Music to improve sleep quality in adults with depression-related insomnia (MUSTAFI): randomized controlled trial.

BACKGROUND: Insomnia in depression is common and difficult to resolve. Unresolved depression-related sleep disturbances increase risk of relapse at high costs for individuals and society. Trials have suggested music for insomnia in various populations, but there is little research on the effectiveness of music for depression-related insomnia. METHODS: We examined the efficacy of a music intervention on insomnia, depression symptoms and quality of life in adults with depression-related insomnia. A two-armed randomized controlled trial was conducted, including depression outpatients with insomnia (n = 112) in a 1:1 ratio to music intervention and waitlist control group. The intervention group listened to music at bedtime for 4 weeks. Participants received treatment as usual during 8 weeks with assessments at baseline, at 4 and 8 weeks. The primary outcome measure was Pittsburgh Sleep Quality Index (PSQI), secondary outcomes comprised Actigraphy, the Hamilton Depression Rating Scale (HAMD-17) and World Health Organisation well-being questionnaires (WHO-5, WHOQOL-BREF). RESULTS: The music intervention group experienced significant improvements in sleep quality and well-being at 4 weeks according to global PSQI scores (effect size = -2.1, 95%CI -3.3; -0.9) and WHO-5 scores (effect size 8.4, 95%CI 2.7;14.0). At 8 weeks, i.e. 4 weeks after termination of the music intervention, the improvement in global PSQI scores had decreased (effect size = -0.1, 95%CI -1.3; 1.1). Actigraphy sleep assessments showed no changes and there was no detection of change in depression symptoms. CONCLUSIONS: Music intervention is suggested as a safe and moderately effective sleep aid in depression-related insomnia. Trial registration: Clinicaltrials.gov. ID NCT03676491.

Emotion stimulus processing in narcolepsy with cataplexy.

Reported brain abnormalities in anatomy and function in patients with narcolepsy with cataplexy led to a project based on qualitative electroencephalography examination and analysis in an attempt to find a narcolepsy with cataplexy-specific brain-derived pattern, or a sequence of brain locations involved in processing humorous stimuli. Laughter is the trigger of cataplexy in these patients, and the difference between patients and healthy controls during the laughter should therefore be notable. Twenty-six adult patients (14 male, 12 female) suffering from narcolepsy with cataplexy and 10 healthy controls (five male, five female) were examined. The experiment was performed using a 256-channel electroencephalogram and then processed using specialized software built according to the scientific research team's specifications. The software utilizes electroencephalographic data recorded during elevated emotional states in participants to calculate the sequence of brain areas involved in emotion processing using non-linear and linear algorithms. Results show significant differences in activation (pre-laughter) patterns between the patients with narcolepsy and healthy controls, as well as significant similarities within the patients and the controls. Specifically, gyrus orbitalis, rectus and occipitalis inferior are active in healthy controls, while gyrus paracentralis, cingularis and cuneus are activated solely in the patients in response to humorous audio stimulus. There are qualitative electroencephalographic-based patterns clearly discriminating between patients with narcolepsy and healthy controls during laughter processing.

Real-world treatment outcomes of transcranial pulsating electromagnetic fields as augmentation therapy for treatment-resistant depression.

BACKGROUND: Treatment outcomes of patients who had received T-PEMF as an augmenting therapy at Aalborg University Hospital, Aalborg, Denmark, was evaluated. METHODS: Patients diagnosed with unipolar depression or bipolar disorder who had received a self-administered 8-week T-PEMF series between November 2019 and April 2023 were included. Data were retrieved from the patients' records. The primary outcome was the Hamilton Rating Scale for Depression 17-item version (HAMD17), both as a continuous measure and with proportions of response and remission reported. RESULTS: A total of 57 patients (65.1 % females, 86.0 % unipolar depression, mean age, 48 ± 14 years) were included. Duration of current depressive episode was almost equally divided for <2 years (38.6 %), 2-5 years (38.6 %) and > 5 years (22.8 %). HAM-D17 decreased significantly from baseline (20.8 (SD: 3.3)) to week 8 (14.5 (SD: 6.2), p < 0.001). An episode duration of 2-5 years was associated with lower odds of response on HAM-D6 (adjusted OR = 0.15, 95 % CI: 0.03; 0.96, p < 0.05) and self-rated HAM-D6 (adjusted OR = 0.09, 95 % CI: 0.01; 0.99, p = 0.05) when compared to an episode duration <2 years. LIMITATIONS: This study is limited by a lack of a control group, limited controlling of confounders, small sample sizes, and an attrition rate of 29.8 % for the primary outcome. CONCLUSION: T-PEMF reduced depressive symptoms in a real-world clinical setting including patients with both unipolar depression and bipolar disorder. Receiving T-PEMF within the first 2 years of the depressive episode was associated with an improved outcome.

Idiopathic Hypersomnia-A Dynamic Simulation Model.

Aims of the study: Commonly used approach to illness assessment focuses on the patient's actual state supplemented by binary records of past events and conditions. This research project was designed to explain subjective experience in idiopathic hypersomnia (IH) patients influenced by their clinical symptoms and comorbidities. Material and Methods: Forty-three IH patients of both sexes (female 60.5%, male 39.5%) were assessed using a detailed structured examination. The interview covered neurologic, psychiatric, and internal medicine anamnesis, medication past and current, substance abuse, work impairment, detailed sleep-related data, specific sleep medication, and a full-length set of questionnaires including depression, quality of life, sleepiness, anxiety, fatigue, insomnia, and sleep inertia. The data were digitized and imported into statistical software (SPSS by IBM), and dynamic simulation software (Vensim by Ventana Systems Inc.) was used to build a causal loop diagram and stocks and flows diagram as a simulation structure. Results: The overall raw data and simulation-based patterns fit at 76.1%. The simulation results also identified the parameters that contribute the most to patients' subjective experience. These included sleep inertia, the refreshing potential of naps, the quality of nocturnal sleep, and the social aspects of the patient's life. Psychiatric disorders influence the overall pattern at a surprisingly low level. The influence of medication has been studied in detail. Although its contribution to the dynamics looks marginal at first sight, it significantly influences the contribution of other variables to the overall patient experience of the disease. Conclusion: Even the simplified dynamic structure designed by the research team reflects the real-life events in patients with IH at the acceptable level of 76.1% and suggests that a similar structure plays an important role in the course of the disease. Therapeutic focus on the parameters identified by the model should enhance the patients' subjective experience throughout illness duration and might even turn the progress from negative into positive. Further research is needed to understand the dynamics of idiopathic hypersomnia in greater detail to better understand the causes and design therapeutic approaches to improve patients' quality of life.

The sight of one's own body: Could qEEG help predict the treatment response in anorexia nervosa?

Aims of the study: The study aims to identify the differences in brain activity between participants with anorexia nervosa and healthy control using visual stimulus conditions combined with the quantitative dense-array EEG recording analysis method called Brain Activation Sequences (BAS). Materials and methods: 23 participants with anorexia nervosa and 21 healthy controls were presented with visual stimuli, including the subject's facial expressions and body images. The 128-channel EEG data were processed using BAS and displayed as activity in up to 66 brain regions. Subsequent cluster analysis was used to identify groups of participants exhibiting area-specific activation patterns. Results: Cluster analysis identified three distinct groups: one including all healthy controls (HC) and two consisting of all participants with anorexia (AN-I with 19 participants and AN-II with four participants). The AN-I and AN-II groups differed in their response to treatment. Comparisons of HC vs. AN confirmed the dominance of the right cerebral hemisphere in participants with anorexia nervosa in two of the three reported conditions. The facial expressions condition, specifically the facial reaction expressing disgust, indicates the existence of a social attentional bias toward faces, whereas emotions remained undetected in participants. High limbic activity, medial frontal gyrus involvement, low fusiform cortex activity, and milder visual cortex activity in healthy controls compared to participants indicate that the facial expression stimulus is perceived by healthy subjects primarily as an emotion, not as the face itself. In the body image condition, participants showed higher activity in the fusiform gyrus and right insula, indicating activation of the brain's "fear network." Conclusion: The study describes a specific pattern of brain activation in response to facial expression of disgust and body images that likely contributes to social-cognitive and behavioral impairments in anorexia. In addition, the substantial difference in the pattern of brain activation within the participants with AN and its association with treatment resistance deserves special attention because of its potential to develop a clinically useful prediction tool and identify potential targets for, for example, neuromodulatory treatments and/or individualized psychotherapy.

A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development.

The allostatic load (AL) model represents an interdisciplinary approach to comprehensively conceptualize and quantify chronic stress in relation to pathologies throughout the life cycle. This article first reviews the AL model, followed by interactions among early adversity, genetics, environmental toxins, as well as distinctions among sex, gender, and sex hormones as integral antecedents of AL. We next explore perspectives on severe mental illness, dementia, and caregiving as unique human models of AL that merit future investigations in the field of developmental psychopathology. A complimenting transdisciplinary perspective is applied throughout, whereby we argue that the AL model goes beyond traditional stress-disease theories toward the advancement of person-centered research and practice that promote not only physical health but also mental health.

Music to improve sleep quality in adults with depression-related insomnia (MUSTAFI): study protocol for a randomized controlled trial.

BACKGROUND: Insomnia is a common sleep disorder for adults with depression, with major impact on their quality of life. Previous trials suggest that listening to music may be helpful in the treatment of sleep disturbances in healthy populations, including students and elderly. In addition, small studies with clinical populations of traumatized refugees, adults with chronic insomnia and adults with depression insomnia add to the evidence base. However, the impact of music listening in the treatment of depression related insomnia is not well documented. OBJECTIVE: To examine the efficacy of music listening on sleep quality, symptoms of depression, and quality of life in adults with depression-related insomnia. METHOD: A single-center randomized controlled trial (RCT) in a two-arm parallel-group design is conducted and reported according to the CONSORT guidelines. The trial consists of an experimental group and a standard care control group. Both groups receive standard treatment for depression following Danish clinical guidelines in an outpatient psychiatry unit. The experimental group listens to music for a minimum of 30 minutes at bedtime for 4 weeks. DISCUSSION: This trial will provide information on the efficacy of music intervention as a non-pharmacological intervention in the treatment of depression-related insomnia. This study will provide novel knowledge concerning music medicine as an evidence-based treatment for depression. TRIAL REGISTRATION: Clinicaltrials.gov. ID NCT03676491, registered on 19 September 2018.

Transcranial pulsed electromagnetic fields for treatment-resistant depression: A multicenter 8-week single-arm cohort study.

BACKGROUND: The efficacy of antidepressant treatment is fair, but the efficacy is considerably lower in patients failing two or more trials underscoring the need for new treatment options. Our study evaluated the augmenting antidepressant effect of 8-weeks transcranial pulsed electromagnetic field (T-PEMF) therapy in patients with treatment-resistant depression. METHODS: A multicenter 8-week single-arm cohort study conducted by the Danish University Antidepressant Group. RESULTS: In total, 58 participants (20 men and 38 women) with a moderate to severe depression as part of a depressive disorder according to ICD-10 who fulfilled criteria for treatment resistance were included, with 19 participants being nonresponders to electroconvulsive therapy during the current depressive episode. Fifty-two participants completed the study period. Scores on the Hamilton Depression Scale 17-items version (HAM-D17) decreased significantly from baseline (mean = 20.6, SD 4.0) to endpoint (mean = 12.6, SD 7.1; N = 58). At endpoint, utilizing a Last Observation Carried Forward analysis, 49 and 28% of those participants with, respectively, a nonchronic current episode (≤2 years; N = 33) and a chronic current episode (>2 years; N = 25) were responders, that is, achieved a reduction of 50% or more on the HAM-D17 scale. At endpoint, respectively, 30 and 16% obtained remission, defined as HAM-D17 ≤ 7. On the Hamilton Scale 6-item version (HAM-D6), respectively, 51 and 16% obtained remission, defined as HAM-D6 ≤ 4. CONCLUSIONS: The findings indicate a potential beneficial role of T-PEMF therapy as an augmentation treatment to ongoing pharmacotherapy in treatment-resistant depression.

Dissociative symptoms and neuroendocrine dysregulation in depression.

BACKGROUND: Dissociative symptoms are traditionally attributed to psychological stressors that produce dissociated memories related to stressful life events. Dissociative disorders and dissociative symptoms including psychogenic amnesia, fugue, dissociative identity-disorder, depersonalization, derealization and other symptoms or syndromes have been reported as an epidemic psychiatric condition that may be coexistent with various psychiatric diagnoses such as depression, schizophrenia, borderline personality disorder or anxiety disorders. According to recent findings also the somatic components of dissociation may occur and influence brain, autonomic and neuroendocrine functions. At this time there are only few studies examining neuroendocrine response related to dissociative symptoms that suggest significant dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. The aim of the present study is to perform examination of HPA axis functioning indexed by basal cortisol and prolactin and test their relationship to psychic and somatoform dissociative symptoms. MATERIAL/METHODS: Basal cortisol and prolactin and psychic and somatoform dissociative symptoms were assessed in 40 consecutive inpatients with diagnosis of unipolar depression mean age 43.37 (SD=12.21). RESULTS: The results show that prolactin and cortisol as indices of HPA axis functioning manifest significant relationship to dissociative symptoms. Main results represent highly significant correlations obtained by simple regression between psychic dissociative symptoms (DES) and serum prolactin (R=0.55, p=0.00027), and between somatoform dissociation (SDQ-20) and serum cortisol (R=-0.38, p=0.015). CONCLUSIONS: These results indicate relationship between HPA-axis reactivity and dissociative symptoms in unipolar depressive patients that could reflect passive coping behavior and disengagement.

Depression, cortisol and somatoform dissociative symptoms.

OBJECTIVE: According to recent findings neuroendocrine response related to dissociative symptoms is related to dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis but HPA axis functioning as related to dissociation is only partially understood. METHOD: With the aim to test the relationship between basal serum cortisol and dissociative symptoms measured as somatoform and psychic dissociation we performed clinical testing and biochemical analysis in 30 inpatients with diagnosis of unipolar depression (mean age 41.46, SD=13.68). RESULTS: The results show that cortisol as an index of HPA axis functioning manifests significant relationship to somatoform dissociative symptoms (r=-0.40; p=0.014). CONCLUSIONS: The result indicates relationship between HPA-axis reactivity and somatoform dissociative symptoms in unipolar depressive patients and suggests that somatoform dissociation presents a defense mechanism related to a passive coping response.

Dissociative symptoms reflect levels of tumor necrosis factor alpha in patients with unipolar depression.

Recent evidence indicates that the nature of interactions between the nervous system and immune system is important in the pathogenesis of depression. Specifically, alterations in pro-inflammatory cytokines have been related to the development of several psychological and neurobiological manifestations of depressive disorder, as well as to stress exposure. A number of findings point to tumor necrosis factor alpha (TNF-α) as one of the central factors in these processes. Accordingly, in the present study, we test the hypothesis that specific influences of chronic stressors related to traumatic stress and dissociation are related to alterations in TNF-α levels. We performed psychometric measurement of depression (Beck Depression Inventory [BDI]-II), traumatic stress symptoms (Trauma Symptom Checklist [TSC]-40), and psychological and somatoform dissociation (Dissociative Experiences Scale [DES] and Somatoform Dissociation Questionnaire [SDQ]-20, respectively), and immunochemical measure of serum TNF-α in 66 inpatients with unipolar depression (mean age 43.1 ± 7.3 years). The results show that TNF-α is significantly related to DES (Spearman R=-0.42, P<0.01), SDQ-20 (Spearman R=-0.38, P<0.01), and TSC-40 (Spearman R=-0.41, P<0.01), but not to BDI-II. Results of the present study suggest that TNF-α levels are related to dissociative symptoms and stress exposure in depressed patients.

Allostatic load as a tool for monitoring physiological dysregulations and comorbidities in patients with severe mental illnesses.

Severe mental illnesses like schizophrenia and bipolar disorder are disabling, chronic conditions that are often accompanied by medical comorbidities. In this theoretical article, we review the allostatic load model representing the "wear and tear" that chronic stress exacts on the brain and body. We propose an innovative way of monitoring physical and psychiatric comorbidities by integrating the allostatic load model into clinical practice. By interpreting peripheral biomarkers differently, medical professionals can calculate a simple, count-based, allostatic load index known to predict diverse stress-related pathologies. In addition to screening for comorbidities, allostatic load indices can be used to monitor the effects of pharmacological and psychosocial interventions. This framework can also be used to generate a dialogue between patient and practitioner to promote preventive and proactive approaches to health care.

Epileptiform activity in alcohol dependent patients and possibilities of its indirect measurement.

BACKGROUND: Alcohol dependence during withdrawal and also in abstinent period in many cases is related to reduced inhibitory functions and kindling that may appear in the form of psychosensory symptoms similar to temporal lobe epilepsy frequently in conditions of normal EEG and without seizures. Because temporal lobe epileptic activity tend to spread between hemispheres, it is possible to suppose that measures reflecting interhemispheric information transfer such as electrodermal activity (EDA) might be related to the psychosensory symptoms. METHODS AND FINDINGS: We have performed measurement of bilateral EDA, psychosensory symptoms (LSCL-33) and alcohol craving (ACQ) in 34 alcohol dependent patients and 32 healthy controls. The results in alcohol dependent patients show that during rest conditions the psychosensory symptoms (LSCL-33) are related to EDA transinformation (PTI) between left and right EDA records (Spearman r = 0.44, p<0.01). CONCLUSIONS: The result may present potentially useful clinical finding suggesting a possibility to indirectly assess epileptiform changes in alcohol dependent patients.