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Keywords:

  • anxiety;
  • clinical staging;
  • depression;
  • youth mental health

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Discussion
  6. Acknowledgements
  7. References

Aim

An estimated 75% of mental disorders begin before the age of 24 and approximately 25% of 13–24-year-olds are affected by mental disorders at any one time. To better understand and ideally prevent the onset of post-pubertal mental disorders, a clinical staging model has been proposed that provides a longitudinal perspective of illness development. This heuristic model takes account of the differential effects of both genetic and environmental risk factors, as well as markers relevant to the stage of illness, course or prognosis. The aim of the Transitions Study is to test empirically the assumptions that underpin the clinical staging model. Additionally, it will permit investigation of a range of psychological, social and genetic markers in terms of their capacity to define current clinical stage or predict transition from less severe or enduring to more severe and persistent stages of mental disorder.

Method

This paper describes the study methodology, which involves a longitudinal cohort design implemented within four headspace youth mental health services in Australia. Participants are young people aged 12–25 years who have sought help at headspace and consented to complete a comprehensive assessment of clinical state and psychosocial risk factors. A total of 802 young people (66% female) completed baseline assessments. Annual follow-up assessments have commenced.

Conclusions

The results of this study may have implications for the way mental disorders are diagnosed and treated, and progress our understanding of the pathophysiologies of complex mental disorders by identifying genetic or psychosocial markers of illness stage or progression.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Discussion
  6. Acknowledgements
  7. References

Mental ill health is the dominant health issue facing young people in the developed world. The incidence and prevalence of mental ill health in adolescents and young adults is well documented[1] and is the highest of any age group.[2, 3] The National Comorbidity Survey Replication indicated that 75% of people with a psychiatric disorder experienced onset by 24 years of age, with the onset of most adult forms of mental disorder falling within a narrow time band from the early teens to the mid-twenties and peaking in the early twenties.[4] This pattern of onset led Insel and Fenton[1] to propose that mental disorders be considered the ‘chronic diseases of the young’.

The clinical profile of mental ill health in young people post-puberty is characterized by mixed symptom patterns, often comorbid with substance misuse.[2, 5, 6] Most likely, these phenotypes reflect the early manifestation of illness, in which undifferentiated or brief ‘sub-syndromal’ symptoms emerge before any more distinct, prolonged or diagnosable disorder (e.g. see[7]). Young people with undifferentiated clinical syndromes or emerging mental disorders experience particular difficulties accessing treatment.[8] This occurs for a number of reasons, including the emphasis in current treatment paradigms on the primacy of formal diagnosis (both at the service and individual level), which marginalizes or excludes young people with sub-threshold or brief symptoms.[8, 9] As young people experience mixed symptom patterns that do not neatly align with current diagnostic systems, often remit but recur, and which may or may not ultimately develop into discrete mental disorders, there is a need to develop an alternative approach to conceptualizing these problems. A clinical staging model of mental disorders may offer a way forward to develop a more appropriate clinicopathological framework for the emergence and progression of mental disorders.[10-12]

Clinical staging is an adjunct to other more formal diagnostic systems. On its own, it does not seek to replace all other systems. It differs from conventional (i.e. categorical) diagnostic practice in that it defines the extent of progression of a disease or illness at a particular point in time; that is, where a person lies along the continuum of the course of illness. The utility of clinical staging is most pronounced for any disease or illness that tends to progress, which may progress or where persistence or progression results in other major or secondary complications. The differentiation of early, brief or milder clinical phenomena from those that accompany illness progression, persistence and chronicity lies at the heart of the concept, which makes it especially useful in young people.[10, 13] It is crucial to allow the inclusion of young people that experience transient mental ill health. Although from a formal diagnosis perspective, these may ultimately be considered ‘false positives’ or ‘phenocopies’ of the early stages of persistent or complex disorders, these young people still have important immediate health care needs and accompanying disability.[6, 14]

The clinical staging model provides a longitudinal perspective relevant to the evolution of illness from an at-risk (i.e. no symptoms), through sub-threshold states through to differentiated illness, and takes account of risk factors and/or markers relevant to the illness, its course and prognosis. We have extended the original model, which focused on the most severe (psychotic or mood) disorders, to hypothesize that a broader range of mental disorders (potentially including bipolar disorder, anxiety disorders with major avoidance, eating disorders and substance dependence) develop from initial non-specific symptoms and syndromes (i.e. a ‘pluripotential state’). This may also reflect a background of specific and non-specific risk factors, including genetic and early environment risks. From the initial non-specific clinical presentation, worsening of symptoms and acquisition of new symptoms occurs, together with progressive neurobiological changes and related neuro-behavioural deficits, until distinguishable mental disorders appear. That is, the natural history of major mental disorders such as mood, anxiety and psychotic disorders is theorized to consist of transitions from being asymptomatic (stage 0), through a stage of undifferentiated general symptoms such as mild anxiety, depressive and/or somatic symptoms (stage 1a), to a worsening of existing symptoms (or the acquisition of new symptoms), whereby the person appears to have an attenuated form of a distinguishable mental disorder (stage 1b), until eventually (at least for some) a ‘threshold diagnosis’ is reached (stage 2; such as mania, severe depression or schizophreniform disorder). After such diagnosis, progression of illness may still occur, with development of chronic symptoms, a pattern of relapses and ongoing functional decline.

Within this model, we propose that transition from one stage of illness to the next is not inevitable. For example, a person with mild anxiety and depressive symptoms may or may not progress to develop a severe depressive or bipolar disorder, just as a person with a first episode of psychosis may or may not progress to a chronic, deteriorating illness. At any one time, there may be a number of possible trajectories. One of the implications of conceptualizing mental disorders this way is that it guides the search for risk factors for transition and progression, or conversely remission and recovery. These risk factors could be underlying risk indicators and/or trait markers, such as genetic markers, brain abnormalities, peripheral biomarkers or abnormal early environment and experiences (e.g. trauma, poor parental bonding). The benefit of identifying these markers is that they may be relevant to differentiating between disorders. However, a challenge in doing this is the ability to distinguish risk indicators from state markers, which will vary depending on a person's current mental state and where they lie on the continuum of progression of illness. For example, further research is needed to determine if social cognitive deficits seen in some young people with early psychosis are due to their symptomatology at the time (i.e. state (or a consequence of the illness) markers) or are an underlying indicator of a disease (a trait marker).

The clinical staging model articulated above is heuristic and requires evaluation and elaboration. It is recognized that the proposed clinical stages and thresholds between any proposed stages may not be valid or accurate, and therefore require robust empirical examination. Furthermore, although there is compelling evidence for focusing on potential trait and state markers and modifiable risk factors for the development of mental illness (e.g. childhood trauma, family history of mental illness, neuroticism, social support, treatment non-response), their validity and relationship to different stages of illness is yet to be well established. We designed a study (the Transitions Study) to:

  1. Establish a cohort of young people who have sought help for mental health problems and longitudinally investigate this cohort to test a clinical staging model of the development and progression of mental disorders; and
  2. To test the validity of a range of markers (clinical, psychological, social and genetic), both in terms of their capacity to:
    1. Define current clinical stage, and
    2. Predict transition between stages of mental ill health in young people. In particular, to determine which variables are vulnerability markers, which are modifiable risk factors, which are consequences of disease and which are epiphenomena.

Specifically, we hypothesized that:

  1. There is a dimensional ‘pluripotential’ state of psychological distress that can evolve into a range of more specific clinical syndromes, including severe depression, mania, psychosis, anxiety with major avoidance and substance dependence.
  2. The pluripotential state and the specific syndromes can be differentiated on a range of factors, including symptoms, disability and patterns of neuropsychological impairment.
  3. There are general factors that predict risk for the pluripotential state of psychological distress, including neuroticism, adverse life events, childhood adversity, social disadvantage and lack of social support.
  4. There are specific factors that differentially predict transition from the pluripotential state to each of the specific clinical syndromes, including attenuated symptoms of the specific syndrome and patterns of neuropsychological impairment.
  5. There are general factors that predict remission from the pluripotential state (e.g. resolution of life events, receiving social support, treatments that reduce distress) and specific factors that predict remission from the clinical syndromes (including receiving syndrome-specific interventions).
  6. Young people who remit from a specific syndrome will tend to have recurrences within the same syndrome. In contrast, young people who remit from the pluripotential state will continue to be at broad/general risk for a range of specific syndromes.

This paper describes the Transitions Study methodology.

Method

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Discussion
  6. Acknowledgements
  7. References

Sample

Potential participants were young people aged 12 to 25 years (inclusive) who sought help from one of four headspace clinical services in Melbourne and Sydney, Australia between January 2011 and August 2012. headspace was established by the Australian Federal Government in 2006 to promote and support early intervention for young people with mental health and substance use disorders. headspace services provide youth-focused mental and general health services (e.g. sexual health consultations), as well as alcohol and drug services and vocational assistance for young people aged 12–25.[9] As headspace focuses both on youth mental health and early intervention, young people may present for care with varying illness severity (e.g. sub-threshold through to severe symptoms and mild to severely impaired functioning) across a range of mental health problems.

A preliminary evaluation of headspace indicates that these clinical services (of which 40 currently operate throughout Australia) have been particularly effective in engaging males, who are generally more reluctant to seek help, but who constituted 43% of clients at the time of the evaluation.[15] The majority of young people either self-refer, or are referred by family, friends, health professionals or school counsellors. Mental health problems, predominantly anxiety and depressive symptoms, are the most common reasons for referral, often in the context of psychosocial issues such as family or relationship/peer conflict. The mean number of treatment sessions at headspace services is seven, and a range of interventions may be provided, including psychoeducation, supportive counselling, cognitive behavioural therapy and medication where clinically indicated.[15]

Procedure

The study protocol was approved by the Human Research Ethics Committees at the University of Melbourne and the University of Sydney. Recruitment of the cohort commenced in January 2011 and ceased in August 2012. Annual follow-up assessments have commenced, and will continue until the study funding concludes in December 2013. All young people aged 12–15 who were receiving a clinical service at one of the headspace recruitment sites during the study period, were English-speaking and able to provide informed consent were approached for participation. There were no exclusion criteria other than significant intellectual disability (e.g. IQ < 65) that would preclude the ability to provide informed consent and complete the study assessment. However, young people who were acutely suicidal, as determined by their assessing or treating headspace clinician, were not approached for study inclusion until their suicidality had resolved to the point of their no longer being at high risk. Young people were contacted by a research assistant (RA) via telephone or in person to discuss the aims and nature of the study and their interest in participating. Contact was made either after the client's intake assessment (with a headspace Access Team clinician) or after their first treatment session with a headspace practitioner. Participants aged 15 years and over provided written informed consent, whereas those aged 12–14 years (inclusive) assented with written informed consent provided by a parent or guardian.

Research assistants with a minimum 4-year graduate psychology degree implemented the study protocol. The RAs were trained in the use of each study measure (see below) and achieved an inter-rater reliability score of at least 0.8 on each of the interviewer-rated clinical measures before recruitment commenced. The RAs conducted structured interviews with each participant using the clinical measures described below before then providing an iPad or laptop for the completion of a range of self-report measures (see risk factors and self-report clinical measures below). Finally, participants separately consented to provide a saliva sample and the RAs conducted height, weight and waist circumference measurements at the conclusion of the assessment. The combined interview, self-report, saliva and weight procedures took approximately 1.5–2 h to complete and participants were compensated with a $20 gift voucher for their time.

Measures

Clinical measures
Interviewer-rated measures
Health services use

A 15-item measure was adapted from the Australian National Mental Health and Wellbeing Survey[3] and asked participants about any health services they had used for mental health problems during both the past 12 months and lifetime. Items examined the types of health care professionals consulted, the nature of any treatments received (e.g. medications, psychological therapies, complementary and alternative medicines, and self-help), and the nature and frequency of hospitalizations.

Quick Inventory of Depressive Symptomatology (QIDS) 16-item adolescent version

The QIDS[16] assesses the presence, during the previous seven days, of the major diagnostic symptoms of depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (sleep disturbance, sad mood, appetite/weight disturbance, poor concentration, self-criticism, suicidal ideation, sleep disturbance, diminished interest, lowered energy/fatigue). Symptoms are rated on a 4-point Likert scale and combined to provide total scores ranging from 0 to 27. Scores above 16 are considered to indicate severe depression.

Self-harm

Two questions that have previously been employed to assess deliberate self-harming behaviours and suicide attempts among adolescents[17] were employed. Participants were asked (yes/no) whether they had deliberately hurt themselves, or done something to try and kill themselves in the past year. Affirmative responses to either question were further probed regarding the method and severity of the self-harming behaviours or suicide attempt.

Young Mania Rating Scale[18]

This 11-item measure indicates the nature and severity of manic symptoms within the past 48 h. Each item is graded across five explicitly defined anchor points (ranging from 0–4 for seven items to 0–8 for four items). The rating of items is based both on subjective report by the participant and the interviewer's behavioural observations. Total scores range from 0 to 60.

Comprehensive Assessment of the At-Risk Mental State (CAARMS[19])

The CAARMS is a semistructured interview that assesses the presence and severity of psychotic symptoms over the past 12 months. The Positive Symptom Scale was used in this study and consists of four subscales: (i) unusual thought content; (ii) non-bizarre ideas; (iii) perceptual abnormalities; and (iv) disorganized speech. Scores for each of the subscales are rated according to their intensity, frequency and duration, pattern of symptoms and level of distress.

WHO-ASSIST

The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST;[20]) assesses problematic or ‘risky’ use of tobacco, alcohol, cannabis and other illicit drugs (e.g. cocaine, amphetamines, sedatives, hallucinogens, inhalants, opioids). The ASSIST consists of seven questions for each drug category, and an eighth question on injecting drug use. It identifies the substances used and the substance-related harm over the participant's lifetime and the past 3 months.

Clinical Global Impressions Scale (CGI[21])

This single-item measure is completed by the interviewer based on their overall clinical impression of the participant, derived from all available information taken throughout the assessment and the interviewer's impression of the participant's functioning, symptoms and behaviour. The CGI indicates the severity of illness, ranked from 1 ‘normal, not ill at all’ to 7 ‘among the most extremely ill patients’. An additional item is used at follow-up to indicate global improvement from 1 ‘very much improved’ to 7 ‘very much worse’ since the previous assessment.

Social and Occupational Functioning Scale (SOFAS[22])

The SOFAS is an observer-rated scale that provides a global assessment of the participant's social and occupational functioning. Scores range between 0 (e.g. unable to function) and 100 (superior functioning), with descriptive anchor points provided for each decile. SOFAS scores in this study were calculated based on the lowest level of functioning in the past year.

Self-report measures
Kessler 10 (K-10)

The K-10[23] was used as a broad measure of psychological distress. Ten questions enquire about negative emotional states experienced during the past 4 weeks. Participants indicated the extent to which they experienced each item using a 5-point Likert scale (total scores range between 10 and 50). Scores between 25 and 29 indicate the likelihood of having a moderately severe mental disorder, with scores between 30 and 50 indicative of severe mental disorder.[23]

SPHERE-12

The SPHERE-12[24] was derived from the 34-item Somatic and Psychological Health Report (SPHERE) questionnaire. The 12-item measure assesses psychological and somatic distress, and comprises six somatic (fatigue, somatic complaints) and six psychological (depression, anxiety) items. Participants indicated the frequency with which they experience each item ‘over the past few weeks’ on a 3-point Likert scale.

GAD-7

The 7-item Generalized Anxiety Disorder scale (GAD-7;[25]) measures core symptoms of generalized anxiety disorder (e.g. feeling nervous, unable to relax, worrying about different things, afraid something awful might happen). Participants rated the frequency with which they have experienced these anxiety symptoms in the past 2 weeks on a 4-point Likert scale.

Overall Anxiety Severity and Impairment Scale (OASIS)

The OASIS[26] consists of five items that measure the frequency and severity of anxiety, level of avoidance behaviours and the extent to which anxiety interferes with work/school/home and social functioning. Participants indicated the extent to which they experienced each item over the past week on a 5-point Likert scale.

SCOFF

The 5-item SCOFF[27] screens for symptoms of eating disorders by addressing core features of anorexia nervosa and bulimia nervosa. The acronym is derived from the five items, which enquire about (i) feeling sick; (ii) losing control; (iii) losing more than one stone in 3 months, (iv) believing yourself to be fat and (v) food dominating your life. Each affirmative answer receives a score of 1, and a total score of 2 or more indicates significant anorexia nervosa or bulimia nervosa symptoms.

Disability Assessment Schedule (WHO-DAS-12)

The 12-item WHO-DAS[28] examines difficulties in performing daily life activities. Participants were asked to rate their difficulty with performing a series of daily life activities during the past 30 days (e.g. maintaining a friendship, daily hygiene) on a 5-point Likert scale. Global scores range from 0 to 100 with higher scores indicating more severe disability.

Quality of Life (WHOQOL-1)

One item from the WHOQOL-100 has previously been used[29] to assess perceptions of overall quality of life in the past 4 weeks. Participants were asked to rate their overall quality of life as one of the following: very poor, poor, neither poor nor good, good, very good.

Saliva

Participants were asked to provide separate consent for the collection of a saliva sample, for the purposes of genetic analysis (e.g. analysing genetic variation in relation to study outcomes, including transitions between clinical stages). Saliva was collected at the conclusion of the interview to ensure that participants has not eaten, drunk, smoked or chewed gum in the preceding 30 min. A standard protocol was used to collect and store the samples in individual saliva pots. Three barcodes were then used to label (i) the tube; (ii) the participant record form; and (iii) and the shipping paperwork. Samples were delivered in batches of 12 to the genetics repository service retained for the study, and were securely stored at room temperature in the interim.

Background and potential risk factors (self-report)
Demographics, education, work and household economics

Twenty-four questions examined the participant's age, gender, languages other than English, time lived in Australia, marital status, accommodation, living arrangements, education, employment, financial problems, income, government benefits and parents' country of birth. Items were adapted from the Australian Bureau of Statistics 2006 census questions[30] and other published sources.[31, 32]

Exercise questionnaire

Six items from the Active Australia Survey[33] examined the frequency with which participants had engaged in three forms of physical activity in the past week, and the time spent (in minutes and/or hours) in each of these activities. Evidence from systematic reviews and meta-analyses indicates the relationship between exercise and decreased levels of both depression[34] and anxiety.[35]

Personality

The 24-item Behavioural Inhibition/Behavioural Activation System (BIS/BAS;[36]) was used as a broad measure of personality traits, including neuroticism. Respondents indicated the extent to which they agreed or disagreed with each item using a 4-point Likert scale. The questionnaire has scales for behavioural inhibition and behavioural activation, with subscales for reward responsiveness, drive and fun-seeking. The scale measures reactivity to punishment and reward and correlates highly with neuroticism and extraversion. However, unlike neuroticism scales, the BIS scale is free of obvious symptom content. There is evidence that the BIS/BAS predicts outcome of depression.[37]

Ruminative style

A brief 10-item questionnaire was used,[38] which was based on a longer, validated scale.[39] Respondents indicated the extent to which they experienced each item using a 4-point Likert scale. Numerous studies have shown that ruminative style predicts chronicity of depression and anxiety (e.g.[39]), including among adolescents.[40]

Life events

A brief list of threatening experiences developed by Brugha and colleagues[41] was adapted, in which two items from the original 12-item list were combined (‘Separation due to marital difficulties’ and ‘Broke off a steady relationship’) due to the low probability of adolescent participants endorsing ‘marital difficulties’. Participants were asked to indicate (yes/no) whether they had experienced each life event in the past 12 months, and if yes, the number of months since the event occurred. There is a substantial literature regarding the relationship between exposure to adverse life events and psychiatric morbidity (see[42]).

Social support

A 20-item scale developed by Schuster et al.[43] was used to assess the presence of both negative and positive social interactions. Participants were asked to indicate the extent to which they experienced each of the items using a 4-point Likert scale. The measure provides scores in the domains of positive and negative social support from friends, family and (if applicable) partner. Negative interactions have been reported as being the more salient predictor of depression.[43]

Parental style

A short version of the Parental Bonding Instrument (PBI) developed by Heider et al.[44] was used. The questionnaire includes nine items for each parent (18 items total), with subscale scores for the domains of care, overprotection and authoritarianism. Participants were asked to remember each parent in the first 16 years of their life (or earlier for 12–15-year-olds) and then rate the frequency with which they experienced each item on a 4-point Likert scale. The PBI has been found to predict risk for anxiety and depression.[45]

Childhood Trauma Questionnaire (CTQ)

The 28-item CTQ[46] inquires about the experience during childhood and adolescence of three types of abuse (emotional, physical and sexual) and two forms of neglect (emotional and physical). A 3-item scale is also used to detect false-negative trauma reports (e.g. ‘I had the perfect childhood’). Participants indicated the extent to which they experienced each item while they were ‘growing up’ according to a 5-point Likert scale. There is substantial evidence that child abuse, particularly sexual abuse, is a risk factor for a range of mental disorders, including mood and psychotic disorders (see[47]).

Sexual orientation

A single item previously used by Jorm et al.[48] was used, in which participants were asked: ‘Would you currently consider yourself to be predominantly: heterosexual (straight), homosexual (gay), bisexual (bi), don't know, don't want to say’. Non-heterosexual orientation has been found to be associated with a range of mental health problems[48] as well as increased suicidality,[49] mediated by discrimination and bullying/harassment experiences.

Age of menarche

There is evidence that early menarche increases the risk of depression.[50] The following single-item question, previously used by Jorm et al.[51] asked (female) participants ‘How old were you when your periods or menstrual cycle started?’.

Discrimination experiences

Three items were adapted from a discrimination scale in the Quality of Life in Newly Diagnosed Epilepsy Instrument (NEWQOL) battery.[52] Participants were asked whether or not, because of their mental health problems, ‘other people: (i) are uncomfortable with me; (ii) treated me as inferior and (iii) preferred to avoid me’.

Sleep

Six items from the Pittsburgh Sleep Quality Index[53] assessed the following over the past month: usual time of going to bed, time to fall asleep (in minutes), usual time of waking, number of hours of sleep and perception of sleep quality. Considerable evidence links sleep disturbance and circadian rhythm abnormalities with mood disorders, particularly mania.[54]

Forensic history

Rates of criminal offending and crime victimization are significantly higher in individuals with mental disorder compared to the general population.[55] Three questions were used to assess whether participants had ever been charged with a criminal offence, convicted of an offence, or been a victim of crime. Affirmative responses were further probed with questions regarding the nature of the offence (e.g. physical assault, theft, drug possession, property damage) and the outcome of any charges or convictions.

Family history of mental disorder

Items regarding family history of emotional/psychological problems and suicide in parents and siblings adapted by King et al.[56] were used. Participants were asked (i) ‘Have any of your family members had a serious psychological or emotional problem? (this refers to conditions such as depression, severe anxiety, nervous breakdown and schizophrenia)’ and (ii) ‘Has anyone in your family taken their own life (i.e. committed suicide)?’ and asked to indicate whether or not (to their knowledge) these questions applied to each parent, and any siblings. Participants with no knowledge of their biological relatives were not required to complete this measure.

Annual follow-up procedure

Participants will be re-contacted 12 months after their baseline interview (i.e. between January 2012 and August 2013) and invited to complete a follow-up assessment. A subset of participants who completed their baseline assessment in 2011 will also be able to be contacted for 24-month follow-up (participants recruited in 2012 are unable to be assessed at the 2-year time point as the study funding concludes at the end of 2013). At the follow-up time points, each interviewer-rated measure is re-administered according to the protocol described above, with the exception of the Health Services Use items, which are amended to enquire only about the past 12 months (rather than lifetime). The K-10, SPHERE-12, GAD-7, OASIS, SCOFF, WHO-DAS and WHO-QOL are also re-administered, along with an abbreviated suite of self-report measures that focus on ‘dynamic’ risk domains that may have changed since baseline assessment, namely, demographics, exercise, social support, life events, sexual orientation, age of menarche, discrimination, sleep and forensic history.

Between baseline and follow-up assessment, participants are contacted via a postcard (mailed or emailed) to provide (i) an update on the project; (ii) a reminder of the upcoming annual assessment; and (iii) inform participants how to notify research staff of any change in their contact details. To maximize the ability to re-contact participants (and retain the cohort), a variety of contact information is collected, including the participant's full name, home address, phone number(s) and email address, as well as the name and contact details of their general practitioner or other health professional, their mother's and father's full names and contact details (where appropriate given family circumstances) and the contact details of at least one friend.

Clinical staging of participants

Each participant is assigned a preliminary clinical stage following their baseline and follow-up assessments. Staging decisions are based on the detailed descriptive criteria provided by Hickie et al. (see Appendix I[12]), which elaborates on McGorry et al.'s[10] original staging model. In essence, this clinical stage is based on the ‘gestalt’ of the participant's presentation, including current major symptoms (severity, frequency, type), previous ‘worst ever’ symptoms and treatments (including hospital admissions), current and past level of risks due to self harm, suicide attempts or other at-risk behaviours and current (as compared with premorbid) levels of functioning. The stage for each participant was formulated following discussion between the RA and their clinical supervisors.

At the end of baseline recruitment, 802 eligible participants were recruited (e.g. consented to participate and meet the inclusion criteria), of whom 66% (n = 529) were female.

Statistical analyses

The fundamental premise of the study (Hypothesis 1) will be evaluated using a range of latent variable methods including confirmatory factor analysis and exploratory structural equation modelling.[57] Algorithms representing staging models defined by expert consensus will also be applied to the data.

Having established the measurement structure of pluripotential status, conventional epidemiological approaches to assessing risk factors for elevation of this dimension (or dimensions) will be used. This will yield estimates of relative risk of having pluripotential status. These methods are equally adaptable to categorical structures, such as the proposed staging models and clinical syndromes. Conventional risk factor analysis will explore predictors of change. Contingent on observation of adequate numbers of particular types of transitions and remissions, we hope to develop a structural model incorporating multiple outcomes. This would enable simultaneous evaluation of the impact of general and specific factors in predicting disorder progression and remission.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Discussion
  6. Acknowledgements
  7. References

This paper describes the Transitions Study, which seeks to empirically test and validate a clinical staging model for the spectrum of psychotic, mood/anxiety, eating and substance use disorders in young people. A range of psychological, social and genetic markers have been tested, in terms of their capacity to define current clinical stage and to predict transition from less disabling to more disabling stages of mental and substance use disorder. The study is innovative in its aims to define phases of vulnerability, earliest clinical manifestations, clinical phenotype at first presentation and later stages of recovery and illness progression in a large cohort of young people who are seeking help for mental health problems.

The implications and clinical significance of this research is the opportunity to develop a simplified and practical approach to diagnosis and treatment selection in the poorly differentiated early stages of mental disorder, which is likely to be much needed given the far greater prevalence of such sub-threshold states in the community, for example, depressive disorders (see[58]). In addition, the ability to determine genetic or psychosocial markers of illness stage (including predictors of transition from less severe to more severe illness forms) would represent a major breakthrough in our understanding of the pathophysiologies of complex mental disorders, including psychosis, severe depression, mania, anxiety with marked avoidance, eating disorders and substance use disorder.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Discussion
  6. Acknowledgements
  7. References

This work was supported by a NHMRC Program Grant (ID: 566529) to McGorry, Jorm, Hickie, Yung and Pantelis.

[Correction added on 31 July 2013, after first online publication: The acknowledgements section was added]

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Discussion
  6. Acknowledgements
  7. References
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