Neuropathic pain and mood disorders in earthquake survivors with peripheral nerve injuries.

Background and purpose:

        Natural disasters, such as earthquakes, frequently result in mood disorders among affected individuals. It is established that neuropathic pain arising from traumatic neuropathies is also linked to mood disorders. This study investigates the influence of neuropathic pain on the development of mood disorders in earthquake survivors with peripheral nerve injuries, following the earthquake centered in Kahramanmaras on February 6, 2023. Additionally, we aim to assess the electro­physiological aspects of neuropathic injuries in these survivors.

The study comprised 46 earth-quake survivors with electrophysiologically confirmed peripheral nerve injuries, with 39 trauma-free survivors serving as the control group. Neuropathic pain, anxiety and depression were assessed using the Douleur Neuropathique 4 (DN4) questionnaire and the Hospital Anxiety and Depression Scale (HADS).

Our findings revealed that the ulnar and peroneal nerves were the most commonly injured structures. Among the survivors with peripheral nerve injury, 31 out of 46 (67%) were found to experience neuropathic pain. Furthermore, plexopathy and multiple extremity injuries were associated with more severe neuropathic pain. However, there was no significant difference in anxiety and depression scores between the two groups and neuropathic pain was found to have no independent effect.

The study indicates that the intensity of neuropathic pain varies based on the localization and distribution of peripheral nerve injuries. However, the presence of peripheral nerve damage or neuropathic pain was not directly associated with HADS scores, suggesting that mood disorders following disasters may have multifactorial causes beyond physical trauma.

Quality of life, mood disorders, and cognitive impairment in adults with ß-thalassemia.

Advances in understanding the disease process in ß-thalassemia supported development of various treatment strategies that resulted in improved survival. Improved survival, however, allowed multiple morbidities to manifest and cemented the need for frequent, lifelong treatment. This has directly impacted patients' health-related quality of life and opened the door for various psychiatric and cognitive disorders to potentially develop. In this review, we summarize available evidence on quality of life, depression and anxiety, suicidality, and cognitive impairment in adult patients with ß-thalassemia while sharing our personal insights from experience in treating patients with both transfusion-dependent and non-transfusion-dependent forms.

Efficacy and safety of agomelatine in epilepsy patients with sleep and mood disorders: An observational, retrospective cohort study.

OBJECTIVE: To evaluate the therapeutic efficacy and safety of agomelatine for treating the sleep and mood disorders in epilepsy patients. METHODS: Retrospective data were derived from 113 epilepsy patients for at least 8 weeks. All the subjects were divided into two groups, one was treated with agomelatine, the other was treated with escitalopram. Their depression and anxiety states were assessed by Hamilton Depression (HAMD) and Hamilton Anxiety (HAMA) Scales. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS: The HAMA, HAMD and PSQI scores in both groups significantly declined after the treatments with agomelatine and escitalopram. However, the agomelatine group exhibited greater improvement in terms of HAMA and PSQI scores compared to the escitalopram group. No severe adverse events were observed in agomelatine group. SIGNIFICANCE: Agomelatine performed better in HAMA and PSQI scores compared to escitalopram, where no significant increase in seizure frequency or side effects were observed. Possibly, agomelatine presents a promising therapeutic option for treating the sleep or mood disorders in epilepsy patients.

Electroencephalography findings in menstrually-related mood disorders: A critical review.

The female reproductive years are characterized by fluctuations in ovarian hormones across the menstrual cycle, which have the potential to modulate neurophysiological and behavioral dynamics. Menstrually-related mood disorders (MRMDs) comprise cognitive-affective or somatic symptoms that are thought to be triggered by the rapid fluctuations in ovarian hormones in the luteal phase of the menstrual cycle. MRMDs include premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and premenstrual exacerbation (PME) of other psychiatric disorders. Electroencephalography (EEG) non-invasively records in vivo synchronous activity from populations of neurons with high temporal resolution. The present overview sought to systematically review the current state of task-related and resting-state EEG investigations on MRMDs. Preliminary evidence indicates lower alpha asymmetry at rest being associated with MRMDs, while one study points to the effect being luteal-phase specific. Moreover, higher luteal spontaneous frontal brain activity (slow/fast wave ratio as measured by the delta/beta power ratio) has been observed in persons with MRMDs, while sleep architecture results point to potential circadian rhythm disturbances. In this review, we discuss the quality of study designs as well as future perspectives and challenges of supplementing the diagnostic and scientific toolbox for MRMDs with EEG.

Relationship between subjective and objective fatigue and sleep characteristics in individuals with anxiety and mood disorders: An exploratory study.

OBJECTIVE: Fatigue and sleep disturbances are important symptoms of anxiety and mood disorders (AMD). Studies about the relationship between these variables usually rely on self-report assessments. Therefore, the aim of our exploratory study was to investigate the independent correlations between subjective and objective fatigue and sleep characteristics in individuals with AMD. METHODS: In sum, 233 individuals with AMD attending a stress-related disorders day care unit (78.5 % females, mean age 39.0 years old) participated in a cross-sectional study. Participants completed the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Multidimensional Fatigue Inventory-20, and Pittsburgh Sleep Quality Index self-report questionnaires, as well as an exercise capacity workload test for assessing objective fatigue and polysomnography monitoring for evaluation of sleep structure. RESULTS: In individuals with AMD, exercise capacity workload was associated with lower percent of stage 1 sleep (ß = - 0.17, p = 0.006), REM latency (ß = -0.13, p = 0.042), and wake after sleep onset (ß = -0.12, p = 0.039). General fatigue was associated with a higher percent of body movements (ß = 0.12, p = 0.047), as well as mental fatigue was associated with a higher percent of body movements (ß = 0.13, p = 0.029), and a higher score on the PSQI (ß = 0.21, p = 0.002). CONCLUSIONS: Objective sleep characteristics were associated with objective assessment of fatigue, while subjective sleep quality was associated with subjectively assessed mental fatigue.

Anxiety and mood disorders in forcibly displaced people across the world.

PURPOSE OF REVIEW: Displaced persons around the world have intensified in the previous decade and are predicted to rise further with greater global instability. The mental health issues involved with fleeing one's home, and attempting to make a new life in a host country need to be understood and addressed. RECENT FINDINGS: Prevalence of anxiety and mood disorders, including posttraumatic stress disorder appear to be higher for displaced peoples than for the population in the host country. This is consistent across different methods. Traumatic life events in the country of origin as well as during flight contribute to symptom severity. Factors in the host country increasing severity including isolation, discrimination, low social support. There are successfully implemented intercultural interventions at the individual level of the practitioner, as well as at the institutional level. SUMMARY: There are many possibilities for successful interventions in displaced people, realizing this at a scale appropriate to the size of the problem remains a challenge.

Risk factors for mood disorders among offspring of parents with bipolar disorder: Findings from a discordant-sibling study.

The purpose of this naturalistic, prospective study was to identify risk factors for mood disorders in offspring of parents with bipolar disorder (BPD) using the discordant-sibling design by comparing premorbid psychopathology or symptoms, temperament, personality traits and coping style as well as the perception of family-related characteristics among affected and unaffected siblings within the same family. This approach controls for confounding by unmeasured genetic and environmental factors shared within families. Our sample comprised 24 families of a parent with BPD with at least one child that developed BPD or major depressive disorder (n = 31), and at least one child who did not. Offspring were followed for a mean duration of 16.2 (s.d: 4.6) years. Information was collected from the offspring themselves. Generalized linear mixed models only revealed differences in three dimensions of the Dimension of Temperament Survey-Revised (DOTS-R) version: Offspring with mood disorders scored higher on "Approach-withdrawal", "Rhythmicity for daily habits", and "Task orientation" than their unaffected siblings. The higher scores, and not lower scores as expected, on these temperament dimensions observed in offspring that subsequently developed mood disorders may reflect increased vulnerability, but they could also mirror premorbid mood swings or strategies to cope with them.

A scoping review of hormonal clinical trials in menstrual cycle-related brain disorders: Studies in premenstrual mood disorder, menstrual migraine, and catamenial epilepsy.

Cyclic variations in hormones during the normal menstrual cycle underlie multiple central nervous system (CNS)-linked disorders, including premenstrual mood disorder (PMD), menstrual migraine (MM), and catamenial epilepsy (CE). Despite this foundational mechanistic link, these three fields operate independently of each other. In this scoping review (N = 85 studies), we survey existing human research studies in PMD, MM, and CE to outline the exogenous experimental hormone manipulation trials conducted in these fields. We examine a broad range of literature across these disorders in order to summarize existing diagnostic practices and research methods, highlight gaps in the experimental human literature, and elucidate future research opportunities within each field. While no individual treatment or study design can fit every disease, there is immense overlap in study design and established neuroendocrine-based hormone sensitivity among the menstrual cycle-related disorders PMD, MM, and CE. SCOPING REVIEW STRUCTURED SUMMARY: Background. The menstrual cycle can be a biological trigger of symptoms in certain brain disorders, leading to specific, menstrual cycle-linked phenomena such as premenstrual mood disorders (PMD), menstrual migraine (MM), and catamenial epilepsy (CE). Despite the overlap in chronicity and hormonal provocation, these fields have historically operated independently, without any systematic communication about methods or mechanisms. OBJECTIVE: Online databases were used to identify articles published between 1950 and 2021 that studied hormonal manipulations in reproductive-aged females with either PMD, MM, or CE. We selected N = 85 studies that met the following criteria: 1) included a study population of females with natural menstrual cycles (e.g., not perimenopausal, pregnant, or using hormonal medications that were not the primary study variable); 2) involved an exogenous hormone manipulation; 3) involved a repeated measurement across at least two cycle phases as the primary outcome variable. CHARTING METHODS: After exporting online database query results, authors extracted sample size, clinical diagnosis of sample population, study design, experimental hormone manipulation, cyclical outcome measure, and results from each trial. Charting was completed manually, with two authors reviewing each trial. RESULTS: Exogenous hormone manipulations have been tested as treatment options for PMD (N = 56 trials) more frequently than MM (N = 21) or CE (N = 8). Combined oral contraceptive (COC) trials, specifically those containing drospirenone as the progestin, are a well-studied area with promising results for treating both PMDD and MM. We found no trials of COCs in CE. Many trials test ovulation suppression using gonadotropin-releasing hormone agonists (GnRHa), and a meta-analysis supports their efficacy in PMD; GnRHa have been tested in two MM-related trials, and one CE open-label case series. Finally, we found that non-contraceptive hormone manipulations, including but not limited to short-term transdermal estradiol, progesterone supplementation, and progesterone antagonism, have been used across all three disorders. CONCLUSIONS: Research in PMD, MM, and CE commonly have overlapping study design and research methods, and similar effects of some interventions suggest the possibility of overlapping mechanisms contributing to their cyclical symptom presentation. Our scoping review is the first to summarize existing clinical trials in these three brain disorders, specifically focusing on hormonal treatment trials. We find that PMD has a stronger body of literature for ovulation-suppressing COC and GnRHa trials; the field of MM consists of extensive estrogen-based studies; and current consensus in CE focuses on progesterone supplementation during the luteal phase, with limited estrogen manipulations due to concerns about seizure provocation. We argue that researchers in any of these respective disciplines would benefit from greater communication regarding methods for assessment, diagnosis, subtyping, and experimental manipulation. With this scoping review, we hope to increase collaboration and communication among researchers to ultimately improve diagnosis and treatment for menstrual-cycle-linked brain disorders.

Interictal Dysphoric Disorder: A disorder with distinct nosography or atypical symptomatology of mood disorders in people with epilepsy? Results from a systematic review.

INTRODUCTION: Mood disorders are the most frequent comorbidities in people with epilepsy. The term Interictal Dysphoric Disorder (IDD) has been used to describe a condition where at least three out of eight symptoms must be present for diagnosis. Symptoms are grouped into three symptom clusters of four "labile depressive" symptoms (anergia, depressed mood, insomnia, and pain), two "labile affective" symptoms (anxiety and fear), and two specific symptoms (euphoric moods and paroxysmal irritability), which are described and can be present in people with epilepsy. There is debate about whether IDD is a distinct disease, or if it is simply a special manifestation of mood disorders in epilepsy. For instance, it may represent an atypical presentation of depression in this population. METHODS: We conducted a systematic review of the literature in 3 databases with the terms "Interictal Dysphoric Disorder" and "mood disorder". A total of 130 articles were selected and, after removing the duplicated applying eligibility criteria, 12 articles were included. RESULTS: Six articles showed positive evidence for the validation of IDD as an independent nosological entity; in contrast, five articles reported inconclusive findings regarding the question; one explicitly questioned significant differences between IDD and mood disorders as nosological constructs. The data available and presented in this systematic review is insufficient to confirm IDD as a distinct diagnostic category. Nevertheless, it is worth noting other researchers have found some validity in this concept, highlighting the strong connection between mood disorders and epilepsy. CONCLUSION: Further research in this area is needed, and additional systematic reviews focusing on other aspects of the construct, such as neurobiological mechanisms, may prove to be helpful.

Validation of the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder-7 in Lithuanian individuals with anxiety and mood disorders.

The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) are short self-report questionnaires used to screen and assess depression and anxiety severity in medical and community samples. However, little is known about their psychometric properties in individuals with anxiety and mood disorders (AMD) This study evaluated the psychometric properties of the PHQ-9 and GAD-7 in individuals with AMD. Individuals (n = 244, mean age 39.9 ± 12.3 years) with AMD completed the PHQ-9, GAD-7, as well as other measures of depression, anxiety, and a structured diagnostic interview. The PHQ-9 and GAD-7 demonstrated good internal consistency (Cronbach's alpha 0.87 and 0.84, respectively). The PHQ-9 and GAD-7 showed a weak correlation with clinician-rated scales HAM-D and HAM-A (r = 0.316, p < 0.01, r = 0.307, p < 0.01, respectively). For the PHQ-9, a cut score of ≥11 resulted in 72% sensitivity and 72% specificity at recognizing depression symptoms. For the GAD-7, a cut score ≥7 resulted in 73% sensitivity and 54% specificity at recognizing any anxiety disorders. The confirmatory factor analysis suggested a two-factor structure ("cognitive/affectional", "somatic") for both the PHQ-9 and GAD-7. In conclusion, the PHQ-9 and GAD-7 have adequate formal psychometric properties as severity measures for symptoms of anxiety and depression in individuals with AMD. The PHQ-9 performs well as a screener using a cut score of ≥11. However, the clinical utility of the GAD-7 as a diagnostic tool for recognition of anxiety disorders is limited.

Development and validation of Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) for Internet Gaming Disorder (IGD) and factor analytic assessment.

OBJECTIVE: To develop and validate Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version (K-SADS-PL) for Internet Gaming Disorder (IGD) in adolescents. METHODS: Questions and threshold criteria of the K-SADS-IGD was generated based on the related section of K-SADS-PL. Then, the sample consist of IGD group and matched control group with no significant difference in psychiatric comorbidities from clinical settings were included to assess the psychometric properties of the K-SADS-IGD. Exploratory and Confirmatory Factor analysis were conducted to evaluate and compare DSM model of IGD and two different Models of IGD proposal in adolescents. RESULTS: Exploratory Factor Analysis of K-SADS-IGD revealed a single factor explaining 61.469% of the total variance. Confirmatory Factor Analysis indicates that although the K-SADS-IGD model fit indices were also acceptable, Model 1, which excluded the 7th criterion of IGD criteria of DSM-5 showed better fit in adolescent population. The Likelihood Ratio Positive and the Likelihood Ratio Negative estimates for the diagnosis of K-SADS-IGD were 31.4 and 0.12, respectively, suggesting that K-SADS-IGD was beneficial for determining the presence and the absence of IGD in adolescents. Also, K-SADS-IGD could detect disordered gamers with significantly low functionality (even after controlling the impact of comorbidities) from non-disordered gamers. CONCLUSION: K-SADS-IGD was found to be a reliable and valid instrument in adolescents. The model excluding 7th criteria of DSM-5 IGD was found to be more consistent than the current DSM-5 IGD model in the adolescent population. Therefore, the diagnostic criteria might be required to adjust according to the age group since the clinical symptomatology of IGD in adolescents may differ from that in adults. The K-SADS-IGD may meet the need for a certain and standardized tool to assess IGD in this population.

Neural basis of memory impairments and relation to functional disability in fully or partially remitted patients with affective disorders.

Bipolar disorder (BD) and major depressive disorder (MDD) are associated with cognitive and functional impairment. Cognitive impairment is often associated with dorsal prefrontal cortex (dPFC) hypo-activity, but the neuronal correlates of functional disability is largely unknown. In this study, 91 patients with affective disorders in full or partial remission (BD, n = 67; MDD, n = 24) with objectively verified cognitive impairment and substantial functional disability underwent neuropsychological assessment and functional magnetic resonance imaging (fMRI) scan during which they completed a strategic picture-encoding task. For comparison, 36 matched healthy controls underwent an identical test protocol. Patients showed encoding-related hypo-activity in the dPFC compared to controls. In patients, lower right dlPFC activity was associated with poorer overall functioning and more antipsychotic drug use. In conclusion, memory impairments were underpinned by failure to recruit the dPFC during task performance which was associated with impaired functioning in fully or partially remitted patients with affective disorders. This aberrant neurocircuitry activity has implications for the design of future pro-cognitive interventions that aim to improve not only cognition but also real-world functioning.

Serum angioneurin levels following electroconvulsive therapy for mood disorders.

OBJECTIVES: The efficacy of electroconvulsive therapy (ECT) in treating mood disorders (MDs) is hypothesized to be mediated by the induction of neurotrophic factors (denoted "angioneurins") that trigger neuronal plasticity. This study aimed to assess the effects of ECT on serum angioneurin levels in patients with MD. METHODS: A total of 110 patients with MDs including 30 with unipolar depression, 25 with bipolar depression (BD), 55 with bipolar mania (BM), and 50 healthy controls were included in the study. Patients were subdivided into two groups: those who received ECT + medication (12 ECT sessions) and those who received only medication (no-ECT). Depressive and manic symptom assessments and measurements of vascular endothelial growth factor (VEGF), fibroblast growth factor-2, nerve growth factor (NGF), and insulin-like growth factor-1 levels in blood samples were performed at baseline and week 8. RESULTS: Patients in the ECT group, specifically those with BD and BM, had significantly increased levels of VEGF compared to their baseline VEGF levels (p = 0.002). No significant changes in angioneurin levels were observed in the no-ECT group. Serum NGF levels were significantly associated with a reduction in depressive symptoms. Angioneurin levels were not associated with manic symptom reduction. CONCLUSIONS: This study hints that ECT may increase VEGF levels with angiogenic mechanisms that amplify NGF signaling to promote neurogenesis. It may also contribute to changes in brain function and emotional regulation. However, further animal experiments and clinical validation are needed.

Why Are Some People with Lower Urinary Tract Symptoms (LUTS) Depressed? New Evidence That Peripheral Inflammation in the Bladder Causes Central Inflammation and Mood Disorders.

Anecdotal evidence has long suggested that patients with lower urinary tract symptoms (LUTS) develop mood disorders, such as depression and anxiety, at a higher rate than the general population and recent prospective studies have confirmed this link. Breakthroughs in our understanding of the diseases underlying LUTS have shown that many have a substantial inflammatory component and great strides have been made recently in our understanding of how this inflammation is triggered. Meanwhile, studies on mood disorders have found that many are associated with central neuroinflammation, most notably in the hippocampus. Excitingly, work on other diseases characterized by peripheral inflammation has shown that they can trigger central neuroinflammation and mood disorders. In this review, we discuss the current evidence tying LUTS to mood disorders, its possible bidirectionally, and inflammation as a common mechanism. We also review modern theories of inflammation and depression. Finally, we discuss exciting new animal studies that directly tie two bladder conditions characterized by extensive bladder inflammation (cyclophosphamide-induced hemorrhagic cystitis and bladder outlet obstruction) to neuroinflammation and depression. We conclude with a discussion of possible mechanisms by which peripheral inflammation is translated into central neuroinflammation with the resulting psychiatric concerns.

Effects of emotional valence and intensity on cognitive and affective empathy after insula lesions.

The insula plays a central role in empathy. However, the complex structure of cognitive (CE) and affective empathy (AE) deficits following insular damage is not fully understood. In the present study, patients with insular lesions (n = 20) and demographically matched healthy controls (n = 24) viewed ecologically valid videos that varied in terms of valence and emotional intensity. The videos showed a person (target) narrating a personal life event. In CE conditions, subjects continuously rated the affective state of the target, while in AE conditions, they continuously rated their own affect. Mean squared error (MSE) assessed deviations between subject and target ratings. Patients differed from controls only in negative, low-intensity AE, rating their own affective state less negative than the target. This deficit was not related to trait empathy, neuropsychological or clinical parameters, or laterality of lesion. Empathic functions may be widely spared after insular damage in a naturalistic, dynamic setting, potentially due to the intact interpretation of social context by residual networks outside the lesion. The particular role of the insula in AE for negative states may evolve specifically in situations that bear higher uncertainty pointing to a threshold role of the insula in online ratings of AE.

Subjective quality of life factorial structure across mental disorders: should we switch to assessing dimensions?

A two-factor structure of subjective quality of life (SQoL) was established for patients with schizophrenia with the dimensions being 'Life and Health' and 'Living Environment'. This study investigated whether the same structure applies in patients with mood and anxiety disorders and, if so, whether the dimension scores differ between the three diagnostic groups. SQoL data of 1366 patients with mood and 419 patients with anxiety disorders obtained on the Manchester Short Assessment of Quality of Life (MANSA) were retrieved from 3 multisite studies. We performed Confirmatory Factor Analyses (CFAs) based on the MANSA SQoL items of each diagnostic sample. Next, through a series of Kruskal-Wallis and Mann-Whitney tests, we compared the scores of the two factors across patients with mood disorders, anxiety disorders and schizophrenia. The two CFAs showed adequate fit of the two-factor structure across mood and anxiety disorders. The dimension scores on 'Life and Health' differed significantly between all three diagnostic groups. They were lowest in patients with anxiety disorders, higher in patients with mood disorders and highest in patients with schizophrenia. However, on the 'Living Environment' dimension, patients with mood disorders had significantly higher scores than patients with schizophrenia, whilst patients with anxiety disorders did not differ significantly from either other group. The findings suggest that a two-factor structure of SQoL applies across mental disorders. The two dimensions vary across diagnostic groups in different ways. Assessing two dimensions of SQoL may provide more specific and relevant information than global scores.

Prolactin-Releasing Peptide Contributes to Stress-Related Mood Disorders and Inhibits Sleep/Mood Regulatory Melanin-Concentrating Hormone Neurons in Rats.

Stress disorders impair sleep and quality of life; however, their pathomechanisms are unknown. Prolactin-releasing peptide (PrRP) is a stress mediator; we therefore hypothesized that PrRP may be involved in the development of stress disorders. PrRP is produced by the medullary A1/A2 noradrenaline (NA) cells, which transmit stress signals to forebrain centers, and by non-NA cells in the hypothalamic dorsomedial nucleus. We found in male rats that both PrRP and PrRP-NA cells innervate melanin-concentrating hormone (MCH) producing neurons in the dorsolateral hypothalamus (DLH). These cells serve as a key hub for regulating sleep and affective states. Ex vivo, PrRP hyperpolarized MCH neurons and further increased the hyperpolarization caused by NA. Following sleep deprivation, intracerebroventricular PrRP injection reduced the number of REM sleep-active MCH cells. PrRP expression in the dorsomedial nucleus was upregulated by sleep deprivation, while downregulated by REM sleep rebound. Both in learned helplessness paradigm and after peripheral inflammation, impaired coping with sustained stress was associated with (1) overactivation of PrRP cells, (2) PrRP protein and receptor depletion in the DLH, and (3) dysregulation of MCH expression. Exposure to stress in the PrRP-insensitive period led to increased passive coping with stress. Normal PrRP signaling, therefore, seems to protect animals against stress-related disorders. PrRP signaling in the DLH is an important component of the PrRP's action, which may be mediated by MCH neurons. Moreover, PrRP receptors were downregulated in the DLH of human suicidal victims. As stress-related mental disorders are the leading cause of suicide, our findings may have particular translational relevance.SIGNIFICANCE STATEMENT Treatment resistance to monoaminergic antidepressants is a major problem. Neuropeptides that modulate the central monoaminergic signaling are promising targets for developing alternative therapeutic strategies. We found that stress-responsive prolactin-releasing peptide (PrRP) cells innervated melanin-concentrating hormone (MCH) neurons that are crucial in the regulation of sleep and mood. PrRP inhibited MCH cell activity and enhanced the inhibitory effect evoked by noradrenaline, a classic monoamine, on MCH neurons. We observed that impaired PrRP signaling led to failure in coping with chronic/repeated stress and was associated with altered MCH expression. We found alterations of the PrRP system also in suicidal human subjects. PrRP dysfunction may underlie stress disorders, and fine-tuning MCH activity by PrRP may be an important part of the mechanism.

Loneliness and mood disorders: consequence, cause and/or unholy alliance?

PURPOSE OF REVIEW: People with persistent depressive disorders and with bipolar disorder are more likely to feel lonely than people in the general population. This evidence update focused on studies in the last 2 years, characterized by the COVID-19 pandemic and consequent social distancing directives. RECENT FINDINGS: Longitudinal studies identified that people who feel lonely are more likely to become depressed or to experience relapse of mood disorders. There is emerging evidence that feelings of loneliness or mandatory social isolation can precede manic episodes. Hence the relationship between loneliness and mood disorders is complex and bidirectional. Interventions were developed to reduce loneliness in people with mental health problems, including depressive disorders, through cognitive modification and/or supported socialisation. No loneliness-focused interventions have been specifically tailored to people with bipolar disorder. SUMMARY: Studies carried out before and during the COVID-19 pandemic found that feelings of loneliness can be both consequences and precursors of persistent depression and bipolar disorder. Mood symptoms and loneliness have a cumulative negative effect on physical and mental health outcomes. Conceptual overlaps and relations between loneliness and mood symptoms should be clarified in qualitative studies. Theory-driven intervention models should be developed and tested in methodologically robust studies.

Contribution of the µ-opioid receptor system to affective disorders in temporal lobe epilepsy: A bidirectional relationship?

OBJECTIVE: Affective disorders are frequent comorbidities of temporal lobe epilepsy (TLE). The endogenous opioid system has been implicated in both epilepsy and affective disorders, and may play a significant role in their bidirectional relationship. In this cross-sectional study, we investigated the association between µ-opioid receptor binding and affective disorders in patients with TLE. METHODS: Nine patients with TLE and depression/anxiety underwent 11 C-carfentanil positron emission tomography (CFN PET) and neuropsychiatric assessment, including the Hospital Anxiety and Depression Scale and the Positive and Negative Affect Schedule. The normalized CFN PET scans were compared with those of 26 age-matched healthy controls. Correlation analyses with affective symptoms were performed by region of interest-based analysis focusing on the limbic circuit and orbitofrontal cortex. RESULTS: We observed widely reduced CFN binding potential (BP) in bilateral frontal lobes and striata in patients with TLE compared to healthy controls. In the TLE group, more severe anxiety and negative affect were associated with decreased CFN BP in the posterior cingulate gyrus. SIGNIFICANCE: In patients with TLE, interictally reduced binding in the opioid system was associated with higher levels of anxiety and negative affect. We speculate that seizure-related agonist-driven desensitization and downregulation of opioid receptors could be a potential underlying pathomechanism.