Imaging the Etiology of Apathy,Anxiety, and Depression in Parkinson’s Disease: Implication for Treatment

Apathy, depression, and anxiety are among the most important non-motor signs of Parkinson’s disease (PD). This may be encountered at early stages of illness and represent a major source of burden. Understanding their pathophysiology is a major prerequisite for efficient therapeutic strategies. Anatomical and metabolic imaging studies have enabled a breakthrough by demonstrating that widespread abnormalities within the limbic circuits notably the orbitofrontal and anterior cingulate cortices, amygdala, thalamus, and ventral striatum are involved in the pathophysiology of depression, anxiety, and apathy in PD. Functional imaging has further shown that mesolimbic dopaminergic but also serotonergic lesions play a major role in the mechanisms of these three neuropsychiatric manifestations, which has direct therapeutic implications.     

Depression and immunity: A role for T cells?

Much attention has been paid to the potential role of the immune system in the pathophysiology of major depression in humans. While activation of innate immune responses currently dominates the research landscape, early studies in depressed patients demonstrating impairment in acquired immune responses, in particular T cell responses, may warrant further consideration. Intriguing data suggest that activated T cells may play an important neuroprotective role in the context of both stress and inflammation. For example, generation of autoreactive T cells through immunization with central nervous system (CNS) specific antigens has been shown to reverse stress-induced decreases in hippocampal neurogenesis as well as depressive-like behavior in rodents. In addition, trafficking of T cells to the brain following stress, in part related to glucocorticoids, has been found to reduce stress-induced anxiety-like behavior. Data indicate that T regulatory cells may also play a role in depression through downregulation of chronic inflammatory responses. Based on the notion that T cells may subserve neuroprotective and anti-inflammatory functions during stress and inflammation, impaired T cell function may directly contribute to the development of depression. Indeed, increased sensitivity to apoptosis as well as reduced responsiveness to glucocorticoids, may not only decrease the availability of T cells in depressed patients, but also may reduce their capacity to traffic to the brain in response to relevant neuroendocrine or immune stimuli. Further elucidation of T cell pathology may lead to new insights into immune system contributions to depression. Moreover, enhancement of T cell function may represent an alternative strategy to treat depression.     

Efficacy and Feasibility of a Tele-health Intervention for Acute Coronary Syndrome Patients with Depression: Results of the “MoodCare” Randomized Controlled Trial

Background

Depression is common after a cardiac event, yet there remain few approaches to management that are both effective and scalable.

Purpose

We aimed to evaluate the 6-month efficacy and feasibility of a tele-health program (MoodCare) that integrates depression management into a cardiovascular disease risk reduction program for acute coronary syndrome patients with low mood.

Methods

A two-arm, parallel, randomized design was used comprising 121 patients admitted to one of six hospitals for acute coronary syndrome.

Results

Significant treatment effects were observed for Patient Health Questionnaire 9 (PHQ9) depression (mean difference [change]?=??1.8; p?=?0.025; effect size: d?=?0.36) for the overall sample, when compared with usual medical care. Results were more pronounced effects for those with a history of depression (mean difference [change]?=??2.7; p?=?0.043; effect size: d?=?0.65).

Conclusions

MoodCare was effective for improving depression in acute coronary syndrome patients, producing effect sizes exceeding those of some face-to-face psychotherapeutic interventions and pharmacotherapy. (Trial Registration Number: ACTRN1260900038623.)     

Treatment of Selective Serotonin Reuptake Inhibitor—Resistant Depression in Adolescents: Predictors and Moderators of Treatment Response

ObjectiveTo advance knowledge regarding strategies for treating selective serotonin reuptake inhibitor (SSRI)-resistant depression in adolescents, we conducted a randomized controlled trial evaluating alternative treatment strategies. In primary analyses, cognitive-behavioral therapy (CBT) combined with medication change was associated with higher rates of positive response to short-term (12-week) treatment than medication alone. This study examines predictors and moderators of treatment response, with the goal of informing efforts to match youths to optimal treatment strategies.MethodYouths who had not improved during an adequate SSRI trial (N = 334) were randomized to an alternative SSRI, an alternative SSRI plus CBT, venlafaxine, or venlafaxine plus CBT. Analyses examined predictors and moderators of treatment response.ResultsLess severe depression, less family conflict, and absence of nonsuicidal self-injurious behavior predicted better treatment response status. Significant moderators of response to CBT + medication (combined) treatment were number of comorbid disorders and abuse history; hopelessness was marginally significant. The CBT/combined treatment superiority over medication alone was more evident among youths who had more comorbid disorders (particularly attention-deficit/hyperactivity disorder and anxiety disorders), no abuse history, and lower hopelessness. Further analyses revealed a stronger effect of combined CBT + medication treatment among youths who were older and white and had no nonsuicidal self-injurious behavior and longer prestudy pharmacotherapy.ConclusionsCombined treatment with CBT and antidepressant medication may be more advantageous for adolescents whose depression is comorbid with other disorders. Given the additional costs of adding CBT to medication, consideration of moderators in clinical decision making can contribute to a more personalized and effective approach to treatment.     

Couple and Family Therapists’ Perceptions of Women’s Depression and Preferred Treatment Modalities: A Cross-National Exploration

The present exploratory study is an initial effort to understand marriage and family therapists’ perceptions regarding women’s depression and preferred treatments in the United States and six other countries—China, Colombia, India, Indonesia, Iran, and the Philippines. With this aim, an online survey was completed by 87 U.S. therapists and 79 non-U.S. therapists. We analyzed the data through multiple t-tests for independent samples. Statistical comparisons of the responses indicated (a) U.S. therapists perceived it was more acceptable for women to talk about feeling depressed than non-U.S. therapists, (b) non-U.S. therapists perceived it was more frequent for women to present with somatic symptoms when depressed than U.S. therapists, (c) non-U.S. therapists reported using individual treatment for women’s depression more frequently than U.S. therapists, (d) U.S. therapists reported using couple or family therapy to treat women’s depression more frequently than non-U.S. therapists, and (e) U.S. therapists perceived husbands and male partners were open to participate in women’s therapy for depression more frequently than non-U.S. therapists. We discuss the clinical and research implications of our findings.     

Self-Efficacy,Poststroke Depression,and Rehabilitation Outcomes: Is There a Correlation?

Background

The sudden live changes of stroke survivors may lead to negative psychological and behavioral outcomes, including anxiety and depressive mood, which may compromise the rehabilitation process. Some personality features, such as self-efficacy, could play an important role in mediating the degree of post-stroke depression. Aim of this study is to investigate the possible correlation between specific psychological dimensions, such as poststroke depression and self-efficacy, and rehabilitation outcomes.

What Is the Role of Brain Stimulation Therapies in the Treatment of Depression?

Brain stimulation therapies have demonstrated efficacy in the treatment of depression and treatment-resistant depression (TRD). Non-invasive brain stimulation in the treatment of depression has grown substantially due to their favorable adverse effect profiles. The role of transcranial direct current stimulation in TRD is unclear, but emerging data suggests that it may be an effective add-on treatment. Repetitive transcranial magnetic stimulation has demonstrated efficacy in TRD that is supported by several multicenter randomized controlled trials. Though, vagus nerve stimulation has been found to be effective in some studies, sham controlled studies were equivocal. Electroconvulsive therapy (ECT) is a well-established brain stimulation treatment for severe depression and TRD, yet stigma and cognitive adverse effects limit its wider use. Magnetic seizure therapy has a more favorable cognitive adverse effect profile; however, equivalent efficacy to ECT needs to be established. Deep brain stimulation may play a role in severe TRD and controlled trials are now underway.     

Efficacy and Safety of Esketamine Nasal Spray Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression—TRANSFORM-3

BackgroundElderly patients with major depression have a poorer prognosis, are less responsive to treatment, and show greater functional decline compared with younger patients, highlighting the need for effective treatment.MethodsThis phase 3 double-blind study randomized patients with treatment-resistant depression (TRD) ≥65 years (1:1) to flexibly dosed esketamine nasal spray and new oral antidepressant (esketamine/antidepressant) or new oral antidepressant and placebo nasal spray (antidepressant/placebo). The primary endpoint was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to day 28. Analyses included a preplanned analysis by age (65–74 versus ≥75 years) and post-hoc analyses including age at depression onset.ResultsFor the primary endpoint, the median-unbiased estimate of the treatment difference (95% CI) was −3.6 (−7.20, 0.07); weighted combination test using MMRM analyses z = 1.89, two-sided p = 0.059. Adjusted mean (95% CI) difference for change in MADRS score between treatment groups was −4.9 (−8.96, −0.89; t = −2.4, df = 127; two-sided nominal p = 0.017) for patients 65 to 74 years versus −0.4 (−10.38, 9.50; t = −0.09, two-sided nominal p = 0.930) for those ≥75 years, and −6.1 (−10.33, −1.81; t = −2.8, df = 127; two-sided nominal p = 0.006) for patients with depression onset <55 years and 3.1 (−4.51, 10.80; t = 0.8, two-sided nominal p = 0.407) for those ≥55 years. Patients who rolled over into the long-term open-label study showed continued improvement with esketamine following 4 additional treatment weeks.ConclusionsEsketamine/antidepressant did not achieve statistical significance for the primary endpoint. Greater differences between treatment arms were seen for younger patients (65–74 years) and patients with earlier onset of depression (<55 years).     

Safety and Efficacy of Repeated Doses of 14.6 or 23.4 % Hypertonic Saline for Refractory Intracranial Hypertension

Background

The efficacy of administering single bolus doses of 14.6 or 23.4 % hypertonic saline (HTS) to treat refractory intracranial hypertension has been demonstrated in the literature and has emerged as an important therapeutic option in treating these patients. However, many institutions lack experience with this therapy and there are few published studies evaluating the safety of repeated bolus dosing of HTS.

Methods

A retrospective review of patients admitted between January 2008 and July 2012 was conducted to evaluate the use of repeated dosing of HTS in patients with refractory intracranial hypertension. The primary objective was to evaluate the safety of repeated dosing of HTS assessed by documented adverse effects such as central pontine myelinolysis (CPM) and severe fluctuations in serum sodium concentrations. Secondary objectives were to evaluate the efficacy of repeated dosing HTS in reducing intracranial pressure (ICP) and to compare the dose–response relationship of 14.6 and 23.4 % doses.

Results

Fifty-five patients were included for evaluation, each receiving an average of 8.9 (range 2–61) doses of HTS. A statistically significant increase in mean serum sodium concentration occurred with the administration of HTS (p < 0.0001). No cases of CPM were identified. The use of HTS was found to be effective based on decreases in ICP after administration (p < 0.0001, mean ICP reduction: 10.1 mmHg, range 3–23.6 mmHg). The efficacy of 23.4 % saline in decreasing ICP was not found to be significantly different than 14.6 % saline (p = 0.23).

Conclusions

Repeat bolus dosing of 14.6 or 23.4 % HTS appears to be relatively safe and effective for treating refractory intracranial hypertension assuming there is frequent electrolyte monitoring and concomitant fluid management.     

From TADS and SOFTADS to TORDIA and Beyond: What’s New in the Treatment of Adolescent Depression?

Major depressive disorder in adolescents is associated with significant morbidity and mortality. Major advances have been made in recent years in the treatment of adolescent depression, with promising outcomes. However, limitations of currently available treatments have prompted attempts to better understand pediatric depression from a broader perspective and to develop more effective treatment strategies in the future.