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Politics and science have become increasingly intertwined. Salient scientific issues, such as climate change, evolution, and stem-cell research, become politicized, pitting partisans against one another. This creates a challenge of how to effectively communicate on such issues. Recent work emphasizes the need for tailored messages to specific groups. Here, we focus on whether generalized messages also can matter. We do so in the context of a highly polarized issue: extreme COVID-19 vaccine resistance. The results show that science-based, moral frame, and social norm messages move behavioral intentions, and do so by the same amount across the population (that is, homogeneous effects). Counter to common portrayals, the politicization of science does not preclude using broad messages that resonate with the entire population.
In a study conducted in the database of a large commercial healthcare insurer, we previously demonstrated that use of a commercial pharmacogenetic assay for individuals with mood disorders was associated with decreased resource utilization and cost in the 6 month period following use compared to propensity-score matched controls. We conducted a post hoc analysis to understand variables associated with high cost savings.
The results and methods of the initial study have previously been described. Cases were individuals with mood and anxiety disorders who received a commercial pharmacogenetic assay (Genomind, King of Prussia PA) to inform pharmacotherapy. 817 tested individuals (cases) with mood and/or anxiety disorders were matched to 2745 controls. Overall costs were estimated to be $1,948 lower in the tested group. The differences were largely the result of lesser emergency room and inpatient utilization for cases. In the present analysis, cost difference for cases compared to their matched controls was rank ordered by decile. High cost savers were arbitrarily defined a priori as the top 20% of savers. Using multivariable modeling techniques, an ordinal logistic regression model was generated in which baseline or follow-up variables were statistically tested for independent associations with high, low, and no cost savings.
606 (74%) of cases were net cost savers compared to their controls (cost difference <0). High cost savers (n=121) saved on average $10,690 compared to their matched controls. They were statistically more likely to have been diagnosed with bipolar disorder (n=33/121) than low cost savers (n=57/485) or non-savers (n=31/211), and had a lower Charlson Comorbidity index. High cost savers had fewer mean number of antidepressants in the baseline period (mean=3.16) compared to non-savers (3.73) but more than low cost savers (2.72) (p<0.05 across groups). In a multivariable model, bipolar, count of antidepressants, outpatient visits, and inpatient visits were statistically associated with being a high cost saver; antidepressant count and all-cause inpatient and outpatient visits in the baseline period were inversely associated with cost savings.
Use of a pharmacogenetic assay was associated with cost-savings in the database of a large commercial insurer. Patients with bipolar disorder were more likely to be high cost savers than individuals with other mood and anxiety disorders.
Investigation of personality traits and pathology in large, generalizable clinical cohorts has been hindered by inconsistent assessment and failure to consider a range of personality disorders (PDs) simultaneously.
We applied natural language processing (NLP) of electronic health record notes to characterize a psychiatric inpatient cohort. A set of terms reflecting personality trait domains were derived, expanded, and then refined based on expert consensus. Latent Dirichlet allocation was used to score notes to estimate the extent to which any given note reflected PD topics. Regression models were used to examine the relationship of these estimates with sociodemographic features and length of stay.
Among 3623 patients with 4702 admissions, being male, non-white, having a low burden of medical comorbidity, being admitted through the emergency department, and having public insurance were independently associated with greater levels of disinhibition, detachment, and psychoticism. Being female, white, and having private insurance were independently associated with greater levels of negative affectivity. The presence of disinhibition, psychoticism, and negative affectivity were each significantly associated with a longer stay, while detachment was associated with a shorter stay.
Personality features can be systematically and scalably measured using NLP in the inpatient setting, and some of these features associate with length of stay. Developing treatment strategies for patients scoring high in certain personality dimensions may facilitate more efficient, targeted interventions, and may help reduce the impact of personality features on mental health service utilization.
Background: Inadequate response to antidepressant monotherapy in women with major depressive disorder is common. Testosterone administration has been shown to be an effective augmentation therapy in depressed hypogonadal men with selective serotonin reuptake inhibitor-resistant depression. However, the effects of low-dose testosterone as augmentation therapy in women with treatment-resistant depression have not been studied.
Methods: Low-dose transdermal testosterone (300 mcg/day, Intrinsa, Procter and Gamble Pharmaceuticals) was administered to nine women with treatment-resistant depression in an 8 week open-label pilot protocol.
Results: There was a statistically significant improvement in mean Montgomery-Asberg Depression Rating Scale (MADRS) scores at 2 weeks, sustained through the 8 week period. Two-thirds of subjects achieved a response to the treatment (decrease in MADRS score of ≥50%) and 33% achieved remission (final MADRS score <10) after 8 weeks of therapy. Mean levels of fatigue, as measured by the MADRS lassitude item, significantly decreased at all time points with a mean 38% decrease from baseline to 8 weeks.
Conclusion: These preliminary pilot data suggest that low-dose transdermal testosterone may be an effective augmentation therapy in women with treatment-resistant depression. Further studies are warranted.
Background:This study examined the prevalence of irritability in patients with bipolar I disorder during an episode of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) major depression who do not meet criteria for a mixed episode.
Method:A chart review of 111 patients with bipolar I disorder treated at the Massachusetts General Hospital Bipolar Clinic between 1998 and 2000 identified 34 patients who met criteria for a DSM-IV major depressive episode in the absence of (1) mood elevation and/or (2) irritability associated with any additional above threshold DSM-IV symptoms of mania. Data gathered from the charts utilized prospective ratings made routinely at each clinic visit using the Clinical Monitoring Form (CMF), a structured assessment instrument which includes modified versions of the mood modules of the Structured Clinical Interview for DSM-IV. Data from these 34 patients were reviewed to determine the presence of irritability.
Results:The frequency of abnormal irritability in these 34 patients followed a bimodal distribution: 26% of the patients showed abnormal irritability ≥75% of the time, compared with 68% of the patients with abnormal irritabihty ≤30% of the time. Of the high-irritability patients, psychomotor agitation was rated as definitely present to a significant degree in 44%. Talkativeness and distractibility were rated present but subthreshold in one patient each. All other symptoms of DSM-IV mania were absent.
Conclusion:Approximately 25% of patients with bipolar I disorder who meet criteria for a DSM-IV major depressive episode also experienced substantial irritability in the absence of associated symptoms of mania. Our results suggest that abnormal irritability is not limited to mania or mixed states.
Studies have shown that there is some efficacy for a number of agents, most notably lithium, in treating bipolar depression. However, the studies also highlight the unfortunate reality that many patients fail to respond adequately to first-line therapies and that there is a need to identify additional options for patients and clinicians. The atypical antipsychotics clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and aripiprazole, have been the focus of increased interest in the treatment of bipolar depression.
The use of antipsychotics in the treatment of depressive episodes is not a particularly novel idea. In 1982, Robertson and Trimble reviewed 34 studies examining the use of typical antipsychotics to augment an antidepressant and noticed modest but generally consistent benefits. More widespread use of these agents in the management of depression has been limited, however, because of concerns about the long-term risk of tardive dyskinesia and the induction of extrapyramidal symptoms that often mimic depressive symptoms.
Clozapine, the first of the atypicals, was applied initially in the treatment of schizophrenia and schizoaffective disorder, where antidepressant effects were noted during open treatment. Subsequent case series described some benefit in dysphoric manias in bipolar disorder as well.
Much of the inditect evidence for antidepressant effects of the atypicals came from studies in major depressive disorder (MDD). For example, a series of eight patients with MDD who failed treatment with a selective serotonin reuptake inhibitor (SSRI) achieved marked and rapid response when risperidone was added to the SSRI. All patients remitted within 1 week; Hamilton Rating Scale for Depression score in these patients declined from a mean of 20.5 to a mean of 2.4 (Slide 11). A subsequent series of 30 patients yielded similar results.
This chapter reviews the evidence for first-line treatment of major depressive disorder (MDD), and strategies for patients with treatment-resistant depression. Many trials have investigated the efficacy of selective serotonin reuptake inhibitors (SSRIs) compared with other antidepressants. Patients with MDD are at higher risk of suicide, and guidelines indicate that patients should be assessed for suicide at the start of treatment and regularly over the course of treatment. As augmenting agents, atypical antipsychotics, lithium, and triiodothyronine (T3) have been studied the most extensively, and shown to have benefit. However, their risks and side-effect profiles may make them less attractive to patients, and patient preference and safety should determine treatment decisions for refractory or chronic MDD. The use of biomarkers, including pharmacogenetic testing, may one day provide more accurate predictors of response or adverse outcomes, allowing targeted treatments and the promise of personalized medicine.
Family studies indicate that major depressive disorder runs in families, although family members’ risk for other psychiatric disorders may also be increased. Twin and adoption studies suggest that about one-third of the liability for MDD is inherited. Studies investigating individual candidate genes have failed to implicate any single gene in MDD risk. Emerging evidence from genome-wide association studies may identify novel risk genes, although any individual genetic variation appears likely to have only modest effect. Whether focusing on clinical subtypes of MDD, or relying on imaging or other biomarkers rather than clinical features, will expedite the process of gene discovery remains to be determined.
An increased incidence of brain white-matter hyperintensities has been
described in major depressive disorder, but the impact of such
hyperintensities on treatment outcome is still controversial.
To investigate the relationship of brain white-matter hyperintensities
with cardiovascular risk factors and with treatment outcome in younger
people with major depressive disorder.
We assessed brain white-matter hyperintensities and cardiovascular risk
factors in 84 people with major depressive disorder prior to initiating
antidepressanttreatment. We also assessed hyperintensities in 35 matched
We found no significant difference in the prevalence of white-matter
hyperintensities between the depression and the control groups.
Left-hemisphere subcortical hyperintensities correlated with lower rates
of treatment response. We found no correlation between global
hyperintensity measures and clinical outcome. Brain white-matter
hyperintensities correlated with hypertension and age and with total
cardiovascular risk score.
Subcortical white-matter hyperintensities in the left hemisphere (but not
in other brain areas) may be associated with poor response to
antidepressant treatment in major depression.
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