Family-focused treatment for adolescents and young adults at high risk for psychosis: results of a randomized trial.
ABSTRACT: Longitudinal studies have begun to clarify the phenotypic characteristics of adolescents and young adults at clinical high risk for psychosis. This 8-site randomized trial examined whether a 6-month program of family psychoeducation was effective in reducing the severity of attenuated positive and negative psychotic symptoms and enhancing functioning among individuals at high risk.Adolescents and young adults (mean age 17.4 ± 4.1 years) with attenuated positive psychotic symptoms, brief and intermittent psychosis, or genetic risk with functional deterioration were randomly assigned to 18 sessions of family-focused therapy for individuals at clinical high risk (FFT-CHR) in 6 months or 3 sessions of family psychoeducation (enhanced care [EC]). FFT-CHR included psychoeducation about early signs of psychosis, stress management, communication training, and problem-solving skills training, whereas EC focused on symptom prevention. Independent evaluators assessed participants at baseline and 6 months on positive and negative symptoms and social-role functioning.Of 129 participants, 102 (79.1%) were followed up at 6 months. Participants in FFT-CHR showed greater improvements in attenuated positive symptoms over 6 months than participants in EC (F1,97 = 5.49, p = .02). Negative symptoms improved independently of psychosocial treatments. Changes in psychosocial functioning depended on age: participants more than 19 years of age showed more role improvement in FFT-CHR, whereas participants between 16 and 19 years of age showed more role improvement in EC. The results were independent of concurrent pharmacotherapy.Interventions that focus on improving family relationships may have prophylactic efficacy in individuals at high risk for psychosis. Future studies should examine the specificity of effects of family intervention compared to individual therapy of the same duration and frequency. Clinical trial registration information-Prevention Trial of Family Focused Treatment in Youth at Risk for Psychosis; http://clinicaltrials.gov/; NCT01907282.
Project description:Adolescents with bipolar disorder (BD) report lower quality of life (QoL) than adolescents with other psychiatric disorders. This study compared the efficacy of family-focused therapy for adolescents (FFT-A) plus pharmacotherapy to brief psychoeducation (enhanced care, or EC) plus pharmacotherapy on self-rated QoL in adolescents with BD over 2 years.Participants were 141 adolescents (mean age: 15.6±1.4yr) with BD I or II who had a mood episode in the previous 3 months. Adolescents and parents were randomly assigned to (1) FFT-A, given in 21 sessions in 9 months of psychoeducation, communication enhancement training, and problem-solving skills training, or (2) EC, given in 3 family psychoeducation sessions. Study psychiatrists provided patient participants with protocol-based pharmacotherapy for the duration of the study. QoL was assessed with The KINDLRQuestionnaire (Ravens-Sieberer and Bullinger, 1998) during active treatment (baseline to 9 months) and during a post-treatment follow-up (9-24 months).The two treatment groups did not differ in overall QoL scores over 24 months. However, adolescents in FFT-A had greater improvements in quality of family relationships and physical well-being than participants in EC. For quality of friendships, the trajectory during active treatment favored EC, whereas the trajectory during post-treatment favored FFT-A.We were unable to standardize medication use or adherence over time. Quality of life was based on self-report rather than on observable functioning.A short course of family psychoeducation and skills training may enhance relational functioning and health in adolescents with BD. The effects of different psychosocial interventions on peer relationships deserves further study.
Project description:Perceived criticism (PC) is a measure of how much criticism from 1 family member "gets through" to another. PC ratings have been found to predict the course of psychotic disorders, but questions remain regarding whether psychosocial treatment can effectively decrease PC, and whether reductions in PC predict symptom improvement. In a sample of individuals at high risk for psychosis, we examined a) whether Family Focused Therapy for Clinical High-Risk (FFT-CHR), an 18-session intervention that consists of psychoeducation and training in communication and problem solving, brought about greater reductions in perceived maternal criticism, compared to a 3-session family psychoeducational intervention; and b) whether reductions in PC from baseline to 6-month reassessment predicted decreases in subthreshold positive symptoms of psychosis at 12-month follow-up. This study was conducted within a randomized controlled trial across 8 sites. The perceived criticism scale was completed by 90 families prior to treatment and by 41 families at 6-month reassessment. Evaluators, blind to treatment condition, rated subthreshold symptoms of psychosis at baseline, 6- and 12-month assessments. Perceived maternal criticism decreased from pre- to posttreatment for both treatment groups, and this change in criticism predicted decreases in subthreshold positive symptoms at 12-month follow-up. This study offers evidence that participation in structured family treatment is associated with improvement in perceptions of the family environment. Further, a brief measure of perceived criticism may be useful in predicting the future course of attenuated symptoms of psychosis for CHR youth.
Project description:Depression and brief periods of (hypo)mania are linked to an increased risk of progression to bipolar I or II disorder (BD) in children of bipolar parents. This randomized trial examined the effects of a 4-month family-focused therapy (FFT) program on the 1-year course of mood symptoms in youth at high familial risk for BD, and explored its comparative benefits among youth in families with high versus low expressed emotion (EE).Participants were 40 youth (mean 12.3±2.8 years, range 9-17) with BD not otherwise specified, major depressive disorder, or cyclothymic disorder who had a first-degree relative with BD I or II and active mood symptoms (Young Mania Rating Scale [YMRS]>11 or Child Depression Rating Scale>29). Participants were randomly allocated to FFT-High Risk version (FFT-HR; 12 sessions of psychoeducation and training in communication and problem-solving skills) or an education control (EC; 1-2 family sessions).Youth in FFT-HR had more rapid recovery from their initial mood symptoms (hazard ratio = 2.69, p = .047), more weeks in remission, and a more favorable trajectory of YMRS scores over 1 year than youth in EC. The magnitude of treatment effect was greater among youth in high-EE (versus low-EE) families.FFT-HR may hasten and help sustain recovery from mood symptoms among youth at high risk for BD. Longer follow-up will be necessary to determine whether early family intervention has downstream effects that contribute to the delay or prevention of full manic episodes in vulnerable youth.
Project description:<h4>Importance</h4>Behavioral high-risk phenotypes predict the onset of bipolar disorder among youths who have parents with bipolar disorder. Few studies have examined whether early intervention delays new mood episodes in high-risk youths.<h4>Objective</h4>To determine whether family-focused therapy (FFT) for high-risk youths is more effective than standard psychoeducation in hastening recovery and delaying emergence of mood episodes during the 1 to 4 years after an active period of mood symptoms.<h4>Design, settings, and participants</h4>This multisite randomized clinical trial included referred youths (aged 9-17 years) with major depressive disorder or unspecified (subthreshold) bipolar disorder, active mood symptoms, and at least 1 first- or second-degree relative with bipolar disorder I or II. Recruitment started from October 6, 2011, and ended on September 15, 2016. Independent evaluators interviewed participants every 4 to 6 months to measure symptoms for up to 4 years. Data analysis was performed from March 13 to November 3, 2019.<h4>Interventions</h4>High-risk youths and parents were randomly allocated to FFT (12 sessions in 4 months of psychoeducation, communication training, and problem-solving skills training; n?=?61) or enhanced care (6 sessions in 4 months of family and individual psychoeducation; n?=?66). Youths could receive medication management in either condition.<h4>Main outcomes and measures</h4>The coprimary outcomes, derived using weekly psychiatric status ratings, were time to recovery from prerandomization symptoms and time to a prospectively observed mood (depressive, manic, or hypomanic) episode after recovery. Secondary outcomes were time to conversion to bipolar disorder I or II and longitudinal symptom trajectories.<h4>Results</h4>All 127 participants (82 [64.6%] female; mean [SD] age, 13.2 [2.6] years) were followed up for a median of 98 weeks (range, 0-255 weeks). No differences were detected between treatments in time to recovery from pretreatment symptoms. High-risk youths in the FFT group had longer intervals from recovery to the emergence of the next mood episode (?2?=?5.44; P?=?.02; hazard ratio, 0.55; 95% CI, 0.48-0.92;), and from randomization to the next mood episode (?2?=?4.44; P?=?.03; hazard ratio, 0.59; 95% CI, 0.35-0.97) than youths in enhanced care. Specifically, FFT was associated with longer intervals to depressive episodes (log-rank ?2?=?6.24; P?=?.01; hazard ratio, 0.53; 95% CI, 0.31-0.88) but did not differ from enhanced care in time to manic or hypomanic episodes, conversions to bipolar disorder, or symptom trajectories.<h4>Conclusions and relevance</h4>Family skills-training for youths at high risk for bipolar disorder is associated with longer times between mood episodes. Clarifying the relationship between changes in family functioning and changes in the course of high-risk syndromes merits future investigation.<h4>Trial registration</h4>ClinicalTrials.gov identifier: NCT01483391.
Project description:Clarifying dynamic fluctuations in resting-state connectivity in individuals at risk for psychosis (termed clinical high risk [CHR]) may inform understanding of psychotic disorders, such as schizophrenia, which have been associated with dysconnectivity and aberrant salience processing. Dynamic functional connectivity (DFC) investigations provide insight into how neural networks exchange information over time. Currently, there are no published DFC studies involving CHR individuals. This is notable, because understanding how networks may come together and disassociate over time could lend insight into the neural communication that underlies psychosis development and symptomatology. A sliding-window analysis was utilized to examine DFC (defined as the standard deviation over a series of sliding windows) in resting-state scans in a total of 31 CHR individuals and 28 controls. Clinical assessments at baseline and 12 months later were conducted. CHR participants exhibited less DFC (lower standard deviation) in connectivity involving areas of both the salience network (SN) and default mode network (DMN) with regions involved in sensory, motor, attention, and internal cognitive functions relative to controls. Within CHR participants, this pattern was associated with greater positive symptoms 12 months later, possibly reflecting a mechanism behind aberrant salience processing. Higher SN-DMN internetwork DFC related to elevated baseline negative symptoms, anxiety, and depression in CHR participants, which may indicate neurological processes underlying worry and rumination. Overall, through highlighting unique DFC properties within CHR individuals and detecting informative links with clinically relevant symptomatology, results support dysconnectivity and aberrant salience processing models of psychosis. (PsycINFO Database Record
Project description:Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P = .041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis.
Project description:Introduction: The prevention of schizophrenia and other psychotic disorders has led researchers to focus on early identification of individuals at clinical high risk (CHR) for psychosis and to treat the at-risk symptoms in the pre-psychotic period. Although at-risk symptoms such as attenuated hallucinations or delusions are common in adolescents and associated with a marked reduction in global functioning, the evidence base of effective interventions for adolescents at CHR state and even ?rst-episode psychosis is limited. Thus, the present protocol describes a study design that combines therapy modules for CHR adolescents with a smartphone application supporting the young individuals between the therapy sessions. The treatment approach "Robin" is based on existing therapy strategies for adolescents with first episode of psychosis and the available recommendations for adults with at-risk symptoms. Methods: The evaluation aims firstly to compare the efficacy of Robin in 30 CHR adolescents aged 14-18 to an active control group (treatment as usual) from a previous study. Primary outcome measures will be at-risk symptomatology, comorbid diagnosis, functioning, self-efficacy, and quality of life. For the prospective intervention condition (16 weekly individual sessions + a minimum 4 family sessions), help-seeking adolescents with CHR for psychosis, aged 14-18, will be recruited over 3 years. At-risk and comorbid symptoms, functioning, self-efficacy, and quality of life are monitored at six time points (baseline, during the treatment period; immediately after intervention; and 6, 12, and 24 months later) and compared with the respective measures of the active control group. Discussion: To the best of our knowledge, this is the first controlled trial to test the efficacy of a specific early psychosis treatment in combination with a smartphone application for adolescents at CHR for developing psychosis. The results of the study are expected to add information that may substantially decrease the burden of CHR adolescents and increase their resilience. It may offer age-adapted and targeted strategies to guide clinicians in the treatment of these vulnerable individuals. Furthermore, research in the field of early intervention will be enriched by our findings. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03829527.
Project description:Negative symptoms are present in the psychosis prodrome. However, the extent to which these symptoms are present prior to the onset of the first episode of psychosis remains under-researched. The goal of this study is to examine negative symptoms in a sample of individuals at clinical high risk (CHR) for psychosis and to determine if they are predictive of conversion to psychosis. Participants (n=138) were all participants in the North American Prodrome Longitudinal Study (NAPLS 1) project. Negative symptoms were assessed longitudinally using the Scale of Prodromal Symptoms. The mean total negative symptom score at baseline was 11.0, with 82.0% of the sample scoring at moderate severity or above on at least one negative symptom. Over the course of 12 months, the symptoms remained in the above moderate severity range for 54.0% of participants. Associations between individual symptoms were moderate, and a factor analysis confirmed that all negative symptoms loaded heavily on one factor. Negative symptoms were more severe and persistent overtime in those who converted to psychosis, significantly predicting the likelihood of conversion. Thus, early and persistent negative symptoms may represent a vulnerability for risk of developing psychosis.
Project description:Background:Schizophrenia, a neurodevelopmental disorder, involves abnormalities in functional connectivity (FC) across distributed neural networks, which are thought to antedate the emergence of psychosis. In a cohort of adolescents and young adults at clinical high risk (CHR) for psychosis, we applied data-driven approaches to resting-state fMRI data so as to systematically characterize FC abnormalities during this period and determine whether these abnormalities are associated with psychosis risk and severity of psychotic symptoms. Methods:Fifty-one CHR participants and 47 matched healthy controls (HCs) were included in our analyses. Twelve of these CHR participants developed psychosis within 3.9 years. We estimated one multivariate measure of FC and studied its relationship to CHR status, conversion to psychosis and positive symptom severity. Results:Multivariate analyses revealed between-group differences in whole-brain connectivity patterns of bilateral temporal areas, mostly affecting their functional connections to the thalamus. Further, more severe positive symptoms were associated with greater connectivity abnormalities in the anterior cingulate and frontal cortex. Conclusions:Our study demonstrates that the well-established FC abnormalities of the thalamus and temporal areas observed in schizophrenia are also present in the CHR period, with aberrant connectivity of the temporal cortex most associated with psychosis risk.
Project description:OBJECTIVE:This study examined racial and ethnic differences in treatment outcomes among participants in a randomized controlled trial of an intervention for first-episode psychosis called NAVIGATE. METHODS:Secondary data analyses were conducted for participants randomly assigned to usual community care (N=181) and NAVIGATE (N=223). Generalized estimating equations assessed whether race and ethnicity were associated with psychiatric symptoms and service use (medication management, family psychoeducation, and individual therapy) over a 24-month treatment period, accounting for baseline symptoms, duration of untreated psychosis, and insurance status. RESULTS:Among persons in usual community care, non-Hispanic blacks scored significantly higher throughout treatment on measures of positive symptoms (?=2.15, p=.010), disorganized thoughts (?=1.15, p=.033), and uncontrolled hostility (?=.74, p=.027), compared with non-Hispanic whites, and non-Hispanic blacks were less likely than non-Hispanic whites to receive individual therapy (OR=.45, p=.001). Families of Hispanic participants in usual community care were less likely than non-Hispanic white families to receive family psychoeducation (OR=.20, p=.01). For NAVIGATE participants, race and ethnicity were not associated with differences in psychiatric symptoms over time; families of non-Hispanic black participants were less likely than those of non-Hispanic white participants to receive family psychoeducation (OR=.53, p=.009). Hispanic participants in NAVIGATE were more likely than non-Hispanic white participants to receive medication management (OR=2.93, p=.001). CONCLUSIONS:In usual community care, non-Hispanic blacks scored higher on measures of psychiatric symptoms and were less likely to receive important services, compared with non-Hispanic whites. In NAVIGATE, racial and ethnic differences in psychiatric symptoms were not evident, although non-Hispanic blacks were less likely than non-Hispanic whites to receive family psychoeducation.