[Show abstract][Hide abstract] ABSTRACT: The Transitions Study was designed to establish a cohort of young people (12-25 years) seeking help for mental health problems, in order to longitudinally explore and refine a clinical staging model of the development and progression of mental disorders. This paper presents the baseline demographic and clinical characteristics of the cohort, particularly the nature and severity of psychopathology.
All eligible young people attending one of four headspace clinical services were invited to participate, and completed a battery of self-report and interviewer-administered measures of psychopathology and functional impairment at baseline, which will be repeated at the annual follow up.
Of 1615 eligible clients, 802 young people (66% women; mean age = 18.3 years) consented to participate and completed baseline assessments (participation rate = 50%). The severity of mental health problems varied, with 51% meeting the criteria for probable caseness related to generalized anxiety, 45% presenting with moderate to severe depressive symptoms and over a third experiencing subthreshold psychotic symptomatology. Disordered eating (32%) and problematic tobacco (56%), cannabis (30%) and alcohol (38%) use also affected a significant proportion. Overall, 39% of the cohort were classed as being functionally impaired at baseline.
The Transitions Study recruited a heterogeneous cohort at baseline in relation to the nature and severity of mental health problems and levels of functional impairment. The variation in clinical presentations within the cohort, from mild, through moderate to severe levels of psychopathology and impairment, increases the likelihood of the Transitions Study ultimately being able to achieve its aims of empirically testing a clinical staging model for mental disorders.
Early Intervention in Psychiatry 03/2014; · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A shallow olfactory sulcus has been reported in schizophrenia, possibly reflecting abnormal forebrain development during early gestation. However, it remains unclear whether this anomaly exists prior to the onset of psychosis and/or differs according to illness stage. In the current study, magnetic resonance imaging was used to investigate the length and depth of the olfactory sulcus in 135 ultra high-risk (UHR) individuals [of whom 52 later developed psychosis (UHR-P) and 83 did not (UHR-NP)], 162 patients with first-episode psychosis (FEP), 89 patients with chronic schizophrenia, and 87 healthy controls. While there was no group difference in the length of the sulcus, UHR-P subjects had significantly shallower olfactory sulcus at baseline as compared with UHR-NP and control subjects. The depth of this sulcus became increasingly more superficial as one moved from UHR-P subjects to FEP patients to chronic schizophrenia patients. Finally, the depth of the olfactory sulcus in the UHR-P subjects was negatively correlated with the severity of negative symptoms. These findings suggest that the altered depth of the olfactory sulcus, which exists before psychosis onset, could be predictive of transition to psychosis, but also suggest ongoing changes of the sulcus morphology during the course of the illness.
Schizophrenia Research 03/2014; · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To develop and examine the feasibility of an online monitoring tool of depressive symptoms, suicidality and side effects.
The online tool was developed based on guideline recommendations, and employed already validated and widely used measures. Quantitative data about its use, and qualitative information on its functionality and usefulness were collected from surveys, a focus group and individual interviews.
Fifteen young people completed the tool between 1 and 12 times, and reported it was easy to use. Clinicians suggested it was too long and could be completed in the waiting room to lessen impact on session time. Overall, clients and clinicians who used the tool found it useful.
Results show that an online monitoring tool is potentially useful as a systematic means for monitoring symptoms, but further research is needed including how to embed the tool within clinical practice.
Early Intervention in Psychiatry 02/2014; · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
Early Intervention in Psychiatry 07/2013; · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Grey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis. Method We examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness. RESULTS: At baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not. CONCLUSIONS: These data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.
Psychological Medicine 05/2013; · 5.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: The ultra-high risk clinical phenotype is associated with substantial distress and functional impairment and confers a greatly enhanced risk for transition to full-threshold psychosis. A range of interventions aimed at relieving current symptoms and functional impairment and reducing the risk of transition to psychosis has shown promising results, but the optimal type and sequence of intervention remain to be established. The aim of this study was to determine which intervention was most effective at preventing transition to psychosis: cognitive therapy plus low-dose risperidone, cognitive therapy plus placebo, or supportive therapy plus placebo.
METHOD: A double-blind, randomized, placebo-controlled 12-month trial of low-dose risperidone, cognitive therapy, or supportive therapy was conducted in a cohort of 115 clients of the Personal Assessment and Crisis Evaluation Clinic, a specialized service for young people at ultra-high risk of psychosis located in Melbourne, Australia. Recruitment commenced in August 2000 and ended in May 2006. The primary outcome measure was transition to full-threshold psychosis, defined a priori as frank psychotic symptoms occurring at least daily for 1 week or more and assessed using the Comprehensive Assessment of At-Risk Mental States. Secondary outcome measures were psychiatric symptoms, psychosocial functioning, and quality of life.
RESULTS: The estimated 12-month transition rates were as follows: cognitive therapy + risperidone, 10.7%; cognitive therapy + placebo, 9.6%; and supportive therapy + placebo, 21.8%. While there were no statistically significant differences between the 3 groups in transition rates (log-rank test P = .60), all 3 groups improved substantially during the trial, particularly in terms of negative symptoms and overall functioning.
CONCLUSIONS: The lower than expected, essentially equivalent transition rates in all 3 groups fail to provide support for the first-line use of antipsychotic medications in patients at ultra-high risk of psychosis, and an initial approach with supportive therapy is likely to be effective and carries fewer risks.
The Journal of Clinical Psychiatry 04/2013; 74(4):349. · 5.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The personality dimension of schizotypy is well established, and schizotypal traits can be taken to represent a proneness toward developing psychosis. Yet, there are competing theories about the latent structure of schizotypy. More specifically, there is controversy over the extent to which this propensity towards psychosis is present only in a small proportion of the population, or whether it is spread dimensionally throughout the general community. On the basis of accumulating research findings the present article argues for a fully dimensional model of schizotypy. It describes recent neurobiological, neuropsychological, social and environmental evidence supporting the idea that schizotypy in healthy populations, and disorders on the schizophrenia spectrum are fundamentally linked. Directions for further research are also considered.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: Vocational recovery is a primary treatment goal of young people with first-episode psychosis (FEP), yet treatment in this domain is often delayed due to concerns that it might be too stressful. This study aimed to examine whether a relationship exists between vocational status and level of perceived stress and daily hassles in FEP. METHODS: Forty-seven FEP participants were recruited upon admission to the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne. Demographics, psychopathology, perceived stress (Perceived Stress Scale; PSS) and daily hassles (Hassles Scale; HS) were measured. RESULTS: Regarding vocational status, 19 participants were unemployed, 13 were employed, 14 were students, and 1 reported 'home duties'. ANOVAs and post hoc tests comparing the first three groups on perceived stress and daily hassles revealed that the mean PSS Total and mean PSS Distress scores of the employed group were significantly lower than those of the unemployed and student groups. Regarding hassles scores, the employed group had a significantly lower mean Hassles Intensity score than the unemployed group. Results were largely unchanged when covariates were included. There were no significant differences between the three groups in levels of anxiety, negative or positive symptoms. The employed group reported lower depression than the student group, but this finding disappeared after controlling for gender. CONCLUSIONS: These results provide preliminary evidence supporting the notion that working or studying is not associated with increased perceived stress or daily hassles in FEP. The findings require replication in larger samples and in different phases of psychosis.
[Show abstract][Hide abstract] ABSTRACT: Objective:Impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis and hyper-activity of this system have been described in patients with psychosis. Conversely, some psychiatric disorders such as post-traumatic stress disorder (PTSD) are characterised by HPA hypo-activity, which could be related to prior exposure to trauma. This study examined the cortisol response to the administration of low-dose dexamethasone in first-episode psychosis (FEP) patients and its relationship to childhood trauma.Method:The low-dose (0.25 mg) Dexamethasone Suppression Test (DST) was performed in 21 neuroleptic-naïve or minimally treated FEP patients and 20 healthy control participants. Childhood traumatic events were assessed in all participants using the Childhood Trauma Questionnaire (CTQ) and psychiatric symptoms were assessed in patients using standard rating scales.Results:FEP patients reported significantly higher rates of childhood trauma compared to controls (p = 0.001) and exhibited lower basal (a.m.) cortisol (p = 0.04) and an increased rate of cortisol hyper-suppression following dexamethasone administration compared to controls (33% (7/21) vs 5% (1/20), respectively; p = 0.04). There were no significant group differences in mean cortisol decline or percent cortisol suppression following the 0.25 mg DST. This study shows for the first time that a subset of patients experiencing their first episode of psychosis display enhanced cortisol suppression.Conclusions:These findings suggest there may be distinct profiles of HPA axis dysfunction in psychosis which should be further explored.
Australian and New Zealand Journal of Psychiatry 11/2012; · 3.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has been suggested that some cases of schizophrenia may be caused by an interaction between physiological risk factors and exposure to certain neurotropic infectious agents such as Herpes Simplex Virus type 1 (HSV1). This study investigated whether HSV1 exposure was associated with structural brain abnormalities in individuals who, because of genetic or other factors, were deemed at ultra high risk (UHR) of developing psychosis. Twenty-five UHR individuals with a history of HSV1 exposure (HSV1+), 33 UHR participants without a history of HSV1 exposure (HSV1-) and 19 healthy controls participated in the study. All participants underwent a T1-weighted structural MRI scan, and HSV1 exposure was determined based on the presence of IgG class antibodies in the blood serum. Voxel based morphometry revealed that the HSV1+ participants exhibited volumetric gray matter reductions in the cuneus, relative to both the HSV1--and healthy control participants (p<0.05, small volume corrected for familywise error). The results of the study suggest that a history of HSV1 infection is associated with volumetric gray matter reductions in individuals at ultra-high risk for developing psychosis, and are consistent with previous studies that have identified structural gray matter abnormalities in HSV1-infected patients with established schizophrenia.
Schizophrenia Research 03/2012; 135(1-3):175-80. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate if low-dose lithium may counteract the microstructural and metabolic brain changes proposed to occur in individuals at ultra-high risk (UHR) for psychosis.
Hippocampal T2 relaxation time (HT2RT) and proton magnetic resonance spectroscopy ((1)H-MRS) measurements were performed prior to initiation and following three months of treatment in 11 UHR patients receiving low-dose lithium and 10 UHR patients receiving treatment as usual (TAU). HT2RT and (1)H-MRS percentage change scores between scans were compared using repeated measures ANOVA and correlated with behavioural change scores.
Low-dose lithium significantly reduced HT2RT compared to TAU (p=0.018). No significant group by time effects was seen for any brain metabolites as measured with (1)H-MRS, although myo-inositol, creatine, choline-containing compounds and NAA increased in the group receiving low-dose lithium and decreased or remained unchanged in subjects receiving TAU.
This pilot study suggests that low-dose lithium may protect the microstructure of the hippocampus in UHR states as reflected by significantly decreasing HT2RT. Larger scale replication studies in UHR states using T2 relaxation time as a proxy for emerging brain pathology seem a feasible mean to test neuroprotective strategies such as low-dose lithium as potential treatments to delay or even prevent the progression to full-blown disorder.
Current pharmaceutical design 02/2012; 18(4):570-5. · 4.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the experience of stress and associated coping responses are thought to play a role in the onset of schizophrenia and other psychotic disorders, there is little empirical evidence to support such a relationship. The relatively recent development of validated and reliable criteria for identifying young people at "ultra" high-risk (UHR) of psychosis has enabled the process of illness onset to be studied more closely than was previously possible.
This longitudinal study compared the experiences of stress and coping between a UHR cohort (N=143) and a healthy comparison group (HC group, N=32).
The UHR group experienced significantly fewer life events over a 12-month period than the HC group, but there was no difference in the experience of minor events or "hassles". However, the UHR group reported feeling significantly more distressed by events, felt they coped more poorly and utilized different coping strategies.
The appraisals made about stressors differentiated the groups and was associated with differences in coping and distress levels. This suggests that treatment strategies focusing on stress management and enhancing coping skills might be important components of preventive interventions.
Behavioural and Cognitive Psychotherapy 07/2011; 40(1):69-88. · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The treatment of psychotic disorders such as schizophrenia, schizophreniform, and bipolar disorder had been viewed with pessimism
until a shift in focus from established or chronic illness to earlier phases of illness around the onset highlighted opportunities
for enhanced recovery. The early psychosis focus emerged from recognition that the underlying nature of the illnesses would
be better studied in this phase of disorder (1). A welcome by-product has been the revival of interest in a realistic preventive treatment approach centering primarily
on enhanced detection and treatment of first episode psychosis (2,3,4, 5). It has also been recognized that even prior to the onset of frank psychosis, during the prodromal phase, the changes underpinning
the illness are already active although less obtrusively, and lead to substantial and progressive distress and disability
(6). The major emphasis to date has been on limiting the psychosocial, and possibly biological (7), damage which flows from delays in treatment which occur even after the onset of frank psychotic symptoms (2, 8). However, to a significant extent, the horse may well have bolted by this stage. The bulk of the early phase psychosocial
disability has generally emerged by the advent of the prepsychotic phase, and could therefore set a ceiling for recovery even
when timely treatment of the first psychotic episode is ultimately available (6, 9,10). This suggests that the prepsychotic phase is the “critical period” (11) par excellence for intervention efforts.
[Show abstract][Hide abstract] ABSTRACT: Recent neuroimaging investigations have identified a relationship between psychotic symptoms in schizophrenia and abnormal brain connectivity. On the basis of the continuum model of psychosis, it was hypothesized that schizotypal traits in healthy control participants would be associated with relatively impaired frontotemporal white matter health as assessed using diffusion tensor imaging. Twenty-one participants (12 women and 9 men aged 18 to 58 years) completed the Schizotypal Personality Questionnaire (SPQ) and underwent diffusion-weighted magnetic resonance imaging scanning as part of a larger study. White matter integrity for the major association fibre tracts was assessed using standard measures of diffusivity, specifically fractional anisotropy (FA) and axial and radial diffusivity. A series of negative binomial regressions yielded significant relationships between reduced FA in seven white matter tracts and increased scores on the SPQ cognitive-perceptual factor. These findings are consistent with research relating brain connectivity to the positive symptoms of schizophrenia, suggesting that the neurobiological bases of schizotypal personality in healthy controls may be analogous to the neurobiological bases of schizophrenia spectrum disorders.
The Journal of nervous and mental disease 05/2011; 199(5):348-53. · 1.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: People experiencing possible prodromal symptoms of psychosis have a very high risk of developing the disorder, but it is not possible to predict, on the basis of their presenting clinical features, which individuals will subsequently become psychotic. Recent neuroimaging studies suggest that there are volumetric differences between individuals at ultra-high risk (UHR) for psychosis who later develop psychotic disorder and those who do not. However, the samples examined to date have been small, and the findings have been inconsistent.
To assess brain structure in individuals at UHR for psychosis in a larger and more representative sample than in previous studies by combining magnetic resonance imaging data from 5 different scanning sites.
A total of 182 individuals at UHR and 167 healthy controls. Participants were observed clinically for a mean of 2 years. Forty-eight individuals (26.4%) in the UHR group developed psychosis and 134 did not.
Magnetic resonance images were acquired from each participant. Group differences in gray matter volume were examined using optimized voxel-based morphometry.
The UHR group as a whole had less gray matter volume than did controls in the frontal regions bilaterally. The UHR subgroup who later developed psychosis had less gray matter volume in the left parahippocampal cortex than did the UHR subgroup who did not.
Individuals at high risk for psychosis show alterations in regional gray matter volume regardless of whether they subsequently develop the disorder. In the UHR population, reduced left parahippocampal volume was specifically associated with the later onset of psychosis. Alterations in this region may, thus, be crucial to the expression of illness. Identifying abnormalities that specifically predate the onset of psychosis informs the development of clinical investigations designed to predict which individuals at high risk will subsequently develop the disorder.
Archives of general psychiatry 05/2011; 68(5):489-95. · 12.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It remains unclear whether brain structural abnormalities observed before the onset of psychosis are specific to schizophrenia or are common to all psychotic disorders. This study aimed to measure regional gray matter volume prior to the onset of schizophreniform and of affective psychoses. We investigated 102 subjects at ultrahigh risk (UHR) of developing psychosis recruited from the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia. Twenty-eight of these subjects developed psychosis subsequent to scanning: 19 schizophrenia, 7 affective psychoses, and 2 other psychoses. We examined regional gray matter volume using 1.5 mm thick, coronal, 1.5 Tesla magnetic resonance imaging and voxel-based morphometry methods of image analysis. Subjects were scanned at presentation and were followed up clinically for a minimum of 12 months, to detect later transition to psychosis. We found that both groups of subjects who subsequently developed psychosis (schizophrenia and affective psychosis) showed reductions in the frontal cortex relative to UHR subjects who did not develop psychosis. The subgroup that subsequently developed schizophrenia also showed smaller volumes in the parietal cortex and, at trend level, in the temporal cortex, whereas those who developed an affective psychosis had significantly smaller subgenual cingulate volumes. These preliminary findings suggest that volumetric abnormalities in UHR individuals developing schizophrenia vs affective psychoses comprise a combination of features that predate both disorders and others that may be specific to the nature of the subsequent disorder.