The neuronal noradrenaline transporter, anxiety and cardiovascular disease

Panic disorder can serve as a clinical model for testing whether mental stress can cause heart disease. Potential neural mechanisms of cardiac risk are the sympathetic activation during panic attacks, continuing release of adrenaline as a co-transmitter in the cardiac sympathetic nerves, and impairment of noradrenaline neuronal reuptake, augmenting sympathetic neural respnses.

The phenotype of impaired neuronal reuptake of noradrenaline: an epigenetic mechanism? We suspect that this phenotype, in sensitizing people to heart symptom development, is a cause of panic disorder, and by magnifying the sympathetic neural signal in the heart, underlies increased cardiac risk. No loss of function mutations of the coding region of the norepinephrine transporter (NET) are evident, but we do detect hypermethylation of CpG islands in the NET gene promoter region. Chromatin immunoprecipitation methodology demonstrates binding of the inhibitory transcription factor, MeCP2, to promoter region DNA in panic disorder patients.

Cardiovascular illnesses co-morbid with panic disorder. Panic disorder commonly coexists with essential hypertension and the postural tachycardia syndrome. In both of these cardiovascular disorders the impaired neuronal noradrenaline reuptake phenotype is also present and, as with panic disorder, is associated with NET gene promoter region DNA hypermethylation. An epigenetic ‘co-morbidity’ perhaps underlies the clinical concordance.

Brain neurotransmitters. Using internal jugular venous sampling, in the absence of a panic attack we find normal norepinephrine turnover, but based on measurements of the overflow of the serotonin metabolite, 5HIAA, a marked increase (six to sevenfold) in brain serotonin turnover in patients with panic disorder. This appears to represent the underlying neurotransmitter substrate for the disorder. Whether this brain serotonergic activation is a prime mover, or consequential on other primary causes of panic disorder, including cardiac sensitization by faulty neuronal noradrenaline reuptake leading to cardiac symptoms and the enhanced vigilance which accompanies them, is unclear at present.

Association of western and traditional diets with depression and anxiety in women

Objective: Key biological factors that influence the development of depression are modified by diet. This study examined the extent to which the high-prevalence mental disorders are related to habitual diet in 1,046 women ages 20–93 years randomly selected from the population.

Method: A diet quality score was derived from answers to a food frequency questionnaire, and a factor analysis identified habitual dietary patterns. The 12-item General Health Questionnaire (GHQ-12) was used to measure psychological symptoms, and a structured clinical interview was used to assess current depressive and anxiety disorders.

Results: After adjustments for age, socioeconomic status, education, and health behaviors, a "traditional" dietary pattern characterized by vegetables, fruit, meat, fish, and whole grains was associated with lower odds for major depression or dysthymia and for anxiety disorders. A "western" diet of processed or fried foods, refined grains, sugary products, and beer was associated with a higher GHQ-12 score. There was also an inverse association between diet quality score and GHQ-12 score that was not confounded by age, socioeconomic status, education, or other health behaviors.

Conclusions: These results demonstrate an association between habitual diet quality and the high-prevalence mental disorders, although reverse causality and confounding cannot be ruled out as explanations. Further prospective studies are warranted.

Habitual physical activity and the risk for depressive and anxiety disorders among older men and women

Background: Regular physical activity is generally associated with psychological well-being, although there are relatively few prospective studies in older adults. We investigated habitual physical activity as a risk factor for de novo depressive and anxiety disorders in older men and women from the general population.
Methods: In this nested case-control study, subjects aged 60 years or more were identified from randomly selected cohorts being followed prospectively in the Geelong Osteoporosis Study. Cases were individuals with incident depressive or anxiety disorders, diagnosed using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP); controls had no history of these disorders.Habitual physical activity,measured using a validated questionnaire, and other exposures were documented at baseline, approximately four years prior to psychiatric interviews. Those with depressive or anxiety disorders that pre-dated baseline were excluded.
Results: Of 547 eligible subjects, 14 developed de novo depressive or anxiety disorders and were classified as cases; 533 controls remained free of disease. Physical activity was protective against the likelihood of depressive and anxiety disorders; OR = 0.55 (95% CI 0.32–0.94), p = 0.03; each standard deviation increase in the transformed physical activity score was associated with an approximate halving in the likelihood of developing depressive or anxiety disorders. Leisure-time physical activity contributed substantially to the overall physical activity score. Age, gender, smoking, alcohol consumption, weight and socioeconomic status did not substantially confound the association.
Conclusion: This study provides evidence consistent with the notion that higher levels of habitual physical activity are protective against the subsequent risk of development of de novo depressive and anxiety disorders.

Depression and anxiety through pregnancy and the early postpartum : an examination of prospective relationships

Background: The aim of this study was to explore the prospective relationship between depressive symptoms and anxiety across pregnancy and the early postpartum.
Methods: Participants (N=207) completed the State–Trait Anxiety Inventory Trait subscale, Beck Depression Inventory, and social support and sleep quality measures at two time points during pregnancy and once in the early postpartum period.
Results: After accounting for the relative stability of anxiety and depression over time, depressive symptoms earlier in pregnancy predicted higher levels of anxiety in late pregnancy and anxiety in late pregnancy predicted higher depressive symptomatology in the early postpartum. A bi-directional model of depression and anxiety in pregnancy was supported.
Limitations: Data were based on self-reports and participating women were predominantly tertiary educated with high family incomes.
Conclusion: Our findings suggest that depressive symptoms precede the development of higher levels of anxiety and that anxiety, even at non-clinical levels, can predict higher depressive symptoms. Clinicians are advised to screen for anxiety and depression concurrently during pregnancy.

The Cool Little Kids randomised controlled trial population-level early prevention for anxiety disorders

Background: The World Health Organization predicts that by 2030 internalising problems (e.g. depression and anxiety) will be second only to HIV/AIDS in international burden of disease. Internalising problems affect 1 in 7 school aged children, impacting on peer relations, school engagement, and later mental health, relationships and employment. The development of early childhood prevention for internalising problems is in its infancy. The current study follows two successful ‘efficacy’ trials of a parenting group intervention to reduce internalising disorders in temperamentally inhibited preschool children. Cool Little Kids is a population-level randomised trial to determine the impacts of systematically screening preschoolers for inhibition then offering a parenting group intervention, on child internalising problems and economic costs at school entry.
Methods/Design: This randomised trial will be conducted within the preschool service system, attended by more than 95% of Australian children in the year before starting school. In early 2011, preschool services in four local government areas in Melbourne, Australia, will distribute the screening tool. The ≈16% (n≈500) with temperamental inhibition will enter the trial. Intervention parents will be offered Cool Little Kids, a 6-session group program in the local community, focusing on ways to develop their child’s bravery skills by reducing overprotective parenting interactions. Outcomes one and two years post-baseline will comprise child internalising diagnoses and symptoms, parenting interactions, and parent wellbeing. An economic evaluation (costconsequences framework) will compare incremental differences in costs of the intervention versus control children to incremental differences in outcomes, from a societal perspective. Analyses will use the intention-to-treat principle, using logistic and linear regression models (binary and continuous outcomes respectively) to compare outcomes between the trial arms.
Discussion: This trial addresses gaps for internalising problems identified in the 2004 World Health Organization Prevention of Mental Disorders report. If effective and cost-effective, the intervention could readily be applied at a population level. Governments consider mental health to be a priority, enhancing the likelihood that an effective early prevention program would be adopted in Australia and internationally.

Association between magnesium intake and depression and anxiety in community-dwelling adults : The Hordaland Health Study

Objective: Systemic inflammation is associated with both the dietary intake of magnesium, and depression. Limited experimental and clinical data suggest an association between magnesium and depression. Thus, there are reasons to consider dietary magnesium as a variable of interest in depressive disorders. The aim of the present study was to examine the association between magnesium intake and depression and anxiety in a large sample of community-dwelling men and women. This sample consisted of 5708 individuals aged 46–49 or 70–74 years who participated in the Hordaland Health Study in Western Norway.

Methods: Symptoms of depression and anxiety were self-reported using the Hospital Anxiety and Depression Scale, and magnesium intake was assessed using a comprehensive food frequency questionnaire.

Results: There was an inverse association between standardized energy-adjusted magnesium intake and standardized depression scores that was not confounded by age, gender, body habitus or blood pressure (β=−0.16, 95% confidence interval (CI)=−0.22 to −0.11). The association was attenuated after adjustment for socioeconomic and lifestyle variables, but remained statistically significant (β=−0.11, 95%CI=−0.16 to −0.05). Standardized magnesium intake was also related to case-level depression (odds ratio (OR)=0.70, 95%CI=0.56–0.88), although the association was attenuated when adjusted for socioeconomic and lifestyle factors (OR=0.86, 95%CI=0.69–1.08). The inverse relationship between magnesium intake and score and case-level anxiety was weaker and not statistically significant in the fully adjusted models.

Conclusion: The hypothesis that magnesium intake is related to depression in the community is supported by the present findings. These findings may have public health and treatment implications.

Prevalence of mood and anxiety disorder in self reported irritable bowel syndrome (IBS). An epidemiological population based study of women

Background Irritable bowel syndrome (IBS) is commonly regarded as a functional disorder, and is hypothesized to be associated with anxiety and depression. This evidence mainly rests on population-based studies utilising self-report screening instruments for psychopathology. Other studies applying structured clinical interviews are generally based on small clinical samples, which are vulnerable to biases. The extant evidence base for an association between IBS and psychopathology is hence not conclusive. The aim of this study was therefore to re-examine the hypothesis using population-based data and psychiatric morbidity established with a structured clinical interview.

Methods Data were derived from a population-based epidemiological study (n = 1077). Anxiety and mood disorders were established using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP) and the General Health Questionnaire (GHQ-12). Current and lifetime IBS was self-reported. Hypertension and diabetes were employed as comparison groups as they are expected to be unrelated to mental health.

Results Current IBS (n = 69, 6.4%) was associated with an increased likelihood of current mood and/or anxiety disorders (OR = 2.62, 95%CI 1.49 - 4.60). Half the population reporting a lifetime IBS diagnosis also had a lifetime mood or anxiety disorder. Exploratory analyses demonstrated an increased prevalence of IBS across most common anxiety and mood disorders, the exception being bipolar disorder. The association with IBS and symptoms load (GHQ-12) followed a curved dose response pattern. In contrast, hypertension and diabetes were consistently unrelated to psychiatric morbidity.

Conclusions IBS is significantly associated with anxiety and mood disorders. This study provides indicative evidence for IBS as a disorder with a psychosomatic aspect.

The prevalence of mood and anxiety disorders in Australian women

Objective: We aimed to report the prevalence, age-of-onset and comorbidity of mood and anxiety disorders in an age-stratified representative sample of Australian women aged 20 years and over.

Method: Mood and anxiety disorders were diagnosed utilising a clinical interview (SCID-I/NP). The lifetime and current prevalence of these disorders was determined from the study population (n = 1095) and standardized to 2006 census data for Australia.

Results: Approximately one in three women (34.8%) reported a lifetime history of any mood and/or anxiety disorder, with mood disorders (30.0%) being more prevalent than anxiety disorders (13.5%). Of these, major depression (23.4%), panic disorder (5.5%) and specific phobia (3.5%) were the most common. The lifetime prevalence of other disorders was low (≤3%). A total of 14.4% of women were identified as having a current mood and/or anxiety disorder, with similar rates of mood (8.9%) and anxiety disorders (8.0%) observed. The median age-of-onset for mood disorders was 27.0 years and 18.5 years for anxiety disorders.

Conclusions: This study reports the lifetime and current prevalence of mood and anxiety disorders in the Australian female population. The findings emphasize the extent of the burden of these disorders in the community.