Antidepressant-induced mania in panic disorder: a single-case study of clinical and functional connectivity characteristics

BackgroundMental health issues, including panic disorder (PD), are prevalent and often co-occur with anxiety and bipolar disorders. While panic disorder is characterized by unexpected panic attacks, and its treatment often involves antidepressants, there is a 20–40% risk of inducing mania (antidepressant-induced mania) during treatment, making it crucial to understand mania risk factors. However, research on clinical and neurological characteristics of patients with anxiety disorders who develop mania is limited.MethodsIn this single case study, we conducted a larger prospective study on panic disorder, comparing baseline data between one patient who developed mania (PD-manic) and others who did not (PD-NM group). We enrolled 27 patients with panic disorder and 30 healthy controls (HCs) and examined alterations in amygdala-based brain connectivity using a seed-based whole-brain approach. We also performed exploratory comparisons with healthy controls using ROI-to-ROI analyses and conducted statistical inferences at a threshold of cluster-level family-wise error-corrected p < 0.05, with the cluster-forming threshold at the voxel level of uncorrected p < 0.001.ResultsThe patient with PD-mania showed lower connectivity in brain regions related to the default mode network (left precuneous cortex, maximum z-value within the cluster = −6.99) and frontoparietal network (right middle frontal gyrus, maximum z-value within the cluster = −7.38; two regions in left supramarginal gyrus, maximum z-value within the cluster = −5.02 and −5.86), and higher in brain regions associated with visual processing network (right lingual gyrus, maximum z-value within the cluster = 7.86; right lateral occipital cortex, maximum z-value within the cluster = 8.09; right medial temporal gyrus, maximum z-value within the cluster = 8.16) in the patient with PD-mania compared to the PD-NM group. One significantly identified cluster, the left medial temporal gyrus (maximum z-value within the cluster = 5.82), presented higher resting-state functional connectivity with the right amygdala. Additionally, ROI-to-ROI analysis revealed that significant clusters between PD-manic and PD-NM groups differed from HCs in the PD-manic group but not in the PD-NM group.ConclusionHere, we demonstrate altered amygdala-DMN and amygdala-FPN connectivity in the PD-manic patient, as reported in bipolar disorder (hypo) manic episodes. Our study suggests that amygdala-based resting-state functional connectivity could serve as a potential biomarker for antidepressant-induced mania in panic disorder patients. Our findings provide an advance in understanding the neurological basis of antidepressant-induced mania, but further research with larger cohorts and more cases is necessary for a broader perspective on this issue

Cost-effectiveness of using amyloid positron emission tomography in individuals with mild cognitive impairment

Background Amyloid positron emission tomography (PET) makes it possible to diagnose Alzheimers disease (AD) in its prodromal phase including mild cognitive impairment (MCI). This study evaluated the cost-effectiveness of including amyloid-PET for assessing individuals with MCI. Methods The target population was 60-year-old patients who were diagnosed with MCI. We constructed a Markov model for the natural history of AD with the amyloid positivity (AP). Because amyloid-PET can detect the AP MCI state, AD detection can be made faster by reducing the follow-up interval for a high-risk group. The health outcomes were evaluated in quality-adjusted life years (QALYs) and the final results of cost-effectiveness analysis were presented in the form of the Incremental Cost-Effectiveness Ratio (ICER). To handle parameter uncertainties, one-way sensitivity analyses for various variables were performed. Results Our model showed that amyloid-PET increased QALYs by 0.003 in individuals with MCI. The estimated additional costs for adopting amyloid-PET amounted to a total of 1250 USD per patient when compared with the cost when amyloid-PET is not adopted. The ICER was 3,71,545 USD per QALY. According to the sensitivity analyses, treatment effect of Donepezil and virtual intervention effect in MCI state were the most influential factors. Conclusions In our model, using amyloid-PET at the MCI stage was not cost-effective. Future advances in management of cognitive impairment would enhance QALYs, and consequently improve cost-effectiveness.This project was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HC15C1509 to JW Han, JH Park, TJ Lee, and HG Jeong). Additional funding came from the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea [HI09C1379 (A092077) to KW Kim]

Investigating the effectiveness of a smart mental health intervention (inMind) for stress reduction during pharmacological treatment for mild to moderate major depressive disorders: Study protocol for a randomized control trial

BackgroundAlthough psychological interventions for stress relief, such as cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR), have been developed, they have not been widely used in treating depression. The use of mobile devices can increase the possibility of actual use by integrating interventions and reducing the difficulty and cost burden of treatment application. This study aims to determine whether “inMind,” an integrated mobile application for stress reduction, developed for the general population, decreases stress for patients with mild to moderate major depressive disorder during the pharmacological treatment period.MethodsThis study is a single-blind, multicenter, randomized, controlled crossover trial. The App, developed in Republic of Korea, provides integrated interventions for stress reduction for the general population through three modules based on mindfulness-based stress reduction, cognitive behavior therapy, and relaxation sounds that are known to be effective in stress reduction (“meditation,” “cognitive approach,” and “relaxation sounds,” respectively). Participants (n = 215) recruited via medical practitioner referral will be randomized to an App first group (fAPP) or a wait list crossover group (dAPP). The study will be conducted over 8 weeks; the fAPP group will use the App for the first 4 weeks and the dAPP group for the next 4 weeks. During all study periods, participants will receive their usual pharmacological treatment. The Depression Anxiety Stress Scale-21 is the primary outcome measure. The analysis will employ repeated measurements using a mixed-model approach.DiscussionThe App can potentially be an important addition to depression treatment because of its applicability and the comprehensive nature of the interventions that covers diverse stress-relieving models.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05312203, identifier 2021GR0585

A Smartphone App (AnSim) With Various Types and Forms of Messages Using the Transtheoretical Model for Cardiac Rehabilitation in Patients With Coronary Artery Disease: Development and Usability Study

BackgroundDespite strong evidence of clinical benefit, cardiac rehabilitation (CR) programs are currently underutilized and smartphone-based CR strategies are thought to address this unmet need. However, data regarding the detailed process of development are scarce. ObjectiveThis study focused on the development of a smartphone-based, patient-specific, messaging app for patients who have undergone percutaneous coronary intervention (PCI). MethodsThe AnSim app was developed in collaboration with a multidisciplinary team that included cardiologists, psychiatrists, nurses, pharmacists, nutritionists, and rehabilitation doctors and therapists. First, a focus group interview was conducted, and the narratives of the patients were analyzed to identify their needs and preferences. Based on the results, health care experts and clinicians drafted messages into 5 categories: (1) general information regarding cardiovascular health and medications, (2) nutrition, (3) physical activity, (4) destressing, and (5) smoking cessation. In each category, 90 messages were developed according to 3 simplified steps of the transtheoretical model of behavioral change: (1) precontemplation, (2) contemplation and preparation, and (3) action and maintenance. After an internal review and feedback from potential users, a bank of 450 messages was developed. ResultsThe focus interview was conducted with 8 patients with PCI within 1 year, and 450 messages, including various forms of multimedia, were developed based on the transtheoretical model of behavioral change in each category. Positive feedback was obtained from the potential users (n=458). The mean Likert scale score was 3.95 (SD 0.39) and 3.91 (SD 0.39) for readability and usefulness, respectively, and several messages were refined based on the feedback. Finally, the patient-specific message delivery system was developed according to the baseline characteristics and stages of behavioral change in each participant. ConclusionsWe developed an app (AnSim), which includes a bank of 450 patient-specific messages, that provides various medical information and CR programs regarding coronary heart disease. The detailed process of multidisciplinary collaboration over the course of the study provides a scientific basis for various medical professionals planning smartphone-based clinical research