First-episode Schizophrenia Spectrum Disorders Research Articles

T86. RELEVANCE OF CANNABIS USE AS A PREDICTOR OF CLINICAL OUTCOME IN FIRST-EPISODE SCHIZOPHRENIA SPECTRUM DISORDER PATIENTS OVER 24 MONTHS OF TREATMENT

BackgroundCannabis use is generally associated with an unfavourable course of illness in first-episode schizophrenia, including non-remission of psychopathology symptoms, higher rates of relapse and re-hospitalization, and poorer functioning. The aim of this study was to explore the influence of cannabis use on clinical and treatment outcomes in first-episode schizophrenia spectrum disorder patients over 24 months of assured antipsychotic treatment.MethodsThe present longitudinal study included 123 minimally treated or antipsychotic-naive first-episode patients assessed over 24 months of treatment with flupenthixol decanoate according to a standardized regimen. Time to relapse, rates of symptomatic and functional remission, as well as recovery were compared between cannabis users (n=41) and non-users (n=82) stratified based on a combination of self-report and urine toxicology results over the course of treatment. In addition, visit-wise changes in psychopathology severity and overall functioning were compared between these two study groups. We hypothesized that 1) ongoing cannabis use would present with more severe psychopathology and poorer overall level of functioning, and 2) rates of remission and recovery would be lower in cannabis users compared to their non-using counterparts.ResultsAt study entry, cannabis-using patients were younger, more likely to be male and to use methamphetamine, and scored lower in social and occupational functioning. Moreover, while cannabis users were more likely to relapse at any point over 24 months of treatment, cannabis non-users were more likely to achieve remission within the first six months, although this effect was not statistically significant. However, our most important finding was the interaction between cannabis use and time for total psychopathology as well as for the PANSS positive factor. While differences were not evident at either study entry or endpoint, cannabis users recovered at a slower rate than non-users.DiscussionThese results suggest a poorer treatment response in cannabis users compared to non-users in the context of assured adherence to antipsychotic medication. Therefore, regardless of the neurobiological impact of cannabis use in schizophrenia, the behaviour of substance use itself needs to be targeted as part of first-line treatment in order to improve the treatment outcomes of substance-using patients.

M122. DEPRESSION IN SCHIZOPHRENIA SPECTRUM DISORDERS: LONGITUDINAL COURSE AND THE RELATIONSHIP WITH OTHER CLINICAL PARAMETERS AND QUALITY OF LIFE

BackgroundThe relationship between schizophrenia and depression is complex. Longitudinal studies on the course of depression in first episode schizophrenia populations are scarce and there are conflicting results on the predictive value of some baseline measures.MethodsWe conducted an open label longitudinal cohort study which included 126 patients with first-episode schizophrenia spectrum disorders treated with long-acting antipsychotic medication over 24 months. Depression was assessed at three monthly intervals using the Calgary Depression Scale for Schizophrenia. Changes in depression over time were assessed using the linear mixed-effect models for continuous repeated measures. The relationship between depression and other clinical parameters was assessed with regression models.ResultsDepressive symptoms were most prominent at baseline and showed highly significant reductions in the first three months (p<0.0001). Majority of the patients with depression improved with antipsychotic medication alone and we found associations between depressive symptoms with insight and poorer quality of life, however only illness awareness (p=0.0035) was the only significant predictor on depression in our regression analysis. There were a few differences between patients who experienced depression during the acute phase of treatment and those in the post-acute phase.DiscussionOur findings suggest that depression in schizophrenia is common and generally responds well to treatment. The relationship between depression and insight has implications for further treatment considerations

Hippocampal subfield volumes and change in body mass over 12 months of treatment in first-episode schizophrenia spectrum disorders

In this study, we explored the relationship between baseline hippocampal subfield volumes and change in body mass over 12 months of treatment in 90 first-episode schizophrenia spectrum disorder patients (66 males, 24 females; mean age= 24.7 ± 6.8 years). Body mass index was assessed in patients at baseline, and at months 3, 6, 9 and 12. Hippocampal subfields of interest were assessed at baseline using a segmentation algorithm included in the FreeSurfer 6.0 software program. Linear regression revealed a significant interactive effect between sex and anterior hippocampus size as predictors of change in body mass over 12 months, adjusting for age, substance use, and treatment duration. In an exploratory post-hoc sub-analysis, partial correlations showed a significant association between weight gain and smaller CA1, CA3 and subiculum volumes in females, but not males, adjusting for age and substance use, with similar trends evident for the CA4 and presubiculum subfields. In conclusion, our findings suggest that smaller anterior hippocampal subfields at baseline are associated with the development of weight gain over the course of treatment in first-episode schizophrenia spectrum disorders in a sex-specific fashion. This may be related to the greater increase in body mass evident for female patients in our study.

Identification of a Serotonin 2A Receptor Subtype of Schizophrenia Spectrum Disorders With Pimavanserin: The Sub-Sero Proof-of-Concept Trial Protocol.

BackgroundAll current approved antipsychotic drugs against schizophrenia spectrum disorders share affinity for the dopamine receptor (D2R). However, up to one-third of these patients respond insufficiently, and in some cases, side-effects outweigh symptom reduction. Previous data have suggested that a subgroup of antipsychotic-naïve patients will respond to serotonin 2A receptor (2AR) blockade.AimsThis investigator-initiated, translational, proof-of-concept study has overall two aims; 1) To test the clinical effectiveness of monotherapy with the newly approved drug against Parkinson's disease psychosis, pimavanserin, in antipsychotic-free patients with first-episode schizophrenia spectrum disorders; 2) To characterize the neurobiological profile of responders to pimavaserin.Materials and EquipmentForty patients will be enrolled in this 6-week open label, one-armed trial with the selective serotonin 2AR antagonist (pimavanserin 34 mg/day). At baseline, patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR using the radioligand [¹¹C]Cimbi-36; structural magnetic resonance imaging (MRI); MR spectroscopy of cerebral glutamate levels and diffusion tensor imaging; cognitive and psychopathological examinations; electrocardiogram, and blood sampling for genetic- and metabolic analyses.Outcome MeasuresThe primary clinical endpoint will be reduction in the Positive and Negative Syndrome Scale (PANSS) positive score. Secondary clinical endpoints comprise multiple clinical ratings (positive and negative symptoms, depressive-, obsessive-compulsive symptoms, quality of life, social functioning, sexual functioning, and side-effects). PET, MRI, and cognitive parameters will be used for in-depth neuropsychiatric characterization of pimavanserin response.Anticipated ResultsClinically, we expect pimavanserin to reduce psychotic symptoms with similar effect as observed with conventional antipsychotics, for which we have comparable historical data. We expect pimavanserin to induce minimal side-effects. Neurobiologically, we expect psychotic symptom reduction to be most prominent in patients with low frontal serotonin 2AR binding potential at baseline. Potential pro-cognitive and brain structural effects of pimavanserin will be explored.PerspectivesSub-Sero will provide unique information about the role serotonin 2AR in antipsychotic-free, first-episode psychosis. If successful, Sub-Sero will aid identification of a “serotonergic subtype” of schizophrenia spectrum patients, thereby promoting development of precision medicine in clinical psychiatry.Clinical Trial RegistrationClinicalTrials, identifier NCT03994965.

The association between childhood trauma and treatment outcomes in schizophrenia spectrum disorders

Childhood trauma exposure has been associated with poorer treatment outcomes in schizophrenia. Most studies to date have been conducted in naturalistic settings in which the outcome may have been mediated by factors such as poor adherence and substance abuse. We compared the effects of high vs low childhood trauma exposure on the treatment response over 24 months in 78 patients with first-episode schizophrenia spectrum disorders who received standardised treatment with a long acting injectable antipsychotic. Compared to the low childhood trauma group (n = 37), the high childhood trauma group (n = 41) received higher doses of antipsychotic medication and were less likely to achieve remission. When age, sex and cannabis use were controlled for, patients with high levels of childhood trauma had a slower treatment response for positive and disorganized symptom domains, although differences did not differ significantly at 24 months. While there were no differences in functional outcomes, self-rated quality of life was the domain that most clearly differentiated the high and low childhood trauma groups. High childhood trauma exposure was associated with lower quality of life scores at baseline, a lesser degree of improvement with treatment, and lower quality of life scores at 24 months.

Ten-year trajectory and outcomes of negative symptoms of patients with first-episode schizophrenia spectrum disorders

This study explored the 10-year trajectories and outcomes of negative symptoms in patients with first-episode schizophrenia-spectrum disorder. Patients were from the historical control study comparing 10-year outcomes between standard care and early intervention services. A total of 298 patients were identified, 214 were successfully interviewed at 10-year follow-up for clinical and functional outcomes and 209 patients were included for final analyses. Information from clinical records were obtained systematically using standardized data entry forms. These information including negative symptoms, hospitalization and employment, monthly for year 1–3 and trimonthly for the year 4–10. Hierarchical cluster analysis was used to explore the 10-year negative symptom clusters. Demographics and early clinical characteristics related to the cluster memberships and different components of negative symptom at 10-year follow-up were further explored. The cluster analysis identified three longitudinal clusters of negative symptoms and 15% of patients were in the relapsed group. There was no difference in cluster membership between the intervention groups. Male gender and duration of hospitalizations in year four were found to be significant determinants of relapse negative symptoms. Lower education level, higher year-one negative symptom score and more months of unemployment during the first 3 years predicted overall negative symptoms at 10-year follow-up. Male gender was found to be a predictor only for avolition and anhedonia and duration of untreated psychosis only predicted anhedonia. These results highlighted the heterogeneity of longitudinal outcomes and the importance of personalized interventions.

A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort).

Background:Antipsychotic-induced weight gain is a common and debilitating side effect of antipsychotics. Although genome-wide association studies of antipsychotic-induced weight gain have been performed, few genome-wide loci have been discovered. Moreover, these genome-wide association studies have included a wide variety of antipsychotic compounds.Aims:We aim to gain more insight in the genomic loci affecting antipsychotic-induced weight gain. Given the variable pharmacological properties of antipsychotics, we hypothesized that targeting a single antipsychotic compound would provide new clues about genomic loci affecting antipsychotic-induced weight gain.Methods:All subjects included for this genome-wide association study (n=339) were first-episode schizophrenia spectrum disorder patients treated with amisulpride and were minimally medicated (defined as antipsychotic use <2 weeks in the previous year and/or <6 weeks lifetime). Weight gain was defined as the increase in body mass index from before until approximately 1 month after amisulpride treatment.Results:Our genome-wide association analyses for antipsychotic-induced weight gain yielded one genome-wide significant hit (rs78310016; β=1.05; p=3.66 × 10−08; n=206) in a locus not previously associated with antipsychotic-induced weight gain or body mass index. Minor allele carriers had an odds ratio of 3.98 (p=1.0 × 10−03) for clinically meaningful antipsychotic-induced weight gain (⩾7% of baseline weight). In silico analysis elucidated a chromatin interaction with 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. In an attempt to replicate single-nucleotide polymorphisms previously associated with antipsychotic-induced weight gain, we found none were associated with amisulpride-induced weight gain.Conclusion:Our findings suggest the involvement of rs78310016 and possibly 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 in antipsychotic-induced weight gain. In line with the unique binding profile of this atypical antipsychotic, our findings furthermore hint that biological mechanisms underlying amisulpride-induced weight gain differ from antipsychotic-induced weight gain by other atypical antipsychotics.

Neighborhood-level predictors of age at onset and duration of untreated psychosis in first-episode psychotic disorders

ObjectiveRecent years have witnessed growing interest in the role of the social environment in the development and outcomes of schizophrenia. We investigated whether neighborhood characteristics are associated with two important prognostic factors in early-course psychosis, age at onset of psychosis (AOP) and duration of untreated psychosis (DUP). MethodsData were collected from patients admitted to the hospital for first-episode schizophrenia-spectrum disorder. We collected data on perceived neighborhood disorder during childhood/adolescence and extracted data on 13 neighborhood characteristics from the American Community Survey based upon individual addresses. Four neighborhood-level factors were derived from factor analysis. Multiple logistic regression analyses assessed the association between specific neighborhood characteristics and the two prognostic factors (earlier AOP and longer DUP) in early-course psychosis. Results143 participants had valid addresses geo-coded. Neighborhood-level residential instability was associated with an earlier AOP (OR = 1.760; p = 0.022) even after controlling for known risk factors (OR = 2.026; p = 0.020) and also after controlling for individual-level residential instability (OR = 1.917; p = 0.037). The general socioeconomic status neighborhood factor (OR = 1.119; p = 0.019) and perceived neighborhood disorder (OR = 1.075; p = 0.005) were associated with a longer DUP. But only perceived neighborhood disorder (OR = 1.146; p = 0.011) remained significant, and general socioeconomic status was close to significant (OR = 1.215; p = 0.062), after controlling for individual-level predictors and socioeconomic status. ConclusionsThis study found evidence that neighborhood-level characteristics (in this case, residential instability) may be associated with earlier AOP, and perceptions of neighborhood disorder are associated with a longer treatment delay. Socioenvironmental factors should be more consistently considered going forward in research on early psychotic disorders.

Early recovery in the first 24 months of treatment in first-episode schizophrenia-spectrum disorders

Studies assessing the treatment outcomes in first-episode schizophrenia have reported mixed results. While symptom improvement is frequently robust, when other domains are considered outcomes are generally poorer. We explored response trajectories, rates and predictors of recovery in the domains of core psychopathology, clinician-rated social and occupational functioning and patient-rated quality of life over 24 months of treatment in 98 patients with first-episode schizophrenia spectrum disorders who were treated with a long-acting antipsychotic medication. There was robust improvement in core psychopathology (effect size d = 3.36) and functionality (d = 1.78), with most improvement occurring within the first six months of treatment. In contrast, improvement in subjective quality of life was less marked (d = 0.37) and slower, only reaching significance after 12 months of treatment. Symptom remission was achieved by 70% of patients and over half met our criteria for functional remission and good quality of life. However, only 29% met the full criteria for recovery. Patients who met the recovery criteria had better premorbid adjustment, were less likely to be of mixed ethnicity and substance use emerged as the only modifiable predictor of recovery. Only 9% of our sample achieved both functional remission and good quality of life despite not being in symptom remission. We found high rates of symptom remission, functional remission and good quality of life in patients, although relatively few achieved recovery by meeting all three of the outcome criteria. Symptom remission is not a necessary prerequisite for functional remission and good quality of life, although few non-remitters achieve other recovery criteria.

Childhood trauma and hippocampal subfield volumes in first-episode schizophrenia and healthy controls

Childhood trauma and schizophrenia are both associated with neuroanatomical abnormalities in the hippocampus, a stress-sensitive structure vulnerable to developmental insults. However, few studies have evaluated the effects of childhood trauma exposure on hippocampal morphometry in minimally treated first-episode schizophrenia patients. Here we aim to investigate the associations of childhood trauma with hippocampal subfield volumes in a cohort of antipsychotic-naive or minimally treated first-episode schizophrenia spectrum disorder patients and matched controls. 79 patients with first-episode schizophrenia spectrum disorder and 82 matched controls completed the childhood trauma questionnaire and underwent MRI assessment. Hippocampal subfields were reconstructed using FreeSurfer 6.0. We considered inter-correlations between the various subfields, by entering them as dependent variables into a multivariate analysis of co-variance (MANCOVA), modeling for interactions between diagnosis, childhood trauma total score and gender while controlling for substance use, scanner sequence and age. MANCOVA revealed a significant interaction between sex, childhood trauma total scores and diagnosis across hippocampal sub-regions (p = 0.012). Bonferroni corrected post-hoc analysis revealed a significant sex*diagnosis*childhood trauma score interaction for the hippocampal fissure (F(1,161) = 9.485,p = .002). Hippocampal fissure size showed a positive relationship with CA structures as well as whole hippocampal size in the larger sample. Findings from the present study suggest that childhood trauma exposure exerts illness-specific effects on hippocampal structures in female patients with first-episode schizophrenia, consistent with increased stress sensitivity in this group.

Depressive psychopathology in first-episode schizophrenia spectrum disorders: a systematic review, meta-analysis and meta-regression.

Despite knowing for many decades that depressive psychopathology is common in first-episode schizophrenia spectrum disorders (FES), there is limited knowledge regarding the extent and nature of such psychopathology (degree of comorbidity, caseness, severity) and its demographic, clinical, functional and treatment correlates. This study aimed to determine the pooled prevalence of depressive disorder and caseness, and the pooled mean severity of depressive symptoms, as well as the demographic, illness, functional and treatment correlates of depressive psychopathology in FES. This systematic review, meta-analysis and meta-regression was prospectively registered (CRD42018084856) and conducted in accordance with PRISMA and MOOSE guidelines. Forty studies comprising 4041 participants were included. The pooled prevalence of depressive disorder and caseness was 26.0% (seven samples, N = 855, 95% CI 22.1-30.3) and 43.9% (11 samples, N = 1312, 95% CI 30.3-58.4), respectively. The pooled mean percentage of maximum depressive symptom severity was 25.1 (38 samples, N = 3180, 95% CI 21.49-28.68). Correlates of depressive psychopathology were also found. At least one-quarter of individuals with FES will experience, and therefore require treatment for, a full-threshold depressive disorder. Nearly half will experience levels of depressive symptoms that are severe enough to warrant diagnostic investigation and therefore clinical intervention - regardless of whether they actually fulfil diagnostic criteria for a depressive disorder. Depressive psychopathology is prominent in FES, manifesting not only as superimposed comorbidity, but also as an inextricable symptom domain.

Ten-year employment patterns of patients with first-episode schizophrenia-spectrum disorders: comparison of early intervention and standard care services.

Little is known about long-term employment outcomes for patients with first-episode schizophrenia-spectrum (FES) disorders who received early intervention services. We compared the 10-year employment trajectory of patients with FES who received early intervention services with those who received standard care. Factors differentiating the employment trajectories were explored. Patients with FES (N = 145) who received early intervention services in Hong Kong between 1 July 2001 and 30 June 2002 were matched with those who entered standard care 1 year previously. We used hierarchical clustering analysis to explore the 10-year employment clusters for both groups. We used the mixed model test to compare cluster memberships and piecewise regression analysis to compare the employment trajectories of the two groups. There were significantly more patients who received the early intervention service in the good employment cluster (early intervention: N = 98 [67.6%]; standard care: N = 76 [52.4%]; P = 0.009). In the poor employment cluster, there was a significant difference in the longitudinal pattern between early intervention and standard care for years 1-5 (P < 0.0001). The number of relapses during the first 3 years, months of full-time employment during the first year and years of education were significant in differentiating the clusters of the early intervention group. Results suggest there was an overall long-term benefit of early intervention services on employment. However, the benefit was not sustained for all patients. Personalisation of the duration of the early intervention service with a focus on relapse prevention and early vocational reintegration should be considered for service enhancement.

Cognitive Profiles and Functional Connectivity in First-Episode Schizophrenia Spectrum Disorders - Linking Behavioral and Neuronal Data.

The character of cognitive deficit in schizophrenia is not clear due to the heterogeneity in research results. In heterogeneous conditions, the cluster solution allows the classification of individuals based on profiles. Our aim was to examine the cognitive profiles of first-episode schizophrenia spectrum disorder (FES) subjects based on cluster analysis, and to correlate these profiles with clinical variables and resting state brain connectivity, as measured with magnetic resonance imaging. A total of 67 FES subjects were assessed with a neuropsychological test battery and on clinical variables. The results of the cognitive domains were cluster analyzed. In addition, functional connectivity was calculated using ROI-to-ROI analysis with four groups: Three groups were defined based on the cluster analysis of cognitive performance and a control group with a normal cognitive performance. The connectivity was compared between the patient clusters and controls. We found different cognitive profiles based on three clusters: Cluster 1: decline in the attention, working memory/flexibility, and verbal memory domains. Cluster 2: decline in the verbal memory domain and above average performance in the attention domain. Cluster 3: generalized and severe deficit in all of the cognitive domains. FES diagnoses were distributed among all of the clusters. Cluster comparisons in neural connectivity also showed differences between the groups. Cluster 1 showed both hyperconnectivity between the cerebellum and precentral gyrus, the salience network (SN) (insula cortex), and fronto-parietal network (FPN) as well as between the PreCG and SN (insula cortex) and hypoconnectivity between the default mode network (DMN) and seeds of SN [insula and supramarginal gyrus (SMG)]; Cluster 2 showed hyperconnectivity between the DMN and cerebellum, SN (insula) and precentral gyrus, and FPN and IFG; Cluster 3 showed hypoconnectivity between the DMN and SN (insula) and SN (SMG) and pallidum. The cluster solution confirms the prevalence of a cognitive decline with different patterns of cognitive performance, and different levels of severity in FES. Moreover, separate behavioral cognitive subsets can be linked to patterns of brain functional connectivity.

Relationship between changes in metabolic syndrome constituent components over 12 months of treatment and cognitive performance in first-episode schizophrenia

Few studies have investigated the longitudinal effects of treatment-emergent metabolic syndrome changes on cognitive performance in first-episode psychosis. The aim of the present study was to determine the associations between changes in metabolic syndrome constituent component over 12months of treatment and end-point cognitive performance in schizophrenia spectrum disorders. This single site-cohort study included 72 minimally treated or antipsychotic-naïve first-episode patients. Cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Our primary objective of interest was the relationship between metabolic syndrome constituent component changes over 12months of treatment and end-point cognitive performance. Secondary objectives included investigating whether this relationship was affected by age, sex, antipsychotic dose, treatment duration and substance use. Weight gain predicted better overall cognition (p = 0.02) at end-point, adjusting for age, sex, substance use, baseline cognitive score and BMI, modal antipsychotic dose and treatment duration. Weight loss (p = 0.04) and substance use (p = 0.01) were both associated with poorer working memory performance at end-point. Low baseline BMI showed differential effects on end-point working memory performance in substance users (unfavorable) compared to non-users (favorable) (p < 0.05). In conclusion, weight gain over the course of antipsychotic treatment is associated with better overall cognitive performance and the working memory domain in first-episode schizophrenia spectrum disorder patients. In contrast, low baseline BMI may represent an unfavorable marker in substance users, who demonstrated weight loss compared to non-users.

Weight gain and metabolic change as predictors of symptom improvement in first-episode schizophrenia spectrum disorder patients treated over 12 months

BackgroundTreatment-emergent weight gain is associated with antipsychotic efficacy in schizophrenia patients treated with clozapine and olanzapine. However, few studies have investigated this relationship in first-episode patients treated with other antipsychotics, in particular those with a lower obesogenic potential.AimTo investigate the relationships between weight gain and associated metabolic changes with psychopathology improvement in relation to age, sex, ethnicity, substance use, treatment duration and antipsychotic dose in first-episode schizophrenia spectrum disorder patients. MethodsThis single site cohort study included 106 minimally treated or antipsychotic-naive patients treated with flupenthixol decanoate over 12 months. Psychopathology was evaluated using the Positive and Negative Syndrome Scale (PANSS) and BMI, fasting blood lipids and glucose were assessed at regular intervals. Linear regression models were constructed to determine the effects of socio-demographic, clinical and metabolic factors as predictors of change in total PANSS score and factor-derived domains. ResultsBMI change scores were inversely correlated with change in PANSS total (R = −0.25; p = 0.011), positive (R = −0.23; p = 0.019), depressive anxiety (R = −0.21; p = 0.031) and disorganized symptoms (R = −0.32; p < 0.001). Linear regression analysis showed that increased BMI and treatment duration both predicted improvement in global psychopathology and disorganized symptoms independent of age, sex, ethnicity, substance use, co-medication with antidepressants and/or anticholinergics, as well as the dose and duration of antipsychotic exposure. ConclusionsOur findings suggest that the relationship between treatment-emergent weight gain and psychopathology improvement is not limited to patients treated with antipsychotics most associated with weight gain, and is not confounded by treatment duration and dose.

Incidence and predictors of acute akathisia in severely ill patients with first-episode schizophrenia treated with aripiprazole or risperidone: secondary analysis of an observational study.

In the antipsychotic treatment of schizophrenia with little medication history, especially in drug-naïve cases, predictors of side effects are important. However, predictors of antipsychotic-induced akathisia remain unclear. This study aimed to investigate the incidence and predictors of acute akathisia in severely ill patients with first-episode schizophrenia spectrum disorders (FES). This is a secondary analysis of our retrospective observational study. Data were obtained from 129 consecutive patients with FES involuntarily hospitalized in a tertiary psychiatric public hospital and treated with aripiprazole or risperidone. The primary outcome was the presence of acute akathisia during the first 1month. A Cox proportional hazard model was used to examine significant predictors of the onset of akathisia. Acute akathisia was diagnosed in 54 patients (42%). Neither antipsychotics (aripiprazole or risperidone), duration of untreated psychosis, iron deficiency, sex, age nor baseline symptomatic severity was identified as an independent predictor of akathisia. Rapid risperidone initiation significantly increased the onset of akathisia (adjusted hazard ratio [HR], 6.47; 95%; 95% confidence interval [CI], 1.94-21.65; p = 0.002), but rapid aripiprazole initiation did not (adjusted HR, 1.08; 95% CI, 0.50-2.31; p = 0.84). A significant interaction was found between rapid antipsychotic initiation and the risk of akathisia with aripiprazole versus risperidone (p = 0.027). Severely ill patients with FES initiating aripiprazole or risperidone could have a high risk for akathisia. Rapid risperidone initiation should be avoided because of the risk for akathisia, and careful monitoring of akathisia may be necessary for all patients initiating aripiprazole.

Latent Iron Deficiency as a Marker of Negative Symptoms in Patients with First-Episode Schizophrenia Spectrum Disorder.

Iron deficiency may alter dopaminergic transmission in the brain. This study investigated whether iron metabolism is associated with negative symptoms in patients with first-episode psychosis. The study enrolled 121 patients with first-episode schizophrenia spectrum disorder, whose duration of treatment was 2 months or less. Negative symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and Clinician-Rated Dimensions of Psychosis Symptom Severity (Dimensional) scale of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Prominent negative symptoms were defined as moderate or severe negative symptoms on the Dimensional scale of the DSM-5. Iron deficiency was defined as a serum ferritin ≤ 20 ng/mL. Patients with iron deficiency were significantly more likely to have prominent negative symptoms (45.2 vs. 22.2%; p = 0.014) and a higher PANSS negative symptoms score (p = 0.046) than those with normal ferritin levels. Patients with prominent negative symptoms had significantly lower ferritin levels (p = 0.025). The significance of these results remained after controlling for the duration of illness and other confounding variables. Our finding of an independent association between iron deficiency and negative symptoms in patients at the very early stage of illness implies that iron dysregulation has an effect on negative symptoms in patients with schizophrenia. The possibility of therapeutic intervention with iron should be further investigated.

Changes in insight over the first 24 months of treatment in schizophrenia spectrum disorders

BackgroundWhile insight in schizophrenia improves with treatment, significant impairments often persist. The degree of persistence is not well characterised. AimsWe assessed patient and clinician-rated changes in insight in acutely ill, minimally treated first-episode schizophrenia spectrum disorder patients over 24 months of standardised treatment with a depot antipsychotic. MethodThis single arm open label longitudinal cohort study included 105 participants with first-episode schizophrenia, schizophreniform or schizoaffective disorder. Insight was assessed at months 0, 6, 12 and 24 using the patient-rated Birchwood Insight Scale (BIS) and clinician-rated global insight item of the Positive and Negative Syndrome Scale (PANSS). Changes in insight over time were assessed using linear mixed-effect models for continuous repeated measures. Relationships between insight and psychopathology, functionality, cognition and quality of life were assessed with regression models. ResultsThere was significant improvement over time for the PANSS insight item (p < 0.0001). However, the only significant improvement for the BIS was with the Need for Treatment subscale (p = 0.01). There were no significant improvements noted for the Symptom Attribution (p = 0.7) and Illness Awareness (p = 0.2) subscales, as well as the BIS Total score (p = 0.6). Apart from depressive symptoms at baseline, there were no significant predictors of patient-rated insight. ConclusionsClinicians should note that, even when treatment is assured and response is favourable, fundamental impairments in patient-rated insight persist.

Comparison of cognitive functions between first-episode schizophrenia patients, their unaffected siblings and individuals at clinical high-risk for psychosis

Cognitive impairment is a core feature of schizophrenia and has been observed in both familial (FHR) and clinical high-risk (CHR) samples. Nonetheless, there is a paucity of research directly contrasting cognitive profiles in these two high-risk states and first-episode schizophrenia. This study aimed to compare cognitive functions in patients with first-episode schizophrenia-spectrum disorder (FES), their unaffected siblings (FHR), CHR individuals and healthy controls. A standardized battery of cognitive assessments was administered to 69 FES patients, 71 help-seeking CHR individuals without family history of psychotic disorder, 50 FHR participants and 68 controls. FES and CHR participants were recruited from territory-wide early intervention service for psychosis in Hong Kong. CHR status was ascertained using Comprehensive Assessment of At-Risk Mental State. Among four groups, FES patients displayed the largest global cognitive impairment and had medium-to-large deficits across all cognitive tests relative to controls. CHR and FHR participants significantly underperformed in most cognitive tests than controls. Among various cognitive tests, digit symbol coding demonstrated the greatest magnitude of impairment in FES and CHR groups compared with controls. No significant difference between two high-risk groups was observed in global cognition and all individual cognitive tests except digit symbol coding which showed greater deficits in CHR than in FHR participants. Clinical and familial risk groups experienced largely comparable cognitive impairment that was intermediate between FES and controls. Digit symbol coding may have the greatest discriminant capacity in distinguishing FES and CHR from healthy controls, and between two high-risk samples.

Ten-year follow up of patients with first-episode schizophrenia spectrum disorder from an early intervention service: Predictors of clinical remission and functional recovery

The long-term recovery rate of patients with schizophrenia-spectrum disorders has been persistently low despite the implementation of early intervention (EI) services internationally. It is, therefore, important to identify the modifiable factors during the early stage of the illness that predict long-term remission and recovery. The aim of this study is to explore the predictive value of the early stage clinical factors on the clinical remission and functional recovery at 10-year follow-up of patients with schizophrenia-spectrum disorders who received a 2-year EI service. Patients who received the EI service throughout the region of Hong Kong between 1st July 2001 and 30th June 2002 and with a diagnosis of schizophrenia-spectrum disorder were identified from the centralized hospital database (Clinical Management system, CMS). Semi-structured clinical interview was conducted at 10-year follow-up with a successful interview rate of 74.3% (n = 107). Clinical data was systematically retrieved each month for the first three years from the CMS and written clinical records using a standardized data entry form based on operationalized definitions. Results found shorter duration of untreated psychosis (DUP) predicted long-term clinical remission; higher educational level and shorter period of unemployment during the initial three years of the illness predicted functional recovery. Higher educational level, longer period of employment and planned medication discontinuation during the initial three years predicted complete recovery. The current study demonstrates the long-term impact of DUP and suggests improvement of employment during the early stage of illness could be a potential target for further improvement of the service.