Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: study design and baseline characteristics.

OBJECTIVE: Intervention during the pre-psychotic period of illness holds the potential of delaying or even preventing the onset of a full-threshold disorder, or at least of reducing the impact of such a disorder if it does develop. The first step in realizing this aim was achieved more than 10 years ago with the development and validation of criteria for the identification of young people at ultra-high risk (UHR) of psychosis. Results of three clinical trials have been published that provide mixed support for the effectiveness of psychological and pharmacological interventions in preventing the onset of psychotic disorder. METHOD: The present paper describes a fourth study that has now been undertaken in which young people who met UHR criteria were randomized to one of three treatment groups: cognitive therapy plus risperidone (CogTher + Risp: n = 43); cognitive therapy plus placebo (CogTher + Placebo: n = 44); and supportive counselling + placebo (Supp + Placebo; n = 28). A fourth group of young people who did not agree to randomization were also followed up (monitoring: n = 78). Baseline characteristics of participants are provided. RESULTS AND CONCLUSION: The present study improves on the previous studies because treatment was provided for 12 months and the independent contributions of psychological and pharmacological treatments in preventing transition to psychosis in the UHR cohort and on levels of psychopathology and functioning can be directly compared. Issues associated with recruitment and randomization are discussed.

Validation of "prodromal" criteria to detect individuals at ultra high risk of psychosis: 2 year follow-up.

BACKGROUND: Identification of individuals "prodromal" for schizophrenia and other psychotic disorders relies on criteria that predict onset within a brief period. Previous trials and biological research have been predicated on the view that certain "ultra high risk" (UHR) criteria detect "the prodrome", but there is a need to test the validity of these criteria. AIM: To assess the predictive validity of the UHR criteria in a clinical population. METHOD: The presence of UHR criteria was determined in 292 help-seeking individuals. At 2 year follow-up the number of new cases of psychotic disorder was assessed. RESULTS: The criteria significantly predicted onset of psychotic disorder within 2 years. The transition rate of 16% was much lower than in initial cohorts (over 40%). CONCLUSIONS: The predictive validity of UHR criteria depends on the sample to which they are applied. Although young help-seekers meeting these criteria are at greater risk of psychotic disorder than those who do not meet them, caution is needed in their management, since a high transition rate can no longer be assumed.

Depressed mood as a risk factor for unprotected sex in young people.

OBJECTIVES: Young people may place themselves and others at risk of sexually transmitted infections (STI) and/or the human immunodeficiency virus (HIV) through engaging in unprotected sex. Mental health problems may play an important role in sex-related risk behaviour. The current research was an investigation of depressed mood and condom use in a help-seeking sample of young people in Melbourne, Australia. METHOD: The sample comprised 76 sexually active young people aged 15-24 years who were referred to ORYGEN Youth Health, a public mental health service in Melbourne, Australia. Controlling for demographic characteristics and substance use, multivariate logistic regression examined depressed mood as a predictor of condom use at last sexual intercourse. RESULTS: Half of the sample reported condom use the last time they had sexual intercourse. Depressed mood, female gender and unemployment increased the likelihood that participants engaged in unprotected sex. CONCLUSION: A high proportion of young people, particularly those who are depressed, are failing to protect themselves from STI/HIV. Mental health services working with young people have the opportunity to implement initiatives aimed at reducing risk of STI/HIV infection.

Testing the Ultra High Risk (prodromal) criteria for the prediction of psychosis in a clinical sample of young people.

Criteria for identifying individuals at imminent risk for onset of a psychotic disorder, that is "prodromal" for psychosis, have recently been described. The current study set out to test the predictive validity of these criteria in a sample of help-seeking young people aged 15-24 years who were referred to, but not necessarily treated at, a psychiatric service. Ultra High Risk (UHR) status was determined at baseline and psychosis status was assessed at 6 month follow up. Baseline psychosocial functioning was also assessed as a possible predictor of psychosis. In the sample of 292 individuals, 119 (40.7%) met UHR criteria. Of these UHR+ people, 12 became psychotic within 6 months and 107 did not. Only one person not meeting UHR criteria developed psychosis in the follow up period. Sensitivity, specificity, positive predictive value and negative predictive value of UHR+ status for prediction of psychosis were, respectively, 0.923 (95% CI 0.621, 1), 0.616 (95% CI 0.556, 0.673), 0.101 (95% CI 0.056, 0.173) and 0.994 (95% CI 0.963, 1). UHR+ individuals were significantly more likely to become psychotic than UHR- individuals (Odds Ratio 19.3, 95% CI 2.5, 150.5). Low functioning at baseline was associated with psychosis onset in the whole sample and in the UHR group. The transition to psychosis rate was much lower than in previous samples. This may be a due to the sample being a more general one, not identified as possibly "prodromal". Other potential causes of this reduction in transition are also explored.

Psychotic-like experiences in nonpsychotic help-seekers: associations with distress, depression, and disability.

Psychotic-like experiences (PLEs) increase the risk of schizophrenia and other psychotic disorders yet are common in the community. Some PLEs, such as those associated with depression, distress, and poor functioning, may confer increased risk. The aim of this study is to determine the prevalence of PLEs in a nonpsychotic clinical sample and to investigate whether any subtypes of PLEs are associated with the above factors. Consecutive referrals to a youth psychiatric service (N = 140) were assessed to measure PLEs, depression, and functioning. PLE data were factor analyzed, and the associations of psychotic subtypes and distress, depression, and disability were analyzed. Three subtypes of PLEs were identified: Bizarre Experiences, Persecutory Ideas, and Magical Thinking. Bizarre Experiences and Persecutory Ideas were associated with distress, depression, and poor functioning. Magical Thinking was not, unless accompanied by distress. Bizarre Experiences and Persecutory Ideas may be more malignant forms of psychotic symptoms, as they are associated with current disability, and may confer increased risk of development of full-blown psychotic disorder.

Mapping the onset of psychosis: the Comprehensive Assessment of At-Risk Mental States.

OBJECTIVE: Recognizing the prodrome of a first psychotic episode prospectively creates the opportunity of intervention, which could delay, ameliorate or even prevent onset. Valid criteria and a reliable methodology for identifying possible prodromes are needed. This paper describes an instrument, the Comprehensive Assessment of At-Risk Mental States (CAARMS), which has been designed for such a purpose. It has two functions: (i) to assess psychopathology thought to indicate imminent development of a first-episode psychotic disorder; and (ii) to determine if an individual meets criteria for being at ultra high risk (UHR) for onset of first psychotic disorder. This paper describes the pilot evaluation of the CAARMS. METHOD: Several methodologies were used to test the CAARMS. First, CAARMS scores in a group of UHR young people and the association between CAARMS scores and the risk of transition to psychotic disorder, were analysed. Second, CAARMS scores in a UHR group were compared to a control group. To assess concurrent validity, CAARMS-defined UHR criteria were compared to the existing criteria for identifying the UHR cohort. To assess predictive validity, the CAARMS-defined UHR criteria were applied to a sample of 150 non-psychotic help-seekers and rates of onset of psychotic disorder at 6-month follow-up determined for the CAARMS-positive (i.e. met UHR criteria) group and the CAARMS-negative (i.e. did not meet UHR criteria) group. The inter-rater reliability of the CAARMS was assessed by using pairs of raters. RESULTS: High CAARMS score in the UHR group was significantly associated with onset of psychotic disorder. The control group had significantly lower CAARMS scores than the UHR group. The UHR criteria assessed by the CAARMS identified a similar group to the criteria measured by existing methodology. In the sample of non-psychotic help-seekers those who were CAARMS-positive were at significantly increased risk of onset of psychotic disorder compared to those who were CAARMS-negative (relative risk of 12.44 (95% CI = 1.5-103.41, p = 0.0025)). The CAARMS had good to excellent reliability. CONCLUSIONS: In these preliminary investigations, the CAARMS displayed good to excellent concurrent, discriminant and predictive validity and excellent inter-rater reliability. The CAARMS instrument provides a useful platform for monitoring subthreshold psychotic symptoms for worsening into full-threshold psychotic disorder.

Patterns of current comorbidity in young help-seekers: implications for service planning and delivery.

OBJECTIVE: To identify the pattern of current comorbidity in young help-seekers referred to a specialist mental health service. METHOD: One hundred and forty-nine participants were assessed for current psychiatric diagnoses following their referral to ORYGEN Youth Health. RESULTS: Seventy-eight per cent of the sample rated for at least one diagnosis with almost half the sample presenting with two or more disorders. Next to comorbid depression and anxiety, comorbidity between substance use disorders and mood and anxiety disorders was the most prominent pattern of comorbidity in the sample. CONCLUSIONS: The present findings suggest that integration between mental health and substance abuse services is well overdue and must be addressed at policy, service system and clinical levels.