Allergic rhinitis: evidence for impact on asthma

Background

This paper reviews the current evidence indicating that comorbid allergic rhinitis may have clinically relevant effects on asthma.

Discussion

Allergic rhinitis is very common in patients with asthma, with a reported prevalence of up to 100% in those with allergic asthma. While the temporal relation of allergic rhinitis and asthma diagnoses can be variable, the diagnosis of allergic rhinitis often precedes that of asthma. Rhinitis is an independent risk factor for the subsequent development of asthma in both atopic and nonatopic individuals. Controlled studies have provided conflicting results regarding the benefits for asthma symptoms of treating comorbid allergic rhinitis with intranasal corticosteroids. Effects of other treatments for comorbid allergic rhinitis, including antihistamines, allergen immunotherapy, systemic anti-IgE therapy, and antileukotriene agents, have been examined in a limited number of studies; anti-IgE therapy and antileukotriene agents such as the leukotriene receptor antagonists have benefits for treating both allergic rhinitis and asthma. Results of observational studies indicate that treating comorbid allergic rhinitis results in a lowered risk of asthma-related hospitalizations and emergency visits. Results of several retrospective database studies in the United States and in Europe indicate that, for patients with asthma, the presence of comorbid allergic rhinitis is associated with higher total annual medical costs, greater prescribing frequency of asthma-related medications, as well as increased likelihood of asthma-related hospital admissions and emergency visits. There is therefore evidence suggesting that comorbid allergic rhinitis is a marker for more difficult to control asthma and worsened asthma outcomes.

Conclusion

These findings highlight the potential for improving asthma outcomes by following a combined therapeutic approach to comorbid allergic rhinitis and asthma rather than targeting each condition separately.

     

ADHD and comorbid conduct problems among adolescents: associations with self-esteem and substance use

Attention-deficit/hyperactivity disorder (ADHD) is a common child and adolescent disorder that is associated with negative outcomes (e.g., emotional and behavioral problems, substance use) and is often comorbid with Conduct Problems (CP). Research findings are mixed as to whether youth with ADHD alone or comorbid ADHD/CP suffer from low self-esteem. Research has also shown links between low self-esteem and ADHD (alone and with CP) with substance use; yet, no research has examined the links between self-esteem and substance use in adolescents with ADHD and CP. The current study examined the relation between ADHD with and without comorbid CP and self-esteem, and whether self-esteem moderated the relation between ADHD and ADHD/CP with substance use among adolescents. We hypothesized that adolescents with comorbid ADHD/CP would experience lower self-esteem than adolescents with ADHD alone or with neither disorder and that self-esteem would moderate the association between ADHD, CP, and substance use. Participants were 62 adolescents who completed the laboratory-based study with a parent. Results suggested that adolescents with comorbid ADHD and CP had significantly lower self-esteem than adolescents with ADHD alone or neither disorder. Self-esteem was not significantly different for adolescents with ADHD alone versus those in the control group. There was one marginally significant interaction between ADHD and self-esteem predicting substance use, such that individuals with comorbid ADHD/CP who also had low self-esteem tended to use more substances. Results have implications for treatments that target adolescents with ADHD and comorbid CP, as these adolescents are at risk for many deleterious outcomes.     

Neurobiology of comorbid post‐traumatic stress disorder and alcohol‐use disorder

Post‐traumatic stress disorder (PTSD) and alcohol‐use disorder (AUD) are highly comorbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of comorbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state‐of‐the‐science on comorbid PTSD and AUD. We summarize epidemiological data documenting the prevalence of this comorbidity, review what is known about the potential neurobiological basis for the frequent co‐occurrence of PTSD and AUD and discuss successes and failures of past and current treatment strategies. We also review animal models that aim to examine comorbid PTSD and AUD, highlighting where the models parallel the human condition, and we discuss the strengths and weaknesses of each model. We conclude by discussing key gaps in our knowledge and strategies for addressing them: in particular, we (1) highlight the need for better animal models of the comorbid condition and better clinical trial design, (2) emphasize the need for examination of subpopulation effects and individual differences and (3) urge cross‐talk between basic and clinical researchers that is reflected in collaborative work with forward and reverse translational impact.     

The Effects of QEEG-Informed Neurofeedback in ADHD: An Open-Label Pilot Study

In ADHD several EEG biomarkers have been described before, with relevance to treatment outcome to stimulant medication. This pilot-study aimed at personalizing neurofeedback treatment to these specific sub-groups to investigate if such an approach leads to improved clinical outcomes. Furthermore, pre- and post-treatment EEG and ERP changes were investigated in a sub-group to study the neurophysiological effects of neurofeedback. Twenty-one patients with ADHD were treated with QEEG-informed neurofeedback and post-treatment effects on inattention (ATT), hyperactivity/impulsivity (HI) and comorbid depressive symptoms were investigated. There was a significant improvement for both ATT, HI and comorbid depressive complaints after QEEG-informed neurofeedback. The effect size for ATT was 1.78 and for HI was 1.22. Furthermore, anterior individual alpha peak frequency (iAPF) demonstrated a strong relation to improvement on comorbid depressive complaints. Pre- and post-treatment effects for the SMR neurofeedback sub-group exhibited increased N200 and P300 amplitudes and decreased SMR EEG power post-treatment. This pilot study is the first study demonstrating that it is possible to select neurofeedback protocols based on individual EEG biomarkers and suggests this results in improved treatment outcome specifically for ATT, however these results should be replicated in further controlled studies. A slow anterior iAPF at baseline predicts poor treatment response on comorbid depressive complaints in line with studies in depression. The effects of SMR neurofeedback resulted in specific ERP and EEG changes.     

Rearing by foster Wistar mother with high level of maternal care counteracts the development of genetic absence epilepsy and comorbid depression in WAG/Rij rats

It has been shown for the first time that rearing by a foster Wistar mother with high level of maternal care (MC) counteracts the expression of genetic absence epilepsy (AE) and comorbid depression – reduces the number, duration and index of spike-wave discharges (SWDs) and immobility time in the forced swimming test, as well as exerts substantial effects on morphology and time-frequency dynamics of SWDs in WAG/Rij rats. It is supposed that increases in MC early in development might be used to counteract epileptogenesis and comorbid depression in people genetically predisposed to AE.     

Disparities in surgical treatment of early-stage non-small-cell lung cancer.

This study involved 1,564 black or white patients diagnosed in 1992 to 1997 with non-small-cell lung cancer, reported to the population-based Connecticut Tumor Registry, who were linked with a statewide hospital discharge database that provided information on comorbid conditions. While only 11.4 percent of patients did not receive surgical treatment (lung resection), this proportion increased with rising age and was higher among patients who resided in a census tract in the highest poverty-rate quintile, were black, not married and had one or more selected comorbid conditions. These associations persisted in logistic regression models that included all of the variables as predictors of surgery. Studies are needed to explain these disparities.     

Internet-Based Cognitive Behavioral Therapy for Insomnia (ICBT-i) Improves Comorbid Anxiety and Depression—A Meta-Analysis of Randomized Controlled Trials

As the internet has become popularized in recent years, cognitive behavioral therapy for insomnia (CBT-i) has shifted from a face-to-face approach to delivery via the internet (internet-based CBT-i, ICBT-i). Several studies have investigated the effects of ICBT-i on comorbid anxiety and depression; however, the results remain inconclusive. Thus, a meta-analysis was conducted to determine the effects of ICBT-i on anxiety and depression. Electronic databases, including PubMed, EMBASE, PsycINFO and the Cochrane Library (throughout May 28, 2015), were systematically searched for randomized controlled trials (RCTs) of ICBT-i. Data were extracted from the qualified studies and pooled together. The standardized mean difference (SMD) and 95% confidence interval (95% CI) were calculated to assess the effects of ICBT-i on comorbid anxiety and depression. Nine records that included ten studies were ultimately qualified. The effect sizes (ESs) were -0.35 [-0.46, -0.25] for anxiety and -0.36 [-0.47, -0.26] for depression, which were stable using a between-group or within-group comparison and suggest positive effects of ICBT-i on both comorbid disorders. Although positive results were identified in this meta-analysis, additional high-quality studies with larger sample sizes are needed in the future.     

Comorbid ADHD and mental health disorders: are these children more likely to develop reading disorders?

While attention-deficit/hyperactivity disorder (ADHD) has been associated with both internalizing and externalizing childhood behaviour disorders, the specific relationship of these comorbid disorders to ADHD and reading problems is less well defined. The present study analysed data from the Australian Twin ADHD Project, which utilized DSM-IV-based ratings of ADHD, separation anxiety disorder, generalized anxiety disorder, depression, conduct disorder, and oppositional defiant disorder for twins and siblings aged 6 to 18 years. While differences between children with and without ADHD were demonstrated for those with separation anxiety disorder, generalized anxiety disorder, depression, conduct disorder, oppositional defiant disorder and a reading disorder, for all age groups, regression analysis of ADHD diagnostic subtypes by age and reading disorder showed that only generalized anxiety disorder remained significant after controlling for ADHD subtypes. Analysis of the mean reading disorder scores in children with and without ADHD showed that children with conduct disorder had significantly more reading problems, as did children with multiple comorbid disorders. In summary, both age and ADHD diagnosis were associated with variations in these comorbid disorders, and multiple comorbid disorders were associated with greater reading impairment.     

Factors associated with acute depressive symptoms in patients with comorbid depression attending cardiac rehabilitation

Background

The literature suggests that comorbid depression, defined in this paper as a history of depression prior to a cardiovascular event, has an impact on later onset depression as well as constituting increased risk of mortality and adverse cardiac events. However, which factors are associated with depression, specifically in patients with comorbid depression, is unclear. Therefore, this paper investigates the factors associated with depression in patients with comorbid depression attending cardiac rehabilitation (CR).

Methods

This observational study used routinely collected data from the British Heart Foundation National Audit of Cardiac Rehabilitation for the time period between April 2012 and March 2017. CR participants with comorbid depression were selected as the study population. An independent t-test and chi-square test were used to compare the association between acute depression symptoms and baseline characteristics in this population.

Results

A total of 2715 CR patients with comorbid depression were analysed. Characteristics associated with acute depressive symptoms in patients with comorbid depression were found to be: young age (MD: 2.71, 95% CI 1.91, 3.50), increased number of comorbidities (MD: -0.50, 95% CI -0.66, ??0.34), increased weight (MD: -1.94, 95% CI -3.35, ??0.52), high BMI (MD: -1.94, 95% CI -3.35, ??0.52), HADS anxiety (MD: -5.17, 95% CI -5.47, ??4.87), comorbid anxiety (52.4%, p <? 0.001), physical inactivity (150?min moderate physical activity a week and 75?min vigorous exercise a week; 27.5%, p <? 0.001; 5.6%, p?<? 0.001 respectively), smoking (12.7%, p?<? 0.001), and being less likely to be partnered (63.6%, p?<? 0.001).

Conclusion

The study demonstrated the association between a variety of clinical and socio-demographic factors and depression. The findings of the research indicated that, at CR baseline assessment, caution must be taken with patients with comorbid depression, specifically those with higher level depressive symptoms at the start of rehabilitation. Furthermore, their multi-comorbid condition must also be taken into account. Patients with higher depression symptoms and comorbid depression scored five points higher on the HADS anxiety scale in comparison to patients with lower level depression symptoms at the start of CR, which demonstrated that anxiety and depression are interrelated and present together.

     

Prevalence of comorbid substance use disorder during long-term central stimulant treatment in adult ADHD

Central stimulant (CS) therapy is a cornerstone in treatment of adult attention-deficit/hyperactivity disorder (ADHD). Substance use disorder (SUD) is a common comorbid disorder of ADHD and might complicate the treatment. Our main objectives were to investigate the prevalence of SUD during CS treatment, and identify variables associated with SUD during the treatment. The collection of data was based on a naturalistic, retrospective approach using the medical records of a cohort of all adult ADHD patients (N = 117) starting treatment with CS in a specific catchment area in the period 1997 to May 2005. A logistic regression model was applied to identify possible predictors of SUD during CS treatment. The study showed no onset of SUD during the CS treatment in the group of patients without comorbid SUD at baseline (mean CS treatment length 41.1 months). In the group of patients with comorbid SUD at baseline, 58.5 % had one or more relapses of SUD during treatment (mean CS treatment length 27.9 months). Younger age and comorbid antisocial personality disorder were associated with relapse. In a logistic regression analysis, cannabis abstinence for more than 12 months was a negative predictor for relapse of SUD. CS treatment does not precipitate onset of SUD in adults without previous SUD.     

Health Impact Index. Development and Validation of a Method for Classifying Comorbid Disease Measured against Self-Reported Health

The objective of this study was to develop a method of classifying comorbid conditions that accounts for both the severity and joint effects of the diseases. The Tromsø Study is a cohort study with a longitudinal design utilizing a survey approach with physical examinations in the Tromsø municipality from 1974 to 2008, where in total 40051 subjects participated. We used Tromsø 4 as reference population and the Norwegian Institute of Public Health (FHI) panel as validation population. Ordinal regression was used to assess the effect of comorbid disease on Self-Reported Health (SRH). The model is controlled for interaction between diseases, mental health, age, and gender. The health impact index estimated levels of SRH. The comparison of predicted and observed SRH showed no significant differences. Spearman’s correlation showed that increasing levels of comorbidity were related to lower levels of SRH (R_S = -0.36, p <.001). The Charlson Comorbidity Index(CCI) was also associated with SRH (r = -.25, p <.001). When focusing on only individuals with a comorbid disease, the relation between SRH and the Health Impact Index (HII) was strengthened (r = -.42, p <.001), while the association between SRH and CCI was attenuated (r = -.14, p <.001). CCI was designed to control for comorbid conditions when survival/mortality is the outcome of interest but is inaccurate when the outcome is SRH. We conclude that HII should be used when SRH is not available, and well-being or quality of survival/life is the outcome of interest.     

Depression, comorbid anxiety disorders, and heart rate variability in physically healthy, unmedicated patients: implications for cardiovascular risk

Context

There is evidence that heart rate variability (HRV) is reduced in major depressive disorder (MDD), although there is debate about whether this effect is caused by medication or the disorder per se. MDD is associated with a two to fourfold increase in the risk of cardiac mortality, and HRV is a robust predictor of cardiac mortality; determining a direct link between HRV and not only MDD, but common comorbid anxiety disorders, will point to psychiatric indicators for cardiovascular risk reduction.

Objective

To determine in physically healthy, unmedicated patients whether (1) HRV is reduced in MDD relative to controls, and (2) HRV reductions are driven by MDD alone, comorbid generalized anxiety disorder (GAD, characterized by anxious anticipation), or comorbid panic and posttraumatic stress disorders (PD/PTSD, characterized by anxious arousal).

Design, Setting, and Patients

A case-control study in 2006 and 2007 on 73 MDD patients, including 24 without anxiety comorbidity, 24 with GAD, and 14 with PD/PTSD. Seventy-three MDD and 94 healthy age- and sex-matched control participants were recruited from the general community. Participants had no history of drug addiction, alcoholism, brain injury, loss of consciousness, stroke, neurological disorder, or serious medical conditions. There were no significant differences between the four groups in age, gender, BMI, or alcohol use.

Main Outcome Measures

HRV was calculated from electrocardiography under a standardized short-term resting state condition.

Results

HRV was reduced in MDD relative to controls, an effect associated with a medium effect size. MDD participants with comorbid generalized anxiety disorder displayed the greatest reductions in HRV relative to controls, an effect associated with a large effect size.

Conclusions

Unmedicated, physically healthy MDD patients with and without comorbid anxiety had reduced HRV. Those with comorbid GAD showed the greatest reductions. Implications for cardiovascular risk reduction strategies in otherwise healthy patients with psychiatric illness are discussed.     

ComorbiditéS associées au trouble déficit de l’attention avec hyperactivité : Données épidémiologiques et implications thérapeutiques

ADHD has become one of the most frequent cause of referrals for children’ behaviour disorders. ADHD is a prevalent psychiatric condition affecting 5% to 9% of school-age children with regards to DSM-IV R diagnostic criteria. In addition, according to the results of different epidemiological studies, patients with ADHD very often experience comorbid conditions in 50% to 90% of the cases. The most frequent comorbidities include externalised disorders, (oppositional defiant disorder, conduct disorders), learning disorders, internalised disorders (anxiety, depression) and tics (chronic motor tics, Tourette’s syndrome). Given their negative impact on the outcome of ADHD in terms of affective and social functioning, and of social and school adaptation, these comorbid conditions should be carefully and systematically searched, even without any actual complaint. Although management of comorbid psychiatric conditions is never simple nor straightforward, therapeutic option should be considered taking into consideration both management of ADHD and specificity of these comorbidities.     

注意缺陷多动障碍共患阅读障碍：认知-脑-基因的多维度研究进展

注意缺陷多动障碍(attention-deficit/hyperactivity disorder,ADHD)和发展性阅读障碍(developmental dyslexia,DD)是两种常见的神经发育性障碍,二者共患的比率高达25%～48%.本文拟从认知-脑-基因等多个维度对ADHD共患DD的研究进展进行综述. ADHD和DD共患的共同认知损害可能是加工速度缺陷,其作为内表型能够很好地帮助解释遗传因素如何通过影响认知功能进而导致出现ADHD共患DD的临床表型.而国内对ADHD共患DD的研究较少,已有的多项研究仅关注ADHD伴学习障碍,但缺乏标准的DD临床诊断标准.本文指出了统一诊断标准、结合多学科研究以及未来个体化训练的必要性.     

Neurocognitive correlates of adult attention-deficit/hyperactivity disorder in a Turkish sample

We established a neuropsychological testing profile among Turkish adults presenting with ADHD controlling for general intelligence and comorbid psychiatric conditions. Adults with ADHD frequently present with comorbid conditions (e.g., mood and substance use/abuse disorders) that may have a detrimental impact on neurocognitive function. Hence, we excluded patients with ADHD meeting criteria for comorbid psychiatric syndromes. A comprehensive neuropsychological test battery was administered to adults with ADHD attending a general psychiatry clinic in Istanbul, Turkey, and healthy control participants. Adults with ADHD demonstrated performance deficits on tests of attention, information processing speed, and general and working memory. Patients with ADHD also reported a significantly greater number of symptoms associated with frontal lobe syndromes (i.e., dysexecutive symptoms and disinhibition). Patients with ADHD demonstrated rather striking deficits on tests of verbal and nonverbal memory. Once information was encoded, however, patients with ADHD do not demonstrate significant information loss. Patients with ADHD and healthy controls did not differ on tests of alternation learning, inhibitory control (error rates), and ToM skills. Findings support the contention that dorsal-prefrontal (rather than ventral-prefrontal) dysfunction is associated with adult ADHD. Unexpectedly, groups did not differ on executive control and fluency tasks. Yet patients with ADHD obtained substantially higher scores on a self-report measure of executive dysfunction. This suggests that dysexecutive symptoms among patients with ADHD in the current study do not reflect set-shifting or organizational deficits. Rather, symptoms may reflect attentional and working memory deficits as well as diminished information processing speed.     

Contribution of neural cell death to depressive phenotypes of streptozotocin-induced diabetic mice

Major depression disorder (MDD) or depression is highly prevalent in individuals with diabetes, and the depressive symptoms are more severe and less responsive to antidepressant therapies in these patients. The underlying mechanism is little understood. We hypothesized that the pathophysiology of comorbid depression was more complex than that proposed for MDD and that neural cell death played a role in the disease severity. To test this hypothesis, we generated streptozotocin (STZ)-induced diabetic mice. These mice had blood glucose levels threefold above controls and exhibited depressive phenotypes as judged by a battery of behavioral tests, thus confirming the comorbidity in mice. Immunohistological studies showed markedly increased TUNEL-positive cells in the frontal cortex and hippocampus of the comorbid mice, indicating apoptosis. This finding was supported by increased caspase-3 and decreased Bcl-2 proteins in these brain regions. In addition, the serum brain-derived neurotrophic factor (BDNF) level of comorbid mice was reduced compared with controls, further supporting the neurodegenerative change. Mechanistic analyses showed an increased expression of mitochondrial fission genes fission protein 1 (Fis1) and dynamin-related protein 1 (Drp1), and a decreased expression of mitochondrial fusion genes mitofusin 1 (Mfn1), mitofusin 2 (Mfn2) and optical atrophy 1 (Opa1). Representative assessment of the proteins Drp1 and Mfn2 mirrored the mRNA changes. The data demonstrated that neural cell death was associated with the depressive phenotype of comorbid mice and that a fission-dominant expression of genes and proteins mediating mitochondrial dynamics played a role in the hyperglycemia-induced cell death. The study provides new insight into the disease mechanism and could aid the development of novel therapeutics aimed at providing neuroprotection by modulating mitochondrial dynamics to treat comorbid depression with diabetes.KEY WORDS: Depression, Diabetes, Comorbidity, Apoptosis, Neurodegeneration, Mitochondria     

Long-Term Ethanol Alcoholization Decreases Levodopa- Induced Aggressive Behavior in Rats

One of the old but still unsolved problems in psychiatry is the treatment of patients with a dual diagnosis of schizophrenia and alcoholism. Numerous clinical studies failed to explain unambiguously the mechanisms of formation of these comorbid disorders. Experimental modeling of dual disorders was carried out using a model of schizophrenia based on the impaired development and dopamine hypothesis of schizophrenia. To model comorbid experimental schizophrenia and alcohol abuse, the dopamine precursors, Levodopa/Carbidopa (LC), were used in combination with 15% ethanol. The aim of this study was to investigate social behavior of rats receiving LC and exposed to intermittent semi-compulsory alcoholization. After three months of the experiment, there were significantly more interactions (including aggressive–attacks, fights, bites) and submissive postures in the group of rats that received LC. Combined LC/ethanol administration did not alter rat social behavior in contrast to ethanol administered alone.     

Comorbid Diseases Interact with Breast Cancer to Affect Mortality in the First Year after Diagnosis—A Danish Nationwide Matched Cohort Study

Background

Survival of breast cancer patients with comorbidity, compared to those without comorbidity, has been well characterized. The interaction between comorbid diseases and breast cancer, however, has not been well-studied.

Methods

From Danish nationwide medical registries, we identified all breast cancer patients between 45 and 85 years of age diagnosed from 1994 to 2008. Women without breast cancer were matched to the breast cancer patients on specific comorbid diseases included in the Charlson comorbidity Index (CCI). Interaction contrasts were calculated as a measure of synergistic effect on mortality between comorbidity and breast cancer.

Results

The study included 47,904 breast cancer patients and 237,938 matched comparison women. In the first year, the strongest interaction between comorbidity and breast cancer was observed in breast cancer patients with a CCI score of ≥4, which accounted for 29 deaths per 1000 person-years. Among individual comorbidities, dementia interacted strongly with breast cancer and accounted for 148 deaths per 1000 person-years within one year of follow-up. There was little interaction between comorbidity and breast cancer during one to five years of follow-up.

Conclusions

There was substantial interaction between comorbid diseases and breast cancer, affecting mortality. Successful treatment of the comorbid diseases or the breast cancer can delay mortality caused by this interaction in breast cancer patients.     

Comorbid Externalising Behaviour in AD/HD: Evidence for a Distinct Pathological Entity in Adolescence

While the profiling of subtypes of Attention Deficit Hyperactivity Disorder (AD/HD) have been the subject of considerable scrutiny, both psychometrically and psychophysiologically, little attention has been paid to the effect of diagnoses comorbid with AD/HD on such profiles. This is despite the greater than 80% prevalence of comorbidity under the DSM-IV-TR diagnostic definitions. Here we investigate the event related potential (ERP) and psychometric profiles of Controls, AD/HD, and comorbid AD/HD (particularly AD/HD+ODD/CD) groups on six neurocognitive tasks thought to probe the constructs of selective and sustained attention, response inhibition and executive function. Data from 29 parameters extracted from a child group (age range 6 to 12; 52 Controls and 64 AD/HD) and from an adolescent group (age range 13 to 17; 79 Controls and 88 AD/HD) were reduced via a Principal Components Analysis, the 6 significant eigenvectors then used as determinants of cluster membership via a Two-Step Cluster Analysis. Two clusters were found in the analysis of the adolescent age group - a cluster dominated by Control and AD/HD participants without comorbidity, while the second cluster was dominated by AD/HD participants with externalising comorbidity (largely oppositional defiant/conduct disorder ODD/CD). A similar segregation within the child age group was not found. Further analysis of these objectively determined clusters in terms of their clinical diagnoses indicates a significant effect of ODD/CD comorbidity on a concurrent AD/HD diagnosis. We conclude that comorbid externalising behaviour in AD/HD constitutes a distinct pathological entity in adolescence.