Assess bipolar disorder subtype and treatment location effects on bipolar disorder core pharmacotherapy. Outpatients not in a syndromal episode referred to the University of Milan and Stanford University Bipolar Disorder Clinics were assessed with SCID for the fourth Edition of the Diagnostic and Statistical Manual of Mood Disorders, and the Systematic Treatment Enhancement Program for Bipolar Disorder Affective Disorders Evaluation, respectively. Prevalence and clinical correlates of antidepressant, antipsychotic, and mood stabilizer use, in aggregate and individually, were compared in bipolar I (BDI) versus II (BDII) patients in Milan/Stanford and in Milan versus Stanford patients, stratified by subtype. Milan/Stanford pooled BDI versus BDII patients significantly more often took antipsychotic (69.8 versus 44.8%), mood stabilizers (68.6 versus 57.7%), and valproate (40.1 versus 17.5%), and less often took antidepressants (23.1 versus 55.6%) and lamotrigine (9.9 versus 25.2%). Milan versus Stanford patients (stratified by bipolar disorder subtype) significantly more often took antipsychotic (BDI and BDII), antidepressants (BDII), and valproate (BDII), and less often took lamotrigine (BDI). Research regarding bipolar disorder core pharmacotherapy relationships with bipolar subtype and treatment location is warranted to enhance clinical management.

Over the next 5 years, the evolving landscape of digital devices available to clinicians and their patients will transform the ways that psychiatrists will be able to treat a wide range of neuropsychiatric conditions. In this article, we forecast how digital phenotyping, a new method of quantifying the lived experience of patients using personal smartphones or wearable technology, may become increasingly necessary for clinicians seeking to engage meaningfully with their patients, especially over extended periods of quiescence in care, when illness vigilance may wane on the part of the patient or clinician, and in care settings with limited access to available psychiatrists. We also explore the potential pitfalls of increased reliance on remote monitoring strategies in the patient-doctor relationship, the data overload problem, and how astute clinicians will manage. Finally, we offer some strategies and emerging best practices for how digital phenotyping might be safely integrated into clinical practice in the future. [ Psychiatr Ann. 2019;49(5):196–201.]

BACKGROUND:Ecological momentary assessment (EMA) is increasingly used to characterize patients' daily lives, monitor mood, and test efficacy of treatment interventions. However, few studies have examined patient characteristics impacting adherence with EMA protocols, and to our knowledge, no such study has been conducted in youth with bipolar disorder (BD). METHODS:As part of a larger observational study, 14- to 21-year-olds diagnosed with BD, and who were between episodes of illness (n = 39, 19.0 ± 2.05 Mean ± Standard Deviation years old, 74.4% female) and psychiatrically healthy controls (n = 47, 18.3 ± 2.40 years old, 66.0% female) completed baseline diagnostic and symptom severity interviews, and were instructed to complete diary assessments of mood, sleep, and behavior electronically three times per day for 21 consecutive days (i.e., in total 5418 (or 63 per person) diary entries). Multiple regression was used to examine effects of BD participants' demographic and clinical characteristics on diary completion rates. RESULTS:53.8 ± 9.3 diary entries per person were actually completed. Adherence rates were high (87.5% of healthy controls and 80.4% of adolescents with BD), but were still significantly poorer in youth with BD. Adequate adherence (≥80%) rates were also significantly poorer in youth with BD relative to healthy controls (56.4% versus 83.0%). Among youth with BD, more lifetime suicide attempts and higher current mood elevation symptom severity predicted significantly poorer adherence. LIMITATIONS:Limited sample size/generalizability. CONCLUSIONS:Findings highlight the importance of considering the impact of patient characteristics on adherence with EMA protocols among youth with severe mental illness.

BACKGROUND:The network approach to psychopathology has become increasingly popular. Little research has examined the dynamic network structure of mental disorders, and, to date, no study has investigated the network dynamics of positive affect, negative affect, and physical activity in bipolar disorder. This represents the first study to estimate the dynamic network structure of affect and physical activity in individuals with and without bipolar I disorder.METHODS:An intensive longitudinal design was used to assess positive affect, negative affect, and actigraphy-based estimates of physical activity. The overall sample consisted of 32 adults with bipolar I disorder and 36 healthy control participants. Eligible participants underwent an 8-week assessment period, in which once-per-day ratings of affect and actigraphy estimates were obtained. Participants were re-assessed on baseline measures afterwards. Dynamic network analysis was used to examine the network structure of affect and physical activity over time. Multilevel models were used to examine the relationship between autocorrelation and changes in depression symptoms among participants with bipolar disorder.LIMITATIONS:The network analyses assume stationarity. Future research should consider time-varying multilevel network models to better account for time trends.RESULTS:The results of the temporal networks indicated that the directed edges between positive and negative affect were mostly positive among individuals with bipolar I disorder. Among healthy control participants, the directed edges between positive and negative affect were mostly negative in direction. Physical activity, as assessed by daily actigraphy indices, was more densely connected in the healthy control network than the bipolar disorder network. Furthermore, the results indicated that critical slowing down predicted worsening of mood symptoms in the bipolar I disorder group.CONCLUSIONS:This study suggests that certain dynamic patterns of affect may be an underlying process that contributes to the maintenance of bipolar disorder. These results have both theoretical and practical implications.

Black and poor children are overrepresented at every stage of the child welfare system, from suspicion of abuse to substantiation. Focusing on stereotypes as a source of bias that leads to these disparities, the current study examines the content and strength of stereotypes relating race and social class to child abuse as viewed by medical professionals. Doctors, nurses, and other medical professionals (Study 1: N = 53; Study 2: N = 40) were recruited in local hospitals and online through snowball sampling. Study 1 identified stereotype content by asking participants to list words associated with the stereotype that either (a) Black or (b) poor children are more likely to be abused by their parents, and responses were organized into construct groups. Study 2 determined stereotype strength by asking participants to rate how strongly the constructs generated in Study 1 related to either the race-abuse or social class-abuse stereotype. The content of stereotypes linking child abuse to Black or poor children are confounded, with approximately half the constructs shared by both stereotypes. Of the 10 shared constructs, only "Stressed" and "Neglect" differed in strength, with both significantly more strongly related to the social class-abuse than race-abuse stereotype, all ts(36-37) <= -2.23, ps <= .03, Cohen's ds >= .71. This research documents the existence, content, and strength of stereotypes that link race and social class to child abuse. These stereotypes have the potential to lead to medical misdiagnosis of abuse for Black and poor children.

Objectives Both sleep disruption and impulsivity are important predictors of the course of bipolar disorder ( BD ). Although sleep disruption has been shown to intensify impulsivity, little research has considered how these two important domains interact within BD . Adolescence is a critical period for the onset of BD , and is often associated with increases in impulsivity and substantial changes in sleep. We tested the hypothesis that disruptions in sleep would increase impulsivity among adolescents, and that this effect would be more pronounced among those with BD . Methods Thirteen‐ to nineteen‐year‐olds diagnosed with BD ‐I ( n = 33, age [mean ± standard deviation (SD)] 16.2 ± 1.66 years, 54.5% female) and psychiatrically healthy controls ( n = 26, age [mean ± SD] 15.5 ± 1.45 years, 55.6% female) reported their past‐week bedtime, rise time, and sleep duration, separately for school days and weekends, and completed a self‐report questionnaire on impulsivity. Stepwise regression was used to examine the effects of sleep on impulsivity, and the moderation of this effect by BD status. Results Adolescents with BD reported significantly higher impulsivity, later and more variable rise time, and more variable time in bed and sleep duration on school days than did controls. Greater change in sleep duration between school days and weekends was associated with significantly more impulsivity among adolescents with BD as compared to controls. Conclusions These findings highlight the important effect of sleep on impulsivity among adolescents with BD and add to the growing evidence that establishing sleep routines may be an important therapeutic target for youth with BD .

Aims: Antidepressant use is controversial in bipolar disorder (BD) due to questionable efficacy/psychiatric tolerability. We assessed demographic/clinical characteristics of baseline antidepressant use in BD patients. Methods: Prevalence and correlates of baseline antidepressant use in 503 BD I and BD II outpatients referred to the Stanford Bipolar Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Results: Antidepressant use was 39.0%, overall, and was higher in BD II versus BD I (46.9% versus 30.5%, p = 0.0002). Both BD I and BD II antidepressant compared to non-antidepressant users had higher rates of complex pharmacotherapy (>= 4 mood stabilizers, antipsychotics, and/or antidepressants) and use of other psychotropics. Antidepressant use in BD II versus BD I was higher during euthymia (44.0% vs. 28.0%) and subsyndromal symptoms (56.1% vs. 28.6%), but not depression or mood elevation. Limitations: American tertiary BD clinic referral sample receiving open naturalistic treatment. Conclusions: In our sample, antidepressant use was higher in BD II versus BD I patients, and was associated with markers of heightened illness severity in both BD I and BD II patients. Additional research is warranted to investigate these complex relationships.

Background: Bipolar disorder (BD) is associated with later sleep and daily activity (evening rather than morning chronotype). Objective chronotype identification (e.g., based on actigraphs/smartphones) has potential utility, but to date, chronotype has mostly been assessed by questionnaires. Given the ubiquity of accelerometer-based devices (e.g. actigraphs/smartphones) worn/used during daytime and tendency to recharge rather than wear at night, we assessed chronotype using daytime (rather than sleep) interval midpoints. Methods: Sixty-one participants with BD type I (BD-I) or II (BD-II) and 61 healthy controls completed 25-50 days of continuous actigraphy. The Composite Scale of Morningness (CSM) was completed by a subset of this group. Daytime activity midpoint was calculated for each daytime interval, excluding naps. Evening chronotype was defined as having a daytime interval midpoint at or after 16:15:00 (4:15:00 PM). Results: BD versus controls had delayed daytime midpoint (mean +/- standard deviation) (16:49:07 +/- 01:26:19 versus 16:12:51 +/- 01:02:14, p < 0.01), and greater midpoint variability (73.3 +/- 33.9 min versus 58.1 +/- 18.3 min, p < 0.01). Stratifying by gender and age, females and adolescents with BD had delayed and more variable daytime midpoints versus controls. Adults with BD had greater midpoint variability than controls. Within-person mean and standard deviations of daytime midpoints were highly correlated with sleep midpoints (r = 0.99, p < 0.01 and r = 0.86, p < 0.01, respectively). Daytime midpoint mean was also significantly correlated with the CSM (r = -0.56, p < 0.01). Limitations: Small sample size; analyses not fully accounting for daytime napping. Conclusions: Wrist actigraphy for determination of daytime midpoints is a potential tool to identify objective chronotype. Exploration of the use of consumer devices (wearables/smartphones) is needed.

Aims: Antidepressants are common in bipolar disorder (BD), but controversial due to questionable efficacy/tolerability. We assessed baseline antidepressant use/depression associations in BD. Methods: Stanford BD Clinic outpatients, enrolled during 2000-2011, assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, were monitored up to two years with the STEP-BD Clinical Monitoring Form while receiving naturalistic expert treatment. Prevalence/correlates of baseline antidepressant use in recovered (euthymic >= 8 weeks)/depressed patients were assessed. Kaplan-Meier survival analyses assessed times to depressive recurrence/recovery in patients with/without baseline anti-depressant use, and Cox Proportional Hazard regression analyses assessed covariate effects. Results: Baseline antidepressant use was significantly (albeit without Bonferroni multiple comparison correction) less among 105 recovered (31.4%) versus 153 depressed (44.4%) patients, and among recovered patients (again without Bonferroni correction), associated with Caucasian race, earlier onset, worse Clinical Global Impression scores, and hastened depressive recurrence (only if mood elevation episodes were not censored), driven by lifetime anxiety disorder, and more (even with Bonferroni correction) bipolar II disorder, lifetime anxiety and eating disorders, and core psychotropics. Baseline antidepressant use among depressed patients was associated with significantly (again without Bonferroni correction) older age, female gender, and more (even with Bonferroni correction) anxiolytics/hypnotics, complex pharmacotherapy, and core psychotropics, but no other unfavorable illness characteristic/current mood symptom, and not time to depressive recovery. Limitations: Tertiary BD clinic referral sample receiving open naturalistic expert treatment. Analyses without/with Bonferroni correction. Conclusions: Additional research is required to assess the complex associations between baseline antidepressant use and longitudinal depressive burden in BD.

Purpose: To retrospectively assess lurasidone effectiveness/efficacy/tolerability in bipolar disorder (BD) patients. Methods: Outpatients assessed with Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation received naturalistically administered (primarily adjunctive) open lurasidone while monitored at visits with the Systematic Treatment Enhancement Program for BD Clinical Monitoring Form. Results: Sixty-one patients (32 type I, 26 type II, 3 type not otherwise specified; mean SD age, 45.1 +/- 14.0 years; 63.9% were female) received lurasidone with 3.1 +/- 1.4 (2 in 88.5%, monotherapy in only 3.3%) other nonanxiolytic/hypnotic prescription psychotropics, started during syndromal depression in 57.4%, subsyndromal depression in 23.0%, and euthymia in 19.7%. Lurasidone was taken for median 126 days, with final dose 55.6 +/- 30.8 mg/d. By final visit taking lurasidone, syndromal depression rate decreased by nearly one-half to 31.1%, and euthymia rate more than doubled to 42.6%, whereas subsyndromal depression rate was unchanged at 23.0%. Clinical Global Impressions-BD-Overall Severity improved significantly only in patients with baseline syndromal depression. Seventy-seven percent of patients discontinued lurasidone after median 103 days, because of adverse events in 54.1% (most often akathisia, sedation/somnolence, nausea, and weight gain), inefficacy in 16.4%, and other reasons in 6.6%; 12.1% had equal to or greater than 7% weight gain, and 3.3% developed hypomania. Limitations to this study were the open design and demographically homogeneous (relatively affluent, predominantly white female) small sample taking complex pharmacotherapy. Conclusions: In American specialty clinic BD outpatients, adjunctive longer-term lurasidone commonly relieved syndromal depression and maintained euthymia, suggesting possible effectiveness/efficacy. However, lurasidone was discontinued in 54.1% because of adverse events, suggesting tolerability limitations in these challenging patients, nearly 90% of whom were already taking at least 2 other nonanxiolytic/hypnotic prescription psychotropics.

Maternal depression is associated with an increased risk for depression in offspring; the factors explaining this association, however, are unclear. We examined coping in a group of 9- to 14-year-old daughters of mothers with and without a history of major depressive disorders. We tested whether daughters’ adaptive coping mediated the association between mothers’ and daughters’ depressive symptoms, and whether these relations were moderated by daughters’ pubertal status. Using moderated mediation analyses, higher levels of maternal depressive symptoms were related to less adaptive coping in daughters, which was related to higher levels of daughters’ depressive symptoms. The mediating effect of coping was evident only for daughters in late stages of pubertal maturation. Early interventions aimed at strengthening coping in girls may have a protective effect on daughters’ risk for depression at later pubertal stages.

Background: Abnormal sleep duration (ASD, < 6 or 9 h) is common in bipolar disorder (BD), and often persists beyond acute mood episodes. Few longitudinal studies have examined the ASD's impact upon BD illness course. The current study examined the longitudinal impact of ASD upon bipolar depressive recurrence/recovery.Methods: Outpatients, referred to the Stanford BD Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation at baseline, and with the Clinical Monitoring Form at monthly follow-ups for up to two years of naturalistic treatment. Prevalence and clinical correlates of ASD in 93 recovered (euthymic 8 weeks) and 153 depressed BD patients were assessed. Kaplan-Meier analyses (Log-Rank tests) assessed relationships between baseline ASD and longitudinal depressive severity, with Cox Proportional Hazard analyses assessing potential mediators.Results: ASD was only half as common among recovered versus depressed BD outpatients, but was significantly associated with hastened depressive recurrence (Log-Rank p = 0.007), mediated by lifetime anxiety disorder and attenuated by lifetime history of psychosis, and had only a non-significant tendency towards association with delayed depressive recovery (Log-Rank p = 0.07). In both recovered and depressed BD outpatients, baseline ASD did not have significant association with any baseline BD illness characteristic.Limitations: Self-reported sleep duration. Limited generalizability beyond our predominately white, female, educated, insured American BD specialty clinic sample.Conclusions: Baseline ASD among recovered BD patients may be a risk marker for hastened depressive recurrence, suggesting it could be an important therapeutic target between mood episodes.

Sleep disturbances are common features of bipolar disorder (BD), yet little is known about trajectories of sleep disturbances in youth with BD. Using longitudinal data, this study assessed the stability of sleep disturbances and their ability to predict symptom progression in adolescents diagnosed with BD compared to controls. Thirteen- to 19-year-olds meeting diagnostic criteria for BD I (n = 19, 16.2 ± 1.75 years, 57.9 % female, 68.4% Caucasian) and psychiatrically healthy age-comparable controls (n = 21, 15.7 ± 1.48 years. 52.4% female, 57.1% Caucasian) were assessed for sleep onset latency, number of awakenings, and wake time, separately for weekdays and weekends using a self-report questionnaire. Sleep indices and symptoms of mania (Young Mania Rating Scale) and depression (Children’s Depression Rating Scale) were assessed at two time points, T1 and T2, approximately 12 months apart. Correlations were used to examine stability of sleep indices across time points and regression models to examine the effects of T1 sleep on T2 symptoms. Adolescents with BD showed low stability on most sleep indices, whereas controls showed high stability on all sleep indices. After controlling for T1 depression symptoms, more T1 weekend awakenings and weekend wake time predicted significantly greater T2 depression symptoms in youth with BD but not in controls. No significant associations were found between T1 sleep and T2 mania symptoms. These findings suggest that increased awakenings and wakefulness on weekends may represent an important therapeutic target for reducing depression in adolescents with BD.

Background: Disturbed sleep timing is common in bipolar disorder (BD). However, most research is based upon self-reports. We examined relationships between subjective versus objective assessments of sleep timing in BD patients versus controls. Methods: We studied 61 individuals with bipolar I or II disorder and 61 healthy controls. Structured clinical interviews assessed psychiatric diagnoses, and clinician-administered scales assessed current mood symptom severity. For subjective chronotype, we used the Composite Scale of Morningness (CSM) questionnaire, using original and modified (1, 3/4, 2/3, and 1/2 SD below mean CSM score) thresholds to define evening chronotype. Objective chronotype was calculated as the percentage of nights (50%, 66.7%, 75%, or 90% of all nights) with sleep interval midpoints at or before (non-evening chronotype) vs. after (evening chronotype) 04:15:00 (4:15:00 a.m.), based on 25-50 days of continuous actigraph data. Results: BD participants and controls differed significantly with respect to CSM mean scores and CSM evening chronotypes using modified, but not original, thresholds. Groups also differed significantly with respect to chronotype based on sleep interval midpoint means, and based on the threshold of 75% of sleep intervals with midpoints after 04:15:00. Subjective and objective chronotypes correlated significantly with one another. Twenty-one consecutive intervals were needed to yield an evening chronotype classification match of >= 95% with that made using the 75% of sleep intervals threshold. Limitations: Limited sample size/generalizability. Conclusions: Subjective and objective chronotype measurements were correlated with one another in participants with BD. Using population-specific thresholds, participants with BD had a later chronotype than controls.

Disruptions in activity are core features of mood states in bipolar disorder (BD). In this study, we sought to identify activity patterns that discriminate between mood states in BD. Locomotor activity was collected by using actigraphy for 6 weeks in participants with interepisode BD Type I (n = 37) or participants with no lifetime mood disorders (n = 39). The 24-hr activity pattern of each participant-day was characterized and within-person differences in activity patterns were examined across mood states. Results showed that among participants with BD, depressive days are distinguished from other mood states by an overall lower activity level and a pattern of later activity onset, a midday elevation of activity, and low evening activity. No distinct within-person activity patterns were found for hypomanic/manic days. Given that activity can be monitored noninvasively for extended time periods, activity pattern identification may be leveraged to detect mood states in BD, thereby providing more immediate delivery of care.

Objective: Sleep disturbances are prevalent, persistent, and impairing features of bipolar disorder. However, the near-term and cumulative impact of the severity and variability of sleep disturbances on symptoms and functioning remains unclear. We examined self-reported daily sleep duration and variability in relation to mood symptoms, medication adherence, cognitive functioning, and concurrent daily affect.Methods: Forty-one outpatients diagnosed with bipolar disorder were asked to provide daily reports of sleep duration and affect collected via ecological momentary assessment with smartphones over eleven weeks. Measures of depressive and manic symptoms, medication adherence, and cognitive function were collected at baseline and concurrent assessment of affect were collected daily. Analyses examined whether sleep duration or variability were associated with baseline measures and changes in same-day or next-day affect.Results: Greater sleep duration variability (but not average sleep duration) was associated with greater depressive and manic symptom severity, and lower medication adherence at baseline, and with lower and more variable ratings of positive affect and higher ratings of negative affect. Sleep durations shorter than 7-8 h were associated with lower same-day ratings of positive and higher same-day ratings of negative affect, however this did not extend to next-day affect.Conclusions: Greater cumulative day-to-day sleep duration variability, but not average sleep duration, was related to more severe mood symptoms, lower self-reported medication adherence and higher levels of negative affect. Bouts of short- or long-duration sleep had transient impact on affect. Day-to-day sleep variability may be important to incorporate into clinical assessment of sleep disturbances in bipolar disorder. (C) 2016 Elsevier Ltd. All rights reserved.