Dopamine receptor 3: A mystery at the heart of cardiac fibrosis.

Dopamine receptors have been extensively studied in the mammalian brain and spinal cord, as dopamine is a vital determinant of bodily movement, cognition, and overall behavior. Thus, dopamine receptor antagonist antipsychotic drugs are commonly used to treat multiple psychiatric disorders. Although less discussed, these receptors are also expressed in other peripheral organ systems, such as the kidneys, eyes, gastrointestinal tract, and cardiac tissue. Consequently, therapies for certain psychiatric disorders which target dopamine receptors could have unidentified consequences on certain functions of these peripheral tissues. The existence of an intrinsic dopaminergic system in the human heart remains controversial and debated within the literature. Therefore, this review focuses on literature related to dopamine receptors within cardiac tissue, specifically dopamine receptor 3 (D3R), and summarizes the current state of knowledge while highlighting areas of research which may be lacking. Additionally, recent findings regarding crosstalk between D3R and dopamine receptor 1 (D1R) are examined. This review discusses the novel concept of understanding the role of the loss of function of D3R may play in collagen accumulation and cardiac fibrosis, eventually leading to heart failure.

Loss of Function in Dopamine D3 Receptor Attenuates Left Ventricular Cardiac Fibroblast Migration and Proliferation in vitro.

Evidence suggests the existence of an intracardiac dopaminergic system that plays a pivotal role in regulating cardiac function and fibrosis through G-protein coupled receptors, particularly mediated by dopamine receptor 3 (D3R). However, the expression of dopamine receptors in cardiac tissue and their role in cardiac fibroblast function is unclear. In this brief report, first we determined expression of D1R and D3R both in left ventricle (LV) tissue and fibroblasts. Then, we explored the role of D3R in the proliferation and migration of fibroblast cell cultures using both genetic and pharmaceutical approaches; specifically, we compared cardiac fibroblasts isolated from LV of wild type (WT) and D3R knockout (D3KO) mice in response to D3R-specific pharmacological agents. Finally, we determined if loss of D3R function could significantly alter LV fibroblast expression of collagen types I (Col1a1) and III (Col3a1). Cardiac fibroblast proliferation was attenuated in D3KO cells, mimicking the behavior of WT cardiac fibroblasts treated with D3R antagonist. In response to scratch injury, WT cardiac fibroblasts treated with the D3R agonist, pramipexole, displayed enhanced migration compared to control WT and D3KO cells. Loss of function in D3R resulted in attenuation of both proliferation and migration in response to scratch injury, and significantly increased the expression of Col3a1 in LV fibroblasts. These findings suggest that D3R may mediate cardiac fibroblast function during the wound healing response. To our knowledge this is the first report of D3R's expression and functional significance directly in mouse cardiac fibroblasts.

Development and preliminary evaluation of a group intervention targeting maternal mental health and mother-infant interactions: a combined qualitative and case series report.

OBJECTIVE AND BACKGROUND: The purpose of this study was to investigate the outcomes of an Emotional Wellbeing Group intervention developed to treat maternal depression and anxiety while concurrently supporting positive development of the mother-infant relationship. METHOD: Five women diagnosed with depressive and/or anxiety disorders and their infants completed the Emotional Wellbeing Group. The participants completed pre- and post- intervention assessments which included self-report measures of mood and the motherhood experience, and a video-taped, unstructured play session between mothers and their infants. RESULTS: Four of the participants reported a clinically significant decrease in their symptoms of anxiety. All mothers reported more positive perceptions of their infants and their experience of motherhood, and showed enhanced maternal sensitivity and responsiveness towards their infants. Depression levels were not shown to improve consistently. CONCLUSION: This study provides initial positive evidence to support future research directions and clinical efforts to develop interventions that target both the treatment of perinatal depression and anxiety and the quality of mother-infant interactions. Clinical insights for mental health professionals working with mothers and infants are presented.

Detecting the severity of perinatal anxiety with the Perinatal Anxiety Screening Scale (PASS).

BACKGROUND: The Perinatal Anxiety Screening Scale (PASS; Somerville et al., 2014) reliably identifies perinatal women at risk of problematic anxiety when a clinical cut-off score of 26 is used. This study aimed to identify a severity continuum of anxiety symptoms with the PASS to enhance screening, treatment and research for perinatal anxiety. METHODS: Antenatal and postnatal women (n=410) recruited from the antenatal clinics and mental health services at an obstetric hospital completed the Edinburgh Postnatal Depression Scale (EPDS), the Depression, Anxiety and Stress Scale (DASS-21), the Spielberg State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory II (BDI), and the PASS. The women referred to mental health services were assessed to determine anxiety diagnoses via a diagnostic interview conducted by an experienced mental health professional from the Department of Psychological Medicine - King Edward Memorial Hospital. Three normative groups for the PASS, namely minimal anxiety, mild-moderate anxiety, and severe anxiety, were identified based on the severity of anxiety indicated on the standardised scales and anxiety diagnoses. RESULTS: Two cut-off points for the normative groups were calculated using the Jacobson-Truax method (Jacobson and Truax, 1991) resulting in three severity ranges: 'minimal anxiety'; 'mild-moderate anxiety'; and 'severe anxiety'. LIMITATIONS: The most frequent diagnoses in the study sample were adjustment disorder, mixed anxiety and depression, generalised anxiety, and post-traumatic stress disorder. This may limit the generalisability of the severity range results to other anxiety diagnoses including obsessive compulsive disorder and specific phobia. CONCLUSIONS: Severity ranges for the PASS add value to having a clinically validated cut-off score in the detection and monitoring of problematic perinatal anxiety. The PASS can now be used to identify risk of an anxiety disorder and the severity ranges can indicate developing risk for early referrals for further assessments, prioritisation of access to resources and tracking of clinically significant deterioration, improvement or stability in anxiety over time.

Reinforcing adherence to antihypertensive medications.

This pilot study evaluated a reinforcement intervention to improve adherence to antihypertensive therapy. Twenty-nine participants were randomized to standard care or standard care plus financial reinforcement for 12 weeks. Participants in the reinforcement group received a cell phone to self-record videos of adherence, for which they earned rewards. These participants sent videos demonstrating on-time adherence 97.8% of the time. Pill count adherence differed significantly between the groups during treatment, with 98.8%±1.5% of pills taken during treatment in the reinforcement condition vs 92.6%±9.2% in standard care (P<.002). Benefits persisted throughout a 3-month follow-up, with 93.8%±9.3% vs 78.0%±18.5% of pills taken (P<.001). Pill counts correlated significantly (P<.001) with self-reports of adherence, which also differed between groups over time (P<.01). Systolic blood pressure decreased modestly over time in participants overall (P<.01) but without significant time-by-group effects. These results suggest that reinforcing medication adherence via cellular phone technology and financial reinforcement holds potential to improve adherence.

The Perinatal Anxiety Screening Scale: development and preliminary validation.

The purpose of this study is to develop a scale (Perinatal Anxiety Screening Scale, PASS) to screen for a broad range of problematic anxiety symptoms which is sensitive to how anxiety presents in perinatal women and is suitable to use in a variety of settings including antenatal clinics, inpatient and outpatient hospital and mental health treatment settings. Women who attended a tertiary obstetric hospital in the state of Western Australia antenatally or postpartum (n = 437) completed the PASS and other commonly used measures of depression and anxiety. Factor analysis was used to examine factor structure, and ROC analysis was used to evaluate performance as a screening tool. The PASS was significantly correlated with other measures of depression and anxiety. Principal component analyses (PCA) suggested a four-factor structure addressing symptoms of (1) acute anxiety and adjustment, (2) general worry and specific fears, (3) perfectionism, control and trauma and (4) social anxiety. The four subscales and total scale demonstrated high to excellent reliabilities. At the optimal cutoff score for detecting anxiety as determined by ROC analyses, the PASS identified 68 % of women with a diagnosed anxiety disorder. This was compared to the EPDS anxiety subscale which detected 36 % of anxiety disorders. The PASS is an acceptable, valid and useful screening tool for the identification of risk of significant anxiety in women in the perinatal period.

A randomized study of reinforcing ambulatory exercise in older adults.

Many older adults do not meet physical activity recommendations and suffer from health-related complications. Reinforcement interventions can have pronounced effects on promoting behavior change; this study evaluated the efficacy of a reinforcement intervention to enhance walking in older adults. Forty-five sedentary adults with mild to moderate hypertension were randomized to 12-week interventions consisting of pedometers and guidelines to walk 10,000 steps/day or that same intervention with chances to win $1-$100 prizes for meeting recommendations. Patients walked an average of about 4,000 steps/day at baseline. Throughout the intervention, participants in the reinforcement intervention met walking goals on 82.5% ± 25.8% of days versus 55.3% ± 37.1% of days in the control condition, p < .01. Even though steps walked increased significantly in both groups relative to baseline, participants in the reinforcement condition walked an average of about 2,000 more steps/day than participants in the control condition, p < .02. Beneficial effects of the reinforcement condition relative to the control condition persisted at a 24-week follow-up evaluation, p < .02, although steps/day were lower than during the intervention period in both groups. Participants in the reinforcement intervention also evidenced greater reductions in blood pressure and weight over time and improvements in fitness indices, ps < .05. This reinforcement-based intervention substantially increased walking and improved clinical parameters, suggesting that larger-scale evaluations of reinforcement-based interventions for enhancing active lifestyles in older adults are warranted. Ultimately, economic analyses may reveal reinforcement interventions to be cost-effective, especially in high-risk populations of older adults.

Antisocial personality disorder is associated with receipt of physical disability benefits in substance abuse treatment patients.

BACKGROUND: Opioid dependence is growing at an alarming rate in the United States, and opioid dependent patients have substantial medical, as well as psychiatric, conditions that impact their ability to work. This study evaluated the association between antisocial personality disorder (ASPD) and receipt of physical disability payments in methadone maintenance patients. METHODS: Using data from 115 drug and alcohol abusing methadone maintained patients participating in two clinical trials, baseline characteristics of individuals receiving (n=22) and those not receiving (n=93) physical disability benefits were compared, and a logistic regression evaluated unique predictors of disability status. RESULTS: Both an ASPD diagnosis and severity of medical problems were significant predictors of disability receipt, ps<.05. After controlling for other variables that differed between groups, patients with ASPD were more than five times likelier to receive physical disability benefits than patients without ASPD (odds ratio=5.66; 95% confidence interval=1.58-20.28). CONCLUSIONS: These results demonstrate a role of ASPD in the receipt of disability benefits in substance abusers and suggest the need for greater understanding of the reasons for high rates of physical disability benefits in this population.

Reliability and validity of the Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) in patients with drug and alcohol use disorders.

Human Immunodeficiency Virus (HIV) and substance use disorders can both significantly impact a patient's quality of life (QOL), and it is, therefore, important to assess QOL throughout treatments for these chronic conditions. This study evaluated the psychometric properties of the Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) in 170 HIV-positive patients who participated in a substance abuse treatment study. Internal consistency of the FAHI was good. Convergent and discriminant validity were generally supported with comparisons to other patient-reported measures. FAHI scores were not significantly associated with viral loads or CD4 counts, and they were similar in patients with and without AIDS. Patients who achieved longer durations of drug and alcohol abstinence during treatment reported better QOL post-treatment. The FAHI appears to be a reliable and valid measure for assessing QOL in HIV-positive patients with concurrent drug and alcohol use disorders.

Financial reinforcers for improving medication adherence: findings from a meta-analysis.

BACKGROUND: Increasingly, financial reinforcement interventions based on behavioral economic principles are being applied in health care settings, and this study examined the use of financial reinforcers for enhancing adherence to medications. METHODS: Electronic databases and bibliographies of relevant references were searched, and a meta-analysis of identified trials was conducted. The variability in effect size and the impact of potential moderators (study design, duration of intervention, magnitude of reinforcement, and frequency of reinforcement) on effect size were examined. RESULTS: Fifteen randomized studies and 6 nonrandomized studies examined the efficacy of financial reinforcement interventions for medication adherence. Financial reinforcers were applied for adherence to medications for tuberculosis, substance abuse, human immunodeficiency virus, hepatitis, schizophrenia, and stroke prevention. Reinforcement interventions significantly improved adherence relative to control conditions with an overall effect size of 0.77 (95% confidence interval, 0.70-0.84; P<.001). Nonrandomized studies had a larger average effect size than randomized studies, but the effect size of randomized studies remained significant at 0.44 (95% confidence interval, 0.35-0.53; P<.001). Interventions that were longer in duration, provided an average reinforcement of $50 or more per week, and reinforced patients at least weekly resulted in larger effect sizes than those that were shorter, provided lower reinforcers, and reinforced patients less frequently. CONCLUSION: These results demonstrate the efficacy of medication adherence interventions and underscore principles that should be considered in designing future adherence interventions. Financial reinforcement interventions hold potential for improving medication adherence and may lead to benefits for both patients and society.

Readmission to psychiatric hospital after treatment for depression with electroconvulsive therapy: the effect of planned readmissions.

OBJECTIVES: To assess the effect of planned readmissions on readmission risk for electroconvulsive therapy (ECT)-treated patients. METHODS: A naturalistic historical study compared the readmission risk for depressed ECT-treated patients to depressed patients not treated with ECT while accounting for planned readmissions. RESULTS: Initial analyses revealed that ECT-treated patients were at greater risk of readmission compared to patients not treated with ECT. However, after accounting for planned readmissions, these differences became nonsignificant. LIMITATIONS: Only readmissions to a single psychiatric hospital were examined. Therefore, these data may underestimate readmission rates. CONCLUSIONS: Not accounting for planned readmissions may lead to overestimations of negative outcome.

The effects of progress monitoring on subsequent readmission to psychiatric care: a six-month follow-up.

BACKGROUND: Monitoring patient progress and providing feedback to clinicians and patients about progress during therapy reduce depressive symptoms at treatment completion. However, the effects of feedback on patient outcomes following treatment completion are unknown. Accordingly, the current study aimed to examine the effect of feedback on readmission to psychiatric hospital following completion of a group psychotherapy program. METHOD: This naturalistic historical follow-up study compared the risk of readmission to a psychiatric hospital for two patient cohorts examined by Newnham et al. (2010a,b); the first cohort received feedback (n=408) during a group psychotherapy program, whereas the second cohort did not receive feedback (n=439). The sample included inpatients and day patients, with primarily depressive and anxiety disorders who routinely completed the World Health Organization's Wellbeing Index. RESULTS: Feedback was associated with fewer readmissions over the six months following completion of the therapy program for patients who, at the point of feedback, were on track to make clinically meaningful improvement by treatment termination. DISCUSSION: The findings suggest feedback could result in cost saving and is associated with improved outcomes following treatment completion for patients deemed on track during therapy.

Predictors of weight loss success. Exercise vs. dietary self-efficacy and treatment attendance.

Pre-treatment diet and exercise self-efficacies can predict weight loss success. Changes in diet self-efficacy across treatment appear to be even stronger predictors than baseline levels, but research on changes in exercise self-efficacy is lacking. Using data from a pilot study evaluating tangible reinforcement for weight loss (N=30), we examined the impact of changes in diet and exercise self-efficacy on outcomes. Multiple regression analyses indicated that treatment attendance and changes in exercise self-efficacy during treatment were the strongest predictors of weight loss. Developing weight loss programs that foster the development of exercise self-efficacy may enhance participants' success.

Mindfulness training for smoking cessation: results from a randomized controlled trial.

BACKGROUND: Cigarette smoking is the leading cause of preventable death in the world, and long-term abstinence rates remain modest. Mindfulness training (MT) has begun to show benefits in a number of psychiatric disorders, including depression, anxiety and more recently, in addictions. However, MT has not been evaluated for smoking cessation through randomized clinical trials. METHODS: 88 treatment-seeking, nicotine-dependent adults who were smoking an average of 20cigarettes/day were randomly assigned to receive MT or the American Lung Association's freedom from smoking (FFS) treatment. Both treatments were delivered twice weekly over 4 weeks (eight sessions total) in a group format. The primary outcomes were expired-air carbon monoxide-confirmed 7-day point prevalence abstinence and number of cigarettes/day at the end of the 4-week treatment and at a follow-up interview at week 17. RESULTS: 88% of individuals received MT and 84% of individuals received FFS completed treatment. Compared to those randomized to the FFS intervention, individuals who received MT showed a greater rate of reduction in cigarette use during treatment and maintained these gains during follow-up (F=11.11, p=.001). They also exhibited a trend toward greater point prevalence abstinence rate at the end of treatment (36% vs. 15%, p=.063), which was significant at the 17-week follow-up (31% vs. 6%, p=.012). CONCLUSIONS: This initial trial of mindfulness training may confer benefits greater than those associated with current standard treatments for smoking cessation.

Concurrent alcohol dependence among methadone-maintained cocaine abusers is associated with greater abstinence.

Concurrent alcohol dependence (AD) among polysubstance abusers has been associated with negative consequences, although it may not necessarily lead to poor treatment outcomes. One of the most efficacious treatments for cocaine abuse is contingency management (CM), but little research has explored the impact of AD on abstinence outcomes, particularly among patients in methadone maintenance. Using data from three trials of CM for cocaine use, we compared baseline characteristics and posttreatment and follow-up cocaine outcomes between methadone-maintained, cocaine-dependent patients (N = 193) with and without concurrent AD, randomized to standard care (SC) with or without CM. Patients with and without concurrent AD had similar baseline characteristics, with the exception that AD patients reported more alcohol use. AD patients achieved longer durations of cocaine abstinence and were more likely to submit a cocaine-negative sample at follow-up than non-AD patients. Patients randomized to CM achieved better outcomes than those randomized to SC, but there was no interaction between treatment condition and AD status. These findings suggest that cocaine-using methadone patients with AD achieve greater cocaine abstinence than their non-AD counterparts and should not necessarily be viewed as more difficult to treat.

Readmission: a useful indicator of the quality of inpatient psychiatric care.

BACKGROUND: The literature is unclear regarding the relationship between hospital outcome (i.e., symptom improvement during a hospital admission) and readmission, questioning the validity of readmission as an indicator of the quality of the previous hospitalization. Thus, the present aim was to examine if hospital outcome is a predictor of readmission and identify the factors that may mask any effects. METHODS: A naturalistic historical study compared the predictors of readmission over the 30 days, 6 months and 5 years following discharge for first-ever admitted inpatients with depression (n=478) to all inpatients regardless of prior hospitalisations and current diagnoses (n=1177). RESULTS: Hospital outcome, as indicated by changes from admission to discharge in scores on symptom measures, during both first-ever admissions and admissions which are not the first, predicted readmissions over all time periods for all patients, not only those with depression. However, this finding was only significant when hospital outcome was assessed by improvements on a patient-reported symptom measure, and not a clinician-rated measure. LIMITATIONS: The sample included inpatients treated at a private psychiatric hospital and therefore it is unknown if these findings can be generalised to patients treated in a public system. CONCLUSIONS: These findings support that readmission may be a useful indicator of the quality of the previous hospitalization.

Food cues in children's television programs.

We examined the nutritional content of and characters' attitudes toward foods depicted in Public Broadcasting System (PBS) television programs aimed at children under age 5. Two-hundred and forty-five episodes from 10 programs were rated, totaling 136 h. There was almost twice the total airtime for depictions of unhealthy (321.03 min) versus healthy (184.72 min) foods, and significantly higher ratings for excessive consumption and valuing (characters' expressions of endorsement) of unhealthy versus healthy foods. Unhealthy foods were shown being valued significantly more than they were shown resulting in negative consequences. Our findings suggest concern for how foods are presented on children's television programs.

The use of an escape contingency and a token economy to increase food acceptance.

Escape (termination of a meal) and token-based differential reinforcement of alternative behavior were used as reinforcement to increase acceptance of food. Using a changing criterion design, the number of bites accepted and consumed was gradually increased to 15 bites per meal. These data suggest that, in some cases, escape may be a potent reinforcer for food acceptance.