenia are moderately associated with soluble leptin receptor levels, even early in the course of the disorder. The higher incidence of the leptin receptor levels is thought to have an impact on lower rates of bioavailability of leptin to cross the blood-brain barrier and thus lend to improved neuroplasticity. Weight very commonly increases over time on antipsychotic medication. These findings are consistent with the known association between weight, and in particular, adipose tissue, and leptin. The negative impact of weight increase on cognitive functioning is rarely considered in the treatment of schizophrenia. However, these findings suggest that they should be an area of concern. Future reports will examine the effects of an exercise intervention on both leptin and cognition.

Background Groups with differential levels of cognitive impairment are increasingly recognized among patients with schizophrenia spectrum disorders. Using cluster analytical techniques, this study sought to explore cognitive clusters in a sample of first-episode psychosis patients and compare levels of symptomatology as well as childhood and adolescent scholastic performance between the resultant groups. Methods Data from 105 first-episode psychosis patients (n=56 with schizophrenia, n=13 with schizoaffective disorder, depressed type, n=36 with schizophreniform disorder) (mean age=22.06, SD=3.79) in the UCLA Aftercare Research Program were used for this analysis. Cognition was assessed using a modified beta version of the MATRICS Consensus Cognitive Battery which consisted of 16 tasks across seven cognitive domains. Symptomatology and developmental scholastic performance were assessed using the Brief Psychiatric Rating Scale and the Cannon-Spoor Premorbid Adjustment Scale respectively. Hierarchical cluster analysis with Ward’s method and squared Euclidean distance was conducted, confirmed by discriminant function analysis and optimized with k-means clustering. Stability of the solution was evaluated through split-sample (random 80% and 70% samples) and alternate method (average linkage method) replication via Cohen’s κ analysis. Results Three clusters were identified: most impaired (n=27), moderately impaired (n=41) and good (n=37). Controlling for multiple comparisons, one-way ANOVAs revealed no significant differences in symptomatology between the groups (p>.008). Significant differences were observed for scholastic performance at three different developmental stages: childhood (p Discussion The findings add to growing evidence that cognitive clusters in FEP mirror that of later-stage schizophrenia. Cognitive clusters were not associated with differences in symptom severity, but reflected differing levels of premorbid scholastic performance during the developmental years. This suggests that performance at school may not just be a risk factor for developing schizophrenia, but also related to the severity of impairment and potentially prognosis.

Background Schizophrenia is a psychiatric disorder characterized by a deficit in reality testing, most often manifest in the form of delusions and hallucinations. Because differentiating real from imagined experiences is critically dependent on episodic and associative memory, deficits in mnemonic processes could be involved in the genesis of impaired reality testing. Prior work has shown that individuals with psychosis exhibit impairment in metamemory, or, awareness and knowledge of one’s own memory and memory processes, and that these impairments may be relevant to the emergence and/or maintenance of psychotic symptoms. Methods In the present study, we used a verbal associative memory paradigm incorporating subject confidence ratings to examine differences in metamemory processes in three separate samples: patients with chronic schizophrenia (CHR; n = 34), patients with recent-onset (first-episode) psychosis (n = 49), and individuals at clinical high risk for psychosis (n = 29) compared to control groups (n = 24, n = 26, and n = 22, respectively). We used an analysis of variance design to examine group differences in confidence gap and knowledge corruption between patients and controls. We further assessed the association of both of these metrics to symptom severity in each patient sample. Results We found that both chronic and first-episode patients displayed significantly decreased confidence gap compared to healthy controls, with patients being more confident in incorrect memory retrievals and less confident in correct memory retrievals as compared to healthy controls. Additionally, compared to healthy controls, chronic patients and first-episode patients showed significantly increased knowledge corruption (the proportion of confident incorrect memory retrievals compared to all confident retrievals). While there were no group differences in confidence gap and knowledge corruption between CHR subjects and healthy controls, decreased confidence gap was significantly correlated with positive symptom severity in CHR subjects, as well as in first-episode subjects. Discussion These findings suggest that underlying deficits in metamemory processes may possibly reflect mechanisms involved in the development and/or maintenance of disrupted reality testing in those with and at risk for psychosis.

The goal of this study was to determine if family burden experienced by the families of individuals with a recent-onset of schizophrenia is associated with whether the individual is able to work or attend school during the first year of treatment. Forty-one participants with a recent first episode of schizophrenia and their families enrolled in two NIMH-funded protocols through the UCLA Aftercare Research Program completed a measure of family burden at baseline. Amount of work during this time was also recorded. Baseline family burden was associated with work status (no work, part-time work, or full-time work) at both the six-month, r = −0.321, p = .04, and one-year time point, r = − 0.47, p = .002. Family burden was also associated with hours participated in work/school hours at the six-month time point, r = −0.390, p = .012, and at the one-year time point, r = −0.492, p = .01. Further exploration into the family burden measure shows that family perceived limited opportunities resulting from the individual's psychiatric disorder was associated with worse functional outcome at all three time points beyond psychiatric symptoms and baseline functioning. Missed opportunities due to a family member's illness may reduce the level of support provided to the individual and thus impact their psychosocial functioning. Our findings suggest that this dimension of family burden is highlighting the importance of and need for more balanced family support to boost functional outcome.

Our objective in the present study was to conduct the first empirical study of the effects of regular physical activity habits and their relationship with brain volume and cortical thickness in patients in the early phase of schizophrenia. Relationships between larger brain volumes and higher physical activity levels have been reported in samples of healthy and aging populations, but have never been explored in first-episode schizophrenia patients. Method: We collected MRI structural scans in 14 first-episode schizophrenia patients with either self-reported low or high physical activity levels. We found a reduction in total gray matter volume, prefrontal cortex (PFC), and hippocampal gray matter volumes in the low physical activity group compared to the high activity group. Cortical thickness in the dorsolateral and orbitofrontal PFC were also significantly reduced in the low physical activity group compared to the high activity group. In the combined sample, greater overall physical activity levels showed a non-significant tendency with better performance on tests of verbal memory and social cognition. Together these pilot study findings suggest that greater amounts of physical activity may have a positive influence on brain health and cognition in first-episode schizophrenia patients and support the implementation of physical exercise interventions in this patient population to improve brain plasticity and cognitive functioning. (JINS, 2015, 21, 868–879)

BackgroundThe number of separable cognitive dimensions in schizophrenia has been debated. Guided by the extant factor analytic literature, the NIMH Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative selected seven cognitive domains relevant to treatment studies in schizophrenia: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. These domains are assessed in the MATRICS Consensus Cognitive Battery (MCCB). The aim of this study was to conduct a confirmatory factor analysis (CFA) of the beta battery of the MCCB to compare the fit of the MATRICS consensus seven-domain model to other models in the current literature on cognition in schizophrenia.MethodUsing data from 281 schizophrenia outpatients, we compared the seven correlated factors model with alternative models. Specifically, we compared the 7-factor model to (a) a single-factor model, (b) a three correlated factors model including speed of processing, working memory, and general cognition, and (c) a hierarchical model in which seven first-order factors loaded onto a second-order general cognitive factor.ResultsMultiple fit indices indicated the seven correlated factors model was the best fit for the data and provided significant improvement in model fit beyond the comparison models.ConclusionsThese results support the assessment of these seven cognitive dimensions in clinical trials of interventions to improve cognition in schizophrenia. Because these cognitive factors are separable to some degree, it is plausible that specific interventions may have differential effects on the domains.

Background Understanding the longitudinal course of negative symptoms, especially in relationship to functioning, in the early phase of schizophrenia is crucial to developing intervention approaches. The course of negative symptoms and daily functioning was examined over a 1-year period following a recent onset of schizophrenia and at an 8-year follow-up point. Methods The study included 149 recent-onset schizophrenia patients who had a mean age of 23.7 (SD = 4.4) years and mean education of 12.9 (SD = 2.2) years. Negative symptom (BPRS and SANS) and functional outcome (SCORS) assessments were conducted frequently by trained raters. Results After antipsychotic medication stabilization, negative symptoms during the first outpatient year were moderately stable (BPRS ICC = 0.64 and SANS ICC = 0.66). Despite this overall moderate stability, 24% of patients experienced at least one period of negative symptoms exacerbation. Furthermore, entry level of negative symptoms was significantly associated with poor social functioning ( r = − .34, p r = − .25, p r = .29, p Discussion Early negative symptoms are fairly stable during the first outpatient year, are predictors of daily functioning at 12 months, and predict negative symptoms 8 years later. Despite the high levels of stability, negative symptoms did fluctuate in a subsample of patients. These findings suggest that negative symptoms may be an important early course target for intervention aimed at promoting recovery.

Background: Unawareness of having a psychotic disorder (ie, poor insight) is a common presentation in schizophrenia. To explore the neuroanatomical substrates of unawareness of psychosis, we examined magnetic resonance imaging (MRI) brain scans of patients early in the course of treatment for schizophrenia. Given the implications of poor insight for medication nonadherence, this topic is of special clinical relevance.

Background: The presence of altered white matter microstructure in disorders involving psychosis is well established, but the nature and developmental course of these changes are not well understood (Peters & Karlsgodt, 2015). It is not clear whether the presence of attenuated frontal white matter anisotropy at any phase of illness indexes a pathophysiological change that occurs only within the prodromal and/or first episode phases, or whether early white matter changes are part of a lifespan trajectory of accelerated white matter degeneration in patients (Schwehm et al., 2016; Wright et al., 2014). It also remains to be determined whether schizophrenia-linked anisotropy changes are the result of axon damage or if they also reflect organizational changes.

Background: Working memory (WM) deficits are part of the constellation of cognitive impairments associated with schizophrenia (SZ). Although WM efficiency may be especially important for patients functioning within academic and employment settings, much of the research on WM in SZ neglects the social context of cognitive performance and fails to consider the extent to which stress may contribute to cognitive dysfunction. This is a crucial oversight considering growing evidence that high levels of cortisol disrupt WM in healthy individuals. Stress may be especially detrimental to cognitive functions in patients who often demonstrate HPA dysregulation including high basal cortisol and attenuated cortisol responses to acute stressors.

It is clear that people with schizophrenia typically have cognitive problems in multiple domains as part of their illness. The cognitive deficits are among the main contributors to limitations in their everyday functioning, including their work recovery. Cognitive remediation has been applied successfully to help people with long-term, persistent schizophrenia to improve their cognitive functioning, but it is only beginning to be applied with individuals who have recently had a first episode of psychosis. Several different approaches to cognitive training have been developed. Some approaches emphasize extensive systematic practice with lower-level cognitive processes and building toward higher-level processes ("bottom-up"), while others emphasize greater focus on high-level cognitive processes that normally integrate and organize lower-level processes ("top-down"). Each approach has advantages and disadvantages for a disorder like schizophrenia, with its multiple levels of cognitive dysfunction. In addition, approaches to cognitive remediation differ in the extent to which they systematically facilitate transfer of learning to everyday functioning. We describe in this article the cognitive training approach that was developed for a UCLA study of people with a recent first episode of schizophrenia, a group that may benefit greatly from early intervention that focuses on cognition and recovery of work functioning. This approach integrated bottom-up and top-down computerized cognitive training and incorporated an additional weekly group session to bridge between computerized training and application to everyday work and school functioning.

Background: In the early course of schizophrenia, premorbid functioning, negative symptoms, and neurocognition have been robustly associated with several domains of daily functioning. Research with chronic schizophrenia patients suggests that attitudinal beliefs may influence daily functioning. However, these relationships have not been examined in recent-onset schizophrenia patients. Methods: The sample consisted of recent-onset schizophrenia outpatients (n = 71) who were on average 21.7 (SD = 3.3) years old, had 12.5 (SD = 1.8) years of education, and 5.9 (SD = 6.3) months since psychosis onset. Patients were assessed for premorbid adjustment, positive and negative symptoms, neurocognition, attitudinal beliefs, and daily functioning. Normal controls (n = 20) were screened for psychopathology and demographically matched to the patients. Results: Comparisons indicated that recent-onset patients had higher levels of dysfunctional attitudes and lower self-efficacy compared to healthy controls (t = 3.35, P < .01; t = −4.1, P < .01, respectively). Dysfunctional attitudes (r = −.34) and self-efficacy (r = .36) were significantly correlated with daily functioning. Negative symptoms were found to mediate the relationship between self-efficacy and daily functioning (Sobel test, P < .01), as well as between dysfunctional attitudes and daily functioning (Sobel test, P < .05). Neurocognition was a significant mediator of the relationship between self-efficacy and daily functioning (Sobel test, P < .05). Discussion: Early course schizophrenia patients have significantly more dysfunctional attitudes and lower self-efficacy than healthy subjects. Both self-efficacy and dysfunctional attitudes partially contribute to negative symptoms, which in turn influence daily functioning. In addition, self-efficacy partially contributes to neurocognition, which in turn influences daily functioning.

Background Research using virtual reality assessment of functional capacity has shown promise as a reliable and valid way to assess treatment response in patients with established schizophrenia. There has been little work on virtual reality based assessments of functional capacity for patients in the early phase of schizophrenia. We examined whether virtual reality based assessment methods reveal functional capacity deficits in young patients and relevant relationships with established measures of neurocognition, functional capacity performance, and daily functioning. Methods The sample consisted of UCLA Aftercare Research Program patients (n=42) who were diagnosed by trained raters administering the SCID and who met criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder, and screened normal control subjects (n=13). Patients were within 2 years of their first psychotic episode upon clinic entry, were an average of 23.2 years old, and had an average of 12.9 years of education. The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) was the computer-based measure of functional capacity. We used the MATRICS Consensus Cognitive Battery (MCCB) as an objective measure of neurocognition and the UCSD Performance-Based Skills Assessment (UPSA) to assess functional capacity performance. The Global Functioning Scale: Role and Social, and the Role Functioning Scale were used to assess work and school performance, familial interactions, and social functioning. Results We were able to confirm that the deficit in functional capacity performance measured using VRFCAT is present in the early course of schizophrenia in that the patients were slower and committed more errors (M=830.41) as compared with normal controls (M=716.84; t=3.0, p

BACKGROUND: Research continues to show that persistent brain inflammation may be one mechanism through which genetic, biological, or environmental risk factors might impact the etiology and psychopathology of schizophrenia. Elevated levels of pro-inflammatory and lower levels of anti-inflammatory cytokines have been reported in meta-analyses of multi-episode schizophrenia patients when compared to controls. Similar findings have been described in meta-analysis in first episode schizophrenia patients for cytokines such as IL1β, sIL2r, IL-6, and TNF-α. Certain cytokines might be key participants in the regulation of neuro-inflammation in schizophrenia. Specifically, IL-6, a pro-inflammatory cytokine, may act as a primary regulator. In fact, IL-6 in multi-episode patients has been associated inversely with symptoms. Yet, little is known about the role these cytokines play in first episode schizophrenia patients and how best to reduce their impact. METHODS: Outpatients in the early course of schizophrenia who were being treated in the UCLA Aftercare Program were assessed at baseline and at a 6-month follow-up point. Patients were within 2 years of their first psychotic episode, were an average of 22.6 years old and had an average of 13.1 years of education. Patients were participants in a RCT of Cognitive Training alone vs Cognitive Training & Exercise. For 25 patients, we assayed blood collected at baseline and 6 months for IL-6. To assess symptoms, we administered the BPRS at baseline and every two weeks up to the 6-month study end point. RESULTS: We examined the relationship between changes in the pro-inflammatory cytokine IL-6 and the change in depression from baseline to the 6-month follow-up point. We found increases in levels of IL-6 were significantly related to increases in BPRS depressive symptoms (n=25, r=.40, p=.04). In examining the RCT effects, the group by time effect was not statistically significant. However, within the Cognitive Training & Exercise group, the number of aerobic exercise sessions completed was significantly correlated with the amount of reduction in brain inflammation as measured by IL-6 (n=13, r=-.63, p=.02). DISCUSSION: This is the first study to examine in first episode schizophrenia patients the longitudinal relationship between cytokines and symptoms over time and the effects of aerobic exercise on cytokines. The study findings indicate that an increase in a pro-inflammatory cytokine is associated with an increase in depressive symptoms during six months of treatment. Associations between cytokine level and depression suggest that inflammation might have deleterious effects on the early course of these symptoms. The reductions observed in IL-6 with aerobic exercise suggests that exercise may be a promising intervention to reduce the deleterious effects of brain inflammation.

Cognitive training (CT) and aerobic exercise have separately shown promise for improving cognitive deficits in schizophrenia. Aerobic exercise releases brain-derived neurotrophic factor, which promotes synaptic plasticity and neurogenesis. Thus, aerobic exercise provides a neurotrophic platform for neuroplasticity-based CT. The combination of aerobic exercise and CT may yield more robust effects than CT alone, particularly in the initial course of schizophrenia. In a pilot study, 7 patients with a recent onset of schizophrenia were assigned to Cognitive Training & Exercise (CT&E) and 9 to CT alone for a 10-week period. Posit Science programs were used for CT. Neurocognitive training focused on tuning neural circuits related to perceptual processing and verbal learning and memory. Social cognitive training used the same learning principles with social and affective stimuli. Both groups participated in these training sessions 2d/wk, 2h/d. The CT&E group also participated in an aerobic conditioning program for 30 minutes at our clinic 2d/wk and at home 2d/wk. The effect size for improvement in the MATRICS Consensus Cognitive Battery Overall Composite score for CT&E patients relative to CT patients was large. Functional outcome, particularly independent living skills, also tended to improve more in the CT&E than in the CT group. Muscular endurance, cardiovascular fitness, and diastolic blood pressure also showed relative improvement in the CT&E compared to the CT group. These encouraging pilot study findings support the promise of combining CT and aerobic exercise to improve the early course of schizophrenia.

Individuals with schizophrenia exhibit marked and disproportional impairment in social cognition, which is associated with their level of community functioning. However, it is unclear whether social cognitive impairment is stable over time, or if impairment worsens as a function of illness chronicity. Moreover, little is known about the longitudinal associations between social cognition and community functioning.Forty-one outpatients with schizophrenia completed tests of emotion processing (Mayer-Salovey-Caruso Emotional Intelligence Test, MSCEIT) and social perception (Relationships Across Domains, RAD) at baseline and approximately five years later. Stability of performance was assessed using paired t-tests and correlations. Longitudinal associations between social cognition and community functioning (Role Functioning Scale, RFS) were assessed using cross-lagged panel correlation analysis.Performance on the two social cognition tasks were stable over follow-up. There were no significant mean differences between assessment points [p's≥0.20, Cohen'sd's≤|0.20|], and baseline performance was highly correlated with performance at follow-up [ρ's≥0.70, ICC≥0.83, p's0.001]. The contemporaneous association between social cognition and community functioning was moderately large at follow-up [ρ=0.49, p=0.002]. However, baseline social cognition did not show a significant longitudinal influence on follow-up community functioning [z=0.31, p=0.76].These data support trait-like stability of selected areas of social cognition in schizophrenia. Cross-lagged correlations did not reveal a significant unidirectional influence of baseline social cognition on community functioning five years later. However, consistent with the larger literature, a moderately large cross-sectional association between social cognition and community functioning was observed. Based on stability and cross-sectional associations, these results suggest that social cognition might have short-term implications for functional outcome rather than long-term consequences.

Background Progress has been made in developing interview-based measures for the assessment of cognitive functioning, such as the Cognitive Assessment Interview (CAI), as co-primary measures that compliment objective neurocognitive assessments and daily functioning. However, a few questions remain, including whether the relationships with objective cognitive measures and daily functioning are high enough to justify the CAI as an co-primary measure and whether patient-only assessments are valid. Methods Participants were first-episode schizophrenia patients (n = 60) and demographically-similar healthy controls (n = 35), chronic schizophrenia patients (n = 38) and demographically similar healthy controls (n = 19). Participants were assessed at baseline with an interview-based measure of cognitive functioning (CAI), a test of objective cognitive functioning, functional capacity, and role functioning at baseline, and in the first episode patients again 6 months later (n = 28). Results CAI ratings were correlated with objective cognitive functioning, functional capacity, and functional outcomes in first-episode schizophrenia patients at similar magnitudes as in chronic patients. Comparisons of first-episode and chronic patients with healthy controls indicated that the CAI sensitively detected deficits in schizophrenia. The relationship of CAI Patient-Only ratings with objective cognitive functioning, functional capacity, and daily functioning were comparable to CAI Rater scores that included informant information. Conclusions These results confirm in an independent sample the relationship of the CAI ratings with objectively measured cognition, functional capacity, and role functioning. Comparison of schizophrenia patients with healthy controls further validates the CAI as an co-primary measure of cognitive deficits. Also, CAI change scores were strongly related to objective cognitive change indicating sensitivity to change.

article i nfo Reduced suppression of the auditory P50 event-related potential has long been associated with schizophre- nia, but the mechanisms associated with the generation and suppression of the P50 are not well understood. Recent investigations have used spectral decomposition of the electroencephalograph (EEG) signal to gain additional insight into the ongoing electrophysiological activity that may be reflected by the P50 suppression deficit. The present investigation extended this line of study by examining how both a traditional measure of sensory gating and the ongoing EEG from which it is extracted might be modified by the presence of concur- rent visual stimulation — perhaps better characterizing gating deficits as they occur in a real-world, complex sensory environment. The EEG was obtained from 18 patients with schizophrenia and 17 healthy control sub- jects during the P50 suppression paradigm and while identical auditory paired-stimuli were presented con- currently with affectively neutral pictures. Consistent with prior research, schizophrenia patients differed from healthy subjects in gating of power in the theta range; theta activity also was modulated by visual stim- ulation. In addition, schizophrenia patients showed intact gating but overall increased power in the gamma range, consistent with a model of NMDA receptor dysfunction in the disorder. These results are in line with a model of schizophrenia in which impairments in neural synchrony are related to sensory demands and the processing of multimodal information.

Context Imaging and post-mortem studies suggest that frontal lobe intracortical myelination is dysregulated in schizophrenia (SZ). Prior MRI studies suggested that early in the treatment of SZ, antipsychotic medications initially increase frontal lobe intracortical myelin (ICM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of ICM decline in chronic SZ is due to medication non-adherence or pharmacokinetics, it may be modifiable by long acting injection (LAI) formulations. Objectives Assess the effect of risperidone formulation on the ICM trajectory during a six-month randomized trial of LAI (RLAI) versus oral (RisO) in first-episode SZ subjects. Design Two groups of SZ subjects (RLAI, N = 9; and RisO, N = 13) matched on pre-randomization oral medication exposure were prospectively examined at baseline and 6 months later, along with 12 healthy controls (HCs). Frontal lobe ICM volume was assessed using inversion recovery (IR) and proton density (PD) MRI images. Medication adherence was tracked. Main outcome measure ICM volume change scores were adjusted for the change in the HCs. Results ICM volume increased significantly (p = .005) in RLAI and non-significantly (p = .39) in the RisO groups compared with that of the healthy controls. A differential between-group treatment effect was at a trend level (p = .093). SZ subjects receiving RLAI had better medication adherence and more ICM increases (chi-square p Conclusions The results suggest that RLAI may promote ICM development in first-episode SZ patients. Better adherence and/or pharmacokinetics provided by LAI may modify the ICM trajectory. In vivo MRI myelination measures can help clarify pharmacotherapeutic mechanisms of action.

Background Although in the early course of schizophrenia relapse prevention is of paramount importance, there is an increasing emphasis on establishing and maintaining sustained periods of symptom remission. Recovery in the early course of illness is also possible, although the rates of recovery are lower than for symptom remission. Symptom remission and recovery rates vary considerably across recent-onset schizophrenia studies because of a lack of consistency in treatment interventions and in applying operational outcome criteria. Method Patients who were within two years of their first psychotic episode (N = 77) that were treated with continuous antipsychotic medication in conjunction with psychosocial interventions (without targeted work rehabilitation) were assessed during the first outpatient year after hospital discharge. Published operational criteria were used to classify symptom remission and recovery. Results The rate of full symptom remission maintained for 6 months was 36%, while the rate of recovery for 6 months was 10%. When the same criteria were applied for a continuous period of one year, 22% of patients were found to achieve symptom remission but only 1% of patients met recovery criteria. Using multivariate prediction, the WAIS Comprehension score was a significant predictor of 6 months of good functional outcome. Conclusions Although some schizophrenia patients can achieve both symptom remission and recovery in the early course of illness, the overall rate of symptom remission during the first post-hospitalization year is much higher than the rate of recovery. This suggests that interventions targeting work and social functioning are likely necessary to raise the chances of recovery. Cognitive factors can be predictive of good functional outcome even in the early course of schizophrenia.

While the role of neurocognitive impairment in predicting functional outcome in chronic schizophrenia is now widely accepted, the results that have examined this relationship in the early phase of psychosis are surprisingly rather mixed. The predictive role of cognitive impairment early in the illness is of particular interest because interventions during this initial period may help to prevent the development of chronic disability. In a University of California, Los Angeles (UCLA) longitudinal study, we assessed schizophrenia patients with a recent first episode of psychosis using a neurocognitive battery at an initial clinically stabilized outpatient point and then followed them during continuous treatment over the next 9 months. Three orthogonal cognitive factors were derived through principal components analysis: working memory, attention and early perceptual processing, and verbal memory and processing speed. All patients were provided a combination of maintenance antipsychotic medication, case management, group skills training, and family education in a UCLA research clinic. A modified version of the Social Adjustment Scale was used to assess work outcome. Multiple regression analyses indicate that the combination of the 3 neurocognitive factors predicts 52% of the variance in return to work or school by 9 months after outpatient clinical stabilization. These data strongly support the critical role of neurocognitive factors in recovery of work functioning after an onset of schizophrenia. Cognitive remediation and other interventions targeting these early cognitive deficits are of major importance to attempts to prevent chronic disability.

This study evaluated the longitudinal stability and functional correlates of social cognition during the early course of schizophrenia. Fifty-five first-episode schizophrenia patients completed baseline and 12-month follow-up assessments of 3 key domains of social cognition (emotional processing, theory of mind, and social/relationship perception), as well as clinical ratings of real-world functioning and symptoms. Scores on all 3 social cognitive tests demonstrated good longitudinal stability with test-retest correlations exceeding .70. Higher baseline and 12-month social cognition scores were both robustly associated with significantly better work functioning, independent living, and social functioning at the 12-month follow-up assessment. Furthermore, cross-lagged panel analyses were consistent with a causal model in which baseline social cognition drove later functional outcome in the domain of work, above and beyond the contribution of symptoms. Social cognitive impairments are relatively stable, functionally relevant features of early schizophrenia. These results extend findings from a companion study, which showed stable impairments across patients in prodromal, first-episode, and chronic phases of illness on the same measures. Social cognitive impairments may serve as useful vulnerability indicators and early clinical intervention targets.

Social cognitive impairments are consistently reported in schizophrenia and are associated with functional outcome. We currently know very little about whether these impairments are stable over the course of illness. In the current study, 3 different aspects of social cognition were assessed (emotion processing, Theory of Mind [ToM], and social relationship perception) at 3 distinct developmental phases of illness: prodromal, first episode, and chronic. In this cross-sectional study, participants included 50 individuals with the prodromal risk syndrome for psychosis and 34 demographically comparable controls, 81 first-episode schizophrenia patients and 46 demographically comparable controls, and 53 chronic schizophrenia patients and 47 demographically comparable controls. Outcome measures included total and subtest scores on 3 specialized measures of social cognition: (1) emotion processing assessed with the Mayer-Salovey-Caruso Emotional Intelligence Test, (2) ToM assessed with The Awareness of Social Inference Test, and (3) social relationship perception assessed the Relationships Across Domains Test. Social cognitive performance was impaired across all domains of social cognition and in all clinical samples. Group differences in performance were comparable across phase of illness, with no evidence of progression or improvement. Age had no significant effect on performance for either the clinical or the comparison groups. The findings suggest that social cognition in these 3 domains fits a stable pattern that has outcome and treatment implications. An accompanying article prospectively examines the longitudinal stability of social cognition and prediction of functional outcome in the first-episode sample.

Cortical thickness reductions in prefrontal and temporal cortices have been repeatedly observed in patients with schizophrenia. However, it remains unclear whether regional variations in cortical thickness may be attributable to disease-related or genetic-liability factors.The structural magnetic resonance imaging data of 48 adult-onset schizophrenia patients, 66 first-degree non-psychotic relatives of schizophrenia patients, 27 community comparison (CC) probands and 77 CC relatives were examined using cortical pattern matching methods to map and compare highly localized changes in cortical gray matter thickness between groups defined by biological risk for schizophrenia.Schizophrenia patients showed marked cortical thinning primarily in frontal and temporal cortices when compared to unrelated CC probands. Results were similar, though less pronounced when patients were compared with their non-psychotic relatives. Cortical thickness reductions observed in unaffected relatives compared to age-similar CC relatives suggestive of schizophrenia-related genetic liability were marginal, surviving correction for the left parahippocampal gyrus and inferior occipital cortex only.Observations of pronounced fronto/temporal cortical thinning in schizophrenia patients replicate prior findings. The lack of marked cortical thickness alterations in non-psychotic relatives of patients, suggests that disease processes are primary contributors toward cortical thickness reductions in the disorder. However, genetic factors may have a larger influence on abnormalities in the medial temporal lobe.

Although malfunctioning of inhibitory processes is proposed as a pathophysiological mechanism in schizophrenia and has been studied extensively with the P50 gating paradigm, the brain regions involved in generating and suppressing the P50 remain unclear. The current investigation used EEG source analysis and the standard S1-S2 paradigm to clarify the neural structures associated with P50 gating in 16 schizophrenia patients and 14 healthy subjects. Based on prior research, the superior temporal gyrus, hippocampus, dorsolateral prefrontal cortex, thalamus, and their dipole moments were evaluated. In modeling the P50, a neural network involving all four brain regions provided the best goodness-of-fit across both groups. In healthy subjects, the P50 ratio score correlated positively with the hippocampal dipole moment ratio, whereas a significant association with the DLPFC dipole moment ratio was observed in schizophrenia patients. In each instance, the neural structure was found to account for unique variance in explaining the P50 ratio, along with some suggestion of DLPFC involvement in healthy subjects.

Whether avoidant personality disorder symptoms are related to neurocognitive impairments that aggregate in relatives of schizophrenics is unknown. We report the relationship between avoidant personality disorder symptoms and neurocognitive performance in the first-degree relatives of probands with schizophrenia. 367 first-degree relatives of probands with schizophrenia and 245 relatives of community controls were interviewed for the presence of avoidant personality symptoms and symptoms of paranoid and schizotypal personality disorders and administered neurocognitive measures. Relationships between neurocognitive measures and avoidant symptoms were analyzed using linear mixed models. Avoidant dimensional scores predicted performance on the span of apprehension (SPAN), 3-7 Continuous Performance Test (3-7 CPT), and Trail Making Test (TMT-B) in schizophrenia relatives. These relationships remained significant on the SPAN even after adjustment for paranoid or schizotypal dimensional scores and on the TMT-B after adjustment for paranoid dimensional scores. Moreover, in a second set of analyses comparing schizophrenia relatives to controls there were significant or trending differences in the degree of the relationship between avoidant symptoms and each of these neurocognitive measures even after adjustments for paranoid and schizotypal dimensional scores. The substantial correlation between avoidant and schizotypal symptoms suggests that these personality disorders are not independent. Avoidant and in some cases schizotypal dimensional scores are significant predictors of variability in these neurocognitive measures. In all analyses, higher levels of avoidant symptoms were associated with worse performance on the neurocognitive measures in relatives of schizophrenia probands. These results support the hypothesis that avoidant personality disorder may be a schizophrenia spectrum phenotype.

Background The search for treatments to remediate cognitive deficits and their functional outcome consequences remains a critical frontier in schizophrenia. Cognitive training and aerobic exercise both show promising moderate impact on cognition and everyday functioning. Aerobic exercise is hypothesized to increase brain-derived neurotrophic factor (BDNF) and thereby stimulate neurogenesis and synaptic plasticity, leading to increased learning capacity. Systematic cognitive training should take advantage of increased learning capacity and be more effective when combined with aerobic exercise. Methods In a recently completed randomized controlled trial, we examined the impact of a 6-month program of Cognitive Training & Exercise (CT&E) compared to Cognitive Training alone (CT) in 47 first-episode schizophrenia outpatients. All participants were provided the same Posit Science computerized cognitive training, four hours/week, using BrainHQ and SocialVille programs. The CT&E group also participated in total body circuit training exercises to enhance aerobic conditioning. The exercise intensity was in the 60–80% of aerobic capacity range, combining clinic and home-based exercise for a target of 150 minutes per week. Results Mixed model analyses demonstrate that the MATRICS Consensus Cognitive Battery Overall Composite improves significantly more by 3 months with CT&E than with CT alone (6.6 vs. 2.2 T-score points, p

Schizophrenia is associated with deficits in P50 suppression to the second stimulus in a pair, a process often conceptualized as a preattentive index of sensory gating. This study assessed the malleability of the deficit by determining whether early attentional control can influence P50 gating across different phases of schizophrenia. Participants included 28 patients in the recent-onset (n = 16) or chronic (n = 12) phase of illness and 28 healthy comparison subjects. During the standard paradigm, chronic schizophrenia patients exhibited impaired P50 suppression relative to healthy subjects, whereas recent-onset schizophrenia patients were intermediate. Directing voluntary attention toward the initial stimulus yielded substantial improvements in the P50 ratio; recent-onset schizophrenia patients achieved ratio scores comparable to those of healthy participants, whereas chronic patients also improved and could no longer be distinguished clearly from the healthy comparison sample. Directing attention toward the second stimulus enhanced P50 amplitude to the second stimulus across groups, possibly because activation of the inhibitory mechanism was overridden or circumvented by task demands. Thus, P50 suppression may be primarily preattentive under standard conditions, but manipulation of early attention can exert a modulatory influence on P50, indicating that the suppression deficit is malleable in schizophrenia without pharmacological agents.

Emotional and motivational dysfunction is fundamental to schizophrenia, and yet, the nature and scope of associated deficits are not well understood. This study assessed the integrity of emotional responding from the perspective of its underlying motivational systems during different phases of schizophrenia. Evaluative, somatic, and autonomic responses were measured during viewing of pictures categorized by emotional content, including threat, mutilation, contamination, illness, pollution, mild erotica, families, food, and nature. Participants were 13 patients at ultra high risk or prodromal for psychosis, 40 first-episode schizophrenia patients, 37 chronic schizophrenia patients, and 74 healthy comparison subjects. Irrespective of phase of illness, schizophrenia patients showed a robust and normal pattern of response across multiple systems, with differential engagement of the defensive and appetitive systems as a function of the motivational significance assigned to specific emotional contexts. Although the integrity of core motivational states also appeared to be intact in prodromal patients, a less consistent pattern of response was observed. As continuing efforts are made to identify emotional and motivational abnormalities in schizophrenia, identified deficits will likely be independent of a fundamental dysfunction in basic emotion and motivation response systems and involve integration with higher order processes.

Visual masking deficit in schizophrenia has been suggested to be a potential vulnerability marker for schizophrenia. An important characteristic of a vulnerability marker is stability over time, but relatively little is known about the longitudinal course of masking performance of schizophrenia patients. In this study, we examined the stability of visual masking performance in recent-onset schizophrenia patients over an 18-month period. We administered both forward and backward masking trials with multiple stimulus onset asynchronies for four masking conditions at three time points (baseline, 6-month, and 18-month). Recent-onset schizophrenia patients showed stable masking performance for both forward and backward conditions over a period of 18 months. Furthermore, the stable performance was observed across all four masking conditions. The findings of this study provide further support for the view that visual masking deficits reflect a possible vulnerability marker for schizophrenia.