Comorbid Mood Disorders Research Articles

Sex Differences in a Rat Model of Peripheral Neuropathic Pain and Associated Levels of Endogenous Cannabinoid Ligands

Chronic neuropathic pain is a major unmet clinical need affecting 10% of the world population, the majority of whom suffer from co-morbid mood disorders. Sex differences have been reported in pain prevalence, perception and response to analgesics. However, sexual dimorphism in chronic neuropathic pain and the associated neurobiology, are still poorly understood. The lack of efficacy and the adverse effects associated with current pharmacological treatments, further underline the need for new therapeutic targets. The endocannabinoid system (ECS) is a lipid signalling system which regulates a large number of physiological processes, including pain. The aim of this study was to investigate sexual dimorphism in pain-, anxiety- and depression-related behaviours, and concomitant alterations in supraspinal and spinal endocannabinoid levels in the spared nerve injury (SNI) animal model of peripheral neuropathic pain. Sham or SNI surgery was performed in adult male and female Sprague-Dawley rats. Mechanical and cold allodynia was tested weekly using von Frey and acetone drop tests, respectively. Development of depression-related behaviours was analysed using sucrose splash and sucrose preference tests. Locomotor activity and anxiety-related behaviours were assessed with open field and elevated plus maze tests. Levels of endocannabinoid ligands and related N-acylethanolamines in supraspinal regions of the descending inhibitory pain pathway, and spinal cord, were analysed 42 days post-surgery. SNI surgery induced allodynia in rats of both sexes. Female-SNI rats exhibited earlier onset and greater sensitivity to cold and mechanical allodynia than their male counterparts. In male rats, SNI induced a significant reduction of rearing, compared to sham controls. Trends for depressive-like behaviours in females and for anxiety-like behaviours in males were observed after SNI surgery but did not reach statistical significance. No concomitant alterations in levels of endogenous cannabinoid ligands and related N-acylethanolamines were observed in the regions analysed. Our results demonstrate differential development of SNI-induced nociceptive behaviour between male and female rats suggesting important sexually dimorphic modifications in pain pathways. SNI had no effect on depression- or anxiety-related behaviours in animals of either sex, or on levels of endocannabinoid ligands and related N-acylethanolamines across the regions involved in the descending modulation of nociception at the time points investigated.

Course and outcome of comorbid mood disorders in children and adolescents with intellectual disability [IDD

AimsThe primary objective of the study is to assess the clinical course and functional outcome of comorbid mood disorders in children and adolescents with Intellectual Disability [IDD]Method53 children and adolescents with varying levels of severity of IDD presenting with comorbid mood disorders diagnosed using Kiddie Schedule for Affective Disorder and Schizophrenia-DSM-5 version [KSADS] were recruited by convenient sampling with the exclusion of autism spectrum disorders. Vineland Social Maturity Scale [VSMS] is used to quantify the severity of ID. Developmental Behaviour Checklist-Parent [DBC-P] version is used to measure psychopathology, Clinical Global severity of illness [CGI-S] to quantify the clinical improvement, and Developmental Disabilities Children's Global Assessment of Severity [DD-CGAS] to assess functional improvement. Prospective naturalistic follow-up was done with assessment points at baseline, 1, 3- and 6-month timeline.Result40 patients were followed up for 6 months period. Overall significant improvement is observed in the dependent variables like CGI, DDCGAS, and DBC-P from baseline to 3 months and then a plateau of improvement from 3 to 6 months. The diagnostic breakup of mood disorders is mania [N = 19], Depression [N = 12], and mixed affective state [N = 9]. Patients with mania had significant improvement in DBC score [F = 12.69, p < 0.001 in repeated measures ANOVA], DDCGAS [p < 0.001], and CGI score [p < 0.03] with an overall remission rate of 42.10% over 6 months period. Patients with depression had significant improvement in DBC score [F = 15.48, p < 0.001], DDCGAS, and CGI score [p < 0.001] with an overall remission rate of 41.7%. None of the patients with mixed affective states had clinical remission with no significant improvement observed in any of the dependent variables measuring course and outcome.ConclusionComorbid psychiatric disorders in children and adolescents with IDD have a guarded prognosis compared to mood disorders in neurotypical children. Comorbid ADHD and caregiver stress majorly influenced the course and outcome in the current study.

Diffusion Tensor Imaging Before and 3 Months After Concentrated Exposure Response Prevention in Obsessive-Compulsive Disorder.

Background: Subtle differences in white matter microstructure have been found in obsessive-compulsive disorder (OCD) compared to controls using diffusion tensor imaging (DTI), but it is unclear if and how this change after treatment. The primary aim of this pre-registered study was to investigate white matter integrity between OCD patients and controls and changes after concentrated exposure and response prevention (ERP).Methods: Fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) and mean diffusivity (MD) were estimated using FMRIB Software Library (FSL). The images were registered to a study-specific template using a longitudinal pipeline based on full tensor information in DTI-TK. Voxel-based analysis was performed using tract-based spatial statistics (TBSS). Using SPSS, we compared the integrity in three bilateral regions of interest (ROI), the sagittal stratum, posterior thalamic radiation and cingulum, in 32 OCD patients and 30 matched healthy controls at baseline. Patients received a four-day concentrated ERP format. We investigated longitudinal changes in 26 OCD patients and 22 healthy controls at 3months follow-up using repeated-measures ANOVA. Exploratory t-tests were conducted for AD and MD. Secondary hypothesis used linear regression to investigate if baseline FA predict treatment outcome 3 months later, and if patients with illness onset before 18 years of age would show lower FA in sagittal stratum. Finally, we performed sensitivity analysis on medication and comorbidity influences on FA.Results: Three months after treatment, 77% of the patients were in remission. Contrary to our hypotheses, we did not find any significant differences in FA, RD, AD or MD between the groups before treatment, nor significant group by time effects in any of the ROI. None of the baseline FA measures significantly predicted treatment outcome. Illness onset before 18 years of age did not significantly predict FA in the sagittal stratum. Adjusting for medication or comorbid anxiety or mood disorder did not influence the results.Conclusions: Although concentrated ERP in OCD lead to high remission, we did not find significant long-term changes by DTI. Future studies will benefit from using larger sample sizes and multi-shell diffusion-weighted imaging when investigating white matter microstructure in OCD and underlying neurobiological mechanisms of treatment.

The Association of Malnutrition, illness duration, and pre-morbid weight status with anxiety and depression symptoms in adolescents and young adults with restrictive eating disorders: a cross-sectional study

BackgroundRestrictive eating disorders (EDs) are often comorbid with anxiety and depression symptoms, placing patients at risk for more severe disease, worse treatment outcomes, and higher rates of mortality. To identify risks for developing such co-morbidities, we assessed the association of malnutrition, ED illness duration, and pre-morbid weight status with symptoms of anxiety and depression in adolescents/young adults (AYAs) with EDs.Methods145 participants with restrictive EDs (anorexia nervosa [AN], other specified feeding and eating disorders [OSFED], avoidant restrictive food intake disorder [ARFID]) were included from the RECOVERY study, a longitudinal web-based registry of AYAs with EDs. We measured malnutrition as percent of expected body mass index (%eBMI), based on participants’ pre-morbid growth trajectory. Outcomes were anxiety and depression scores from the Generalized Anxiety Disorder 7-item (GAD-7) and Center for Epidemiologic Studies Depression (CES-D) scales. We used multiple linear regression to examine the association of malnutrition, ED duration, and pre-morbid weight status with symptoms of anxiety and depression.ResultsMean (SD) age was 16.4(3.0) years; 87% were female; 89% white; 85% had AN, 6% OSFED, 10% ARFID. Of these, 2/3 had ED symptoms ≥1 year, 1/3 had previous higher level of ED care (HLOC), and half were taking psychiatric medications. Mean %eBMI was 90% (range 57–112%). Mean GAD-7 was 9.4(5.9) and CES-D was 24(13.8), indicating most participants had clinically significant anxiety and/or depression. Degree of malnutrition was not significantly associated with anxiety or depression adjusting for age, sex, sexual orientation, ED diagnosis, and use of psychiatric medication. Those with longer duration of ED symptoms had higher depression scores after adjusting for malnutrition, HLOC, length of ED symptoms, and time in our care (p = 0.038). Patients with pre-morbid BMIs ≥75th percentile had lower depression scores than those with pre-morbid BMIs <75th percentile (p = 0.014).ConclusionsWe find high degree of clinically relevant anxiety and depression symptoms in a population of AYAs with EDs. Our findings suggest that factors beyond malnutrition play a role in the co-morbid mood and anxiety disorders in this population. Overall, rapid ED diagnosis and comprehensive treatment for patients with EDs across the weight spectrum—and especially those with psychiatric co-morbidities—will likely aid in recovery.

Interoceptive attention regulation in Ehlers-Danlos syndromes: associations between pain and psychiatric symptom severity.

The current project replicated recent findings that pain, anxiety, and depression are common in individuals with EDS+. The ability to focus and control somatic attention appears to be protective and a potential target for interventions in EDS+.

Association between neurological outcome and poststroke comorbid mood and anxiety disorders: A real-life experience.

IntroductionPoststroke depression (PSD) and anxiety (PSA) are prevalent and have a strong impact on functional outcome. Beside stroke severity, little is known on their clinical determinants. This study investigated the association between stroke mechanism, neurological poststroke complications and remaining vascular risk factors and the presence of comorbid PSD and PSA, termed poststroke emotional distress (PSED).MethodsThis was a retrospective analysis of a prospectively compiled medical records database of consecutive patients evaluated during a follow‐up visit 3‐ to 4‐month poststroke. HAD scale was used to define PSED category (PSD+PSA vs. NoPSD+NoPSA). Stroke mechanism and poststroke complications were identified clinically or using appropriate scales. Their association with PSED was tested using a multivariate logistic regression model.ResultsThe sample included 2,300 patients (male: 64.8%); 19% had a PSED and 56.39% were free of any depression or anxiety. The most frequent poststroke complications were fatigue/fatigability (58.4%), sleep problems (26.7%), and pain (20.4%). While no association was observed between PSED and stroke mechanism, higher functional disability (OR:1.572), lower cognitive abilities (OR:0.953), sleep problems (OR:2.334), pain (OR:1.478), fatigue/fatigability (OR:2.331), and abnormal movements (OR:2.380) were all independent risk factors. Persisting tobacco consumption (OR:1.360) was the only vascular significant risk factor.ConclusionsThe frequency of comorbid PSED remains high (1/5 patient) despite improved awareness of these conditions. The association between poststroke complications and the presence of PSED emphasizes the need for standardized neurological and psychological evaluations at follow‐up. These results foster the need to improve the management of addictive behaviors to reduce the burden of PSED.

An online intervention for increasing physical activity in individuals with mood disorders at risk for cardiovascular disease: Design considerations

BackgroundPhysical activity can mitigate the risk of cardiovascular diseases, but the presence of mood disorders makes it challenging to follow or develop a regular exercise habit. We conducted an online comparative effectiveness study (Healthy Hearts Healthy Minds) to evaluate whether an online psychosocial intervention adjunctive to an activity monitor (Fitbit) can improve adherence to physical activity among individuals with mood disorders who have or are at-risk for cardiovascular disease (CVD). MethodsIn this paper, we explore design considerations (including both procedural challenges and achievements) of relevance to our study. ResultsChallenges of this study included navigating a complex IRB review process, integrating two study platforms, automating study procedures, and optimizing participant engagement. Achievements of this study included building trust with collaborators, leveraging existing online communities, generating daily data reports, and conducting patient-centered research. LimitationsThese design considerations are based on a single online comparative effectiveness study, and other online intervention studies may be presented with other unique challenges that are specific to their study format or aims. Consistent with some of the generalizability challenges facing other online studies, participants in this study were overall highly educated (most had at least a college degree). ConclusionsWe successfully conducted a large-scale virtual online intervention to increase physical activity of participants with comorbid mood and cardiovascular disorders by overcoming substantial operational and technical challenges. We hope that this exploration of design considerations in the context of our online study can inform upcoming online intervention studies.

Treatment Outcomes in a Partial Hospital Program for Patients with Social Anxiety Disorder: The Effects of Comorbid Major Depression

Although previous studies have examined the impact of comorbid major depressive disorder (MDD) on social anxiety disorder (SAD), the results have been somewhat mixed. Furthermore, most studies have been conducted in inpatient or outpatient settings. Given the large body of literature that suggests that this particular comorbidity can have negative effects on treatment efficacy and outcomes, it is important to continue to explore its impact. The present study aims to clarify contradictions in the literature and expands on previous studies by examining patients in a partial hospitalization setting. Patients at Rhode Island Hospital with a diagnosis of SAD were compared to those with comorbid SAD and MDD on pre-treatment and post-treatment measures of anxiety and depression. The results indicated that while the comorbid group showed significantly less improvement post-treatment on anxiety symptoms and constructs related to remission from depression, they did not show significantly less improvement on depression symptoms. The implications of these results for clinical practice are discussed. KEYWORDS: Social Anxiety Disorder; Major Depressive Disorder; Comorbid Anxiety Disorders; Comorbid Mood Disorders; Treatment Outcomes; Partial Hospitalization Program

Baseline Predictors of Discontinuation of Prescription Drug Therapy for IBS-C: Cohort Analysis at an Integrated Healthcare System.

Effective prescription drug treatment of constipation-predominant irritable bowel syndrome (IBS-C) requires patients to remain on daily therapy, yet predictive factors to optimize treatment selection are unknown. We assessed whether common comorbidities including chronic overlapping pain conditions (COPCs), mood disorders, or concurrent medications influence the risk of discontinuing IBS-C prescription drug therapy. We included all IBS-C patients who initiated treatment with the secretagogues linaclotide or lubiprostone across the Michigan Medicine healthcare system between 2012 and 2016. A Cox proportional hazards model was constructed to model time-to-treatment discontinuation as a valid, quantifiable measure of IBS medication persistence using hazards ratios (HR) with 95% confidence intervals (CI). Our cohort included 225 patients on linaclotide and 492 on lubiprostone (mean age 48.3years, 86.9% women, 46.6% with at least one COPC, 60.3% with at least one mood disorder) with an average follow-up of 2.1years. Patients with at least one COPC (HR = 0.566; 95%CI = 0.371-0.863) and also women (HR = 0.535; 95%CI = 0.307-0.934) had a lower risk of discontinuing linaclotide, while COPCs predicted a trend toward increased discontinuation of lubiprostone (HR = 1.254; 95%CI = 0.997-1.576). Age, comorbid mood disorders, and baseline use of narcotics or benzodiazepines did not significantly mediate the risk of treatment discontinuation; our findings remained stable in univariate and multivariable analyses. COPCs and sex appear to influence the likelihood of discontinuation of two commonly prescribed secretagogues, while mood disorders, narcotics, and benzodiazepines may not. Routine assessment for comorbid COPCs prior to initiating therapy may optimize IBS-C treatment selection and outcomes in practice.

Chronic Pain and Mood Disorders in Asian Americans.

Purpose: Pain and mood disorder frequently coexist. Yet, for Asian Americans (AAs), scant information about pain and mood disorder is available. Our aims were to compare (1) the rates of pain and mood disorders and (2) the magnitude of associations between pain and mood disorders between AAs and European Americans (EAs), and across different Asian subgroups.Methods: An analytical data was constructed from the Collaborative Psychiatric Epidemiology Studies (CPES), a representative sample of community-residing U.S. adults (n = 9,871). Pain morbidity was assessed by self-report. Mood disorders, including major depression and anxiety disorders, were assessed using the diagnostic interview. Analysis included descriptive statistics and multivariate logistic regression modeling. All analyses were weighted to approximate the U.S. populations, and controlled for sociodemographic and immigration characteristics.Results: Greater proportion of EAs, compared to AAs, endorsed lifetime pain (56.8% vs. 35.8%). Having life pain disorders elevated the likelihood of lifetime mood disorder by more than 2-folds (weight adjusted odds ratio (WAOR): 2.12, 95% CI: 1.77, 2.55). Having pain disorders over the past 12 months elevated the likelihood of mood disorder in the same time period by more than 3-folds (WAOR: 3.29, 95% CI: 2.02, 5.37) among AAs. The magnitude of the association between pain and psychiatric morbidity were greater in Vietnamese Americans compared to other AAs and EAs.Discussion: The conventional belief that rates of pain and mood disorders are greater in AAs than EAs may need to be further examined. Vietnamese Americans may be particularly vulnerable for experience of comorbid pain and mood disorders.

The impact of generalized anxiety disorder in obsessive-compulsive disorder patients.

Despite generalized anxiety disorder (GAD) being one of the most prevalent comorbidities in obsessive-compulsive disorder (OCD), few studies have researched its impact on the OCD phenotype. The present study investigated how the sociodemographic and clinical profile of people with OCD with comorbid GAD differs from people with OCD without comorbid GAD. We hypothesised that the phenotype of the comorbid group would be closely related to GAD, in that it would more likely be female, have an earlier age at onset of OCD, and show an increased severity of fear-related OCD symptoms (aggressive, sexual/religious, and contamination dimensions), more avoidant behaviours, greater suicidality, more severe anxiety symptoms, and increased rates of comorbid anxiety and mood disorders. The study included 867 participants with OCD, with GAD being comorbid in 33.56%. Mann-Whitney U tests, chi-square tests with continuity correction, and logistic regressions were performed. Results showed that comorbid GAD was uniquely associated with an increased number of avoidant behaviours, greater anxiety severity, panic disorder without agoraphobia, social phobia, specific phobia, and type II bipolar disorder. These results illustrate the clinical severity associated with this comorbidity and highlight markers that can aid diagnosis of GAD in OCD. Future studies should investigate whether this comorbidity has an impact on the treatment of OCD.

Adolescents With Attention-Deficit/Hyperactivity Disorder: Adverse Behaviors and Comorbidity

Purpose and ObjectiveThere is growing evidence that adolescents with ADHD develop long-term impairments and adverse outcomes, yet less is known about their adverse behaviors. To quantify rates of mental health comorbidities in adolescents with ADHD and compare the risks of adverse behaviors among adolescents with and without ADHD. MethodsWe performed a cohort analysis of 6,483 youth from the National Comorbidity Survey Adolescent Supplement (NCS-A), a nationally representative in-person structured diagnostic interview of adolescents aged 14–18 years focusing on mental, emotional, and behavioral disorders. Main Outcomes: (1) Percentages with comorbid anxiety, mood, disruptive behavior, and substance use disorders. (2) Strength of associations of ADHD with several adverse behaviors, including suicidal symptoms, aggression, behavior regulation, life events, education, and substance use. Odds ratios were adjusted for age, sex, and race. ResultsAmong the sample of 6,483 adolescents, overall, 9.5% met the criteria for ADHD. Most (69.5%) of adolescents with ADHD had at least one comorbid mental health condition. As compared to adolescents without ADHD, those with ADHD were significantly more likely to have had a suicide attempt (aOR 2.9, 95% CI = 1.3–6.6) and to have had perpetrated physical aggression (aOR 2.3, 95% CI = 1.7–3.2). Adolescents with ADHD were also more likely to have been expelled from school or fired from a job (aOR 3.3, 95% CI = 1.7–6.5) and to have had problems related to drinking alcohol (95% CI = 1.2–2.9). ConclusionsADHD in adolescents is a complicated disorder with elevated risks for a wide range of adverse behaviors.

Psychiatric Comorbidity and Inpatient Characteristics of Older Adolescents with Opioid Use Disorders in the U.S

Objective: The opioid crisis has substantially affected health services utilization. Hospitalizations for opioid use disorders (OUD) have increased significantly among adolescents and youth in the United States. This study examined the characteristics of hospitalization for OUD among older adolescents with comorbid psychiatric disorders (CPD). Methods: This analysis focused on older adolescents where OUD was given as the primary reason for hospital admission. Multivariable logistic regressions were performed to identify demographic and clinical factors associated with OUD hospitalizations with CPD, using secondary data from the Nationwide Inpatient Sample. Results: CPD was documented in 58% of OUD adolescent inpatients. Mood and anxiety were the most common types of CPD. Several demographics variables discriminated between OUD inpatients with vs without CPD. The odds of having comorbid mood disorders were nearly 2 times greater for female than for male adolescents and were significantly higher for adolescents from Midwest regions compared with those from Northeast and West regions. Conclusions: Hospitalizations due to OUD were tripled for adolescents with CPD relative to adolescents without CPD; nearly half of the adolescents hospitalized with OUD had mood disorders. Specific primary care and access to mental health treatment strategies should target groups most at risk for both OUD and mood related disorders.

The Comorbidity of Schizophrenia Spectrum and Mood Disorders in Autism Spectrum Disorder.

Individuals with autism spectrum disorder are often diagnosed with at least one or more accompanying disorders. Most studies reported prevalence of the psychiatric comorbidities among these individuals; however, the incidence of developing comorbidities is unclear. This study used Taiwan's claims database and aimed to investigate the incidence of developing major psychiatric comorbidities in individuals with autism spectrum disorder and whether the incidence was moderated by gender, autism-spectrum disorder subtypes, and autism-associated neurodevelopmental conditions. A total of 3,837 individuals with autism spectrum disorder (2,929 autistic disorder, 447 Asperger syndrome, 461 pervasive developmental disorder-not otherwise specified) and 38,370 comparison subjects, who were matched by age and gender, were included. The incidences of schizophrenia spectrum, bipolar, and major depressive disorders was examined. The results showed that the incidences of schizophrenia spectrum (9.7 per 1,000 person-year), bipolar disorder (7.0 per 1,000 person-year), and major depressive disorder (3.2 per 1,000 person-year) were significantly higher than the comparison group across all three subtypes of autism-spectrum disorder. Individuals with pervasive developmental disorder-not otherwise specified had higher risk for major depressive disorder than autistic disorder. Females with Asperger syndrome had significant higher risk for schizophrenia spectrum than males. The comorbidity rate dramatically dropped when the autism-associated neurodevelopmental conditions were taken into account. Our findings suggested that the incidences of major psychiatric comorbidities were higher in autism spectrum disorder and influenced by autism subtypes, gender, and autism-associated neurodevelopmental conditions. LAY SUMMARY: We examined whether people with autism spectrum disorder (ASD) have higher incidence of schizophrenia, bipolar disorders, and major depression using a large claims database. The results showed the incidences of these mental illness among individual with ASD were significantly higher than those without ASD. In addition, the incidences were influenced by autism subtypes, gender, and comorbid neurodevelopmental conditions.

Coping strategies that reduce suicidal ideation: An ecological momentary assessment study

BackgroundWhile suicide-specific psychosocial interventions often teach coping skills to suicidal individuals, little is known about the strategies that individuals intuitively use on their own to cope with suicidal ideation in everyday life. AimsThe present study used Ecological Momentary Assessment (EMA) to examine the effectiveness of specific coping strategies individuals use naturally to reduce the intensity of suicidal thinking. MethodFifty participants endorsing suicidal ideation with co-morbid mood disorder and borderline personality disorder completed one week of EMA. Real-time use, perceived effectiveness of 7 common coping strategies and intensity of suicidal ideation were assessed at 6 epochs (i.e., timepoints) each day. ResultsParticipants reported using an average of 4 coping strategies per epoch. Factor analysis (FA) (exploratory followed by confirmatory FA) identified two coping factors: one that included distraction/positive activity-based strategies (i.e., keeping busy, socializing, positive thinking, and doing something good for self) and a second that contained mindfulness-oriented strategies (i.e., finding perspective, calming self, and sitting with feelings until they pass). Although participants perceived all coping strategies as effective, only strategies in the first factor, distraction/positive activity-oriented strategies, lowered the intensity of suicidal thoughts in everyday life. Furthermore, baseline suicidal ideation was inversely related to overall use of coping strategies and particularly use of coping strategies that were found to lead to lowered suicidal ideation. ConclusionsDistraction/positive activity based strategies are helpful in decreasing suicidal ideation in the short-term. These findings can help clinicians advise patients about strategies to use to cope with suicidal thoughts to prevent acting on them in a crisis and they also have the potential to inform development of psychosocial interventions to prevent suicide.

Bioinformatics identification and pharmacological validation of Kcnn3/KCa2 channels as a mediator of negative affective behaviors and excessive alcohol drinking in mice

Mood disorders are often comorbid with alcohol use disorder (AUD) and play a considerable role in the development and maintenance of alcohol dependence and relapse. Because of this high comorbidity, it is necessary to determine shared and unique genetic factors driving heavy drinking and negative affective behaviors. In order to identify novel pharmacogenetic targets, a bioinformatics analysis was used to quantify the expression of amygdala K+ channel genes that covary with anxiety-related phenotypes in the well-phenotyped and fully sequenced family of BXD strains. We used a model of stress-induced escalation of drinking in alcohol-dependent mice to measure negative affective behaviors during abstinence. A pharmacological approach was used to validate the key bioinformatics findings in alcohol-dependent, stressed mice. Amygdalar expression of Kcnn3 correlated significantly with 40 anxiety-associated phenotypes. Further examination of Kcnn3 expression revealed a strong eigentrait for anxiety-like behaviors and negative correlations with binge-like and voluntary alcohol drinking. Mice treated with chronic intermittent alcohol exposure and repeated swim stress consumed more alcohol in their home cages and showed hypophagia on the novelty-suppressed feeding test during abstinence. Pharmacologically targeting Kcnn gene products with the KCa2 (SK) channel-positive modulator 1-EBIO decreased drinking and reduced feeding latency in alcohol-dependent, stressed mice. Collectively, these validation studies provide central nervous system links into the covariance of stress, negative affective behaviors, and AUD in the BXD strains. Further, the bioinformatics discovery tool is effective in identifying promising targets (i.e., KCa2 channels) for treating alcohol dependence exacerbated by comorbid mood disorders.

Physiological Changes During Conscious and Unconscious Emotional Reactions in Persons with Temporal Lobe Epilepsy: A Pilot Study

Emotions play an important role in the provocation of epileptic and psychogenic non- epileptic seizures (PNES) and can be part of the seizure semiology. In both epilepsy and PNES, there is a high prevalence of comorbid mood disorders which are often described as the main factor contributing to poorer quality of life [1]. Especially in temporal lobe epilepsy (TLE), diverse emotional disturbances are described, that are connected with the involvement of the limbic system in this type of epilepsy.

Familial aggregation of anxiety disorder subtypes and anxious temperament in the NIMH Family Study of Affective Spectrum Disorders

BackgroundEvidence from family and twin studies suggests that mood and anxiety disorders, and related temperamental factors may share common etiologic factors. We examine the familial aggregation and coaggregation of anxiety disorder subtypes and anxiety-related temperamental traits, and their association with mood disorders. MethodsA total of 477 probands and 549 first-degree adult relatives from a large community based family study of affective spectrum disorders completed semi-structured diagnostic interviews and self-reported assessments of temperamental traits including: negative affectivity on the ‘Positive and Negative Affect Schedule’ (PANAS), neuroticism anxiety on the ‘Zuckerman-Kuhlman Personality Questionnaire’ (ZKPQ), and anxiety sensitivity on the ‘Anxiety Sensitivity Index’ (ASI). ResultsThe anxiety-related temperamental traits of negative affectivity, neuroticism anxiety and anxiety sensitivity had significant familial specificity, even after controlling for comorbid mood and anxiety disorders in probands and relatives. Yet, these traits in probands did not predict anxiety disorders in relatives. Although some anxiety subtypes were familial, there were no longer familial links between anxiety disorder subtypes (generalized anxiety disorder, social anxiety or panic disorder) after controlling for mood disorder subtypes in probands and relatives. LimitationsCross-sectional interviews were used to estimate disorders, and self-report measures were used for temperamental traits. ConclusionsThese results confirm previous research regarding familial overlap between anxiety subtypes and mood disorders, however their shared liability cannot be fully explained by anxiety-related temperamental traits. These findings suggest that anxiety-related temperamental traits may indicate a vulnerability for mood and anxiety disorders or a potential consequence of these conditions.

Sleep and Mood Disorders Among Youth.

This article reviews the literature on mood disorders and sleep disorders among children and adolescents. Research suggests that sleep plays an important role in the development, progression, and maintenance of mood disorder symptoms among children and adolescents. Sleep problems as early as maternal perinatal insomnia may predict and predate depression among youth. Children and adolescents who develop comorbid mood disorders and sleep problems represent a particularly high-risk group with more severe mood episode symptoms, higher rates of self-harm and suicidality, and less responsivity to treatment. Treatment research supports the idea that sleep problems can be improved through behavioral interventions.

Albiflorin Attenuates Mood Disorders Under Neuropathic Pain State by Suppressing the Hippocampal NLRP3 Inflammasome Activation During Chronic Constriction Injury.

BackgroundNeuropathic pain is a multifaceted and ubiquitous disease across the globe. Mood disorders, such as anxiety and depression, are frequently observed in patients suffering from neuropathic pain. Both neuropathic pain and comorbid mood disorders seriously impact quality of life. Accumulated evidence shows that activation of the NOD-like receptor protein 3 (NLRP3) inflammasome is involved in the neuroinflammatory pathogenesis of neuropathic pain, anxiety, and depression. However, the role of the NLRP3 inflammasome in the pathological process of anxiety and depression under the neuropathic pain state has not been fully described. Albiflorin, a monoterpene glycoside, may be a potential regulator of the NLRP3 inflammasome, but it is not clear whether albiflorin relates to NLRP3 inflammasome activation.MethodsWe used a systematic pharmacological method to confirm whether the activation of the NLRP3 inflammasome in the hippocampus was involved in the development of neuropathic pain associated with mood disorders and whether albiflorin could be an effective treatment for these symptoms.ResultsThe NLRP3 inflammasome contributed to the neuropathic pain and comorbid anxiety and depression-like behaviors induced by chronic constriction injury of the sciatic nerve, and albiflorin may relieve these symptoms via inhibition of the NLRP3 inflammasome activity. Moreover, albiflorin enhanced the translocation of the nuclear factor erythroid 2-related factor 2 into the nucleus and suppressed nuclear factor-kappa B activity in the hippocampus.ConclusionsAlbiflorin, as a potential therapeutic agent, might greatly improve the overall symptoms of neuropathic pain.