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Objective: There is increasing interest in early intervention and detection strategies for youth at-risk of developing a serious mental illness (SMI). Little is known about early factors that may be related to the later development of a SMI; thus, the aim of this study was to determine what clinical factors might relate to the development of in this study psychosis, bipolar disorder and severe or recurrent major depression in at-risk youth., Method: The sample consisted of 162 youth aged 12-26 years at different stages of risk. Thirty-one participants developed a SMI during the study. Those who made a transition were compared on a range of baseline clinical and functional measures with those who did not make the transition. A Cox regression model was used to assess the association between measures and later development of a SMI., Results: Female sex, attenuated psychotic symptoms as assessed with the Scale of Psychosis-Risk Symptoms (SOPS) and ratings on the K-10 Distress Scale, were found to be significantly associated with the later transition to mental illness. Females were 2.77 times more likely to transition compared to males. For the SOPS and K-10 scales, there is a 14% increase in the transition rate relative to a one-scale increase in SOPS and a 7% increase in the transition rate relative to a one-point increase in the K-10., Conclusions: Results from these longitudinal data provide further insight into the specific clinical measures that may be pertinent in early detection of mental illnesses., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Identifying early biomarkers of serious mental illness (SMI)-such as changes in brain structure and function-can aid in early diagnosis and treatment. Whole brain structural and functional connectomes were investigated in youth at risk for SMI., Methods: Participants were classified as healthy controls (HC; n = 33), familial risk for serious mental illness (stage 0; n = 31), mild symptoms (stage 1a; n = 37), attenuated syndromes (stage 1b; n = 61), or discrete disorder (transition; n = 9) based on clinical assessments. Imaging data was collected from two sites. Graph-theory based analysis was performed on the connectivity matrix constructed from whole-brain white matter fibers derived from constrained spherical deconvolution of the diffusion tensor imaging (DTI) scans, and from the correlations between brain regions measured with resting state functional magnetic resonance imaging (fMRI) data., Results: Linear mixed effects analysis and analysis of covariance revealed no significant differences between groups in global or nodal metrics after correction for multiple comparisons. A follow up machine learning analysis broadly supported the findings. Several non-overlapping frontal and temporal network differences were identified in the structural and functional connectomes before corrections., Conclusions: Results suggest significant brain connectome changes in youth at transdiagnostic risk may not be evident before illness onset., (© 2022. The Author(s).)

Background: Adults with significant childhood trauma and/or serious mental illness may exhibit persistent structural brain changes within limbic structures, including the amygdala. Little is known about the structure of the amygdala prior to the onset of SMI, despite the relatively high prevalence of trauma in at-risk youth., Methods: Data were gathered from the Canadian Psychiatric Risk and Outcome study. A total of 182 youth with a mean age of 18.3 years completed T1-weighted MRI scans along with clinical assessments that included questionnaires on symptoms of depression and anxiety. Participants also completed the Childhood Trauma and Abuse Scale. We used a novel subfield-specific amygdala segmentation workflow as a part of FreeSurfer 6.0 to examine amygdala structure., Results: Participants with higher trauma scores were more likely to have smaller amygdala volumes, particularly within the basal regions. Among various types of childhood trauma, sexual and physical abuse had the largest effects on amygdala subregions. Abuse-related differences in the right basal region mediated the severity of depression and anxiety symptoms, even though no participants met criteria for clinical diagnosis at the time of assessment., Conclusion: The experience of physical or sexual abuse may leave detectable structural alterations in key regions of the amygdala, potentially mediating the risk of psychopathology in trauma-exposed youth.

Background: In their early stages, serious mental illnesses (SMIs) are often indistinguishable from one another, suggesting that studying alterations in brain activity in a transdiagnostic fashion could help to understand the neurophysiological origins of different SMI. The purpose of this study was to examine brain activity in youth at varying stages of risk for SMI using functional magnetic resonance imaging tasks (fMRI) that engage brain systems believed to be affected., Methods: Two hundred and forty three participants at different stages of risk for SMI were recruited to the Canadian Psychiatric Risk and Outcome (PROCAN) study, however only 179 were scanned. Stages included asymptomatic participants at no elevated risk, asymptomatic participants at elevated risk due to family history, participants with undifferentiated general symptoms of mental illness, and those experiencing attenuated versions of diagnosable psychiatric illnesses. The fMRI tasks included: (1) a monetary incentive delay task; (2) an emotional Go-NoGo and (3) an n-back working memory task., Results: Strong main effects with each of the tasks were found in brain regions previously described in the literature. However, there were no significant differences in brain activity between any of the stages of risk for SMI for any of the task contrasts, after accounting for site, sex and age. Furthermore, results indicated no significant differences even when participants were dichotomized as asymptomatic or symptomatic., Conclusions: These results suggest that univariate BOLD responses during typical fMRI tasks are not sensitive markers of SMI risk and that further study, particularly longitudinal designs, will be necessary to understand brain changes underlying the early stages of SMI., (© 2020 John Wiley & Sons Australia, Ltd.)

Objective: The objective of this study was to identify a sample of youth in distinct stages of risk for the development of a serious mental illness (SMI) according to a published clinical staging model and to follow this sample longitudinally to determine clinical changes over time. This article reports the 6- and 12-month follow-up of the cohort., Methods: This study recruited 243 youth, ages 12 to 25. The sample included (a) 42 healthy controls, (b) 41 nonhelpseeking individuals with no mental illness but some risk of SMI, for example, having a first-degree relative with an SMI (stage 0), (c) 53 youth experiencing distress and mild symptoms of anxiety or depression (stage 1a), and (d) 107 youth with attenuated symptoms of SMIs such as bipolar disorder or psychosis (stage 1b). Participants completed a range of measures assessing depression, anxiety, mania, suicide ideation, attenuated psychotic symptoms, negative symptoms, anhedonia and beliefs about oneself at baseline, 6- and 12-months., Results: There were few changes for healthy controls and stage 0 participants, although approximately 7% did move to a symptomatic stage within 12-months. Of stage 1a participants, 50% remained symptomatic, with 7.5% moving to stage 1b or developing a SMI. Approximately 9% of stage 1byouth developed a SMI within 12-months and approximately one-third had remission of symptoms during the follow-up., Conclusions: Results suggest that the implementation of a transdiagnostic staging model may be useful in youth mental health and support consideration of clinical stage-based treatment for youth with early features of risk., (© 2020 John Wiley & Sons Australia, Ltd.)

Identifying biomarkers of serious mental illness, such as altered white matter microstructure, can aid in early diagnosis and treatment. White matter microstructure was assessed using constrained spherical deconvolution of diffusion imaging data in a sample of 219 youth (age 12-25 years, 64.84% female) across 8 sites. Participants were classified as healthy controls (HC; n = 47), familial risk for serious mental illness (n = 31), mild-symptoms (n = 37), attenuated syndromes (n = 66), or discrete disorder (n = 38) based on clinical assessments. Fractional anisotropy (FA) and mean diffusivity (MD) values were derived for the whole brain white matter, forceps minor, anterior cingulate, anterior thalamic radiations (ATR), inferior fronto-occipital fasciculus, superior longitudinal fasciculus (SLF), and uncinate fasciculus (UF). Linear mixed effects models showed a significant effect of age on MD of the left ATR, left SLF, and left UF, and a significant effect of group on FA for all tracts examined. For most tracts, the discrete disorder group had significantly lower FA than other groups, and the attenuated syndromes group had higher FA compared to HC, with few differences between the remaining groups. White matter differences in MDD are most evident in individuals following illness onset, as few significant differences were observed in the risk phase., (Copyright © 2021. Published by Elsevier B.V.)

Aim: The aim of this paper is to describe the substance use of participants who are at-risk for serious mental illness (SMI)., Method: The Canadian Psychiatric Risk and Outcome study (PROCAN) is a two-site study of 243 youth and young adults aged 13 to 25 years, categorized into four groups: healthy controls (n = 42), stage 0 (asymptomatic individuals with risk of SMI typically family high risk; n = 41), stage 1a (distress disorder or mild symptoms of anxiety or depression; n = 53) and stage 1b (attenuated syndromes, including bipolar disorder or psychosis; n = 107). Substance use measures were administered at baseline, 6- and 12-months., Results: At baseline, the most commonly reported substance used in the past month was alcohol (43.6%), followed by cannabis (14.4%) and tobacco (12.4%). There were no significant group differences in use. 42.4% of all participants reported ever using cannabis in their lifetime, whereas 21.4% reported currently using cannabis. There were no group differences in ever having used cannabis. Regarding lifetime substance abuse disorders, cannabis use disorder (5.7%) and alcohol use disorder (4.5%) were the most common and more often reported in stage 1b participants relative to other groups. Furthermore, alcohol, cannabis and tobacco use remained relatively consistent at 6- and 12-month follow-ups when compared to baseline use., Conclusion: Alcohol was the most commonly used substance followed by cannabis and tobacco. Although substance use did not differ between those at different stages of risk, overall prevention strategies are still warranted for youth at-risk for SMI, especially those who are more symptomatic and potentially at greater risk of developing an SMI., (© 2020 John Wiley & Sons Australia, Ltd.)

Aim: Certain personality traits may be related to an increased risk of developing a severe mental illness (SMI). This study examined differences in personality characteristics in a sample of youth at-risk of SMI across different clinical stages compared to healthy controls (HCs)., Method: Personality characteristics were assessed with the NEO-Five-Factor Inventory-3 for 41 non-help seeking asymptomatic youth with risk factors for SMI (Stage 0), 52 youth with early mood and anxiety symptoms and distress (Stage 1a), 108 youth with an attenuated psychiatric syndrome (Stage 1b), and 42 HCs., Results: Symptomatic participants scored significantly higher in neuroticism, and lower in extraversion, and conscientiousness compared to non-symptomatic participants. Compared to published norms, symptomatic participants had ratings of extraversion and conscientiousness in the low range and those with attenuated psychiatric syndromes scored high on neuroticism., Conclusion: The observed personality profiles of the symptomatic stages were similar to reported profiles for discrete disorders. Early identification of this profile could aid identification of those at risk of SMI., (© 2020 John Wiley & Sons Australia, Ltd.)

Longitudinal changes in white matter connectivity were assessed in a sample of youth at-risk for serious mental illness (n=183; age 12-25). Diffusion tensor imaging (DTI) was acquired at baseline and 12 months from youth recruited across two sites and classified as healthy controls (n=36), familial risk (n=30), mild-symptoms (n=41), attenuated syndromes (n=70), or transition (n=9) based on clinical assessments. Fractional anisotropy (FA) and mean diffusivity (MD) values were derived for the whole brain white matter, forceps minor, anterior cingulate, anterior thalamic radiations, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, and uncinate fasciculus. MANCOVA analysis controlling for site, sex, and age showed no significant group differences in FA and MD at baseline or at 12 months. Linear mixed effects analysis showed a significant effect for time for most white matter tracts, but no effect for group, or group by time interaction. Transdiagnostic risk groups have similar profiles of WM connectivity and similar rates of change over time., Competing Interests: Declaration of Competing Interest JA has received research support from National Institute of Mental Health, Brain Canada and the Mathison Centre at the University of Calgary. SHK has received funding or honoraria from the following sources: Abbott, Allergan, AstraZeneca, BMS, Brain Cells Inc., Brain Canada, Clera, CIHR, Eli Lilly, Janssen, Lundbeck, Lundbeck Institute, OMHF, Ontario Brain Institute, Otsuka, Pfizer, Servier, St. Jude Medical, Sunovion and Xian-Janssen. GM has been on advisory board or speaker for Allergen, Lundbeck, Lilly, Pfizer, Janssen. MKS, PDM, GG, SB, BM, JW, and CL list no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: Functional impairment is common in serious mental illness (SMI). This study assessed social and role functioning in a sample of youth at risk of SMI who met different stages of risk based on a transdiagnostic clinical staging model described by McGorry and colleagues., Method: The sample consisted of 243 male and female youths aged 12-26 and included: non-help-seeking youth with risk factors (stage 0; n = 41); youth with mild symptoms (stage 1a; n = 52); youth with attenuated psychiatric syndromes (stage 1b; n = 108); and healthy controls (HCs; n = 42). Social and role functioning were assessed with the Global Functioning: Social and Role scales., Results: Participants in stage 1b (attenuated syndromes) had significantly poorer social and role functioning than stage 0 participants and HCs (P < .001) and poorer social functioning than stage 1a (P < .05). Stage 1a participants had significantly poorer social functioning than HCs (P < .01) and significantly poorer role functioning than stage 0 participants (P < .01). Participants in stages 1a and 1b did not significantly differ from each other in role functioning only., Conclusions: This study demonstrates that mild to moderate functional impairments are present in young people experiencing subthreshold psychiatric symptoms and distress in the absence of a diagnosable mental illness. Results partially validate the model in that social although not role functioning declines across the stages., (© 2019 John Wiley & Sons Australia, Ltd.)

Aim: To investigate sleep behaviours of youth at-risk for serious mental illness (SMI)., Methods: This study included 243 youth, ages 12 to 25:42 healthy controls, 41 asymptomatic youth at-risk for mental illness (stage 0); 53 help-seeking youth experiencing distress (stage 1a) and 107 youth with attenuated syndromes (stage 1b). The Pittsburgh Sleep Quality Index was used to assess sleep dysfunction., Results: Stage 1b individuals indicated the greatest deficit in global sleep dysfunction (F = 26.18, P < .0001). Stages 1a and 1b reported significantly worse subjective sleep quality, a longer sleep latency, increased use of sleep medications as well as greater daytime dysfunction compared to the asymptomatic groups., Conclusion: Research investigating sleep behaviours of youth considered to be at-risk for SMI is limited. This study provides early evidence that sleep disturbances are worse for individuals considered to be at higher risk of illness development., (© 2019 John Wiley & Sons Australia, Ltd.)

Childhood trauma has been shown to have detrimental consequences on mental health. It is unknown what impact childhood trauma may have on the early trajectory of serious mental illness (SMI). The purpose of this article is to estimate the baseline prevalence, perceived impact, and duration of trauma that occurred before the age of 18 years in youth at risk for SMI using a transdiagnostic approach. This study included 243 youths, ages 12 to 25 years (42 healthy controls, 43 non-help-seeking individuals [stage 0], 52 help-seeking youth experiencing distress and possibly mild symptoms of anxiety or depression [stage1a], and 108 youth demonstrating attenuated symptoms of an SMI such as bipolar disorder or psychosis [stage 1b]). Participants completed an adapted version of the Childhood Trauma and Abuse scale. There were high frequencies of reported trauma across all stages. Symptomatic individuals experienced more trauma and bullying. Stage 1b individuals reported more physical abuse. Stage 1b also indicated psychological bullying to have a longer duration and impact on their lives. Future work should aim to clarify the complex interrelations between trauma and risk of SMI.

Objective: The aim was to describe treatment history including medications, psychosocial therapy and hospital visits of participants in the Canadian Psychiatric Risk and Outcomes Study (PROCAN)., Methods: PROCAN is a 2-site study of 243 youth/young adults aged 12 to 25 y, categorized into 4 groups: healthy controls ( n = 42), stage 0 (non-help seeking, asymptomatic with risk mainly family history of serious mental illness (SMI); n = 41), stage 1a (distress disorders; n = 52) and stage 1b (attenuated syndromes; n = 108). Participants were interviewed regarding lifetime and current treatments, including medications, psychosocial therapies and hospital visits., Results: The number receiving baseline medications differed significantly across groups ( P < 0.001): 0% healthy controls, 14.6% stage 0, 32.7% stage 1a and 34.3% stage 1b. Further, 26.9% and 49.1% of stage 1a and stage 1b participants received psychosocial therapy at baseline, indicative of statistically significant differences among the groups ( P < 0.001). Similar results were observed for lifetime treatment history; stage 1b participants had the highest frequency of lifetime treatment. Medications started in adulthood (>18 y of age) were the most common for initiation of treatment compared to childhood (0 to 12 y) and adolescence (13 to 17 y) for stage 1a and 1b participants. Lifetime mental health hospital visits differed significantly across groups ( P < 0.001) and were most common in stage 1b participants (29.6%) followed by stage 1a (13.5%), stage 0 (4.9%) and healthy controls (2.4%)., Conclusion: We found that treatment history for participants in the PROCAN study differed among the at-risk groups. Future initiatives focused on determining the effects of treatment history on SMI are warranted.

There is a growing literature which suggests that neurocognitive deficits may be markers of susceptibility for serious mental illness development. This study assessed neurocognitive functioning in a sample of youth at risk of serious mental illness across different clinical stages as described by McGorry and colleagues and compared them to healthy controls. The sample was 243 male and female youths aged 12-26 and included: asymptomatic participants with psychiatric risk factors (Stage 0; n = 41); youth with early mood or anxiety symptoms (Stage 1a; n = 52); youth with attenuated psychiatric syndromes (Stages 1b; n = 108); and healthy controls (n = 42). The neurocognitive battery included IQ measures and the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. Participants in Stage 1b had lower scores than healthy controls on the composite score of neurocognitive performance, across all IQ measures, and in the domains of processing speed, working memory, attention and problem solving. They also had lower scores than subjects in Stage 0 across most IQ measures and in the domains of processing speed and working memory. This study increases what is known about neurocognitive performance associated with different stages of serious mental illness development., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: There is evidence that family functioning can be impaired in families of individuals with schizophrenia, first-episode psychosis, bipolar disorder, and recurrent depression, which are considered to be serious mental illnesses (SMI). Poor family functioning is one of the predictors of the course of SMI. However, it is unclear if poor family functioning is a result of illness, or conversely if poor family leads to higher risk of illness. Nonetheless, family functioning may be impaired even before the onset of illness, and little is known about earlier stages of risk and the importance of the family environment for youth at-risk for SMI., Objective: The present study aimed to examine differences in family functioning in a sample of youth at-risk of SMI across different clinical stages compared to healthy controls (HCs)., Methods: Family functioning was evaluated with the Family Adaptability and Cohesion Evaluation Scales-IV (FACES-IV) for 41 non-help seeking youth with risk factors for SMI (Stage 0), 52 help-seeking youth with early mood and anxiety symptoms and distress (Stage 1a), 108 youth with an attenuated psychiatric syndrome (Stage 1b), and 42 HCs., Results: Results from multivariate linear regression analyses showed that participants in Stage 1a and Stage 1b significantly differ from participants in Stage 0 and HCs on most of the family functioning scales. However, these results were statistically but not clinically significant as the percentile values for each group fell within the same clinical ranges. The only clinical difference was that participants in stages 1a and 1b were somewhat less satisfied with their family compared to healthy controls and stage 0 participants., Conclusions: An examination of group mean values demonstrated no difference in family functioning between the different groups with all groups in the healthy functioning range. However, family satisfaction is lower in youth at-risk for SMI who present with early signs of mood, anxiety or subthreshold psychotic symptoms than other participants. Early family psychoeducational interventions could be beneficial to improve family functioning., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Most mental disorders begin in adolescence; however, there are gaps in our understanding of youth mental health. Clinical and policy gaps arise from our current inability to predict, from amongst all youth who experience mild behavioural disturbances, who will go on to develop a mental illness, what that illness will be, and what can be done to change its course and prevent its worsening to a serious mental illness (SMI). There are also gaps in our understanding of how known risk factors set off neurobiological changes that may play a role in determining who will develop a SMI. Project goals are (i) to identify youth at different stages of risk of SMI so that intervention can begin as soon as possible and (ii) to understand the triggers of these mental illnesses., Method: This 2-site longitudinal study will recruit 240 youth, ages 12-25, who are at different stages of risk for developing a SMI. The sample includes (a) healthy individuals, (b) symptom-free individuals who have a first-degree relative with a SMI, (c) youth who are experiencing distress and may have mild symptoms of anxiety or depression, and (d) youth who are already demonstrating attenuated symptoms of SMI such as bipolar disorder or psychosis. We will assess, every 6 months for one year, a wide range of clinical and psychosocial factors to determine which factors can be used to predict key outcomes. We will also assess neuroimaging and peripheral markers. We will develop and validate a prediction algorithm that includes demographic, clinical and psychosocial predictors. We will also determine if adding biological markers to our algorithm improves prediction., Discussion: Outcomes from this study include an improved clinical staging model for SMI and prediction algorithms that can be used by health care providers as decision-support tools in their practices. Secondly, we may have a greater understanding of clinical, social and cognitive factors associated with the clinical stages of development of a SMI, as well as new insights from neuroimaging and later neurochemical biomarker studies regarding predisposition to SMI development and progression through the clinical stages of illness.