Disorders - Bipolar Disorders
Singappuli,
P., Sonuga-Barke, E., Kyriakopoulos, M.
Antipsychotic medications are used in a
wide range of mental health and neurodevelopmental conditions in children and adolescents. Their efficacy and tolerability with long-term use have
not been clearly established. We aimed to conduct a systematic review and meta-analysis to evaluate the long-term use of antipsychotics in children
and adolescents. All relevant double-blind randomized control trials (RCTs), on any antipsychotic used for 12 weeks or longer in any mental
health/neurodevelopmental condition in this age group, were included. We evaluated several efficacy and tolerability measures. Meta-analysis was
performed for adverse events. Seven RCTs were identified (n = 939, age = 5-17 years), four on aripiprazole and three on risperidone. All studies
reported symptomatic/functional improvements or more time before discontinuation with antipsychotics compared to placebo. Weight gain was identified
as a significant side effect with antipsychotics. Serum prolactin was reduced with aripiprazole and increased with risperidone, and abdominal
pain/discomfort, respiratory tract infections, were more common with Aripiprazole compared to placebo. Musculoskeletal pain may be more common with
aripiprazole compared to placebo. Use of antipsychotics for 12 weeks or longer may be associated with symptomatic/functional improvements, but may be
associated with additional side effects compared to short-term treatment. Further research in this population is needed. Copyright ©
CNS Spectrums, 27(5) : 570-
587
- Year: 2022
- Problem: Bipolar Disorders, Psychosis Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Scott, K., Becker, S. J., Helseth, S. A., Saldanha, I. J., Balk, E. M., Adam, G. P., Konnyu, K. J., Steele, D. W.
BACKGROUND: Co-occurring mental health and substance use (SU) disorders among adolescents are common, with two-thirds of adolescents
who seek SU treatment also requiring support for mental health. Primary care physicians play a key role in the pharmacological treatment of mental
health disorders among adolescents, however, little is known about the impact of these treatments on SU outcomes. OBJECTIVE(S): This systematic
review summarizes the evidence regarding commonly used pharmacotherapy interventions for mental health and their impact on adolescent SU. METHOD(S):
Literature searches were conducted across five databases as part of a larger systematic review of adolescent SU interventions. Studies were screened
for eligibility by two researchers, and study data were extracted regarding study design, patient and treatment characteristics and results. Risk of
bias analyses and qualitative syntheses were completed to evaluate the strength of the evidence and the impact of pharmacotherapy on SU outcomes.
RESULT(S): Ten randomized controlled trials exploring seven pharmacotherapies met criteria for inclusion. All studies had low to moderate risk of
bias. Four studies evaluated pharmacotherapy for co-occurring depression and SU, three evaluated attention deficit hyperactivity disorder and SU, and
three evaluated bipolar disorder and SU. Five of the 10 studies also included a behavioural intervention. We found no evidence that pharmacotherapy
for co-occurring mental health diagnoses impacted SU. CONCLUSION(S): Family medicine clinicians prescribing pharmacotherapy for mental health should
be aware that additional interventions will likely be needed to address co-occurring SU. Copyright © The Author(s) 2021. Published by Oxford
University Press. All rights reserved.For permissions, please e-mail: [email protected].
Family Practice, 39(2) : 301-310
- Year: 2022
- Problem: Bipolar Disorders, Depressive Disorders, Suicide or self-harm with comorbid mental disorder, Substance Use Disorders (any)
- Type: Systematic reviews
-
Stage: At risk (indicated or selected prevention), Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Selective serotonin reuptake inhibitors (SSRIs), Antidepressants
(any), Atypical Antipsychotics (second
generation), Anticonvulsants/mood stabilisers (excl. lithium), Lithium, Medications used to treat substance abuse
Riccobene, T., Riesenberg, R., Yeung,
P. P., Earley, W. R., Hankinson, A. L.
Objective: Cariprazine is a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor
partial agonist approved to treat adults with schizophrenia and manic/mixed or depressive episodes associated with bipolar I disorder. This
sequential-cohort, dose-escalation study was the first to evaluate the pharmacokinetic, safety, and tolerability profile of cariprazine and its two
major active metabolites, desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR), in pediatric patients with schizophrenia or bipolar I
disorder. Method(s): This phase I open-label study enrolled patients with schizophrenia (13-17 years of age) or bipolar I disorder (10-17 years of
age). Patients met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for schizophrenia or bipolar I disorder
and had Positive and Negative Syndrome Scale (PANSS) total scores >=70 or Young Mania Rating Scale (YMRS) total scores >=20. Patients were assigned
to one of four treatment groups to receive 6 weeks of cariprazine treatment through slow titration to 1.5, 3, or 4.5 mg/d or fast titration to 4.5
mg/d. Pharmacokinetics, adverse events (AEs), and various safety parameters were analyzed. Efficacy was evaluated as an exploratory outcome. Result
(s): A total of 50 participants were enrolled. Based on mean trough levels, steady state appeared to be reached within 1-2 weeks for cariprazine and
DCAR and within 4-5 weeks for DDCAR. Systemic exposure of cariprazine, DCAR, and DDCAR generally increased approximately in proportion to the
increases in dose from 1.5 to 4.5 mg/d. The most frequent treatment-related, treatment-emergent AEs included sedation, parkinsonism, tremor,
dystonia, and blurred vision. Improvements from baseline on the PANSS and YMRS were observed throughout treatment. Conclusion(s): In this first
investigation of cariprazine in a pediatric population with schizophrenia or bipolar disorder, pharmacokinetic parameters were consistent with those
observed in adults. Cariprazine appeared to be safe and tolerable in children and adolescents. Copyright © 2022, Mary Ann Liebert, Inc.
Journal of Child and Adolescent
Psychopharmacology, 32(8) : 434-443
- Year: 2022
- Problem: Bipolar Disorders, Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Lei, D., Li, W., Tallman, M. J., Strakowski, S. M., DelBello, M. P., Rodrigo Patino, L., Fleck, D. E., Lui, S., Gong,
Q., Sweeney, J. A., Strawn, J. R., Nery, F. G., Welge, J. A., Rummelhoff, E., Adler, C. M.
Disrupted topological organization of brain functional networks has been widely reported in
bipolar disorder. However, the potential clinical implications of structural connectome abnormalities have not been systematically investigated. The
present study included 109 unmedicated subjects with acute mania who were assigned to 8 weeks of treatment with quetiapine or lithium and 60 healthy
controls. High resolution 3D-T1 weighted magnetic resonance images (MRI) were collected from both groups at baseline, week 1 and week 8. Brain
networks were constructed based on the similarity of morphological features across brain regions and analyzed using graph theory approaches. At
baseline, individuals with bipolar disorder illness showed significantly lower clustering coefficient (Cp) (p = 0.012) and normalized
characteristic path length (lambda) (p = 0.004) compared to healthy individuals, as well as differences in nodal centralities across multiple brain
regions. No baseline or post-treatment differences were identified between drug treatment conditions, so change after treatment were considered in
the combined treatment groups. Relative to healthy individuals, differences in Cp, lambda and cingulate gyrus nodal centrality were
significantly reduced with treatment; changes in these parameters correlated with changes in Young Mania Rating Scale scores. Baseline structural
connectome matrices significantly differentiated responder and non-responder groups at 8 weeks with 74% accuracy. Global and nodal network
alterations evident at baseline were normalized with treatment and these changes associated with symptomatic improvement. Further, baseline
structural connectome matrices predicted treatment response. These findings suggest that structural connectome abnormalities are clinically
significant and may be useful for predicting clinical outcome of treatment and tracking drug effects on brain anatomy in bipolar disorder. Clinical
Trials Registration: Name: Functional and Neurochemical Brain Changes in First-episode Bipolar Mania Following Successful Treatment with Lithium or
Quetiapine. URL: https://clinicaltrials.gov/. Registration number: NCT00609193. Name: Neurofunctional and Neurochemical Markers of Treatment Response
in Bipolar Disorder. URL: https://clinicaltrials.gov/. Registration number: NCT00608075. Copyright © 2022, The Author(s), under exclusive licence to
American College of Neuropsychopharmacology.
Neuropsychopharmacology, 47(11) : 1961-1968
- Year: 2022
- Problem: Bipolar Disorders
- Type: Controlled clinical trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Lithium
Goldstein, T., Merranko, J., Rode, N., Sylvester, R., Sakolsky, D., Diler, R., Hafeman, D., Birmaher, B.
Introduction: Nearly 50% of youth with bipolar
spectrum disorder (BD) attempt suicide. Although adjunctive psychotherapy is a critical component of optimal treatment for BD, little is known about
effective psychotherapy approaches for this population, and no intervention examined to date expressly targets suicide risk in adolescents with BD.
We examined the efficacy of DBT for adolescents with BD in decreasing risk for suicidal behavior. Method(s): 100 adolescents diagnosed with BD (I =
14, II = 28, research operationalized NOS criteria = 58) via semi-structured interview were randomized to receive 1 year of DBT (n = 47) or Standard
of Care psychotherapy (SOC, n = 53), both adjunct to pharmacotherapy, at a specialty clinic. Adolescents were evaluated by trained assessors blind to
treatment group at baseline and again quarterly throughout 1-year follow-up. We examined suicide attempt over follow-up as assessed via the
Adolescent Longitudinal Follow-Up Evaluation (ALIFE). Result(s): There were no differences between treatment groups in demographic or clinical
variables at baseline. In intent to treat analyses, there were no significant differences in rates of suicide attempt over follow-up between youth
who received DBT (46.8%) and youth who received SOC (47.2%). However, a mixed Poisson regression model demonstrated a significant 3-way interaction
between treatment group, time and history of suicide attempt (both baseline p = 0.02 and lifetime, p = 0.03), indicating that for youth with a
history of suicidal behavior, DBT was significantly more effective at preventing suicidal behavior over follow-up. Conclusion(s): For adolescents
with BD who have a history of suicidal behavior, DBT demonstrates efficacy in reducing risk for suicide attempt over 1-year.
Bipolar Disorders, 24(Supplement
1) : 30
- Year: 2022
- Problem: Bipolar Disorders, Suicide or self-harm behaviours (excluding non-suicidal self-harm)
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions
(any), Dialectical behavioural therapy
(DBT)
Findling, R.
L., Atkinson, S., Bachinsky, M., Raiter, Y., Abreu, P., Ianos, C., Chappell, P.
Objective: To evaluate the acute efficacy, safety, and tolerability of flexibly dosed ziprasidone in
children and adolescents with Bipolar I Disorder (BD-I). Methods: Participants, 10-17 years of age, meeting The Diagnostic and Statistical Manual of
Mental Disorders, 5th edition criteria, were randomized 1:1 in a 4-week double-blind (DB) study, to receive ziprasidone (20-80 mg/twice a day) or
placebo. Some were then enrolled in a 26-week open-label extension (OLE) study. The primary efficacy measure was the Young Mania Rating Scale (YMRS)
total score. Results: A total of 171 participants entered this randomized DB study and 23 continued into the OLE study. The mean (SD) age of the
combined sample was 13.4 (2.1) years, 44.4% were male, and 66.7% were white. The demographic characteristics of participants who received ziprasidone
(n = 86) or placebo (n = 85) were similar. The primary objective was met: the mean difference for ziprasidone versus placebo in the YMRS total score
was -4.23 (95% confidence interval: -7.14 to -1.32; p = 0.005) indicating an effect size of 0.58. The most common adverse events (AEs) in the
ziprasidone group were somnolence (31.4%), fatigue (22.1%), and nausea (14%). The mean Fridericia-corrected QT interval (QTcF) intervals in the
ziprasidone group were moderately prolonged relative to the placebo group at all study visits. No participants had QTcF intervals >=480 msec or an
increase from baseline >=60 msec. No AEs indicative of QT prolongation occurred. Weight, body mass index (BMI), and BMI z-scores, and metabolic
measures were similar in both treatment groups. The data from the OLE study will be reported separately. Conclusions: Ziprasidone was effective in
children and adolescents with BD-I in a manic episode, replicating the results of a previous study with a similar design (Findling et al. 2013).
Overall, ziprasidone was safe and well tolerated with no meaningful effects on weight or metabolic parameters. Trial registration:
ClinicalTrials.gov. NCT02075047 and NCT03768726.
Journal of Child and Adolescent Psychopharmacology, 32(3) : 143-
152
- Year: 2022
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Diao, X., Luo, D., Wang, D., Lai, J., Li, Q., Zhang, P., Huang, H., Wu, L., Lu, S., Hu, S.
The clinical efficacy of lurasidone
and quetiapine, two commonly prescribed atypical antipsychotics for bipolar depression, has been inadequately studied in young patients. In this
randomized and controlled study, we aimed to compare the effects of these two drugs on cognitive function, emotional status, and metabolic profiles
in children and adolescents with bipolar depression. We recruited young participants (aged 10-17 years old) with a DSM-5 diagnosis of bipolar
disorder during a depressive episode, who were then randomly assigned to two groups and treated with flexible doses of lurasidone (60 to 120 mg/day)
or quetiapine (300 to 600 mg/day) for consecutive 8 weeks, respectively. All the participants were clinically evaluated on cognitive function using
the THINC-it instrument at baseline and week 8, and emotional status was assessed at baseline and the end of week 2, 4, and 8. Additionally, the
changes in weight and serum metabolic profiles (triglyceride, cholesterol, and fasting blood glucose) during the trial were also analyzed. In
results, a total of 71 patients were randomly assigned to the lurasidone group (n = 35) or the quetiapine group (n = 36), of which 31 patients
completed the whole treatment course. After an 8-week follow-up, participants in the lurasidone group showed better performance in the Symbol Check
Reaction and Accuracy Tests, when compared to those in the quetiapine group. No inter-group difference was observed in the depression scores,
response rate, or remission rate throughout the trial. In addition, there was no significant difference in serum metabolic profiles between the
lurasidone group and the quetiapine group, including triglyceride level, cholesterol level, and fasting blood glucose level. However, the quetiapine
group presented a more apparent change in body weight than the lurasidone group. In conclusion, the present study provided preliminary evidence that
quetiapine and lurasidone had an equivalent anti-depressive effect, and lurasidone appeared to be superior to quetiapine in improving the cognitive
function of young patients with bipolar depression.
, 15(11) : 14
- Year: 2022
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
DelBello, M. P., Kadakia, A., Heller, V., Singh, R., Hagi, K., Nosaka, T., Loebel, A.
OBJECTIVE: To assess the relative efficacy and safety of second-generation antipsychotics for
treating major depressive episodes in youths with bipolar disorder., METHOD: A systematic literature review using PRISMA guidelines and network
meta-analysis (NMA) of randomized controlled trials (RCTs) of second-generation antipsychotics for bipolar depression in youths 10 to 18 years of age
was conducted. Efficacy measures included Children's Depression Rating Scale, Revised (CDRS-R) and Clinical Global Impressions-Bipolar Disorder-
Severity Depression (CGI-BP-S-depression) and Overall (CGI-BP-S-overall) scores. Available safety outcomes included discontinuations (all-cause, lack
of efficacy, adverse events), metabolic parameters (weight change, cholesterol, triglycerides, glucose), changes in prolactin, and somnolence.
Results from the NMA were reported as mean changes from baseline or odds ratios (OR) with 95% credible intervals (CrIs)., RESULTS: Four RCTs
comparing placebo to lurasidone, quetiapine (1 each for immediate- and extended-release), and the olanzapine-fluoxetine combination (OFC) met all of
the inclusion criteria. Lurasidone and OFC demonstrated similar and statistically significant improvements in CDRS-R, but quetiapine did not
(lurasidone: -5.70 [-8.66, -2.76]; OFC: -5.01 [-8.63, -1.38]; quetiapine: -1.85 [-5.99, 2.27]). Lurasidone was associated with smaller changes in
weight, cholesterol, and triglycerides from baseline compared to OFC and quetiapine. There were no differences in changes in glucose levels among
antipsychotics. In addition, lurasidone was associated with smaller change in prolactin levels compared to OFC but not quetiapine., CONCLUSION:
Evidence from 4 studies in this NMA indicated that lurasidone and OFC, but not quetiapine, were efficacious for the treatment of bipolar depression
in youths. Lurasidone was associated with less weight gain and smaller impacts on cholesterol and triglycerides compared with quetiapine and OFC.
Copyright © 2021 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
Journal of the American Academy of Child and Adolescent Psychiatry, 61(2) : 243-
254
- Year: 2022
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Weinstein, S., Gruhn, M., West, A.
Aims: Suicide risk in pediatric bipolar disorder (BD) is a significant public health problem. To guide the development of targeted
suicide interventions for this at-risk population, this study examined (1) psychosocial correlates of suicidal ideation (SI) in youth with BD that
may dictate targets for intervention; (2) SI response to manualized psychotherapy for pediatric BD (Child-and Family-Focused Cognitive Behavioral
Therapy, CFF-CBT) versus treatment-as- usual (TAU); and (3) psychosocial factors corresponding to SI treatment response. Method(s): Participants
included 72 youth aged 7-13 (M = 9.19, SD = 1.61) with DSM-IV- TR bipolar I, II, or NOS and a parent/caregiver participating in a randomized trial
examining CFF-CBT versus TAU. Both treatments consisted of 11 weekly and 6 monthly sessions. Current SI and psychosocial correlates were assessed at
baseline, post-treatment, and 6-month follow-up. Result(s): Current ideation was prevalent: 41% endorsed any ideation, and 31% endorsed planful
ideation. Higher family rigidity and lower self-esteem were significant predictors of planful ideation at baseline (OR = 1.19, 0.89, respectively; p
< 0.05). Models examined changes in SI likelihood and intensity across treatment. All youth improved in SI across treatment (p < 0.05), but group
differences (CFF-CBT v. TAU) were not significant. Mediation analyses explored mechanisms of SI improvement across conditions; improvement in family
rigidity, self-esteem, and family functioning corresponded to reduction in SI across treatment (p < 0.05). Conclusion(s): Early intervention for
youth with BD may reduce SI even in a nonspecialized treatment. Results also highlight child self-esteem and family rigidity as key treatment targets
to reduce suicide risk in pediatric BD.
Bipolar Disorders, 23(SUPPL
1) : 47
- Year: 2021
- Problem: Bipolar Disorders, Suicide or self-harm behaviours (excluding non-suicidal self-harm), Suicide or self-harm with comorbid mental disorder
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder), At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions
(any), Cognitive & behavioural therapies (CBT)
Veluri, N., Patel, J., Patel, R., Manchado, T., Diler, R.
Objectives:
This session aims to evaluate the efficacy in the reduction of depressive symptoms, and the safety and tolerability of second-generation
antipsychotics (SGAs) to manage pediatric bipolar disorder (PBD). Method(s): We conducted a systematic review of RCTs for PBD in MEDLINE, Scopus, and
Embase. A total of 6 out of 569 studies met the criteria for inclusion in the meta-analysis, including quetiapine (3 studies), lurasidone (2
studies), and olanzapine-fluoxetine combination (OFC; 1 study). RevMan was used for statistical analysis, and the mean difference (MD) between the
mean Children's Depression Rating Scale-Revised (CDRS-R) score is used to measure the treatment difference between SGA and placebo. Result(s):
Lurasidone is the most efficacious in reducing depressive symptoms (MD = -5.66; 95% CI, -8.05 to -3.28) in PBD, followed by OFC (MD = -5.00; 95% CI,
-8.3 to -1.8) and quetiapine (MD = -2.28; 95% CI, -6.44 to 1.87). The response was significantly higher for lurasidone (59.5% vs 36.5%; p < 0.001)
and OFC (78.2% vs 59.2%; p = 0.003) compared with placebo. There was no statistically significant MD in treatment and response rates between
quetiapine and placebo in all RCTs. The weighted mean CDRS-R total score difference was -4.87 (95% CI, -6.67 to -3.07), and the overall effect was
significant (p < 0.00001). Importantly, the p value for heterogeneity was 0.86, which indicated that there was no heterogeneity between outcomes of
the studies. The most effective response was seen with lurasidone with the number needed to treat (NNT) of 4.3, followed by OFC (NNT = 5.3) and
quetiapine (NNT = 12.5 to 25). Discontinuation due to adverse events was greater with OFC (14.1%, majorly due to weight gain) than with quetiapine
(3.3%-5.9%) and lurasidone (1.7%). Conclusion(s): Our findings showed lurasidone and OFC as first-line treatment for acute depressive episodes in PBD
because they were more efficacious than placebo. Quetiapine requires further trials due to the high placebo rate, although the generalization to
\"real-world\" clinical effectiveness is difficult to assess. SGAs have varying side-effect profiles that should be taken into account at the patient
level. RCTs of treatments for PBD remain scarce, thereby pressing the need for more research. BRD, TREAT, APSCopyright © 2021
Journal of the American Academy of Child and Adolescent Psychiatry, 60(10
Supplement) : S214
- Year: 2021
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Van-Meter, A., Stoddard, J., Penton-Voak, I., Munafo, M. R.
BACKGROUND: Bipolar disorder (BD) is associated with emotion interpretation biases that can exacerbate
depressed mood. Interpretation bias training (IBT) may help; according to the \"virtuous cycle\" hypothesis, interpreting others' emotions as
positive can lead to interactions that improve mood. Our goals were to determine whether IBT can shift emotion interpretation biases and demonstrate
clinical benefits (lower depressed mood, improved social function) in people with BD.\rMETHOD: Young adults with BD were recruited for three sessions
of computer-based IBT. Active IBT targets negative emotion bias by training judgments of ambiguous face emotions towards happy judgments.
Participants were randomized to active or sham IBT. Participants reported on mood and functioning at baseline, intervention end (week two), and week
10.\rRESULTS: Fifty participants (average age 22, 72% female) enrolled, 38 completed the week 10 follow-up. IBT shifted emotion interpretations
(Hedges g = 1.63). There was a group-by-time effect (B = -13.88, p < .0001) on self-reported depression; the IBT group had a larger decrease in
depressed mood. The IBT group also had a larger increase in perceived familial support (B = 3.88, p < .0001). Baseline learning rate (i.e., how
quickly emotion judgments were updated) was associated with reduced clinician- (B = -54.70, p < 0.001) and self-reported depression (B = -58.20, p =
0.009).\rCONCLUSION: Our results converge with prior work demonstrating that IBT may reduce depressed mood. Additionally, our results provide support
for role of operant conditioning in the treatment of depression. People with BD spend more time depressed than manic; IBT, an easily disseminated
intervention, could augment traditional forms of treatment without significant expense or side effects.
, 282 : 876-
884
- Year: 2021
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions
(any), Technology, interventions delivered using technology (e.g. online, SMS)
Singh, M., Nimarko, A., Garrett,
A., Walshaw, P., Chang, K., Miklowitz, D.
Background: Compared
to standard psychoeducation (EC), family focused therapy for high-risk youth (FFT-HR) is associated with stronger pre- to post-connectivity between
the ventrolateral prefrontal cortex (VLPFC) and anterior default mode network (aDMN) in symptomatic youth at high risk (HR) for bipolar disorder
(BD). How these changes relate to symptom change and global functioning is poorly understood. We investigated treatment-related changes in intrinsic
connectivity, symptoms, and functioning following FFT-HR versus EC. Method(s): HR youth (N=34; age 9-17 years; mean 14 years, 56% girls) with
depressive symptoms and at least one relative with BD were randomly assigned to FFT-HR (12 sessions of psychoeducation, communication, and problem-
solving) or EC (6 family/individual psychoeducation sessions). Pretreatment to post-treatment changes in intrinsic network connectivity in FFT-HR
(n=16) or EC (n=18) youth were related to symptom and functional changes, covarying for age, sex, site, and socioeconomic status. Result(s): FFT-HR-
assigned youth had increased VLPFC-aDMN connectivity from pre- to post-treatment (p=.003), whereas EC youth showed no significant change over time
(p=.11) (treatment by time interaction, [t(31)=3.33, CI 95% [0.27, 1.14], p=.002]. Reduction in depression severity inversely correlated with
enhanced aDMN (r= -.71) connectivity in FFT-HR but not in EC (r=-.07) group (z=-2.17, p=.015). Improved functional impairment from pre-to-post
treatment correlated with stronger post-treatment anterior DMN connectivity (r=.97) in the FFT-HR but not in EC (r=.16) youth (z=5.1, p<0.01).
Conclusion(s): FFT-HR is associated with stronger pre- to post-connectivity between the VLPFC and aDMN, with stronger aDMN connectivity corresponding
to improved depression severity and functioning, suggesting enhanced self- and illness awareness and emotion regulation. Supported By: R01R01MH093676
(Miklowitz), R01MH093666 (Chang), and the Brain and Behavior Research Foundation (Chang). Keywords: High Familial Risk, Bipolar Disorder, Family
Focused Therapy, Resting State Connectivity, Default Mode Network Copyright © 2021
Biological Psychiatry, 89 (9
Supplement) : S80-S81
- Year: 2021
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions
(any), Family therapy, Psychoeducation