WBRT vs. APBI: an interim report of patient satisfaction and outcomes.

PURPOSE: To determine differences in patient's reported quality of life and self-reported breast cosmesis between whole breast radiation therapy (WBRT) and accelerated partial breast irradiation (APBI) via single and multi-lumen high-dose-rate (HDR) brachytherapy for women with early stage breast cancer. MATERIAL AND METHODS: Patient information was retrospectively reviewed and survey data were prospectively collected for women treated between 2004 to 2014 (APBI) and 2012 to 2014 (WBRT). Criteria for APBI treatments were ER+ (after 2010), N0 (after 2010), T < 3 cm, and post-menopausal. All patients were given a survey with modified FACIT (Functional Assessment of Chronic Illness Therapy) breast quality of life questions to rate their amount of pain, self-consciousness, low energy, presence of lymphedema, and breast cosmesis. RESULTS: 242 APBI patients and 59 WBRT patients were identified. In the WBRT cohort, 34 women met departmental criteria for APBI treatment (WBRT who were APBI eligible). The FACIT survey was completed by 80 women treated with APBI (33%; mean follow-up time of 14 months), and 26 women treated with WBRT who were APBI eligible (76%; mean follow-up time of 26 months). During the first year post-treatment, low energy (p = 0.009), self-consciousness (p = 0.0004), and lymphedema (p = 0.0002) scores were significantly lower in the APBI cohort when compared to women treated with WBRT who were APBI eligible. During the second year post-treatment, women treated with APBI reported significantly better breast cosmesis (p = 0.04). The single-lumen balloon (score = 6.3/10) was found to be associated with worse cosmesis compared to the multi-lumen balloons (Mammosite ML and Contura; score = 8.2/10; p = 0.002). There were no significant differences in rates of recurrence between balloons or treatments (p > 0.05). CONCLUSIONS: APBI treated patients reported higher cosmetic satisfaction than patients in the matched WBRT cohort. Quality of life scores tended to improve over time. Multi-lumen catheters provided superior cosmetic results compared to single-lumen catheters.

The effects of carbamazepine on prefrontal activation in manic youth with bipolar disorder.

This preliminary study investigated the neurofunctional effects of carbamazepine-extended release (XR) treatment in 11 manic youth with bipolar disorder during performance of a sustained attention task, the Continuous Performance Task - Identical Pairs version (CPT-IP), during functional magnetic resonance imaging (fMRI). All patients underwent baseline fMRI, and 10 patients were scanned again at endpoint. Nine demographically matched healthy youth, who were scanned once, served as controls. Carbamazepine-XR treatment was associated with normalization of activation in right Brodmann area 10 (BA). These results suggest that carbamazepine-XR treatment may correct prefrontal dysfunction in adolescent mania.

Neurofunctional changes in adolescent cannabis users with and without bipolar disorder.

AIMS: To compare regional brain activation among adolescents with bipolar disorder and co-occurring cannabis use disorder. DESIGN: Cross-sectional study. SETTING: Cincinnati, OH, USA. PARTICIPANTS: Adolescents with bipolar disorder (BP, n = 14), adolescents with cannabis use disorder (MJ, n = 13), adolescents with co-occurring cannabis use and bipolar disorders (BPMJ, n = 25) and healthy adolescents (HC, n = 15). MEASUREMENTS: Cannabis craving, substance use, Blood Oxygenation Level Dependent (BOLD) signal assessed by the Marijuana Craving Questionnaire (MCQ), Teen-Addiction Severity Index (T-ASI) and a cannabis cue-reactivity task during a functional magnetic resonance imaging (fMRI) session, respectively. FINDINGS: The BP group exhibited significantly greater brain activation than the BPMJ group in the right amygdala (F = 4.14, P = 0.046), left nucleus accumbens (F = 3.8, P = 0.02), left thalamus (F = 3.8, P < 0.05) and the right thalamus (F = 6.2, P = 0.02). The BP group exhibited significantly greater activation than the HC group in the left nucleus accumbens (F = 11.5, P = 0.0001), right thalamus (F = 4.9, P = 0.03) and the left striatum (F = 3.6, P = 0.04). Left amygdala activation of the BPMJ group trended towards being significantly negatively correlated with the number of joints smoked (R = -0.4, P = 0.06). CONCLUSIONS: Bipolar adolescents with comorbid cannabis use do not exhibit the same over-activation of the regions involved in emotional processing as seen in adolescents with bipolar disorder alone. The absence of these findings in patients with comorbid bipolar and cannabis use disorders suggests that these individuals may have a unique endophenotype of bipolar disorder or that cannabis use may alter brain activation uniquely in bipolar disorder patients who use cannabis.

N-acetyl aspartate levels in adolescents with bipolar and/or cannabis use disorders.

OBJECTIVE: Bipolar and cannabis use disorders commonly co-occur during adolescence, and neurochemical studies may help clarify the pathophysiology underlying this co-occurrence. This study compared metabolite concentrations in the left ventral lateral prefrontal cortex among adolescents with bipolar disorder (bipolar group; n = 14), adolescents with a cannabis use disorder (cannabis use group; n = 13), adolescents with cannabis use and bipolar disorders (bipolar and cannabis group; n = 25), and healthy adolescents (healthy controls; n = 15). We hypothesized that adolescents with bipolar disorder (with or without cannabis use disorder) would have decreased N-acetyl aspartate levels in the ventral lateral prefrontal cortex compared to the other groups and that the bipolar and cannabis group would have the lowest N-acetyl aspartate levels of all groups. METHODS: N-acetyl aspartate concentrations in the left ventral lateral prefrontal cortex were obtained using proton magnetic resonance spectroscopy. RESULTS: Adolescents with bipolar disorder showed significantly lower left ventral lateral prefrontal cortex N-acetyl aspartate levels, but post hoc analyses indicated that this was primarily due to increased N-acetyl aspartate levels in the cannabis group. The cannabis use disorder group had significantly higher N-acetyl aspartate levels compared to the bipolar disorder and the bipolar and cannabis groups (p = .0002 and p = .0002, respectively). Pearson correlations revealed a significant positive correlation between amount of cannabis used and N-acetyl aspartate concentrations. CONCLUSIONS: Adolescents with cannabis use disorder showed higher levels of N-acetyl aspartate concentrations that were significantly positively associated with the amount of cannabis used; however, this finding was not present in adolescents with comorbid bipolar disorder.

Antidepressant tolerability in anxious and depressed youth at high risk for bipolar disorder: a prospective naturalistic treatment study.

OBJECTIVE: Depressive and anxiety disorders are common in youth who are at risk for bipolar disorder (i.e., youth who have at least one parent with bipolar disorder) and antidepressants are commonly prescribed as treatment. However, there are few data regarding the safety and tolerability of antidepressants in this population. Therefore, we sought to prospectively examine the effects of these medications in children and adolescents who are diagnosed with depressive or anxiety disorders and have a parent with bipolar I disorder. METHODS: Youth aged 9-20 years, with at least one parent with bipolar I disorder [high risk (HR)], were recruited (n = 118) and assessed using semi-structured diagnostic interviews. Participants were prospectively evaluated using a modified version of the Longitudinal Interval Follow-up Evaluation to assess changes in affective and anxiety symptoms and were treated naturalistically. RESULTS: Over the course of 43-227 weeks (mean duration of follow-up: 106 ± 55 weeks), 21% (n = 25) of youth had antidepressant exposure and, of these, 57% (n = 12) had an adverse reaction (e.g., irritability, aggression, impulsivity, or hyperactivity) that led to antidepressant discontinuation. Those patients who experienced an adverse reaction were significantly younger than those who did not (p = 0.02) and discontinuation of antidepressant therapy secondary to an adverse event occurred at an average of 16.7 ± 17.4 weeks (median: 11 weeks, range: 2-57 weeks). Cox proportional hazard analyses yielded a hazard ratio of 0.725 (p = 0.03), suggesting that there is a 27% decrease in the likelihood of an antidepressant-related adverse event leading to discontinuation with each one-year increase in age. CONCLUSIONS: Antidepressant medications may be poorly tolerated in youth with a familial risk for developing mania. Controlled studies further assessing treatments for depression and anxiety in HR youth are urgently needed.

The effects of ziprasidone on prefrontal and amygdalar activation in manic youth with bipolar disorder.

BACKGROUND: Prior research has found that manic adolescents with bipolar disorder exhibit neurofunctional changes in the amygdala and prefrontal cortex following treatment with some pharmacological agents. We examined the neurofunctional effects of ziprasidone in manic adolescents. METHOD: Manic adolescents with bipolar disorder (n=23) participated in a placebo-controlled study of ziprasidone and underwent a functional magnetic resonance imaging scanning session while performing a task of sustained attention at baseline, prior to treatment as well as on days 7 and 28 (or early termination) of treatment. A comparison group of healthy adolescents (n=10) participated in a single scanning session. Region of interest analyses were performed to assess activation changes associated with treatment in Brodmann Areas (BA) 10, 11 and 47 and in the amygdala. RESULTS: Compared with placebo, treatment with ziprasidone was associated with greater increases over time in right BA 11 and 47 activation. These effects were not associated with differences in symptom improvement between the treatment groups. Patients who subsequently responded to ziprasidone showed significantly greater deactivation in the right Brodmann area 47 at baseline than those who did not respond to ziprasidone. Similarly, among the bipolar adolescents who were treated with ziprasidone, baseline activation in right BA 47 was negatively correlated with improvement in Young Mania Rating Scale (YMRS) score. LIMITATIONS: The small sample size limits the ability to detect significant group differences in other regions of interest. Healthy comparison subjects were scanned only at a single timepoint, which limits the interpretation of the results. Ziprasidone is not currently approved by the United States Food and Drug Administration for the treatment of adolescents with mania, and, therefore, the clinical relevance of these results is limited. CONCLUSIONS: The increases in right BA 11 and 47 activation observed during sustained attention tasks following ziprasidone treatment and the association identified between lower baseline BA 47 activation and ziprasidone treatment response suggests that ziprasidone may correct prefrontal dysfunction in manic adolescents with bipolar disorder.

Neurocircuitry of generalized anxiety disorder in adolescents: a pilot functional neuroimaging and functional connectivity study.

BACKGROUND: Dysfunction of neural systems responsible for the processing of emotional stimuli is hypothesized to be involved in the pathophysiology of generalized anxiety disorder (GAD) in adolescents. We used standard fMRI and functional connectivity analyses to examine the functional neurocircuitry of GAD in adolescents. METHODS: Ten adolescents with GAD and 10 healthy comparison subjects underwent fMRI while performing a continuous performance task with emotional and neutral distractors. Standard event-related voxel-wise fMRI and steady-state functional connectivity analyses were performed. RESULTS: Increased activation was observed in the left medial prefrontal cortex and right ventrolateral prefrontal cortex (VLPFC) in response to emotional images compared to neutral imagines in youth with GAD. Connectivity analyses using the right VLPFC seed region suggested decreased connectivity between this region and the bilateral medial prefrontal cortex. Connectivity analyses using the right amygdala seed region revealed decreased correlation with the posterior cingulate cortex in adolescents with GAD. The left amygdala seed region demonstrated increased connectivity with the ipsilateral precuneus in youth with GAD compared to healthy subjects. CONCLUSIONS: In addition to increased activation of the medial prefrontal cortex and right VLPFC, we observed altered connectivity between the amygdala or VLPFC and regions, which subserve mentalization (e.g. posterior cingulate cortex, precuneus, and medial prefrontal cortex). This suggests that structures that regulate emotion and affect interact abnormally with key structures that are involved in mentalization, a process known to be disrupted in GAD.

Health-related quality of life as measured by the child health questionnaire in adolescents with bipolar disorder treated with olanzapine.

AIM: To examine health-related quality of life (HRQoL) in adolescents with bipolar disorder before and after double-blind treatment with olanzapine or placebo. METHODS: Parents or legal guardians of 160 adolescents with a manic or mixed episode associated with bipolar I disorder were asked to rate their child's health using the Child Health Questionnaire-Parental Form 50 at baseline, before receiving medication, and then again at the end of participation in a 3-week double-blind placebo-controlled study of olanzapine. RESULTS: Adolescents in both treatment groups began and ended the study with significantly lower scores than normalized values of healthy peers on several HRQoL subscales (lower ratings indicate more impaired functioning), especially those assessing psychosocial factors. However, participants receiving olanzapine exhibited greater improvement than those in the placebo group across multiple HRQoL subscales, including the Behavior, Family activities, and Mental health subscales. Reduction in manic symptoms was associated with improvement in HRQoL values. CONCLUSIONS: As expected, manic adolescents with bipolar disorder exhibit abnormalities in psychosocial, rather than physical factors associated with HRQoL. Treatment with olanzapine had a greater effect on multiple domains of psychosocial functioning compared with placebo, suggesting that in addition to improving manic symptoms, pharmacologic interventions may lessen some of psychosocial deficits experienced by adolescents with bipolar disorder. However, following 3 weeks of treatment, adolescents with bipolar disorder continued to exhibit deficits in several aspects of psychosocial functioning, indicating that additional pharmacologic and psychosocial interventions may be necessary to further improve functional outcome.

Progression of amygdala volumetric abnormalities in adolescents after their first manic episode.

OBJECTIVE: Although previous neuroimaging studies suggest that adolescents with bipolar disorder exhibit smaller amygdala volumes compared with healthy adolescents, whether these abnormalities are present at illness onset or instead develop over time remains unclear. The aim of this study was to conduct a prospective longitudinal investigation comparing amygdala neurodevelopment among adolescents after their first manic episode, adolescents with attention-deficit/hyperactivity disorder (ADHD), and healthy adolescents. METHOD: A total of 30 adolescents hospitalized for their first manic/mixed episode associated with bipolar disorder, 29 adolescents with ADHD, and 24 demographically matched healthy teens underwent magnetic resonance imaging scanning at index assessment and approximately 12 months later. Adolescents with bipolar disorder were prospectively evaluated using diagnostic interviews and with symptom rating scales. RESULTS: Mixed models examining the group × time effect for both left (p = .005) and right (p = .002) amygdala volumes were statistically significant. Change in left (p = .01) and right (p = .0008) amygdala volumes from baseline to 12 months were significantly different among groups. Specifically, left amygdala volumes increased over time in healthy adolescents (p = .008) and adolescents with ADHD (p = .0009), but not in adolescents with bipolar disorder (p = .3). Right amygdala volume increased over time in adolescents with ADHD (p < .001), but not in healthy adolescents nor in adolescents with bipolar disorder (p = .1 and p = .3, respectively). In adolescents with bipolar disorder, baseline total amygdala volume was significantly greater in those who subsequently achieved symptomatic recovery as compared with those who did not achieve recovery (p = .02). CONCLUSIONS: Adolescents with mania do not exhibit normal increases in amygdala volume that occur during healthy adolescent neurodevelopment.