Duration of the psychosis prodrome and its relationship to duration of untreated psychosis across all 12 DSM-IV psychotic diagnoses: Evidence for a trans-diagnostic process associated with resilience.

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.

Mixed-effects models reveal prediction of long-term outcome by duration of untreated psychosis (DUP) and illness (DUI) varies with quantile gradation but is invariant with time across 7 years in the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS).

While associations between duration of untreated psychosis (DUP) and outcome have been widely reported, how long these relationships endure following initiation of treatment and how such associations are distributed across the range of DUP values encountered remain unclear. This study investigates prospectively (i) whether prediction of outcome by DUP and by duration of untreated illness (DUI) diminishes, remains stable or increases in the long term after initiating treatment, and (ii) whether these relationships for differing indices of outcome vary across gradations of DUP-DUI values. Sixty-two subjects were evaluated prospectively for DUP, DUI, premorbid features, psychopathology and quality of life at both first episode psychosis (FEP) and at 7-year follow-up; functionality and service engagement were assessed at follow-up. Data were analysed using mixed-effects models for DUP and DUI quantiles. Prediction by longer DUP and DUI of greater psychopathology, particularly negative symptoms, and lower quality of life remained stable between FEP and follow-up; longer DUP and DUI also predicted lower functionality and service engagement at follow-up. While most associations were confined to the longest DUP-DUI quartile, those between DUP-DUI and negative symptoms and quality of life were distributed in a graded manner across DUP-DUI quartiles. Material confounding with premorbid features, including lead-time bias, was not supported. These findings suggest that benefits of reducing DUP-DUI may endure for at least a decade beyond FEP and that even modest reductions in DUP-DUI may confer particular advantage in the more debilitating and intransigent domain of impairment.

20-Year Prospective, Sequential Follow-Up Study of Heterogeneity in Associations of Duration of Untreated Psychosis With Symptoms, Functioning, and Quality of Life Following First-Episode Psychosis.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A snapshot of ABO, RH, and JK blood group systems in modern Ireland.

OBJECTIVES: This study aimed to capture a snapshot of the Irish population to determine if there had been any changes in the ABO and RH blood group system (BGS) distribution from previous Irish studies and to establish an Irish JK BGS frequency, providing real time donor information to the Irish Blood Transfusion Service (IBTS). BACKGROUND: Ireland's population is constantly increasing and becoming more diverse, this has potential implications for the IBTS to provide blood with extended phenotypes for certain cohorts of patients. MATERIALS AND METHODS: All first time blood donors had relevant testing performed in the Automated Donor Grouping (ADG) laboratory using the Beckman Coulter PK7300 analyzer with appropriate antisera by validated methods. All pertinent information and test results were categorized and analyzed. RESULTS: The number of donors tested was 3427. ABO phenotype: A: 29.82%, B: 12.02%, O: 54.95% and A,B: 3.21%. RHD: 82.26%. RHCE: R1R1: 17.62%, R2R2: 2.89%, R1R2: 13.95%, R1r: 33.35%, R2r: 13.07%, Ror: 1.25%, R1RZ: 0.06%, R2RZ: 0.06%, r'r: 0.55%, r″r: 0.53%, rr: 16.66%. Kidd phenotype: Jk(a + b+): 49.63%, Jk(a-b+): 23.34%, Jk(a + b-): 27.02%. CONCLUSION: The observed frequencies for the relevant BGSs remained relatively unchanged to the prevalence values expected; however, statistically significant differences between the 2015 study and some of the previous studies were found for ABO distribution. 14.24% of the first time donors were born outside Ireland and statistically significant differences (P-value < 0.001) were noted for aspects of the ABO and Rh phenotype distribution for the Irish born donors (BiI) vs those born outside Ireland (BoI).

Systematic comparison of duration of untreated illness versus duration of untreated psychosis in relation to psychopathology and dysfunction in the Cavan-Monaghan first episode psychosis study (CAMFEPS).

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.

Systematic epidemiological and clinical comparisons across all 12 DSM-IV psychotic diagnoses in the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS).

BACKGROUND: Research on psychotic illness is loosening emphasis on diagnostic stringency in favour of including a more dimensionally based conceptualization of psychopathology and pathobiology. However, to clarify these notions requires investigation of the full scope of psychotic diagnoses. METHODS: The Cavan-Monaghan First Episode Psychosis Study ascertained cases of first episode psychosis across all 12 DSM-IV psychotic diagnoses via all routes to care: public, private or forensic; home-based, outpatient or inpatient. There was no arbitrary upper age cut-off and minimal impact of factors associated with variations in social milieu, ethnicity or urbanicity. Cases were evaluated epidemiologically and assessed for psychopathology, neuropsychology, neurology, antecedent factors, insight and quality of life. RESULTS: Among 432 cases, the annual incidence of any DSM-IV psychotic diagnosis was 34.1/100 000 of population and encompassed functional psychotic diagnoses, substance-induced psychopathology and psychopathology due to general medical conditions, through to psychotic illness that defied contemporary diagnostic algorithms. These 12 DSM-IV diagnostic categories, including psychotic disorder not otherwise specified, showed clinical profiles that were consistently more similar than distinct. CONCLUSIONS: There are considerable similarities and overlaps across a broad range of diagnostic categories in the absence of robust discontinuities between them. Thus, psychotic illness may be of such continuity that it cannot be fully captured by operational diagnostic algorithms that, at least in part, assume discontinuities. This may reflect the impact of diverse factors each of which acts on one or more overlapping components of a common, dysfunctional neuronal network implicated in the pathobiology of psychotic illness.

The iHOPE-20 study: mortality in first episode psychosis-a 20-year follow-up of the Dublin first episode cohort.

PURPOSE: Increased mortality rates have been found in those with a diagnosis of psychosis; studies suggest a shortened life expectancy of up to 20 years less than that of the general population. This study aimed to investigate the mortality of a first episode psychosis cohort at 20-year follow-up, compare it to that of the general Irish population, and explore whether the mortality gap has changed over time. METHODS: 171 individuals diagnosed with a first episode psychosis identified between 1995 and 1999 in a community mental health service were traced. Mortality was established by matching death certificates to deceased cohort members (using name, age at date of death, and address at date of death). Date of first presentation to service was used as date of entry point and date of death or end of follow-up as the end point. RESULTS: Of the 171 cases there were 20 deaths during follow-up. Nine deaths were attributed to natural causes; 7 to unnatural causes; and 4 were unknown. Comparing standardised mortality rates at 20-year follow-up to those at 12 year showed a reduction in rates over time. CONCLUSION: Findings suggest that the mortality gap in people with schizophrenia and other psychoses remains high, especially in young males.

The iHOPE-20 study: Relationships between and prospective predictors of remission, clinical recovery, personal recovery and resilience 20 years on from a first episode psychosis.

OBJECTIVE: Knowledge of outcome in psychotic illness is limited by the paucity of very long-term epidemiologically representative studies of incidence first episode psychosis (FEP) cohorts that measure and compare outcomes reflecting modern clinical practice, mental health policy and research agendas. Our study aimed to address this gap. METHOD: iHOPE-20 is a prospective 20-year follow-up study of a FEP incidence cohort (N = 171) conducted between 2014 and 2017 in Ireland. Data from previous studies and medical records were used to recruit cohort members. We assessed remission, clinical recovery, personal recovery and resilience at 20 years; explored the relationships between these outcomes and examined the predictive value of baseline characteristics in determining them. RESULTS: At follow-up, 20 out of 171 cohort members (11.70%) were deceased. We assessed 80 out of 151 alive cohort members (53% recruitment rate); 65% were in remission; 35.2% were in Full Functional Recovery and 53.7% confirmed they were fully recovered according to their personal definition of recovery. A complex array of relationships between outcomes was found. Outcomes were better for people who had a short duration of untreated psychosis, displayed higher premorbid social adjustment (between the ages of 5-11) and at baseline, were older, not living alone, in full-time employment, given a non-affective diagnosis, and had lower Global Assessment of Functioning scores. CONCLUSION: Among participants, full remission of psychotic symptoms and personally defined recovery was not just possible but likely in the very long term. However, attaining positive functional outcomes and building resilience in FEP remain key challenges for mental health services.

Disagreement between service-users and clinicians assessment of physical health during early psychosis.

AIMS: Physical illnesses account for the majority of excess deaths following psychosis; access to care and treatment is inequitable and schizophrenia has now been dubbed the life-shortening disease. We compared service-users and clinician's perspectives of their physical health assuming that one of the fundamental issues in prompting screening and treatment is the view that health is poor. METHODS: Data comprising sample characteristics, diagnosis, symptoms, insight, antecedents to psychosis and physical health perspectives were obtained prospectively as part of a larger epidemiological study of first-episode psychosis. We compared physical health perspectives between service-users and clinicians and examined clinical correlates. RESULTS: Contrary to our expectations, we found that service-users reported poorer physical health over time than clinicians did. CONCLUSION: Reconciling service-users and clinician's views of physical health may be an important step towards collaborative care and improving access to better quality healthcare for serious mental illness.

Functional outcome and service engagement in major depressive disorder with psychotic features: comparisons with schizophrenia, schizoaffective disorder and bipolar disorder in a 6-year follow-up of the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS).

OBJECTIVE: While long-term outcome following a first psychotic episode is well studied in schizophrenia (SZ), schizoaffective disorder (SA), and bipolar disorder (BD), major depressive disorder with psychotic features (MDDP) has received less investigation. This study compares MDDP with SZ, SA, and BD at 6-year follow-up. METHODS: At 6 years after a first psychotic episode, follow-up data on psychopathology, functioning, quality of life, and service engagement were obtained for 27 cases of MDDP in comparison to 60 SZ, 27 SA, and 35 BD. RESULTS: Positive psychotic symptoms were less prominent in MDDP and BD than in SZ and SA. Negative symptoms, impaired functioning, and reduction in objectively determined quality of life were less prominent in MDDP and BD, intermediate in SA and most prominent in SZ. However, subjectively determined quality of life was indistinguishable across diagnoses. Service engagement was highest for MDDP, intermediate for SA and BD, and lowest for SZ. CONCLUSIONS: At 6-year follow-up, these diagnoses are characterized by quantitative rather than qualitative differences in psychopathology, functionality, quality of life, and service engagement, with considerable overlap between them. These findings suggest that MDDP should join SZ, SA, and BD in a milieu of psychosis that transcends arbitrary boundaries.

Understanding the relationship between duration of untreated psychosis and outcomes: A statistical perspective.

AIM: Although the relationships between duration of untreated psychosis (DUP) and outcomes are often assumed to be linear, few studies have explored the functional form of these relationships. The aim of this study is to demonstrate the potential of recent advances in curve fitting approaches (splines) to explore the form of the relationship between DUP and global assessment of functioning (GAF). METHODS: Curve fitting approaches were used in models to predict change in GAF at long-term follow-up using DUP for a sample of 83 individuals with schizophrenia. RESULTS: The form of the relationship between DUP and GAF was non-linear. Accounting for non-linearity increased the percentage of variance in GAF explained by the model, resulting in better prediction and understanding of the relationship. CONCLUSION: The relationship between DUP and outcomes may be complex and model fit may be improved by accounting for the form of the relationship. This should be routinely assessed and new statistical approaches for non-linear relationships exploited, if appropriate.

Clozapine Use in a Cohort of First-Episode Psychosis.

PURPOSE/BACKGROUND: For approximately one third of individuals treated for psychosis or schizophrenia, antipsychotic medications will have little or no therapeutic benefit. Clozapine remains the sole medication approved for treatment-resistant schizophrenia, and studies have demonstrated its superior efficacy in reducing psychotic symptoms. METHODS/PROCEDURES: Data were collected from the medical records of people who originally presented with a first-episode psychosis between 1995 and 1999 (N = 171). Data were obtained from first presentation up to December 31, 2013 or until the patient was discharged or transferred. Information on service use and physical health was gathered using a data collection template designed specifically for this audit. FINDINGS/RESULTS: Twenty-eight (16.3%) of the cohort were prescribed clozapine. Data were available for 24 individuals. Of this clozapine subsample, the mean age at baseline was 23.11 (SD = 4.58); 82.14% (n = 23) were male; and 82.14% (n = 23) had a baseline diagnosis of schizophrenia. The mean time to first trial of clozapine was 6.7 years. The mean number of antipsychotics prescribed before clozapine trial was 4.85. After the initiation of clozapine, the mean number of hospital admissions reduced from 6.04 per year to 0.88 per year. IMPLICATIONS/CONCLUSIONS: Nearly 1 in 5 of the original cohort was considered to have a suboptimal response to trials of antipsychotic medication. The use of clozapine for treatment-resistant schizophrenia is underutilized, and better understanding of the barriers to prescribing clozapine is necessary given the implications for patient's quality of life and hospital admission rates. Physical health data further emphasizes the importance of physical health monitoring in this vulnerable population.

Subjective and objective quality of life at first presentation with psychosis.

AIM: Quality of life (QOL) in first-episode psychosis (FEP) is impaired when compared to non-clinical controls and several clinical factors including symptoms and untreated psychosis have been linked with poorer QOL. Measurement methods are varied, however, resulting in inconsistent findings and there is a need to simultaneously combine subjective and objective measures of QOL. METHODS: We examined both subjective (n = 128) and objective QOL (n = 178) in a catchment area cohort of individuals with FEP (n = 222) to determine correspondence between patient satisfaction and clinician-rated functional domains. We also examined the contribution of sociodemographic and clinical characteristics to both subjective and objective QOL. RESULTS: There were complex relationships between subjective and objective QOL domains in that patient's assessments of health status (psychological well-being, symptoms/outlook, physical health) were not correlated with clinicians but there were strong correlations between social functioning domains (occupation, social relations, financial status and activities of daily living) assessed by patients and clinicians. Longer duration of untreated psychosis, being treated as an inpatient, higher positive symptoms and poorer social functioning in client-rated QOL domains predicted poorer objective QOL. CONCLUSION: We found that both subjective and objective assessments of QOL displayed a degree of clinical utility demonstrated by relationships between clinical factors and both QOL perspectives. Moreover, the lack of association between patient characteristics and QOL shows some potential malleability of QOL outcomes through intervention as there were several clinical factors linked with both subjective and objective QOL.

Socioeconomic status at birth and risk for first episode psychosis in rural Ireland: Eliminating the features of urbanicity in the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS).

BACKGROUND: There is a paucity of research on the relationship between social environment at birth and risk for psychosis in rural settings. This study examined the relationship between individual- and neighbourhood-level socioeconomic indicators proximal to the time of birth and risk for a first psychotic episode in a rural context using a prospective dataset of unusual epidemiological completeness. METHODS: A matched case-control design was used. 186 cases were identified from the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS) and 679 age- and sex-matched controls from the same rural setting were identified and analysed for relationships with individual and neighbourhood-level socioeconomic indicators at the level of Electoral Divisions. RESULTS: While neither the distribution nor the ordinal scale of parental social class differed between cases and controls, logistic regression revealed both parental social class III and increasing level of rurality to be associated (p≤0.05) with reduced risk for affective psychosis. There was a prominent relationship (p<0.001) between lower parental social class and older age at first presentation [mean age at first presentation for all psychoses: social class I, 22.8; social class VI, 44.3]. CONCLUSIONS: These findings indicate modest effects of individual- and neighbourhood-level socioeconomic indicators and risk for psychosis by place at birth within a rural environment. Thus, these factors are not confined to large urban settings and apply across the urban-rural continuum. The substantive finding in relation to age at first presentation may indicate that a gradient of socioeconomic position is influential on delay in presentation to mental health services.

The relationship between mental health literacy regarding schizophrenia and psychiatric stigma in the Republic of Ireland.

BACKGROUND: There is an unclear relationship between mental health literacy (MHL) and psychiatric stigma. MHL is associated with both positive and negative attitudes to mental illness. To our knowledge, no published peer reviewed study has examined this relationship in the Republic of Ireland. AIMS: This study was conducted to assess MHL regarding schizophrenia and the degree of psychiatric stigma displayed by the general public in the Republic of Ireland. METHOD: A face-to-face in-home omnibus survey was conducted with a representative sample of residents of the Republic of Ireland. Participants (N = 1001) were presented with a vignette depicting schizophrenia and were asked questions to determine their ability to recognise the condition and to ascertain their attitudes towards schizophrenia and mental illness. RESULTS: Among the participants, 34.1% correctly identified schizophrenia. Higher age, higher socioeconomic status, and an urban geographic location predicted identification. Those who did not correctly identify schizophrenia were significantly more optimistic about recovery and perceived people with schizophrenia as less dangerous. However, only the relationship with perceived dangerousness was considered robust. CONCLUSIONS: Participants with higher MHL displayed more negative attitudes to mental illness. Findings have implications internationally for MHL and anti-stigma campaigns.

Glasgow Antipsychotic Side-effects Scale for Clozapine - Development and validation of a clozapine-specific side-effects scale.

OBJECTIVE: The authors developed and validated a clozapine-specific side-effects scale capable of eliciting the subjectively unpleasant side-effects of clozapine. METHODS: Questions from the original Glasgow Antipsychotic Side-effects Scale (GASS) were compared to a list of the most commonly reported clozapine side-effects and those with a significant subjective burden were included in the GASS for Clozapine (GASS-C). The original authors of the GASS and a group of mental health professionals from the UK and Ireland were enlisted to comment on the questions in the GASS-C based on their clinical experience. 110 clozapine outpatients from two sites completed the GASS-C, the original GASS and a repeat GASS-C. Statistical analyses were performed using SPSS for Windows version 19. RESULTS: The GASS-C was shown to have construct validity, in that Spearman's correlation coefficient was 0.816 (p<0.001) with the original GASS, whilst Cohen's kappa coefficient was >0.77 (p<0.001) for one question and >0.81 (p<0.001) for remaining relevant questions. GASS-C was also shown to have strong test-retest reliability, in that Cronbach's alpha coefficient was >0.907 (p<0.001), whilst Cohen's kappa coefficient was >0.81 (p<0.001) for 12 questions and >0.61 (p<0.001) for the remaining four questions. CONCLUSION: The GASS-C is a valid and reliable clinical tool to enable a systematic assessment of the subjectively unpleasant side-effects of clozapine. Future research should focus on how the scale can be utilised as a clinical tool to improve real-world outcomes such as adherence to clozapine therapy and quality of life.

The factor structure and clinical utility of formal thought disorder in first episode psychosis.

BACKGROUND: Formal thought disorder (FTD) is a core feature of psychosis, however there are gaps in our knowledge about its prevalence and factor structure. We had two aims: first, to establish the factor structure of FTD; second, to explore the clinical utility of dimensions of FTD in order to further the understanding of its nosology. METHODS: A cross-validation study was undertaken to establish the factor structure of FTD in first episode psychosis (FEP). The relative utility of FTD categories vs. dimensions across diagnostic categories was investigated. RESULTS: The prevalence of clinically significant FTD in this FEP sample was 21%, although 41% showed evidence of disorganised speech, 20% displayed verbosity and 24% displayed impoverished speech. A 3-factor model was identified as the best fit for FTD, with disorganisation, poverty and verbosity dimensions (GFI=0.99, RMR=0.07). These dimensions of FTD accurately distinguished affective from non-affective diagnostic categories. A categorical approach to FTD assessment was useful in identifying markers of clinical acuteness, as identified by short duration of untreated psychosis (OR=2.94, P<0.01) and inpatient treatment status (OR=3.98, P<0.01). CONCLUSION: FTD is moderately prevalent and multi-dimensional in FEP. Employing both a dimensional and categorical assessment of FTD gives valuable clinical information, however there may be a need to revise our conceptualisation of the nosology of FTD. The prognostic value of FTD, as well as its neural basis, requires elucidation.