Bipolar depression: a review of treatment options.

Bipolar depression (BD-D) is both common and incredibly challenging to treat. Even treated individuals with BD-D experience depression approximately 19% of the time, and subsyndromal depression an additional 18%. This stands in clear contrast to the approximately 10% of time spent in hypomania and 1% of time spent in mania. Despite this high illness burden, there remain relatively few treatment options approved by the US Food and Drug Administration for BD-D. Of the approved medications, four are second-generation antipsychotics (SGAs) and one is an SGA combined with an antidepressant. However, particularly when used long-term, antipsychotics can pose a significant risk of adverse effects, raising the clinical conundrum of weighing the risks associated with long-term antipsychotic use versus the risk of relapse when patients are off medications. Here, we review commonly used treatments for BD-D, including antipsychotics, classic mood stabilisers, electroconvulsive therapy and psychotherapy. We then address the somewhat controversial topic of antidepressant use in BD-D. Finally, we summarise emerging treatment options and highlight ongoing clinical trials. We hope this review will help compare the risks and benefits of several common and novel options for the treatment of patients with BD-D. In doing so, we also hope this review will aid the individualised selection of treatments based on each patient's history and treatment goals.

Opening Minds through Art: A preliminary study evaluating the effects of a creative-expression program on persons living with dementia and their primary care partners.

For people living with dementia and their care partners, a decline in the ability to effectively communicate can cause significant distress. However, in recent decades, the arts have emerged as an effective care modality in fostering communication and expression for those with declining verbal skills and memory loss. Opening Minds through Art (OMA) is a national initiative that empowers people living with dementia by facilitating creative expression and social engagement through art-making in partnership with trained college student volunteers. Research has demonstrated that participation in the program benefits quality of life for those living with dementia and also improves student attitudes toward dementia. To date, however, no research has involved primary care partners. We implemented an OMA program at three residential care homes in State College, Pennsylvania, with residents cocreating artwork alongside primary care partners (i.e., a family member or primary medical personnel) over the course of four art-making sessions. We evaluated the effects of participation on quality of life and care partner burnout through pre-post use of "emotional thermometers" (measuring levels of distress, anxiety, depression, anger, and perceived quality of life), the National Institute of Health NIH emotional support scale, and the NIH caregiver assessment (care partner burnout). For people living with dementia, participation significantly increased perceived quality of life while decreasing distress, anxiety, depression, and anger (p < .01; n = 12) after each class; however, the intervention did not significantly impact perceived emotional support. For care partners, participation significantly lowered post-intervention measures of burnout and self-rated stress (p < .01; n = 9). This preliminary study suggests that a structured art-based activity appears to positively impact acute mood for patients and, importantly, decrease care partner burnout. Future research can bring more robust methods to bear in determining how to use OMA and other arts interventions to optimize social support for people living with dementia and their care partners.

Prolonged functional cerebral asymmetry as a consequence of dysfunctional parvocellular paraventricular hypothalamic nucleus signaling: An integrative model for the pathophysiology of bipolar disorder.

Approximately 45 million people worldwide are diagnosed with bipolar disorder (BD). While there are many known risk factors and models of the pathologic processes influencing BD, the exact neurologic underpinnings of BD are unknown. We attempt to integrate the existing literature and create a unifying hypothesis regarding the pathophysiology of BD with the hope that a concrete model may potentially facilitate more specific diagnosis, prevention, and treatment of BD in the future. We hypothesize that dysfunctional signaling from the parvocellular neurons of the paraventricular hypothalamic nucleus (PVN) results in the clinical presentation of BD. Functional damage to this nucleus and its signaling pathways may be mediated by myriad factors (e.g. immune dysregulation and auto-immune processes, polygenetic variation, dysfunctional interhemispheric connections, and impaired or overactivated hypothalamic axes) which could help explain the wide variety of clinical presentations along the BD spectrum. The neurons of the PVN regulate ultradian rhythms, which are observed in cyclic variations in healthy individuals, and mediate changes in functional hemispheric lateralization. Theoretically, dysfunctional PVN signaling results in prolonged functional hemispheric dominance. In this model, prolonged right hemispheric dominance leads to depressive symptoms, whereas left hemispheric dominance correlated to the clinical picture of mania. Subsequently, physiologic processes that increase signaling through the PVN (hypothalamic-pituitaryadrenal axis, hypothalamic- pituitary-gonadal axis, and hypothalamic-pituitary-thyroid axis activity, suprachiasmatic nucleus pathways) as well as, neuro-endocrine induced excito-toxicity, auto-immune and inflammatory flairs may induce mood episodes in susceptible individuals. Potentially, ultradian rhythms slowing with age, in combination with changes in hypothalamic axes and maturation of neural circuitry, accounts for BD clinically presenting more frequently in young adulthood than later in life.

Relationships between ovarian hormone concentrations and mental rotations performance in naturally-cycling women.

Circulating gonadal hormones have been linked to variation in the structure and function of the adult human brain, raising the question of how cognition is affected by sex hormones in adulthood. The impacts of progestogens and estrogens are of special interest due to the widespread use of hormone supplementation. Multiple studies have analyzed relationships between ovarian hormones and mental rotation performance, one of the largest known cognitive sex differences; however, results are conflicting. These discrepancies are likely due in part to modest sample sizes and reliance on self-report measures to assess menstrual cycle phase. The present study aimed to clarify the impact of progestogens and estrogens on visuospatial cognition by relating mental rotation task performance to salivary hormone concentrations. Across two studies totaling 528 naturally-cycling premenopausal women, an internal meta-analysis suggested a small, positive effect of within-subjects changes in progesterone on MRT performance (estimate = 0.44, p = 0.014), though this result should be interpreted with caution given multiple statistical analyses. Between-subjects differences and within-subject changes in estradiol did not significantly predict MRT. These results shed light on the potential cognitive effects of endogenous and exogenous hormone action, and the proximate mechanisms modulating spatial cognition.

Considering a Potential Role of Linalool as a Mood Stabilizer for Bipolar Disorder.

Epidemiologic studies suggest that the lifetime prevalence of bipolar spectrum disorders ranges from 2.8 to 6.5 percent of the population. To decrease morbidity and mortality associated with disease progression, pharmacologic intervention is indicated for the majority of these patients. While a number of effective treatment regimens exist, many conventional medications have significant side effect profiles that adversely impact patients' short and long-term well-being. It is thus important to continue advancing and improving therapeutic options available to patients. This paper reviews the limitations of current treatments and examines the chemical compound Linalool, an alcohol found in many plant species, that may serve as an effective mood stabilizer. While relatively little is known about Linalool and bipolar disorder, the compound has been shown to have antiepileptic, anti-inflammatory, anxiolytic, anti-depressive, and neurotrophic effects, with mechanisms that are comparable to current bipolar disorder treatment options.

A prospective community engagement initiative to improve clinical research participation in patients with peripheral artery disease.

OBJECTIVE: Patients diagnosed with peripheral artery disease are difficult to recruit into clinical trials. However, there is currently no high-quality, patient-centered information explaining why peripheral artery disease patients choose to participate or not participate in clinical research studies. METHODS: The current study was a prospective community engagement initiative that specifically asked patients with and without peripheral artery disease: (1) what motivates them to participate in clinical research studies, (2) their willingness to participate in different research procedures, (3) the barriers to participation, (4) preferences about study design, and (5) demographic and disease-related factors influencing participation. Data were gathered through focus groups (n = 19, participants aged 55-79 years) and mailed questionnaires (n = 438, respondents aged 18-85 years). RESULTS: More than half of the respondents stated that they would be willing to participate in a study during evening or weekend time slots. Peripheral artery disease patients (n = 45) were more willing than those without peripheral artery disease (n = 360) to participate in drug infusion studies (48% versus 18%, p < 0.001) and trials of investigational drugs (44% versus 21%, p < 0.001). Motivating factors and barriers to participation were largely consistent with previous studies. CONCLUSION: Adults in our geographic region are interested in participating in clinical research studies related to their health; they would like their doctor to tell them what studies they qualify for and they prefer to receive a one-page advertisement that has color pictures of the research procedures. Peripheral artery disease patients are more willing than those without peripheral artery disease to participate in drug infusion studies, trials of investigational drugs, microneurography, and spinal/epidural infusions.