TaKeTiNa Music Therapy for Outpatient Treatment of Depression: Study Protocol for a Randomized Clinical Trial.

BACKGROUND/OBJECTIVES: Depression is a prevalent and debilitating illness that significantly affects psychological and physical well-being. Apart from conventional therapies such as psychotherapy and medication, individuals with depression often lack opportunities for activities that are generally perceived as enjoyable, such as music, meditation, and arts, which have demonstrated therapeutic effectiveness. TaKeTiNa music therapy has been employed as a therapeutic intervention for more than two decades. However, there is a notable absence of well-designed clinical trials investigating its antidepressant effects, a gap we aim to address in our current study. Furthermore, shifts in the progression of depression may manifest both psychologically, by influencing emotional states, and physiologically, by leading to alterations in lipid and sphingolipid metabolism, cortisol levels, and immune system function. Our study seeks to analyze the impact of TaKeTiNa music therapy on both levels. METHODS: This is a prospective monocentric randomized waitlist-controlled clinical trial. It investigates the influence of TaKeTiNa music therapy on patients with major depression in an outpatient setting. Therefore, interested persons are randomly assigned to two groups, an intervention group or a control group, after completing a screening procedure. The intervention group starts with an eight-week TaKeTiNa music therapy intervention. The waiting group receives the same therapy program after completing the follow-up period. Blood and saliva sampling as well as responses to questionnaires are obtained at specific time points. DISCUSSION: Our study investigates the effects of TaKeTiNa music therapy, a non-pharmacological antidepressant treatment option, on depressive symptoms. We also address functional and causal immunological changes; hormonal changes, such as changes in cortisol levels; and metabolic changes, such as changes in serum lipids and sphingolipids, during the course of depression. We expect that this study will provide evidence to expand the range of treatment options available for depression.

Magnitude and determinants of excess total, age-specific and sex-specific all-cause mortality in 24 countries worldwide during 2020 and 2021: results on the impact of the COVID-19 pandemic from the C-MOR project.

INTRODUCTION: To examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age. METHODS: Total, age-specific and sex-specific weekly all-cause mortality was collected for 2015-2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015-2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models. RESULTS: Excess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively. CONCLUSION: This study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.

Peripheral Upregulation of Parkinson's Disease-Associated Genes Encoding α-Synuclein, ß-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression.

Due to the high comorbidity of Parkinson's disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we investigated the peripheral expression levels of three primarily PD-associated genes: α-synuclein (SNCA), lysosomal enzyme ß-glucocerebrosidase (GBA1), and UDP-glucose ceramide glucosyltransferase (UGCG) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated n = 63, medicated n = 66) and controls (remitted MDD n = 39, healthy subjects n = 61). We observed that expression levels of SNCA (p = 0.036), GBA1 (p = 0.014), and UGCG (p = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of GBA1 and UGCG decreased in medicated patients during three weeks of therapy. Additionally, in subgroups, expression was positively correlated with the severity of depression and anxiety. Furthermore, we identified correlations between the gene expression levels and PD-related laboratory parameters. Our findings suggest that SNCA, GBA1, and UGCG analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.

Masculine depression and its problem behaviors: use alcohol and drugs, work hard, and avoid psychiatry!

The gender role influences vulnerability to mental illness. Substance use, even critical in scale, is perceived as masculine, just like hard (over-)work, while not seeking help. With the ongoing separation between gender and sex, masculine norms become more relevant also to females' mental health. The male depression concept highlights the role of male symptoms in affective disorders. However, the empirical evidence is still limited. Here, we use the denomination 'masculine depression' to open the category for female patients and tested substance use patterns, health services' utilization, and working hours as predictors in a case-control study of 163 depressed in-patients (44% women; masculine vs. non-masculine depression according to a median split of the Male Depression Rating Scale-22) and 176 controls (51% women). We assessed higher depression severity in patients with masculine (vs. non-masculine) depression. Masculine depression (vs. non-masculine depression and vs. no depression) was predicted by more frequent and critical use of alcohol (including binge drinking), tobacco, and illicit drugs, and by longer working times. Moreover, fewer health services contacts due to mental complaints during the previous year were associated with masculine (vs. non-masculine) depression. Alarmingly, even critical substance misuse was not significantly associated with more frequent health services contacts; however, the higher the depression severity, the more contacts the patients reported. Here, we provide evidence that patients with masculine depression are highly burdened and undertreated, which applies equally to female and male patients. This study identified promising targets to establish specialized care offers.

The fearlessness about death scale's efficacy for differentiating suicide attempts from non-suicidal self-injury, a meta-analysis.

We used multivariate meta-analysis modeling variances and covariances of suicidal ideation, suicide attempts, and non-suicidal self-injury to investigate if the Fearlessness About Death scale differentiated between suicide attempts and non-suicidal self-injury. The systematic search yielded 27 studies that fulfilled the inclusion criteria. The association of suicidal ideation with suicide attempts was comparable to the association of suicidal ideation with non-suicidal self-injury. The Fearlessness About Death scale weakened both associations to a comparative degree. These results cast doubt on the clinical utility of the Fearlessness About Death scale, as well as the self-assessment of suicidal ideation, suicide attempts and non-suicidal self-injury.

Psychometric properties of the German Penn Alcohol Craving Scale.

Craving for alcohol is an important diagnostic criterion in alcohol use disorder (AUD) and an established predictor of future relapse. The 5-item Penn Alcohol Craving Scale (PACS) is one of the most widely used questionnaires to quantify craving and has been translated into different languages. It is assumed that the PACS constitutes one factor, although theoretical considerations suggest an additional second factor. We conducted stability and factor analyses (principal component and confirmatory factor analyses) of the German PACS (PACS-G) in samples of patients with AUD from the following three German study sites: Erlangen, N = 188 (mean age: 47.1 years, 43.5% female); Mannheim, N = 440 (45.5 years, 28.6% female); Hannover, N = 107 (48.1 years, 48.6% female). In our samples, the 2-factor solution of the PACS-G version is more stable than the internationally assumed 1-factor solution. The resulting two PACS-G subscores 'difficulty to resist' (items 4 and 5) and 'thoughts about alcohol' (items 1, 2, and 3) have an internal consistency (Cronbach's alpha) of 0.80 ≤ α ≤ 0.90, m = 0.86 and 0.86 ≤ α ≤ 0.91, m = 0.89 with an overlap of R2 = 62%. We found good convergent validity assessed via the Craving Automatized Scale-Alcohol and the Obsessive-Compulsive Drinking Scale, but also correlations with depression and anxiety assessed via the Beck's Depression and Anxiety Inventories. This study is the first to provide evidence for a 2-factor solution ('difficulty to resist' and 'thoughts about alcohol') underlying the PACS-G version.

Suicide mortality among physicians, dentists, veterinarians, and pharmacists as well as other high-skilled occupations in Austria from 1986 through 2020.

Some evidence puts health professionals at increased risk of suicide, especially females, whereas other research suggests a lower risk in high-skilled occupations. This study investigated the suicide risk of four health professions (physicians, dentists, veterinarians, pharmacists) and three other high-skilled occupations (notaries, lawyers, tax advisors/public accountants) in Austria compared to the general population, and analyzed suicide methods across occupations. Data was collected from professional associations and Austrian cause-of-death statistics to determine suicide cases. Gender-specific standardized mortality ratios (SMRs), crude and age-adjusted suicide rates and frequencies for suicide methods were calculated for each profession (maximum time span 1986-2020). Among males, only veterinarians had a significantly elevated suicide risk compared to the general population. Physicians and tax advisors/public accountants had a significantly lower suicide risk. Among females, the veterinarians, physicians, and pharmacists had a significantly elevated suicide risk; for dentists, it was also elevated, though non-significantly. Age-adjusted suicide rates showed a smaller gap between men and women in all professions compared to the general population. Poisoning was the predominant suicide method among health professions, except dentists. These findings are consistent with some of the prior literature and call for specific suicide prevention efforts in health professions, focusing on women.

Macrophage Migration Inhibitory Factor in Major Depressive Disorder: A Multilevel Pilot Study.

Macrophage migration inhibitory factor (MIF) is a controversially discussed inflammatory marker in major depressive disorder (MDD). While some studies show an association of high MIF protein levels with depression, animal models have yielded conflicting results. Thus, it remains elusive as to whether MIF plays an anti- or pro-depressive role. Therefore, we aimed to examine the potential of MIF at the genetic, expression and protein levels as a risk factor and biomarker to diagnose, monitor, or predict the course of MDD. Patients with a current major depressive episode (n = 66 with, and n = 63 without, prior medication) and remitted patients (n = 39) were compared with healthy controls (n = 61). Currently depressed patients provided a second blood sample after three weeks of therapy. Depression severity was assessed by self-evaluation and clinician rating scales. We genotyped for three MIF polymorphisms and analyzed peripheral MIF expression and serum levels. The absence of minor allele homozygous individuals in the large group of 96 female patients compared with 10-16% in female controls suggests a protective effect for MDD, which was not observed in the male group. There were no significant group differences of protein and expression levels, however, both showed predictive potential for the course of depression severity in some subgroups. While MIF protein levels, but not MIF expression, decreased during treatment, they were not associated with changes in depression severity. This project is the first to investigate three biological levels of MIF in depression. The data hint toward a genetic effect in women, but do not provide robust evidence for the utility of MIF as a biomarker for the diagnosis or monitoring of MDD. The observed predictive potential requires further analysis, emphasizing future attention to confounding factors such as sex and premedication.

Elevated Oxytocin Receptor Blood Concentrations Predict Higher Risk for, More, and Earlier 24-Month Hospital Readmissions after In-Patient Detoxification in Males with Alcohol Use Disorder.

Alcohol use disorder (AUD) is a major global mental health challenge. Knowledge concerning mechanisms underlying AUD and predictive biomarkers of AUD progression and relapse are insufficient. Recently, addiction research is focusing attention on the oxytocin system. However, to our knowledge, blood concentrations of the oxytocin receptor (OXTR) have not yet been studied in AUD. Here, in sex-separated analyses, OXTR serum concentrations were compared between early-abstinent in-patients with AUD (113 men, 87 women) and age-matched healthy controls (133 men, 107 women). The OXTR concentrations were correlated with sex hormone and oxytocin concentrations and alcohol-related hospital readmissions during a 24-month follow-up. In male patients with AUD, higher OXTR concentrations were found in those with an alcohol-related readmission than in those without (143%; p = 0.004), and they correlated with more prospective readmissions (ρ = 0.249; p = 0.008) and fewer days to the first readmission (ρ = -0.268; p = 0.004). In men and women, OXTR concentrations did not significantly differ between patients with AUD and controls. We found lower OXTR concentrations in smokers versus non-smokers in female patients (61%; p = 0.001) and controls (51%; p = 0.003). In controls, OXTR concentrations correlated with dihydrotestosterone (men, ρ = 0.189; p = 0.030) and testosterone concentrations (women, ρ = 0.281; p = 0.003). This clinical study provides novel insight into the role of serum OXTR levels in AUD. Future studies are encouraged to add to the available knowledge and investigate clinical implications of OXTR blood concentrations.

Bioimpedance Body Measures and Serum Lipid Levels in Masculine Depression.

Background: Major depressive disorder (MDD) is a main reason for suicide, and serum lipids are involved in both affective disorders and related suicidal behavior. Moreover, masculine depression has been suggested as a subtype of depression with an increased risk for suicide. Here, we studied the relationship between body measures, serum lipids, suicidal thoughts, and masculine depression. Methods: Depressed patients (44% women) were divided by a sex-separated median-split into a group of 81 "patients with masculine depression" (mean age ± standard error: 36.4 ± 1.6 years) and a group of 82 "patients with non-masculine depression" (age 45.7 ± 1.6 years) according to the Male Depression Risk Scale. We compared body measures, serum lipid levels, and past suicidal ideation between these groups and explored differences between these groups and 176 healthy controls (51% women; age 37.2 ± 1.0 years). Results: Patients with masculine depression did not significantly differ from patients with non-masculine depression in any of the body measures, lipid markers, or suicidal thoughts. Compared to healthy controls, both patient groups showed significantly higher body fat (B[masculine depression] = 0.041 and B[non-masculine depression] = 0.050), lower high-density lipoprotein (HDL) cholesterol (B = -0.045 and -0.044), and a higher risk for suicidal thoughts (B = 3.927 and 2.663) than healthy controls. Suicidal thoughts were significantly associated with lower low-density lipoprotein (LDL)/HDL ratios (B = -0.455) in patients with depression and with higher LDL cholesterol levels (B = 0.020) in healthy controls subjects. Limitation: Correlational study design and focus on in-patients. Conclusion: In the studied cohort, masculine depression was not significantly associated with the analyzed parameters of body measures, serum lipids, or suicidal thoughts in in-patients with depression.

Sulphated dehydroepiandrosterone serum levels are reduced in women with alcohol use disorder and correlate negatively with craving: A sex-separated cross-sectional and longitudinal study.

Previous studies have established a role of sex hormones in alcohol use disorder (AUD).Only few clinical investigations with low numbers of patients with AUD have focused on the sulphated form of dehydroepiandrosterone (DHEA-S), despite its function as a neuromodulating sex steroid on receptors in the central nervous system (γ-aminobutyric acid type A, N-methyl-D-aspartate, sigma-1 receptors). DHEA-S serum levels were compared between 200 inpatients with AUD (44% women) admitted for withdrawal treatment and 240 healthy controls (45% women) and analysed longitudinally in patients from early abstinence (baseline) to a median of 5 days later. We also correlated DHEA-S levels with craving, liver enzyme activities, and prospective alcohol-related readmissions during a 24-month follow-up. DHEA-S concentrations were lower in female patients than in female healthy controls during baseline (70%) and decreased from baseline to follow-up in the female and male patients groups (down to: women, 92%; men, 76%). Baseline DHEA-S concentrations correlated with the total and obsessive subscales of the Obsessive-Compulsive Drinking Scale and with maximum visual analogue scale craving scores in female patients (Rho ≤ -0.240) and gamma-glutamyl transferase activity in female (Rho = -0.292) and male (Rho = -0.391) patients. DHEA-S did not significantly predict outcome. We found interactions with smoking behaviour and age. This is the first study based on large cohorts of inpatients with AUD undergoing a qualified detoxification treatment to provide sex-separated evidence for associations of DHEA-S serum concentrations with AUD and related phenotypes. The results stimulate further investigations whether DHEA-S directly influences alcohol craving building a basis to develop sex-sensitive prevention and treatment strategies.

Excess all-cause mortality and COVID-19-related mortality: a temporal analysis in 22 countries, from January until August 2020.

BACKGROUND: This study aimed to investigate overall and sex-specific excess all-cause mortality since the inception of the COVID-19 pandemic until August 2020 among 22 countries. METHODS: Countries reported weekly or monthly all-cause mortality from January 2015 until the end of June or August 2020. Weekly or monthly COVID-19 deaths were reported for 2020. Excess mortality for 2020 was calculated by comparing weekly or monthly 2020 mortality (observed deaths) against a baseline mortality obtained from 2015-2019 data for the same week or month using two methods: (i) difference in observed mortality rates between 2020 and the 2015-2019 average and (ii) difference between observed and expected 2020 deaths. RESULTS: Brazil, France, Italy, Spain, Sweden, the UK (England, Wales, Northern Ireland and Scotland) and the USA demonstrated excess all-cause mortality, whereas Australia, Denmark and Georgia experienced a decrease in all-cause mortality. Israel, Ukraine and Ireland demonstrated sex-specific changes in all-cause mortality. CONCLUSIONS: All-cause mortality up to August 2020 was higher than in previous years in some, but not all, participating countries. Geographical location and seasonality of each country, as well as the prompt application of high-stringency control measures, may explain the observed variability in mortality changes.

mRNA Expression of SMPD1 Encoding Acid Sphingomyelinase Decreases upon Antidepressant Treatment.

Major depressive disorder (MDD) is a severe psychiatric condition with key symptoms of low mood and lack of motivation, joy, and pleasure. Recently, the acid sphingomyelinase (ASM)/ceramide system has been implicated in the pathogenesis of MDD. ASM is a lysosomal glycoprotein that catalyzes the hydrolysis of sphingomyelin, an abundant component of membranes, into the bioactive sphingolipid ceramide, which impacts signaling pathways. ASM activity is inhibited by several common antidepressant drugs. Human and murine studies have confirmed that increased ASM activity and ceramide levels are correlated with MDD. To define a molecular marker for treatment monitoring, we investigated the mRNA expression of SMPD1, which encodes ASM, in primary cell culture models, a mouse study, and a human study with untreated MDD patients before and after antidepressive treatment. Our cell culture study showed that a common antidepressant inhibited ASM activity at the enzymatic level and also at the transcriptional level. In a genetically modified mouse line with depressive-like behavior, Smpd1 mRNA expression in dorsal hippocampal tissue was significantly decreased after treatment with a common antidepressant. The large human study showed that SMPD1 mRNA expression in untreated MDD patients decreased significantly after antidepressive treatment. This translational study shows that SMPD1 mRNA expression could serve as a molecular marker for treatment and adherence monitoring of MDD.

Sleep apnoea and incident malignancy in type 2 diabetes.

BACKGROUND: Sleep apnoea and type 2 diabetes (T2D) have been linked to malignancy. The aim of the present study was to evaluate the association between sleep apnoea and incidence of malignancy in patients with T2D. METHODS: The DIACORE (DIAbetes COhoRtE) study is a prospective, population-based cohort study in T2D patients. In the sleep disordered breathing substudy, the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and percentage of night-time spent with a peripheral oxygen saturation of <90% (t sat90%) were assessed using a two-channel ambulatory monitoring device. Malignancy diagnoses were gathered using self-reported medical history data validated by medical records. Hazard ratios (HRs) for incident malignancy were derived by Cox regression adjusting for sex, age, body mass index, smoking status, alcohol intake, socioeconomic status and HbA1c. RESULTS: Of 1239 patients with T2D (mean age 67 years, 41% female, mean body mass index 30.9 kg·m-2), 79 (6.4%) were first-time diagnosed with a malignancy within a median follow-up period of 2.7 years (interquartile range 2.2-4.5 years). AHI, ODI and t sat90% were not associated with incident malignancy. In subgroup analysis, females showed increased cancer risk per AHI unit (adjusted HR 1.03 per AHI unit, 95% CI 1.00-1.06; p=0.028) and severe sleep apnoea (defined as AHI ≥30 events·h-1; adjusted HR 4.19, 95% CI 1.39-12.77; p=0.012). This was not seen in males, and a significant interaction was observed (interaction terms p=0.048 and p=0.033, respectively). CONCLUSION: Sleep apnoea was not associated with incident malignancy in T2D patients. However, stratified analysis revealed a significant association between sleep apnoea and incident malignancy in females, but not in males.

Ex vivo glucocorticoid receptor-mediated IL-10 response predicts the course of depression severity.

Directly measuring hypothalamic pituitary adrenal (HPA) axis function, an important player in affective disorders, is intensive and invasive. A crucial component of this system, the activity of the glucocorticoid receptor (GR), can be assessed ex vivo instead. Here, we investigated GR sensitivity in patients with major depressive disorder (MDD) to determine its predictive potential. Psychometric data and blood samples were collected from patients experiencing a major depressive episode (MDE, n = 87), healthy control subjects (n = 49), and patients with remitted MDD (n = 31) at baseline and (for patients) after median 20 days of follow-up after treatment as usual. Blood cells were stimulated ex vivo with lipopolysaccharide and the effect was suppressed by increasing dexamethasone (DEX) concentrations. The resultant cytokine secretion profile (for IL-6, IL-10, and TNF-α) was considered indicative of GR activity. Higher baseline scores of the Montgomery-Åsberg Depression Rating Scale (MADRS) were associated with a stronger decrease of logIC IL-6 (indicating an increase of GR sensitivity). Higher baseline logEC IL-10 (indicating a lower GR sensitivity) and a stronger reduction of logEC IL-10 (indicating a stronger increase in GR sensitivity) were associated with a stronger decrease in the MADRS score. Patients with remitted MDD showed higher logIC TNF-α values (indicating lower GR sensitivity) in comparison to patients with a current MDD at baseline and follow-up. Initially low GR sensitivity measured ex vivo in peripheral blood cells that increases over the course of treatment could serve as a predictive marker for stronger improvement in depression severity.

A Rare Case of Vascular Proliferation in the Mandible of a Juvenile Horse.

A fast growing, circumscribed, unilateral swelling of the right mandible of a juvenile horse was observed. Within few weeks, the continuously growing mass reached dimensions ranging from 7 to 10 cm in diameter and resulted in loss of the first deciduous premolar of the affected side. The animal was euthanized due to lesion progression. Histologically the mandibular swelling consisted of numerous variably sized vascular structures, partly filled with erythrocytes and embedded in a loosely arranged fibrous stroma within the medullary cavity of the mandible. Juvenile mandibular angiomatosis was diagnosed. To the authors' knowledge this is the first description of this rare entity in the mandible of a foal.

Physical Activity and Body Composition Are Associated With Severity and Risk of Depression, and Serum Lipids.

BACKGROUND: Physical activity and a healthy body composition are said to reduce the risk of major depressive disorder. Nonetheless, deeper insight is needed into which specific forms of physical activity (and their relation to body composition) are effective in improving and preventing depressive symptoms. METHODS: We compared different self-reported physical activities of the Global Physical Activity Questionnaire and body composition measures between patients with a current major depressive episode (MDE; N = 130) and healthy control subjects (N = 61). These parameters were also tested for correlations with depression severity and serum lipid levels in patients and controls. RESULTS: Patients with a current MDE reported significantly fewer hours spent on total physical activity, walking or bicycling for travel, and vigorous-intensity activities at leisure than healthy control subjects. More time spent on vigorous-intensity activities at work, less time spent on walking or bicycling for travel, higher body fat mass, and lower body muscle mass correlated significantly with stronger depression severity. Physical activity and body measures correlated significantly with serum lipid levels. LIMITATIONS: Self-reports of physical activity, only short-term follow-up of 20 days, cross-sectional study design without examination of causal role of exercise. CONCLUSIONS: More time spent on traveling by foot or by bike is especially associated with a lower risk of and milder depression. These results highlight the differential role of physical activity in depression.

Histological characterization and biochemical analysis of paraspinal muscles in neuromuscularly healthy subjects.

INTRODUCTION: There are no generally accepted histopathological reference values in paraspinal skeletal muscle biopsies. METHODS: We examined multifidii muscle biopsies from 20 neuromuscularly healthy subjects using routine histological stains and biochemical analyses of respiratory chain enzymes. RESULTS: Staining showed incomplete myopathic features, such as increased variability in fiber size, type 1 hypertrophy, rounded fiber shape, endomysial fibrosis, and replacement by adipose tissue. Acid phosphatase reaction was positive in up to 35% of the selected muscle fibers. Mitochondrial changes were obvious but revealed no selective age dependence. Reduced complex I, cytochrome c oxidase (COX), and citrate synthase (CS) could be observed. CONCLUSIONS: Because the increased variability in morphological details can easily be misinterpreted as myopathic changes, analysis of paraspinal muscles should take into consideration that incomplete myopathic features and reduced oxidative enzyme activities for complex I, COX, and CS are normal variations at this location.

Dopamine D(3) receptors and salt-dependent hypertension.

Alterations in the dopaminergic system may contribute to the pathogenesis of hypertension. Dopamine D(3) receptors have been shown to be involved in the regulation of sodium balance and hemodynamics in rodents. For determining the role of D(3) receptors in salt-dependent hypertension, clearance experiments were performed in anesthetized salt-sensitive (DS) and salt-resistant (DR) Dahl rats that were fed a standard diet with either normal (0.2%) or high (4%) sodium content for 21 to 26 d, which induced hypertension in DS but not in DR rats. The D(3) receptor agonist R(+)-7-hydroxydipropyl-aminotetralin (7-OH-DPAT) increased GFR by up to 35% and urinary sodium excretion by up to 4.4-fold in DR rats that were on both normal and high-sodium diet. 7-OH-DPAT-induced natriuresis also was observed in DS rats that were on normal diet but not in hypertensive DS rats that were on high-salt diet. No GFR response to 7-OH-DPAT was found in DS rats, irrespective of sodium diet. The diminished functional response to D(3) receptor stimulation in DS rats was associated with a significantly lower [(3)H]-7-OH-DPAT binding to renal membrane protein when comparing DS with DR rats. Consequently, DR rats were treated with BSF 135170, a novel, highly selective D(3) receptor antagonist, for 29 d. Whereas no change in systolic BP was observed during normal diet, high sodium intake significantly increased BP by almost 40 mmHg. In summary, both expression and function of the renal dopamine D(3) receptor are impaired in salt-sensitive Dahl rats. Together with the induction of salt-dependent hypertension in genetically salt-resistant Dahl rats by D(3) receptor blockade, the data strongly suggest that the deficiency in dopamine D(3) receptors represents an important pathophysiological factor in the development of salt-dependent hypertension.