The Ultra-high Risk for Psychosis groups: Evidence to maintain the status quo.

McHugh, M.J1., McGorry, P.D1., Yuen, H.P1., Hickie, I2., Thompson, A3., de Haan, L4.,Mossaheb, N.5, Smesny, S6., Lin, A7., Markulev, C1.,Schloegelhofer, M5,8., Wood, S.J9,10., Nieman, D11,Hartmann, J.A1., Nordentoft, N12., Schaefer, M1., Amminger, G.P 1, Yung, A13*, Nelson, B1*

1. Orygen, The National Centre for Excellence in Youth Mental Health, 35 Poplar Rd, Parkville, VIC, Australia;

2. Brain and Mind Research Institute, University of Sydney, Sydney, Australia;3. Division of Mental Health and Wellbeing, The University of Warwick, Coventry, UK.4. Department of Psychiatry, Early Psychosis Section, Academic Medical Centre,

University of Amsterdam, The Netherlands;5. Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna,

Austria;6. Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany;7. Telethon Kids Institute, The University of Western Australia, Australia;8. Department of Child and Adolescent Psychiatry, Medical University Vienna, Vienna,

Austria.9. School of Psychology, University of Birmingham, Birmingham, UK;10. Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne

& Melbourne Health, Melbourne, Australia;11. Department of Psychiatry, Academic Medical Center, University of Amsterdam,

Amsterdam, the Netherlands;12. Mental Health Centre Copenhagen, Mental health Services Capital Region of Denmark,

Denmark;13. Psychiatric Centre Copenhagen, University of Copenhagen, Denmark.14. Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester,

UK.

Corresponding Author:

Meredith J. McHughOrygen, The National Centre of Excellence in Youth Mental Health35 Poplar RdParkville, VIC, 3052, AustraliaEmail: meredith.mchugh@orygen.org.auPh: +61793422800

Word count:Abstract: 229Text body: 2798

Abstract

1

Individuals are considered Ultra-High-Risk (UHR) for psychosis if they meet a set of

standardised criteria including presumed genetic vulnerability (Trait), or a recent history of

Attenuated Psychotic Symptoms (APS) or Brief Limited Intermittent Psychotic Symptoms

(BLIPS). Recent calls to revise these criteria have arisen from evidence that Trait, APS and

BLIPS groups may transition to psychosis at different rates. Concurrently, it has become clear

that the UHR status confers clinical risk beyond transition to psychosis. Specifically, most UHR

individuals will not develop psychosis, but will experience high rates of non-psychotic disorders,

persistent APS and poor long-term functional outcomes. Rather than focus on transition, the

present study investigated whether UHR groups differ in their broader clinical risk profile by

examining baseline clinical characteristics and long-term outcomes other than transition to

psychosis. Four UHR groups were defined: Trait-only, APS-only, Trait+APS, and any BLIPS.

Participants ( N = 702) were recruited upon entry to early intervention services and followed-up

over a period of up to 13 years (Mean=4.53, SD=3.84). The groups evidenced similar symptom

severity (SANS for negative symptoms, BPRS for positive and depression/anxiety symptoms)

and psychosocial functioning (SOFAS, GAF, QLS) at baseline and follow-up as well as similar

prevalence of non-psychotic disorders at follow-up. Our findings demonstrate that UHR groups

evidence a similar clinical risk profile when we expand this beyond transition to psychosis, and

consequently support maintaining the existing UHR criteria.

2

It has been two decades since Yung and colleagues (Yung and McGorry, 1996a) introduced a set

of standardised criteria to identify individuals at Ultra-High-Risk (UHR) of developing a

psychotic disorder (also known as the At Risk Mental State or ‘prodromal’ phase of psychosis).

Since this time, the UHR paradigm has provided a window into risk factors and aetiological

mechanisms involved in psychosis onset and an opportunity to trial preventive interventions (van

der Gaag et al., 2013). To be considered UHR, help-seeking individuals must be in the age range

of highest risk for psychosis (late adolescence, early adulthood) and meet one or more of the

following 3 criteria: 1) Attenuated Psychotic Symptoms (APS): sub-threshold positive psychotic

symptoms during the past 12 months; 2) Brief Limited Intermittent Psychotic Symptoms

(BLIPS): frank psychotic symptoms for less than one week which resolve spontaneously; 3)

Genetic vulnerability (Trait) – meet criteria for Schizotypal Personality Disorder or have a first-

degree relative with a psychotic disorder. Each risk criteria must also be associated with a

deterioration in functioning or chronic low functioning1.

Over the years, evidence has pointed to variability between groups defined by these UHR criteria

in relation to risk of transitioning to a psychotic disorder (Fusar-Poli et al., 2015; Nelson et al.,

2013, 2011) . A history of BLIPS (regardless of APS or Trait risk) has consistently been linked to

the highest risk of transitioning to a psychotic disorder (Fusar-Poli et al., 2015; Nelson et al.,

2013, 2011) . Presumed genetic vulnerability (Trait) with no history of APS or BLIPS (Trait-

only) confers the lowest transition risk (Fusar-Poli et al., 2015; Nelson et al., 2011) . An early

study found that the combination of genetic vulnerability and APS (Trait+APS) was strongly

predictive of transition to psychosis by twelve months (Yung et al., 2004) . However, more recent

evidence suggests similar risk trajectories for Trait+APS individuals and individuals who meet

1 The requirement for deterioration in functioning has changed over the years (see Table 1 for a summary of the changes).

3

APS criteria alone (APS-only) (Fusar-Poli et al., 2015; Nelson et al., 2011) .

Evidence of variability in transition risk has prompted some researchers to challenge the current

composition of the UHR criteria. In a guidance paper for the European Psychiatric Association,

Schultz-Lutter and colleagues recommended that having a first-degree relative with a psychotic

illness should not be considered a clinical marker of risk for psychosis even in the presence of

functional decline (Schultze-lutter et al., 2015) . Others have proposed that BLIPS should be

treated as a separate clinical entity based on both higher transition risk and diagnostic overlap

with DSM/ICD brief psychotic disorders (Fusar-Poli et al., 2015) .

Concurrently, it has become increasingly evident that clinical implications of UHR status extend

beyond risk of transition to psychosis. Most individuals who meet UHR criteria will not develop

a psychotic disorder (Nelson et al., 2013; Simon et al., 2011) but will experience persistent

attenuated psychotic symptoms (de Wit et al., 2014a; Simon et al., 2011) , poor psychosocial

functioning (Rutigliano et al., 2016a) and high rates of non-psychotic disorders (de Wit et al.,

2014b; Lin et al., 2015; Rutigliano et al., 2016b) . Such findings have driven a reframing of UHR

as a clinical state signifying pluripotent, transdiagnostic risk and the need for clinical care, rather

than simply a marker of psychosis risk (McGorry et al., 2006; McGorry and Nelson, 2016; Yung

et al., 2012) .

In the current study we investigated possible differences between the UHR groups in clinical risk

other than transition to psychosis. Specifically, we examined baseline clinical characteristics

known to contribute to poor outcomes in UHR populations, including symptom severity (Fusar-

Poli et al., 2013; Nelson et al., 2013; Seidman et al., 2010) , psychosocial functioning (Nelson et

al., 2013; Seidman et al., 2010) , duration of symptoms prior to first contact with clinical services

4

(Nelson et al., 2013) and the year that individuals entered clinical services (Nelson et al., 2013;

Simon et al., 2014; Yung et al., 2007) . We also examined long-term non-transition outcomes

including symptom severity, psychosocial functioning and the prevalence of non-psychotic

disorders . A large cohort ( N = 702) of UHR individuals were recruited at entry to treatment and

re-assessed up to thirteen years later. For consistency with previous studies (Fusar-Poli et al.,

2015; Nelson et al., 2011) , we defined four combinations of UHR risk group: Trait-only, APS-

only, Trait+APS, and any BLIPS (regardless of Trait or APS criteria). If the UHR groups defined

here engender truly distinct psychopathological risk profiles, we would expect group differences

to emerge in baseline characteristics and long-term non-transition outcomes.

2. Methods

2.1 Participants and Setting

The present sample (N = 702) were recruited between 1995 and 2013, across 10 research sites in

Australia (Melbourne, Sydney), the Netherlands (Amsterdam), Germany (Jena), Switzerland

(Basel, Zurich), Austria (Vienna), Denmark (Copenhagen), Singapore, and Hong Kong (Pok Fu

Lam). Each site has an established early psychosis clinical service that conducts research with

UHR clients. From 1995 to 2006 participants were recruited for UHR research studies at the

Melbourne site only (N = 398). These included three intervention (Berger et al., 2012; McGorry

et al., 2002; Yung et al., 2011) and four cohort studies (Phillips et al., 2009; Thompson et al.,

2007; Yung et al., 2003, 1996). This is the same group as previously reported in the PACE 400

long-term follow-up study (Nelson et al., 2013), excluding 18 participants for whom UHR risk

group could not be determined. The sample (recruited to baseline studies between 1995 and

2006) were followed up between 2007-2008 (for full details see Nelson et al, 2013). The

5

remaining 304 participants were recruited from 2010 to 2013 across the 10 research sites listed

as part of a large multi-site intervention study (Neurapro; Markulev et al., 2015; McGorry et al.,

2017).

Participants were required to meet criteria for at least one of the three UHR groups (APS, BLIPS

or Trait risk). Criteria used to assess each are summarized in Table 1. As illustrated, over the

years there have been changes in the requirement for functional deterioration across the three risk

groups as well as in measures used to assess risk. Exclusion criteria were known history of a

psychotic episode (treated or untreated); known organic cause of symptoms (e.g., epilepsy); or a

lifetime antipsychotic dose equivalent to or greater than 15mg of haloperidol.

2.2 Measures

2.2.1 UHR Status. Measures and methods used to assess UHR status from 1995 to 2013 are

outlined in Table 1.

2.2.2 Symptoms and psychosocial functioning. The Brief Psychiatric Rating Scale (BPRS;

Overall and Gorhum, 1962) was administered to assess positive symptoms (BPRS Psychosis

subscale) and depression/anxiety (BPRS Depression and Anxiety subscale). Negative symptoms

were assessed with the Schedule for the Assessment of Negative Symptoms (SANS; Andreasen,

1982). Psychosocial functioning was assessed with the Global Assessment of Functioning (GAF;

American Psychiatric Association, 1994), Social and Occupational Functioning Assessment

Scale (SOFAS; American Psychiatric Association, 1994) and Quality of Life Scale (QLS;

Heinrichs et al., 1984). SOFAS scores are reported for follow-up only as this measure was not

administered at baseline prior to 2010. QLS and GAF were available at baseline and follow-up,

but only for members of the PACE 400 subcohort.

6

2.2.3 Non-psychotic disorders. The presence of Axis I non-psychotic disorders at follow-up was

determined with the Structured Clinical Interview for DSM-IV disorders (SCID-IV; First et al.,

2002).

2.3 Procedures

Participants completed baseline assessments at entry to the clinical service. Follow-up interviews

were conducted in 91.1% (n=277) of the Neurapro cohort and 71.1% (n=283) of the PACE 400

cohort. For PACE 400 participants, where face-to-face interviews were not possible assessments

were conducted over the phone. Full details of follow-up procedures for the PACE 400 cohort

are reported elsewhere (Nelson et al., 2013). Mean time to follow-up interviews was 11.35

months (range 1.05 to 21.48 months) and 78.62 months (range 5.15 – 156.59 months) for the

Neurapro and PACE 400 cohorts respectively.

2.4 Data analysis

Group differences at baseline and follow-up for BPRS, SANS, GAF and QLS were examined

using general linear models with group (4 levels: Trait-only, Trait+APS, APS-only and any

BLIPS) as a fixed factor. Where baseline group differences in sample characteristics were

present (Table 2), models were run with and without including these characteristics as covariates.

Alpha was set at p = .01 at each time point (baseline, follow-up) for primary outcome variables

to adjust for multiple comparisons. Group differences in the prevalence of non-psychotic

disorders were examined using a logistic regression model with the presence or absence of non-

psychotic disorders as a binary outcome variable. We defined three levels of baseline year (1995-

1999, 2000-2006 and 2010-2013) to capture changes in transition rate over the years (Nelson et

7

al., 2013), as well as changes in methods and measures for assessing UHR status over time (see

Table 1).

3. Results

3.1 Sample characteristics

Table 2 presents baseline demographic and clinical characteristics for each of the four risk

groups. As illustrated, the APS-only group were, on average, younger at baseline than Trait-only

(p<.001) and Trait +APS (p = .018) and any BLIPS (p = .026) individuals. Groups also differed

in terms of year recruited into the study (baseline year: 1995-1999, 2000-2006, 2010-2013)

largely driven by a decline in any BLIPS and an increase in APS-only in later years (see Figure 1

and Table 2). Consequently, years to follow-up interview also differed between the groups. APS-

only individuals had the shortest time to follow-up relative to all other groups (all ps<.001). Any

BLIPS had a longer time to follow-up than Trait-only (p = .033) and Trait+APS (p = .003).

Across the sample, baseline year was highly correlated with time to follow-up interview, r(558)

= -.92, p<.001, due to the fact that participants from earlier baseline years necessarily had a

longer time to follow up.

3.2 Do the UHR risk groups vary in symptom severity and psychosocial functioning at baseline?

Figure 2, Table 3 and Table S1 summarise mean symptom severity (BPRS and SANS) and

functioning (GAF and QLS) at baseline and follow-up across the four UHR risk groups, and

present significant group differences where these emerged. Group effects emerged for the BPRS

Psychotic subscale at baseline, F(3, 685) = 20.07, p<.001), reflecting significantly lower scores

at baseline in Trait-only individuals relative to all other groups (ps< .001). Groups also varied at

baseline in GAF scores, F(3, 393) = 6.50, p <.001, with any BLIPS individuals showing higher

8

GAF scores at baseline compared to all other groups (all ps < .002). No baseline group

differences were observed for BPRS Anxiety and Depression (p=.523), SANS (p=.087) or QLS

(p = .320). This pattern of results remained the same after controlling for age at baseline.

3.3 Do the UHR risk groups vary on long-term non-transition outcomes?

The UHR risk groups did not differ at follow-up on either symptom severity (SANS, BPRS

Psychotic, BPRS Anxiety and Depression: all ps > .190; see Table S1 and Figure 2) or

psychosocial functioning (GAF, QLS, SOFS: all ps >. 293; see Table S1, Table 3 and Figure 2).

Additionally, the proportion of individuals meeting criteria for at least one Axis 1 non-psychotic

disorder at follow-up did not differ between the groups (p = .477, see Table 3). Results of long-

term outcomes analyses remained the same after controlling for age at baseline and time to

follow-up interview.

4. Discussion

In recent years the criteria that define UHR groups have been called into question due to

differences observed between these groups in transition risk (Fusar-Poli et al., 2015; Schultze-

lutter et al., 2015). At the same time, it has become evident that as a clinical entity UHR status

reflects more than simply a marker of psychosis risk, and may be more aptly considered a

transdiagnostic risk state signifying the need for clinical care (van Os and Guloksuz, 2017). The

present study thus aimed to compare UHR groups (APS-only, Trait-only, Trait+APS, any

BLIPS) in their broader psychopathological profile by exploring clinical characteristics at entry

into treatment as well as long-term outcomes other than onset of psychosis.

As expected (based on the definition of UHR criteria) Trait-only individuals reported less severe

positive psychotic symptoms at baseline. No other group differences in symptom severity at

9

baseline were observed. Notably, while Trait-only individuals presented with less severe baseline

positive symptoms at baseline they did not differ from the other groups in their negative

symptom severity. Zubin’s (Zubin, 1985) Vulnerability model considers negative symptoms,

such as social withdrawal and blunted affect, to be enduring characteristics that precede

psychosis onset and reflect underlying vulnerability to developing a psychotic disorder, which is

consistent with this finding. Alternatively, heightened negative symptoms could be secondary to

elevated depression and anxiety in this group (Lincoln et al., 2016). We found no evidence of

group differences in long-term non-transition outcomes, including symptom severity (BPRS,

SANS), psychosocial functioning (GAF, QLS, SOFAS) and prevalence of non-psychotic

disorders at follow-up. Our findings conflict with a recent study reporting that BLIPS individuals

were at lower risk of developing non-psychotic disorders than individuals with APS (Fusar-Poli

et al., 2017).

Interestingly, in the present sample we observed a significant shift in the proportion of UHR

groups over the years sampled (1995-2013). Most notably, we see an increasing proportion of

APS individuals in later years and a declining proportion of any BLIPS individuals. Earlier

detection of at-risk individuals may, at least in part, explain this effect. If we assume that a

history of APS can precede the occurrence of BLIPS (Shah et al., 2017; Yung and McGorry,

1996b), then it is possible that earlier detection (prior to BLIP onset) is resulting in a greater

proportion of individuals presenting with APS and a drop in individuals presenting with BLIPS

at treatment entry (Nelson et al., 2016). That our APS-only group were younger at treatment

entry is consistent with this conjecture. In conjunction, increased public awareness of early

intervention services and UHR criteria, as well as clinic screening processes (Wiltink et al.,

10

2015), could be resulting in a disproportionate increase in APS-only individuals being referred to

clinical services.

It is also important to highlight that the ‘any BLIPS’ group contained proportionally more

individuals recruited during earlier years when transition rates were higher (Nelson et al., 2013),

and had, on average, a longer time to follow-up, hence more opportunity to transition. It will be

important for future studies to consider whether these factors are contributing to the appearance

of group differences in transition risk. Unfortunately, sample size limitations prevented us from

fully exploring this in the present study.

Overall, our findings show a strong degree of homogeneity in both baseline characteristics and

long-term non-transition outcomes between the four UHR risk groups. This is critical given that

most UHR individuals will not develop a psychotic disorder (Nelson et al., 2013; Simon et al.,

2011), but do evidence poor long-term outcomes including high rates of non-psychotic disorders,

poor psychosocial functioning and persistent APS (de Wit et al., 2014a; Lin et al., 2015;

Rutigliano et al., 2016a). Thus if we consider the UHR construct as not simply a marker of

psychosis, but rather a transdiagnostic risk state signifying the need for clinical care (van

Prooijen et al., 2006), our findings do not support the segregation of UHR groups into separate

clinical entities as others have called for (Fusar-Poli et al., 2015; Schultze-lutter et al., 2015).

Some limitations of the present study should be noted. Firstly, it is possible that group

differences in non-transition outcomes were diluted by variance in treatment received and other

unmeasured participant and therapeutic factors that may contribute to variability in outcome

measures. It is also possible that the different study sites contributed variability to outcomes that

we could not measure in the present study due to the relatively small number of participants

11

recruited from sites other than Melbourne. Additionally, although we found no difference in the

prevalence of non-psychotic disorders across the risk groups, sample size limitations precluded

our capacity to explore types of non-psychotic disorders across groups.

Notwithstanding the aforementioned limitations, the present findings contrast with earlier results

by indicating a similarity in the clinical risk profile of the four UHR risk groups at entry to

clinical services and in long-term functional outcomes. Based on our findings we believe there is

currently insufficient evidence to support further partitioning the UHR population according to

the risk groups studied here. Pathways to psychosis are varied and likely involve a multitude of

interacting, time-varying factors. Rather than adopting further diagnostic ‘silos’, we believe that

efforts to assay true risk for psychosis that consider the complex array of social, psychological,

genetic and neurobiological mechanisms will be most fruitful. Moreover, the high rate of non-

psychotic disorders at follow-up across all groups reinforces the clinical utility of the UHR

construct and our view that it identifies a pluripotent, transdiagnostic risk state (McGorry and

Nelson, 2016), the identification of which can be further refined in an expanded set of ‘at risk’

criteria (Hartmann et al., In Press).

Funding

This work was funded by the Colonial Foundation Philanthropic Trust; Stanley Medical

Research Institute, and National Health and Medical Research Council Program Grant (#566529

and #350241). The Authors have declared that there are no conflicts of interest in relation to the

subject of this study.

Acknowledgments

The authors would especially like to thank the participants of all the studies and the researchers

involved in the original research studies.

12

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Table 1.Criteria for assessing Ultra-High-Risk for psychosis status from 1995 to 2013.

Criteria/Measure Attenuated Psychotic Symptoms (APS)

Brief limited intermittent psychotic symptoms (BLIPS)

Trait and state risk factors (Trait)

Symptom/Trait requirement

Presence of attenuated (subthreshold) positive psychotic symptoms within past 12 months

Presence of frank psychotic symptoms for < 1 week within the past 12 months, which spontaneously resolve (i.e., without treatment)

Presumed genetic vulnerability based on presence of schizotypal personality disorder or a first-degree relative with a psychotic disorder

Measures 1995-1999-BPRS/CASH(Yung et al., 2003, 1996)2000-2006 - CAARMS

1995-1999- BPRS/CASH(Yung et al., 2003, 1996)2000-2006 - CAARMS

1995-2013 - FIGS and SCID-II

Drop in functioning/ sustained low functioning required

1995-2006: N/A2010-2013:30% drop in SOFAS score for a month within the past year OR SOFAS score of 50 or less for the past 12 months or longer.

1995-2006: N/A2010-2013:30% drop in SOFAS score for a month within the past year OR SOFAS score of 50 or less for the past 12 months or longer.

1995-2006: 30% drop in GAF score within the past 12 months OR GAF score of 50 or less for the past 12 months or longer.2010-2013:30% drop in SOFAS score for a month within the past year OR SOFAS score of 50 or less for the past 12 months or longer.

Note: BPRS = Brief Psychiatric Rating Scale(Overall and Gorhum, 1962); CASH = Comprehensive Assessment of

Symptoms and History(Andreasen et al., 1992);CAARMS = Comprehensive Assessment of at-risk Mental

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States(Yung et al., 2005); FIGS = Family Interview for Genetic Studies(Initiative, 1992); SCID-II = Structured

Clinical Interview for DSM-III-R/DSM-IV Personality Disorders (First et al., 1997, 1995).

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Table 2.Baseline sample characteristics across the 4 UHR risk groups: Trait-only, APS-only, Trait+APS and Any BLIPS

Participant characteristics

Trait-only

n= 78

APS-only

n = 449

Trait+APS

n = 105

Any BLIPS

n = 70

Statistic P value N

Age at baseline 20.79 (4.71) 19.02 (3.64) 19.98 (3.90) 20.14 (4.32) F(3, 698) = 6.10 <.001 702

Gender (% male) 40 (50.6%) 205 (45.7%) 46 (44.2%) 35 (50.0%) χ2(3) = 1.23 .743 702

Baseline year (N, %)

1995 – 1999 (n = 161)

2000 – 2006 (n = 237)

2010-2013 (n = 304)

25 (15.5%)

30 (12.7%)

23 (7.6%)

69 (42.9%)

149 (62.9%)

231 (76.0%)

27 (16.8%)

42 (17.7%)

36 (11.8%)

40 (24.8%)

16 (6.8%)

14 (4.6%)

χ2(6) = 75.40 < .001 702

Time to follow-up interview

(years)

4.73 (4.10) 3.12 (3.32) 4.47 (4.04) 6.42 (4.50) F(3, 556) =

14.96

<.001 560

Duration of symptoms prior to

first contact with clinical

services (days), Mean (SD)

562.88

(1047.35)

677.46 (874.82) 664.87 (795.47) 487.37

(833.30)

F(3, 657) = 1.16 .325 661

Proportion receiving research

treatment (N, %) (vs treatment

as usual)

29 (36.7) 222 (49.4) 43 (41.3) 31 (44.3) χ2(3) = 5.85 .119 702

a.

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Table 3. Transition to psychosis and SOFAS and diagnostic outcomes according to UHR risk group

Participant characteristics

Trait-only

n= 76

APS-only

n = 430

Trait+APS

n = 103

Any BLIPS

n = 69

Test Statistic P value N

SOFAS at follow-upa, Mean, SD 68.37 (17.40) 68.40 (15.87) 64.47 (15.32) 67.47 (18.38) F(3, 508) = 1.24 .293 3

Proportion with non-psychotic

Axis I disorders at follow-up

(N, %)b

28 (53.8) 216 (64.3) 47(64.4) 22 (50.0) χ2(3) = 2.49 .477 505

b. Group differences were examined with general linear model with and without including age at baseline and time to follow-up

as covariates. Inclusion of covariates did not affect the results. We therefore report results of models without covariates.

c. Test statistic reflects Wald test on the group coefficient in a logistic regression model including age at baseline and baseline

year as covariates.

24

25

Figure 1. Proportion of UHR sample recruited between 1995 to 1999 (N = 161), 2000 to 2006 (N = 237) and 2010 to 2013 (N = 304) that met criteria for Trait-only, APS-only, Trait+APS and any BLIPS.

26Figure 2. Mean symptom severity and psychosocial functioning at baseline and follow-up for UHR risk groups. Error bars reflect +/- 1 standard error of the mean (SEM). BPRS = Brief Psychiatric Rating Scale, SANS = Schedule for the Assessment of Negative Symptoms; QLS = Quality of Life Scale; GAF = Global Assessment of Functioning.