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1.  Effects of Comorbid Anxiety Disorders on the Longitudinal Course of Pediatric Bipolar Disorders 
OBJECTIVE
To examine the longitudinal effects of comorbid anxiety disorders in youth with bipolar spectrum disorder (BP).
METHOD
As part of the Course and Outcome of Bipolar Youth study, 413 youth, ages 7 to 17 years who met criteria for DSM-IV BP-I (n=244), BP-II (n=28), and operationally defined bipolar disorder not otherwise specified (BP-NOS) (n=141) were included. Subjects were followed on average 5 years using the Longitudinal Interval Follow-up Evaluation. Effects of anxiety on the time to mood recovery and recurrence and percentage of time with syndromal and subsyndromal mood symptomatology during the follow-up period were analyzed.
RESULTS
At intake and during the follow-up, 62% of youth with BP met criteria for at least one anxiety disorder. About 50% of the BP youth with anxiety had ≥ 2 anxiety disorders. Compared to BP youth without anxiety, those with anxiety had significantly more depressive recurrences and significantly longer median time to recovery. The effects of anxiety on recovery disappeared when the severity of depression at intake was taken into account. After adjusting for confounding factors, BP youth with anxiety, particularly those with ≥ 2 anxiety disorders, spent significantly less follow-up time asymptomatic and more time with syndromal mixed/cycling and subsyndromal depressive symptomatology compared to those without anxiety.
CONCLUSIONS
Anxiety disorders are common and adversely affect the course of BP in youth, as characterized by more mood recurrences, longer time to recovery, less time euthymic, more time in mixed/cycling and depressive episodes. Prompt recognition and the development of treatments for BP youth with anxiety are warranted.
doi:10.1016/j.jaac.2013.09.020
PMCID: PMC3868011  PMID: 24342387
anxiety disorders; bipolar disorders; longitudinal study
2.  Two-Year Course of Generalized Anxiety Disorder, Social Anxiety Disorder, and Panic Disorder in a Longitudinal Sample of African American Adults 
Objective
Anxiety disorders are the most common group of psychiatric disorders in adults. In addition to high prevalence, anxiety disorders are associated with significant functional impairment, and published research has consistently found them to have a chronic course. To date, very little research has explored the clinical characteristics and prospective course of anxiety disorders in racial and ethnic minority samples. The aims of this paper are to present clinical and demographic characteristics at intake and prospective two-year course findings in a sample of African American adults.
Methods
Data are presented from 152 African Americans diagnosed with generalized anxiety disorder (GAD, n = 94), social anxiety disorder (SAD, n = 85), and panic disorder with agoraphobia (PDA, n = 77) who are participating in the Harvard/Brown Anxiety Research Project-Phase II (HARP-II). HARP-II is an observational, prospective, longitudinal study of the course of anxiety disorders. Participants were interviewed at intake and annually for 2 years of follow-up. Probabilities of recovery over two years of follow-up were calculated using standard survival analysis methods.
Results and Conclusions
Survival analyses revealed a chronic course for all anxiety disorders, with rates of recovery of 0.23, 0.07, and 0.00 over two years for GAD, SAD, and PDA, respectively. These rates of recovery were lower than those reported in predominantly Non-Latino White longitudinal samples, especially for SAD and PDA, suggesting that anxiety disorders may have a more chronic course for African Americans, with increased psychosocial impairment and high rates of co-morbid Axis-I disorders. Clinical implications of these findings are discussed.
doi:10.1037/a0034382
PMCID: PMC3951438  PMID: 24041233
anxiety disorders; longitudinal course; African American; recovery; social phobia; social anxiety disorder; generalized anxiety disorder; panic disorder; agoraphobia
3.  Management of Traumatic Wounds and a Novel Approach to Delivering Wound Care in Children 
Advances in Wound Care  2014;3(4):335-343.
Significance: The costs and morbidity of pediatric traumatic wounds are not well known. The literature lacks a comprehensive review of the volume, management, and outcomes of children sustaining soft tissue injury. We briefly review the existing literature for traumatic wounds such as open fractures and burns. Such injuries require dedicated wound care and we propose a novel approach for more efficient and more effective delivery of dedicated pediatric wound care.
Recent Advances: New pediatric literature is emerging regarding the long-term effects of wound care pain in traumatic injuries—especially burns. A variety of wound dressings and alternative management techniques exist and are geared toward reducing wound care pain. Our institution utilizes a unique model to provide adequate sedation and pain control through a dedicated pediatric wound care unit. We believe that this model reduces the cost of wound care by decreasing emergency department and operating room visits as well as hospital length of stay.
Critical Issues: First, medical costs related to pediatric traumatic wound care are not insignificant. The need for adequate pain control and sedation in children with complex wounds is traditionally managed with operating room intervention. Afterward, added costs can be from a hospital stay for ongoing acute wound management. Second, morbidities of complex traumatic wounds are shown to be related to the acute wound care received.
Future Directions: Further guidelines are needed to determine the most effective and efficient care of complex traumatic soft tissue injuries in the pediatric population.
doi:10.1089/wound.2013.0465
PMCID: PMC3985539  PMID: 24761364
4.  Predictors of First-Onset Substance Use Disorders During the Prospective Course of Bipolar Spectrum Disorders in Adolescents 
Objective
Substance use disorders (SUD) are common and problematic in bipolar disorder (BP). We prospectively examined predictors of first-onset SUD among adolescents with BP.
Method
Adolescents (12–17 years old; N=167) in the Course and Outcome of Bipolar Youth (COBY) study fulfilling criteria for BP-I, BP-II, or operationalized BP not otherwise specified, without SUD at intake, were included. Baseline demographic, clinical, and family history variables, and clinical variables assessed during follow-up, were examined in relation to first-onset SUD. Participants were prospectively interviewed every 38.5±22.2 weeks for an average of 4.25±2.11 years.
Results
First-onset SUD developed among 32% of subjects, after a mean of 2.7±2.0 years from intake. Lifetime alcohol experimentation at intake most robustly predicted first-onset SUD. Lifetime oppositional defiant disorder and panic disorder, family history of SUD, low family cohesiveness, and absence of antidepressant treatment at intake were also associated with increased risk of SUD, whereas BP subtype was not. Risk of SUD increased with increasing number of these six predictors: 54.7% of subjects with ≥3 predictors developed SUD vs. 14.1% of those with <3 predictors (Hazard Ratio 5.41 95% CI 2.7–11.0 p<0.0001). Greater hypo/manic symptom severity in the preceding 12 weeks predicted greater likelihood of SUD onset. Lithium exposure in the preceding 12 weeks predicted lower likelihood of SUD.
Conclusions
This study identifies several predictors of first-onset SUD in the COBY sample which, if replicated, may suggest targets of preventive interventions for SUD among youth with BP. Treatment-related findings are inconclusive and must be interpreted tentatively given the limitations of observational naturalistic treatment data. There is a substantial window of opportunity between BP and SUD onset during which preventive strategies may be employed.
doi:10.1016/j.jaac.2013.07.009
PMCID: PMC3787940  PMID: 24074469
bipolar; predictors; prevention; prospective; substance use disorder
5.  Longitudinal Trajectories and Associated Baseline Predictors in Youths With Bipolar Spectrum Disorders 
The American journal of psychiatry  2014;171(9):990-999.
Objective
The authors sought to identify and evaluate longitudinal mood trajectories and associated baseline predictors in youths with bipolar disorder.
Method
A total of 367 outpatient youths (mean age, 12.6 years) with bipolar disorder with at least 4 years of follow-up were included. After intake, participants were interviewed on average 10 times (SD=3.2) over a mean of 93 months (SD=8.3). Youths and parents were interviewed for psychopathology, functioning, treatment, and familial psychopathology and functioning.
Results
Latent class growth analysis showed four different longitudinal mood trajectories: “predominantly euthymic” (24.0%), “moderately euthymic” (34.6%), “ill with improving course” (19.1%), and “predominantly ill” (22.3%). Within each class, youths were euthymic on average 84.4%, 47.3%, 42.8%, and 11.5% of the follow-up time, respectively. Multivariate analyses showed that better course was associated with higher age at onset of mood symptoms, less lifetime family history of bipolar disorder and substance abuse, and less history at baseline of severe depression, manic symptoms, suicidality, subsyndromal mood episodes, and sexual abuse. Most of these factors were more noticeable in the “predominantly euthymic” class. The effects of age at onset were attenuated in youths with lower socioeconomic status, and the effects of depression severity were absent in those with the highest socioeconomic status.
Conclusions
A substantial proportion of youths with bipolar disorder, especially those with adolescent onset and the above-noted factors, appear to be euthymic over extended periods. Nonetheless, continued syndromal and subsyndromal mood symptoms in all four classes underscore the need to optimize treatment.
doi:10.1176/appi.ajp.2014.13121577
PMCID: PMC4164021  PMID: 24874203
6.  ADEQUACY OF TREATMENT RECEIVED BY PRIMARY CARE PATIENTS WITH ANXIETY DISORDERS 
Depression and anxiety  2013;31(5):443-450.
Background
We examined the adequacy of pharmacotherapy and psychotherapy received by primary care patients with anxiety disorders over up to 5 years of follow-up.
Method
Five hundred thirty-four primary care patients at 15 US sites, who screened positive for anxiety symptoms, were assessed for anxiety disorders. Those meeting anxiety disorder criteria were offered participation and interviewed again at six and 12 months postintake, and yearly thereafter for up to 5 years. We utilized existing definitions of appropriate pharmacotherapy and created definitions of potentially adequate psychotherapy/cognitive-behavioral therapy (CBT).
Results
At intake, of 534 primary care participants with anxiety disorders, 19% reported receiving appropriate pharmacotherapy and 14% potentially adequate CBT. Overall, 28% of participants reported receiving potentially adequate anxiety treatment, whether pharmacotherapy, psychotherapy, or both. Over up to five years of follow-up, appropriate pharmacotherapy was received by 60% and potentially adequate CBT by 36% of the sample. Examined together, 69% of participants received any potentially adequate treatment during the follow-up period. Over the course of follow-up, primary care patients with MDD, panic disorder with agoraphobia, and with medicaid/medicare were more likely to receive appropriate anxiety treatment. Ethnic minority members were less likely to receive potentially adequate care.
Conclusions
Potentially adequate anxiety treatment was rarely received by primary care patients with anxiety disorders at intake. Encouragingly, rates improved over the course of the study. However, potentially adequate CBT remained much less utilized than pharmacotherapy and racial-ethnic minority members were less likely to received care, suggesting much room for improved dissemination of quality treatment.
doi:10.1002/da.22209
PMCID: PMC4157338  PMID: 24190762
anxiety disorders; primary healthcare; cognitive behavioral therapy; pharmacotherapy; dissemination/implementation; panic disorder/agoraphobia; generalized anxiety disorder; PTSD/posttraumatic stress disorder; social phobia/social anxiety disorder
7.  Risk of Suicidal Behavior With Antidepressants in Bipolar and Unipolar Disorders 
Objective
To examine the risk ofsuicidal behavior (suicide attempts and deaths) associated with antidepressants in participants with bipolar I, bipolar n, and unipolar major depressive disorders.
Design
A 27-year longitudinal (1981-2008) observational study ofmood disorders (Research Diagnostic Criteria diagnoses based on Schedule Dr Afi:ctive Disorders and Schizophrenia and review ofmedical records) was used to evaluate antidepressants and risk Dr suicidal behavior. Mixed-efi:cts logistic regression models examined propensity Dr antidepressant exposure. Mixed-efi:cts swvival models that were matched on the propensity score examined exposure status as a risk factor for time until suicidal behavior.
Setting
Five US academic medical centers.
Results
Analyses of206 participants with bipolar I disorder revealed 2,010 exposure intervals (980 exposed to antidepressants; 1,030 unexposed); 139 participants with bipolar II disorder had 1 ,407 exposure intervals (694 exposed; 713 unexposed); and 361 participants with unipolar depressive disorder had 2, 745 exposure intervals (1,328 exposed; 1,417 unexposed). Propensity score analyses confinned that more severely ill participants were more likely to initiate antidepressant treatment. In mixed-elects swvival analyses, those with bipolar I disorder had a significant reduction in risk of suicidal behavior by 54% (HR = 0.46; 95% CI, 0.31-0.69; t = -3.74; P < .001) during periods of antidepressant exposure compared to propensity-matched unexposed intervals. Similarly, the risk was reduced by 35% (HR = 0.65; 95% CI, 0.43-0.99; t = −2.01; P = .045) in bipolar II disorder. By contrast, there was no evidence of an increased or decreased risk with antidepressant exposure in unipolar disorder.
Condusions
Based on obsetVational data adjusted Dr propensity to receive antidepressants, antidepressants may protect patients with bipolar disorders but not unipolar depressive disorder from suicidal behavior.
doi:10.4088/JCP.13m08744
PMCID: PMC4142755  PMID: 25093469
8.  The Bi-Directional Relationship Between Parent–Child Conflict and Treatment Outcome in Treatment-Resistant Adolescent Depression 
Objective
To examine the bidirectional relationship between parent–child discord and treatment outcome for adolescent treatment-resistant depression.
Method
Depressed youth who had not responded to an adequate course of a selective serotonin reuptake inhibitor (SSRI) were randomized to either a switch to another SSRI or venlafaxine, with or without the addition of cognitive behavior therapy (CBT) in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study. The Conflict Behavior Questionnaire was used to assess adolescent (CBQ-A) and parent-reported (CBQ-P) parent–child discord. The impact of remission on parent–child conflict, and the differential impact of medication and CBT on the CBQ-A and CBQ-P, were assessed using generalized linear models.
Results
Although there were no differential treatment effects on parent or adolescent-report of conflict, remission was associated with improvement in the CBQ-P. In general, intake family conflict did not predict remission, except in the sub-group of participants whose parents reported clinically significant parent–child conflict at intake, for whom high levels of parent-reported conflict predicted a lower likelihood of remission. Conflict also did not moderate treatment response.
Conclusions
Remission of depression may be sufficient to reduce parent-reported parent–child conflict. However, higher parent-reported conflict, in the clinically significant range, predicts a lower likelihood of remission from depression. Clinical trial registration information—Treatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://clinicaltrials.gov/;NCT00018902.
doi:10.1016/j.jaac.2013.01.012
PMCID: PMC3737571  PMID: 23582868
parent–child conflict; selective serotonin reuptake inhibitor (SSRI); cognitive behavior therapy (CBT); venlafaxine; depression
9.  Age of Onset and the Prospectively Observed Course of Illness in Bipolar Disorder 
Journal of affective disorders  2012;146(1):34-38.
Background
To test the validity of age-of-onset grouping in bipolar disorder through the use of prospectively observed time in mood episodes.
Methods
Age-of-onset ranges from prior admixture analyses were used to divide 427 individuals with bipolar I or bipolar II disorder into early-, middle- and late- onset groups. These were compared by the proportions of weeks depressed and manic or hypomanic during a mean (SD) prospective follow-up of 17.4 (8.4) years.
Results
As predicted, the group with the earliest onsets reported at intake more previous episodes, more suicide attempts and panic attacks. An early age of onset, but not current age, was predictive of significantly more time in depressive episodes during follow-up but was not predictive of time in manic or hypomanic episodes.
Limitations
This was a naturalistic study with no control of treatment so variability in treatment may have obscured relationships between predictors and outcomes. Age of onset was retrospectively determined and subject to inaccuracies in recall.
Conclusions
An early age of onset conveys, to a modest degree, a poorer prognosis as expressed in more depressive morbidity.
doi:10.1016/j.jad.2012.08.031
PMCID: PMC3605729  PMID: 23062746
bipolar disorder; age-of-onset; follow-up; prognosis
10.  Manic Symptoms in Youth With Bipolar Disorder: Factor Analysis by Age of Symptom Onset and Current Age 
Journal of affective disorders  2012;145(3):409-412.
Background
Factor analysis has been used to identify potential clinical subtypes of mania in pediatric bipolar disorder. Results vary in the number of factors retained. The present study used a formal diagnostic instrument to examine how symptoms of mania in young people are expressed, depending on age of symptom onset and current age.
Methods
Trained clinicians completed the Schedule of Affective Disorders and Schizophrenia for School-Age Children (K-SADS) Mania Rating Scale (MRS) with parents of 163 children with child-onset of symptoms (before age 12), 94 adolescents with child-onset of symptoms, and 90 adolescents with adolescent-onset of symptoms (after age 12). Factor analysis of symptom ratings during the most severe lifetime manic episode was performed for each age group.
Results
Symptom factor structures were established for each age group. Two factors were evident for children with child-onset of symptoms (“activated/pleasure seeking” and “labile/disorganized”), one factor was present for adolescents with child-onset of symptoms (“activated/pleasure seeking/disorganized”) and two factors were evident for adolescents with adolescent-onset of symptoms (“activated/pleasure seeking” and “disorganized/psychotic”). The factor structures for children with child-onset and adolescents with adolescent-onset of symptoms were highly similar, with the latter factor structure including psychotic symptoms.
Limitations
Limitations include reliance on retrospective parent report and potential issues with generalizability.
Conclusions
Findings suggest mania symptomatology is largely similar when examined by both age of onset and current age, with some notable differences. Specifically, psychotic symptoms begin emerging as a distinct factor in adolescents with adolescent-onset of symptoms.
doi:10.1016/j.jad.2012.06.024
PMCID: PMC3535567  PMID: 23021377
pediatric bipolar disorder; course; onset
11.  Use of Mental Health Services in Transition Age Youth with Bipolar Disorder 
Journal of psychiatric practice  2013;19(6):10.1097/01.pra.0000438185.81983.8b.
Objectives
There is concern that treatment of serious mental illness in the United States declines precipitously following legal emancipation at age 18 years and transition from specialty youth clinical settings. We examined age transition effects on treatment utilization in a sample of youth with bipolar disorder.
Methods
Youth with bipolar disorder (N = 413) 7–18 years of age were assessed approximately twice per year (mean interval 8.2 months) for at least 4 years. Annual use of any individual, group, and family therapy, psychopharmacology visits, and hospitalization at each year of age, and monthly use from ages 17 through 19 years, were examined. The effect of age transition to 18 years on monthly visit probability was tested in the subsample with observed transitions (n = 204). Putative sociodemographic moderators and the influence of clinical course were assessed.
Results
Visit probabilities for the most common modalities—psychopharmacology, individual psychotherapy, and home-based care— generally fell from childhood to young adulthood. For example, the annual probability of at least one psychopharmacology visit was 97% at age 8, 75% at age 17, 60% at age 19, and 46% by age 22. Treatment probabilities fell in transition-age youth from age 17 through 19, but a specific transition effect at age 18 was not found. Declines did not vary based on sociodemographic characteristics and were not explained by changing severity of the bipolar illness or functioning.
Conclusions
Mental health treatment declined with age in this sample of youth with bipolar disorder, but reductions were not concentrated during or after the transition to age 18 years. Declines were unrelated to symptom severity or impairment.
doi:10.1097/01.pra.0000438185.81983.8b
PMCID: PMC3885866  PMID: 24241500
bipolar disorder; longitudinal studies; treatment use; transition-age youth; children; adolescents
12.  Dysfunctional Attitudes as a Moderator of Pharmacotherapy and Psychotherapy for Chronic Depression 
Journal of psychiatric research  2012;47(1):113-121.
Objective
Individuals with chronic depression exhibit heterogeneous responses to treatment. Important individual differences may therefore exist within this particularly difficult to treat population that act as moderators of treatment response.
Method
The present study examined whether pretreatment levels of dysfunctional attitudes (DA) moderated treatment response in a large sample of chronically depressed individuals. Data were taken from the Research Evaluating the Value of Augmenting Medication with Psychotherapy (REVAMP) treatment study – a multi-site treatment and augmentation study of 808 chronically depressed individuals. REVAMP comprised two phases: 1) a 12-week open-label antidepressant trial and 2), a subsequent phase, in which phase 1 non-remitters (N=491) were randomized to either receive an ongoing medication algorithm alone, medication plus cognitive behavioral analysis system of psychotherapy, or medication plus brief supportive psychotherapy.
Result
In phase 1, compared to the pharmacotherapy response of patients with lower DA scores, the response for patients with higher DA scores was steeper, but leveled off towards the end of the phase. In phase 2, DA predicted a differential response in the medication only arm, but not in the two psychotherapy+medication conditions. Specifically, in the phase 2 medication only condition, patients with higher DA improved while those with lower DA scores did not.
Conclusion
These results indicate that the relation between DA and treatment response in chronic depression is complex, but suggest that greater DA may be associated with a steeper reduction and/or better response to pharmacotherapy.
doi:10.1016/j.jpsychires.2012.09.018
PMCID: PMC3501539  PMID: 23102821
dysfunctional attitudes; predictor; treatment; response; chronic depression
13.  The drive-wise project: driving simulator training increases real driving performance in healthy older drivers 
Background: Age-related cognitive decline is often associated with unsafe driving behavior. We hypothesized that 10 active training sessions in a driving simulator increase cognitive and on-road driving performance. In addition, driving simulator training should outperform cognitive training.
Methods: Ninety-one healthy active drivers (62–87 years) were randomly assigned to one of three groups: (1) a driving simulator training group, (2) an attention training group (vigilance and selective attention), or (3) a control group. The main outcome variables were on-road driving and cognitive performance. Seventy-seven participants (85%) completed the training and were included in the analyses. Training gains were analyzed using a multiple regression analysis with planned orthogonal comparisons.
Results: The driving simulator-training group showed an improvement in on-road driving performance compared to the attention-training group. In addition, both training groups increased cognitive performance compared to the control group.
Conclusion: Driving simulator training offers the potential to enhance driving skills in older drivers. Compared to the attention training, the simulator training seems to be a more powerful program for increasing older drivers' safety on the road.
doi:10.3389/fnagi.2014.00085
PMCID: PMC4026721  PMID: 24860497
cognitive training; training effects; driving simulator; on-road driving performance; cognitive performance
14.  Non-physical practice improves task performance in an unstable, perturbed environment: motor imagery and observational balance training 
For consciously performed motor tasks executed in a defined and constant way, both motor imagery (MI) and action observation (AO) have been shown to promote motor learning. It is not known whether these forms of non-physical training also improve motor actions when these actions have to be variably applied in an unstable and unpredictable environment. The present study therefore investigated the influence of MI balance training (MI_BT) and a balance training combining AO and MI (AO+MI_BT) on postural control of undisturbed and disturbed upright stance on unstable ground. As spinal reflex excitability after classical (i.e., physical) balance training (BT) is generally decreased, we tested whether non-physical BT also has an impact on spinal reflex circuits. Thirty-six participants were randomly allocated into an MI_BT group, in which participants imagined postural exercises, an AO+MI_BT group, in which participants observed videos of other people performing balance exercises and imagined being the person in the video, and a non-active control group (CON). Before and after 4 weeks of non-physical training, balance performance was assessed on a free-moving platform during stance without perturbation and during perturbed stance. Soleus H-reflexes were recorded during stable and unstable stance. The post-measurement revealed significantly decreased postural sway during undisturbed and disturbed stance after both MI_BT and AO+MI_BT. Spinal reflex excitability remained unchanged. This is the first study showing that non-physical training (MI_BT and AO+MI_BT) not only promotes motor learning of “rigid” postural tasks but also improves performance of highly variable and unpredictable balance actions. These findings may be relevant to improve postural control and thus reduce the risk of falls in temporarily immobilized patients.
doi:10.3389/fnhum.2014.00972
PMCID: PMC4255492  PMID: 25538598
mental training; motor imagery learning; observational learning; balance control; posture control
15.  Cross-Limb Interference during Motor Learning 
PLoS ONE  2013;8(12):e81038.
It is well known that following skill learning, improvements in motor performance may transfer to the untrained contralateral limb. It is also well known that retention of a newly learned task A can be degraded when learning a competing task B that takes place directly after learning A. Here we investigate if this interference effect can also be observed in the limb contralateral to the trained one. Therefore, five different groups practiced a ballistic finger flexion task followed by an interfering visuomotor accuracy task with the same limb. Performance in the ballistic task was tested before the training, after the training and in an immediate retention test after the practice of the interference task for both the trained and the untrained hand. After training, subjects showed not only significant learning and interference effects for the trained limb but also for the contralateral untrained limb. Importantly, the interference effect in the untrained limb was dependent on the level of skill acquisition in the interfering motor task. These behavioural results of the untrained limb were accompanied by training specific changes in corticospinal excitability, which increased for the hemisphere ipsilateral to the trained hand following ballistic training and decreased during accuracy training of the ipsilateral hand. The results demonstrate that contralateral interference effects may occur, and that interference depends on the level of skill acquisition in the interfering motor task. This finding might be particularly relevant for rehabilitation.
doi:10.1371/journal.pone.0081038
PMCID: PMC3849090  PMID: 24312523
16.  Recovery from Multiple Episodes of Bipolar I Depression 
The Journal of clinical psychiatry  2013;74(3):10.4088/JCP.12m08049.
Objectives
To describe the duration of bipolar I major and minor depressive episodes and factors associated with time to recovery.
Method
219 participants with bipolar I disorder based on Research Diagnostic Criteria analogs to DSM-IV-TR criteria were recruited from 1978–1981 and followed for up to 25 years. Psychopathology was assessed with the Longitudinal Interval Follow-up Evaluation. The probability of recovery over time from multiple successive depressive episodes was examined with survival analytic techniques, including mixed-effects grouped-time survival models.
Results
The median duration of major depressive episodes was 14 weeks, and over 70% recovered within 12 months of onset of the episode. The median duration of minor depressive episodes was 8 weeks, and approximately 90% recovered within 6 months of onset of the episode. Aggregated data demonstrated similar durations of the first three major depressive episodes. However, for each participant with multiple episodes of major depression or minor depression, the duration of each episode was not consistent (intraclass correlation coefficient=0.07 and 0.25 for major and minor depression, respectively). The total number of years in episode over follow-up with major plus minor depression prior to onset of a major depressive episode was significantly associated with a decreased probability of recovery from that episode; with each additional year, the likelihood of recovery was reduced by 7% (hazard ratio: 0.93, 95% CI: 0.89–0.98, p=0.002).
Conclusions
Bipolar I major depression generally lasts longer than minor depression, and the duration of multiple episodes within an individual varies. However, the probability of recovery over time from an episode of major depression appears to decline with each successive episode.
doi:10.4088/JCP.12m08049
PMCID: PMC3837577  PMID: 23561241
17.  Psychiatric treatment received by primary care patients with panic disorder with and without agoraphobia 
Psychiatric services (Washington, D.C.)  2009;60(6):10.1176/appi.ps.60.6.823.
Objective
Although the majority of individuals with panic disorder first present to the primary care setting, little is known about the psychiatric treatment primary care patients with the disorder typically receive. The purpose of the current study was to explore characteristics of treatment received by those with panic disorder with and without agoraphobia, examine demographic and clinical predictors of receiving treatment, and explore treatment barriers.
Methods
This study uses data from the Primary Care Anxiety Project (PCAP), which is a naturalistic, longitudinal study of anxiety disorders in primary care patients. This study presents data on 235 PCAP participants diagnosed with panic disorder with (N=150) or without agoraphobia (N=85) at the study intake assessment.
Results
Many patients with panic disorder were not receiving psychiatric treatment at study intake, with those without agoraphobia being less likely to receive treatment. Psychotropic medications were the treatment of choice, with SSRIs/SNRIs being the most commonly received class of medications. Only 39% of those with panic disorder with agoraphobia and 24% of those without agoraphobia were receiving psychotherapy, and use of empirically supported interventions was rare. The most common treatment barriers were: not believing in utilizing medication/therapy for emotional problems and not receiving a treatment recommendation from one’s provider.
Conclusions
The findings suggest a need for better treatment dissemination, in addition to making interventions more accessible and/or adapting them to the particular needs of primary care patients.
doi:10.1176/appi.ps.60.6.823
PMCID: PMC3831269  PMID: 19487354
18.  Occupational Impairment and Social Anxiety Disorder in a Sample of Primary Care Patients 
Journal of affective disorders  2010;130(0):10.1016/j.jad.2010.09.024.
Background
Social Anxiety Disorder (SAD) is the second most prevalent psychiatric condition in the US. Because of the inherent nature of SAD, it may cause impairments in workplace functioning, particularly compared to other anxiety disorders that do not necessarily lead to social impairments. In this study, we compared workplace functioning in primary care patients with SAD to patients with other anxiety disorders and comorbid Major Depressive Disorder (MDD).
Methods
Data are obtained from the Primary Care Anxiety Project (PCAP), a naturalistic, longitudinal study of anxiety disorders in 539 primary care patients. We examined intake demographic and interviewer-assessed ratings of workplace functioning.
Results
Results revealed patients with SAD and MDD had significantly decreased workplace functioning, compared to individuals with other anxiety disorders. Furthermore, results showed patients with SAD were greater than two-times more likely to be unemployed, but expected to work, than all other patients.
Limitations
Workplace functioning was not measured objectively and the sample may not be representative of the general population.
Conclusions
These findings highlight the particular need to assess for the presence of undereducation and underperformance at work and/or underemployment in individuals with SAD, as they are at most risk for these impairments. Additionally, early detection and intervention in individuals with or at risk for SAD may curb the future impact of social anxiety on occupational attainment.
doi:10.1016/j.jad.2010.09.024
PMCID: PMC3831271  PMID: 20934220
Social Anxiety Disorder; primary care; occupational functioning
19.  Psychiatric Treatment in Primary Care Patients with Anxiety Disorders: A Comparison of Care Received from Primary Care Providers and Psychiatrists 
The American journal of psychiatry  2007;164(2):10.1176/appi.ajp.164.2.276.
Objective
To examine the psychiatric treatment received by primary care patients with anxiety disorders and compare treatment from primary care physicians and psychiatrists.
Method
Primary care patients at 15 U.S. sites were screened for anxiety symptoms at the time of a medical visit. Those screening positive were interviewed to assess for anxiety disorders. Information on psychiatric treatment received and provider of pharmacological treatment was collected.
Results
Of 539 primary care participants with at least one anxiety disorder, almost half (47.3%) were untreated. Nearly 21% were receiving only medication for psychiatric problems, 7.2% received psychotherapy alone, and 24.5% received both medication and psychotherapy. Patients getting psychopharmacologic treatment received similar medications, often at similar dosages, regardless of whether their prescriber was a primary care physician or a psychiatrist. One exception was that patients were less likely to be taking benzodiazepines if their provider was a primary care physician. Those receiving medications from a primary care provider were also less likely to be in psychotherapy. Overall, patients with more functional impairment, more severe symptoms, and comorbid major depression were more likely to receive mental health treatment. Members of racial/ethnic minority groups were less likely to be treated. Frequently endorsed reasons by patients for not receiving pharmacological treatment were that the primary care physician did not recommend it and not believing in taking medication for emotional problems.
Conclusions
Nearly half of primary care patients with anxiety disorders were not treated. However, when treated, care received from primary care physicians and psychiatrists was relatively similar.
doi:10.1176/appi.ajp.164.2.276
PMCID: PMC3831273  PMID: 17267791
20.  Characteristics and Predictors of Social Phobia Course in a Longitudinal Study of Primary Care Patients 
Depression and anxiety  2010;27(9):10.1002/da.20676.
Background
Social Phobia (SP) is a prevalent disorder in primary care settings. To date, few researchers have examined the natural course of SP in primary care. We examined the natural course and predictors of recovery in a large sample of primary care patients.
Methods
Data are obtained from the Primary Care Anxiety Project (PCAP), a naturalistic, longitudinal study of anxiety disorders in primary care patients. The current report pertains to 182 patients with SP at intake. We examined intake demographic and clinical variables as predictors of recovery within the five years of follow-up.
Results
The probability of recovery from SP during the 5 year follow-up period was .40. At intake, a longer duration of SP episode, co-morbid Panic Disorder with Agoraphobia, lower psychosocial functioning, and the presence of a medical condition predicted lower rates of recovery.
Conclusions
These findings highlight the chronicity of SP, as well as factors that may affect its naturalistic course. It is imperative that primary care physicians and mental health specialists assess for and treat SP in their practices. Future research is warranted to further examine the effect of medical and psychiatric comorbidity on SP course.
doi:10.1002/da.20676
PMCID: PMC3826438  PMID: 20186979
Social Phobia; Social Anxiety Disorder; Primary Care; Course; Prospective
21.  Assessing Rates and Predictors of Tachyphylaxis During the Prevention of Recurrent Episodes of Depression With Venlafaxine ER for Two Years (PREVENT) Study 
Psychopharmacology bulletin  2009;42(3):5-20.
Background
Antidepressant tachyphylaxis describes the return of apathetic depressive symptoms, such as fatigue and decreased motivation, despite continued use of a previously effective treatment.
Methods
Data were collected from a multiphase, double-blind, placebo-controlled study that assessed the efficacy of venlafaxine extended release (ER) during 2 sequential 1-year maintenance phases (A and B) in patients with recurrent major depressive disorder (MDD). The primary outcome was the cumulative probability of tachyphylaxis in patients receiving venlafaxine ER, fluoxetine, or placebo. Tachyphylaxis was defined as Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) scored ≥ 7 in patients with prior satisfactory therapeutic response. A Kaplan-Meier estimate of the cumulative probability of not experiencing tachyphylaxis, and a 2-sided Fisher exact test was used to assess the relationship between tachyphylaxis and recurrence.
Results
The maintenance phase A population was comprised of 337 patients (venlafaxine ER [n = 129], fluoxetine [n = 79], placebo [n = 129]), whereas 128 patients (venlafaxine ER [n = 43], fluoxetine [n = 45], placebo [n = 40]) were treated during maintenance phase B. No difference in the probability of experiencing tachyphylaxis were observed between the active treatment groups during either maintenance phase; however, a significant difference between venlafaxine ER and placebo was observed at the completion of maintenance phase A. A significant relationship between tachyphylaxis and recurrence was observed.
Limitations
Despite demonstrating psychometric validity and reliability, the current definition of tachyphylaxis has not been widely studied
Conclusions
Although no significant differences were observed in the probability of tachyphylaxis among patients receiving active treatment, the relationship between tachyphylaxis and recurrence suggests that tachyphylaxis may be a predrome of recurrence.
PMCID: PMC3806307  PMID: 19752838
loss of antidepressant response; psychopharmacology; major depressive disorder; serotonin norepinephrine reuptake inhibitor; Rothschild Scale for Antidepressant Tachyphylaxis
22.  Course of illness following prospectively observed mania or hypomania in individuals presenting with unipolar depression 
Bipolar disorders  2012;14(6):664-671.
Objectives
In a well-defined sample, we sought to determine what clinical variables, some of potential nosological relevance, influence subsequent course following prospectively observed initial episodes of hypomania or mania (H/M).
Methods
We identified 108 individuals in the National Institute of Mental Health Collaborative Depression Study diagnosed with unipolar major depression at intake who subsequently developed H/M. We assessed time to repeat H/M based on whether one had been started on an antidepressant or electroconvulsive therapy within eight weeks of developing H/M, had longer episodes, or had a family history of bipolar disorder.
Results
Modeling age of onset, treatment-associated H/M, family history of bipolar disorder, duration of index H/M episode, and psychosis in Cox regression analysis, family history of bipolar disorder (n = 21) was strongly associated with repeat episodes of H/M [hazard ratio (HR) = 2.01, 95% confidence interval (CI): 1.06–3.83, p = 0.03]. Those with treatment-associated episodes (n = 12) were less likely to experience subsequent episodes of H/M, though this was not significant in the multivariate model (HR = 0.25, 95% CI: 0.06–1.05, p = 0.06). These individuals also had a later age of onset for affective illness and were more likely to be depressed. Duration of illness with a temporal resolution of one week, psychosis, and age of onset were not associated with time to repeat H/M episode.
Conclusions
Family history of bipolar disorder influences course of illness even after an initial H/M episode. In this select sample, treatment-associated H/M did not appear to convey the same risk for a course of illness characterized by recurrent H/M episodes.
doi:10.1111/j.1399-5618.2012.01041.x
PMCID: PMC3432672  PMID: 22816725
bipolar disorder; depressive disorder; antidepressants; prospective studies
23.  Impact of Treatments for Depression on Comorbid Anxiety, Attentional, and Behavioral Symptoms in Adolescents With Selective Serotonin Reuptake Inhibitor–Resistant Depression 
Objective
To assess the relative efficacy of antidepressant medication, alone and in combination with cognitive behavioral therapy (CBT), on comorbid symptoms of anxiety, attention, and disruptive behavior disorders in participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial.
Method
Adolescents with selective serotonin reuptake inhibitor (SSRI)–resistant depression (N = 334) were randomly assigned to a medication switch alone (to another SSRI or to venlafaxine) or to a medication switch plus CBT. Anxiety, attention-deficit/hyperactivity disorder (ADHD), and disruptive behavior disorder (DBD) symptoms were assessed by psychiatric interview and self-report at regular intervals between baseline and 24 weeks. The differential effects of medication and of CBT, and the impact of remission on the course of comorbid symptoms and diagnoses, were assessed using generalized linear mixed models.
Results
Remission was associated with a greater reduction in scalar measures of anxiety, ADHD, and DBDs, and a greater decrease in the rate of diagnosed anxiety disorders. The correlations between the changes in symptoms of depression on the CDRS-R and anxiety, ADHD, and oppositional symptoms were modest, ranging from r = 0.12 to r = 0.28. There were no significant differential treatment effects on diagnoses, or corresponding symptoms.
Conclusion
The achievement of remission had a beneficial effect on anxiety, ADHD, and DBD symptoms, regardless of the type of treatment received. There were no differential effects of medication or CBT on outcome, except for a nonsignificant trend that those adolescents treated with SSRIs showed a greater decrease in rates of comorbid DBDs relative to those treated with venlafaxine.
doi:10.1016/j.jaac.2013.02.013
PMCID: PMC3756470  PMID: 23622849
antidepressants; cognitive behavioral therapy (CBT); comorbidity; Treatment of Resistant Depression in Adolescents (TORDIA); secondary outcomes
24.  Predictors of the long-term course of comorbid PTSD: A naturalistic prospective study 
Objectives
The study examined the long-term course of posttraumatic stress disorder (PTSD) by analyzing rates of recurrence and the predictive value of comorbid psychiatric disorders and psychosocial functioning.
Methods
This study is based on diagnostic assessments administered at intake and subsequent follow-up interviews over a period of 15 years in a sample of 90 anxiety-disordered patients with comorbid PTSD who participated in the Harvard Brown Anxiety Research project (HARP). Kaplan–Meier life table analysis revealed a 0.20 probability of full remission during the 15 years of follow-up.
Results
Latent growth model (LGM) analysis revealed that the number of trauma exposures was a predictor of a worse course of PTSD but only during some intervals of the 15-year follow-up. Subjects with full social phobia were more likely to experience worsening of PTSD over time in comparison with subjects with less severe social phobia. Role functioning in the areas of household and employment was a significant predictor of a declining course of PTSD.
Conclusions
These findings revealed the dynamic nature of the predictive value of traumatic experiences, the deleterious effect of social phobia and the long term effect of psychosocial functioning on the course of PTSD. Implications for treatment planning and development of interventions for PTSD are discussed.
doi:10.3109/13651501.2012.667113
PMCID: PMC3755033  PMID: 22536784
PTSD; longitudinal studies; long-term course; clinical predictors of PTSD; social anxiety; psychosocial functioning
25.  Effective Components of TORDIA Cognitive–Behavioral Therapy for Adolescent Depression: Preliminary Findings 
In this report, we conducted a secondary analysis of the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study to explore the impact of specific cognitive–behavioral therapy (CBT) treatment components on outcome. In TORDIA, 334 youths (ages 12 to 18 years) with major depressive disorder who had failed to respond to an adequate course of selective serotonin reuptake inhibitor (SSRI) medication were randomized to a medication switch (either to an alternative SSRI or venlafaxine) with or without 12 weeks of adjunctive CBT. Participants who had more than 9 CBT sessions were 2.5 times more likely to have adequate treatment response than those who had 9 or fewer sessions. CBT participants who received problem-solving and social skills treatment components, controlling for number of sessions and other confounding variables, were 2.3 and 2.6 times, respectively, more likely to have a positive response. These preliminary findings underscore the importance of receiving an adequate number of sessions to attain an adequate clinical response. Finally, social skills and problem solving may be active elements in CBT for adolescent depression and should be considered in treatment by those working with seriously depressed youths.
doi:10.1037/a0017411
PMCID: PMC3705725  PMID: 19968380
cognitive–behavioral therapy; adolescent depression; treatment components

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