While duration of the psychosis prodrome (DPP) attracts attention in relation to the developmental trajectory of psychotic illness and service models, fundamental issues endure in the context of dimensional-spectrum models of psychosis. Among 205 epidemiologically representative subjects in the Cavan-Monaghan First Episode Psychosis Study, DPP was systematically quantified and compared, for the first time, across all 12 DSM-IV psychotic diagnoses. DPP was also compared with duration of untreated psychosis (DUP) and each was then analysed in relation to premorbid features across three age ranges: <12, 12-15 and 16-18 years. For each diagnosis, medians for both DPP and DUP were shorter than means, indicating common right-skewed distributions. Rank orders for both DPP and DUP were longest for schizophrenia, intermediate for other schizophrenia-spectrum psychoses, psychotic depression and psychotic disorder not otherwise specified, and shortest for brief psychotic disorder, bipolar disorder and substance-induced psychotic disorder, though with overlapping right-skewed distributions. DPP was longer than DUP for all diagnoses except substance-induced psychotic disorder. Across functional psychotic diagnoses, longer DPP was predicted by higher premorbid intelligence and better premorbid adjustment during age 16-18 years. These findings indicate that, trans-diagnostically, DPP and DUP share right-skewed continuities, in accordance with a dimensional-spectrum model of psychotic illness, and may reflect a unitary process that has been dichotomized at a subjective threshold along its trajectory. Better premorbid functioning during age 16-18 years appears to confer resilience by delaying progression to overt psychotic symptoms and may constitute a particular target period for psychosocial interventions.

The impact of the duration of untreated psychosis on the outcomes of schizophrenia has been extensively studied. However, there is a notable gap in the current understanding of the relationship between the duration of untreated prodromal symptoms (DUPrS) and the development of psychosis in individuals at clinical high risk (CHR). A sample of 704 individuals with CHR was identified through a structured interview, of who 145 (20.6 %) converted to psychosis (CHR-C) during the 3-year follow-up. The DUPrS was defined as the period between the onset of the first attenuated psychotic positive symptom and the commencement of professional assistance at mental health services. Quantile regression was applied for quantile levels between 0.1 and 0.9, and adjusted for age, sex, and education.The overall sample had a mean DUPrS of 7.1 months. No significant differences were observed in the DUPrS between the CHR-C and non-converter (CHR-NC) groups. Quantile regression analysis highlighted variations in the effects of the DUPrS on clinical variables across the different quantiles. We observed a positive association between DUPrS rank and positive symptoms below the 0.3 quantile, while a positive association between DUPrS rank and negative symptoms above the 0.3 quantile (except 0.7 and 0.9 quantile). A longer DUPrS (> 3 months) was associated with younger age (odds ratio [OR] = 0.948, p = 0.003), a higher proportion of women (OR = 1.474, p = 0.003), higher baseline global function (OR = 1.044, p = 0.003), lower previous global function (OR = 0.921, p < 0.001), and higher negative symptoms (OR = 1.061, p = 0.001). This study sheds light on the pivotal role of DUPrS as a potential intermediary factor in the complex pathway of psychosis.

UNASSIGNED: Self-stigma impedes recovery process and is associated with poorer clinical and functional outcomes in people with psychotic disorders. However, there is limited research specifically examining self-stigma in the early stage of illness, and mixed findings were observed regarding factors associated with increased self-stigma. We aimed to investigate the rate and correlates of self-stigma in a cohort of adult patients with early psychosis using a comprehensive array of clinical, treatment and other illness-related variables.
UNASSIGNED: A total of 101 Chinese adult early psychosis patients aged 26-55 years who had received three-year psychiatric treatment for first psychotic episode in Hong Kong and completed self-stigma assessment were included for the current investigation. A broad range of assessments encompassing socio-demographics, premorbid adjustment, onset and illness profiles, symptom severity, psychosocial functioning, treatment characteristics and medication side-effects were conducted.
UNASSIGNED: Twenty-eight (27.7%) patients had moderate-to-high levels of self-stigma. Univariate linear regression analyses showed that age at study entry, sex, educational level, age at psychosis onset, duration of untreated psychosis (DUP), insight level, global psychosocial functioning, and the use of second-generation antipsychotic were related to self-stigma levels. Final multivariable regression model revealed that female sex, younger age at entry, longer DUP and better insight were independently associated with higher levels of self-stigma.
UNASSIGNED: More than one-fourth of early psychosis patients experienced significant self-stigma, highlighting an unmet need for early detection and intervention of self-stigma in the initial years of illness. Further investigation is warranted to clarify trajectories and predictors of self-stigma in the early illness course.

Determining the extent to which relationships between duration of untreated psychosis (DUP) and outcome endure longitudinally across the lifetime course of psychotic illness requires prospective, systematic studies of epidemiologically representative incidence cohorts across decades. Transience, persistence, or heterogeneity in associations between DUP and distinct outcome domains are yet to be investigated over such time frames.
Prospective, sequential follow-up studies of an epidemiologically representative first-episode psychosis incidence cohort in Ireland were conducted at 6 months and 4, 8, 12, and 20 years (N=171). Linear mixed-model analyses were applied to determine whether prospective associations of DUP with symptoms, functioning, and quality of life were consistent or varied across psychotic illness trajectory over a 20-year period. Evaluations included time, DUP quartile, and DUP quartile-by-time interaction effects.
Prospective, sequential follow-ups showed positive and negative symptoms, function, and quality of life to exhibit distinct trajectories of improvement in relation to shorter DUP. Despite heterogeneity in course and relationship to premorbid features, associations between shorter DUP and greater improvement were still evident 20 years after the first psychotic episode. Across the long-term course of psychotic illness, trajectories of association between shorter DUP and better outcome differed between domains of psychopathology, functionality, and quality of life. Nevertheless, such associations with shorter DUP were sustained for at least 20 years.
These profiles indicate that while associations between DUP and long-term outcome can vary according to the domain of outcome, they are sustained across decades in a manner that could not be fully accounted for in terms of premorbid features or lead-time bias.

Aberrations in intracortical myelination are increasingly being considered as a cardinal feature in the pathophysiology of schizophrenia. We investigated the network-level distribution of intracortical myelination across various cortex depths. We enrolled 126 healthy subjects and 106 first-episode drug-naïve schizophrenia patients. We used T1w/T2w ratio as a proxy of intracortical myelination, parcellated cortex into several equivolumetric surfaces based on cortical depths and mapped T1w/T2w ratios to each surface. Non-negative matrix factorization was used to generate depth-dependent structural covariance networks (dSCNs) of intracortical myelination from 2 healthy controls datasets-one from our study and another from 100-unrelated dataset of the Human Connectome Project. For patient versus control comparisons, partial least squares approach was used; we also related myelination to clinical features of schizophrenia. We found that dSCNs were highly reproducible in 2 independent samples. Network-level myelination was reduced in prefrontal and cingulate cortex and increased in perisylvian cortex in schizophrenia. The abnormal network-level myelination had a canonical correlation with symptom burden in schizophrenia. Moreover, myelination of prefrontal cortex correlated with duration of untreated psychosis. In conclusion, we offer a feasible and sensitive framework to study depth-dependent myelination and its relationship with clinical features.

This study systematically compared duration of untreated illness (DUI) with duration of untreated psychosis (DUP) in prediction of impairment at first-episode psychosis and investigated the extent to which these relationships are influenced by premorbid features. The Cavan-Monaghan First Episode Psychosis Study ascertained cases of first-episode psychosis in rural Ireland via all routes to care with limited variations in socioeconomic milieu. Cases were evaluated for DUI and DUP and assessed clinically for psychopathology, neuropsychology, neurology, insight and quality of life, together with premorbid features. Analyses then determined prediction of clinical assessments by DUI versus DUP. The study population consisted of 163 cases of first episode psychosis, among which 74 had a schizophrenia spectrum disorder. Shorter DUI but not DUP predicted less severe positive and general symptoms, while shorter DUP and particularly DUI predicted less severe negative symptoms; neither shorter DUP nor shorter DUI predicted less severe cognitive impairment or fewer neurological soft signs; shorter DUP and DUI predicted increased quality of life; shorter DUI but not DUP predicted greater insight. Only prediction of quality of life was weakened by consideration of premorbid features. Results were generally similar across the two diagnostic groupings. The present findings systematically delineate associations with DUI versus DUP across domains of impairment in first episode psychosis. They suggest that DUI may reflect a more insidious process than DUP and that reduction in DUI may be associated with more consistent and broader diminutions in impairment than for DUP.

OBJECTIVE: We analyzed the brain structure of schizophrenia patients from multiple perspectives to explore the relationship between the duration of untreated psychosis (DUP) and clinical outcomes.
METHODS: For 85 patients and 86 controls, clinical symptoms and cognitive function were evaluated, magnetic resonance imaging (MRI) and free surfer analysis were used to extract the cortical indicator, such as brain cortex thickness, surface area, volume, and so on. The patients were divided into four subgroups according to the boundary of March, June and two year due to the distribution and median of DUP. Finally multi-group comparison and correlation analysis for above indicators were analysed.
RESULTS: DUP was associated with the surface area of the left insula, parsorbitalis, right hippocampus, superior frontal gyrus, frontal pole, and temporal pole; DUP mainly influenced the cortical thickness of left posterior cingulate gyrus, postcentral gyrus, right lateral occipital cortex, parsopercularis, medial orbitofrontal cortex, and the bilateral precentral gyrus. For cortical volume, DUP significantly affected left postcentral gyrus, right precuneus, lateral occipital cortex, parsopercularis, lingual gyrus, superior temporal gyrus, bilateral cuneus, pericalcarine cortex, precentral gyrus,superior parietal lobule, and insula.The first three months after onset is a critical period for the deterioration of cortical morphology and clinical function.
CONCLUSIONS: DUP in first-episode schizophrenia is associated with cortical morphological changes of temporal lobe, precentral, orbitofrontal cortex and the majority of medial regions of occipital lobe, it is very important to conduct early intervention for patients.

To examine the association between referral source and duration of untreated psychosis (DUP) and explore determinants of referral source; when adjusting for pathways to care, positive and negative symptoms, diagnosis and socio-demographic characteristics.
A total of 140 subjects with first episode psychosis (FEP) were enrolled from a pilot early intervention service for psychosis in Northern Malawi between June 2009 and September 2012. Logistic regression analyses were used to quantify the associations between variables of interest.
Age ranged between 18 and 65 at assessment, with median, 33. Median DUP was 12.5 months. First contact did not independently determine DUP. Long DUP (>6 months) was associated with referral from community based volunteer (CBV) or traditional healer (TH), a unit increase in severity of negative symptoms and having schizophrenia, which was also associated with referral from CBV or TH. Additionally, being unemployed was associated with referral from CBV or TH. However, a unit increase in the number of times religious advice (RA) was sought, GP was contacted and severity of positive symptoms was associated with referral by GP.
Mental health awareness is justified for this population and collaboration with THs in identifying and treating patients with psychosis may help reduce treatment delays. Access to mental health services ought to improve, particularly for the unemployed group. Future studies should consider adjusting for referral source when ascertaining first contact source as a predictor of DUP.

Somatic symptoms and motor abnormalities have been consistently reported as typical symptoms of schizophrenia, but evidence linking impaired functional connectivity among the primary sensory-motor network and its associations to schizophrenia is largely lacking. The present study aims to examine abnormal functional connectivity in the sensory-motor network in schizophrenia and its associations with the duration of untreated psychosis and medication treatment effects. We hypothesize that patients with schizophrenia suffer from disrupted functional connectivity between the sensory-motor subnetworks. The degree of impairment in the connectivity could reflect the duration of untreated psychosis and predict outcomes of medication treatment.
At baseline, resting-state functional magnetic resonance imaging data were acquired from 60 first-episode patients with drug-naïve schizophrenia (36 were female) and 60 matching normal control subjects (31 were female). After 2 months, 23 patients who received medication treatment and 32 normal control subjects were rescanned. Functional connectivity among subnetworks in the sensory-motor system was compared between the groups and correlated with the duration of untreated psychosis and the treatment outcome.
Patients with schizophrenia showed significantly disrupted functional connectivity in the sensory-motor network. The degree of impairment reflected the duration of untreated psychosis and motor-related symptoms. It further predicted the improvement of positive scores after medication.
These findings suggest that functional connectivity in the sensory-motor network could indicate the severity of neural impairment in schizophrenia, and it deserves more attention in the search for neuroimaging markers for evaluating neural impairment and prognosis.

Our previous study has found that a long duration of untreated prodromal symptoms (DUPrS) does not increase the conversion risk to psychosis in individuals with attenuated psychosis syndrome (APS). However, whether a long DUPrS will lead to other poor outcomes remains unknown. The purpose of this study was to analyse the association between the DUPrS and outcomes (symptomatic and functional recovery) in APS population. A post hoc analysis was performed in 391 individuals with APS as identified by the structured interview. APS subjects had follow-up interviews every 6 months for 2 years following diagnosis. Poor functional outcome was defined as a Global Assessment of Functioning (GAF) score less than 60 at the time of follow-up. Poor symptomatic outcome was defined as at least one of the positive symptoms rated scores of 3 or higher. A post hoc analysis was performed in 391 individuals with APS as identified by the structured interview. APS subjects had follow-up interviews every 6 months for 2 years following diagnosis. Poor functional outcome was defined as a Global Assessment of Functioning (GAF) score less than 60 at the time of follow-up. Poor symptomatic outcome was defined as at least one of the positive symptoms rated scores of 3 or higher. Of total 391 individuals, 334 were followed up for 2 years to assess clinical outcome, 82 (24.6%) had shown conversion to psychosis, 79 (23.7%) met the criteria of poor functioning outcome, and 145 (43.4%) met the criteria of poor symptomatic outcome. A significant correlation between GAF scores and DUPrS was observed in the non-converter group, but not in the converters. Individuals with APS who had a longer DUPrS were correlated with poorer functional outcome. However, it was not correlated with poorer symptomatic outcome. While a longer DUPrS was not related to poor symptomatic outcome, it was significantly related to poor functional outcome. Our findings highlight the importance of reducing DUPrS to decrease future functional impairment in populations at risk for psychosis.