Social inequalities in patient-reported outcomes among older multimorbid patients--results of the MultiCare cohort study.

Introduction: In this article three research questions are addressed: (1) Is there an association between socioeconomic status (SES) and patient-reported outcomes in a cohort of multimorbid patients? (2) Does the association vary according to SES indicator used (income, education, occupational position)? (3) Can the association between SES and patient-reported outcomes (self-rated health, health-related quality of life and functional status) be (partly) explained by burden of disease?

Methods: Analyses are based on the MultiCare Cohort Study, a German multicentre, prospective, observational cohort study of multimorbid patients from general practice. We analysed baseline data and data from the first follow-up after 15 months (N = 2,729). To assess burden of disease we used the patients' morbidity data from standardized general practitioner (GP) interviews based on a list of 46 groups of chronic conditions including the GP's severity rating of each chronic condition ranging from marginal to very severe.

Agreement between self-reported and general practitioner-reported chronic conditions among multimorbid patients in primary care - results of the MultiCare Cohort Study.

Background: Multimorbidity is a common phenomenon in primary care. Until now, no clinical guidelines for multimorbidity exist. For the development of these guidelines, it is necessary to know whether or not patients are aware of their diseases and to what extent they agree with their doctor.

A comparative study demonstrated that prevalence figures on multimorbidity require cautious interpretation when drawn from a single database.

Objective: We investigated the degree of comparability of the prevalence of chronic diseases and disease combinations in the elderly in two databases comparable with regard to diseases included, sex and age of the patients (65-85 years), and cutoff score for case definition.

Study Design And Setting: One study is based on chart-supported interviews with the primary care physicians within a cohort study of 3,189 multimorbid elderly patients. The second study analyzed claims data from ambulatory care delivered to the multimorbid members of one German Health Insurance (n = 70,031).

Association of amygdala volumes with cortisol secretion in unipolar depressed patients.

Major depressive disorder (MDD) is accompanied by morphological changes of brain structures which are of great importance in the neural circuitry mediating depression like the hippocampus and the amygdala. Hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA) system resulting in enhanced glucocorticoid secretion can often be observed during depression and has been thought to play an important role in inducing these morphological changes. We used magnetic resonance imaging to investigate alterations of amygdala and hippocampal volumes in 86 in-patients with unipolar depression and 87 healthy controls, and we then correlated amygdala and hippocampal volumes of 76 in-patients with the area under the curve of cortisol secretion in the dexamethasone/corticotropin releasing hormone (Dex/CRH) test at baseline and during short-term antidepressant therapy.

A variant of the neuronal amino acid transporter SLC6A15 is associated with ACTH and cortisol responses and cognitive performance in unipolar depression.

Major depressive disorder (MDD) is accompanied by both cognitive impairments and a hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA) system, resulting in an enhanced glucocorticoid secretion. Cortisol acts via mineralocorticoid and glucocorticoid receptors densely located in the hippocampus, a brain area that is important regarding cognitive functions and especially memory functions. Recently, a variant (rs1545843) affecting transcription of the human SLC6A15 gene has been associated with depression in a genome-wide association study.

The influence of age, gender and socio-economic status on multimorbidity patterns in primary care. First results from the multicare cohort study.

Background: Multimorbidity is a phenomenon with high burden and high prevalence in the elderly. Our previous research has shown that multimorbidity can be divided into the multimorbidity patterns of 1) anxiety, depression, somatoform disorders (ADS) and pain, and 2) cardiovascular and metabolic disorders. However, it is not yet known, how these patterns are influenced by patient characteristics.

The functional coding variant Asn107Ile of the neuropeptide S receptor gene (NPSR1) is associated with schizophrenia and modulates verbal memory and the acoustic startle response.

Recently, the neuropeptide S (NPS) neurotransmitter system has been identified as a promising psychopharmacological drug target given that NPS has shown anxiolytic-like and stress-reducing properties and memory-enhancing effects in rodent models. NPS binds to the G-protein-coupled receptor encoded by the neuropeptide S receptor gene (NPSR1). A functional variant within this gene leads to an amino-acid exchange (rs324981, Asn107Ile) resulting in a gain-of-function in the Ile107 variant which was recently associated with panic disorder in two independent studies.

PCLO rs2522833 modulates HPA system response to antidepressant treatment in major depressive disorder.

Variant rs2522833 of the Piccolo-encoding gene PCLO has recently been found to be associated with major depressive disorder (MDD). PCLO encodes a presynaptic cytomatrix protein which influences monoamine neurotransmitter release. Piccolo could therefore play an important role in treatment response to antidepressant therapy and the improvement of alterations in HPA system reactivity.

Antiplatelet effects of antidepressant treatment: a randomized comparison between escitalopram and nortriptyline.

Introduction: Depressive disorders have been identified as independent risk factors for coronary heart disease. The present study (i) compared platelet function of depressed patients with that of healthy controls, (ii) analysed possible aggregability changes during 3 months of treatment with antidepressants, and (iii) sought to assess different effects of escitalopram and nortriptyline on platelet aggregation.

Methods: Blood samples of 91 major depressed patients and 91 healthy controls were analysed with whole blood aggregometry in a case-control setting.

Reduced cardio-respiratory coupling after treatment with nortriptyline in contrast to S-citalopram.

Objective: Major depressive disorder is associated with increased cardiac mortality. A decrease in vagal modulation related to reduced heart rate variability might contribute to increased mortality among many other factors. We sought to examine the hypothesis that nortriptyline treatment will be associated with a decrease in heart rate variability and coupling between heart rate and respiration compared to treatment with S-citalopram.

DNA sequence variants of the FKBP5 gene are associated with unipolar depression.

FKBP5 is a glucocorticoid receptor-regulating co-chaperone of hsp-90 and, therefore, is suggested to play a role in the regulation of the hypothalamic-pituitary-adrenocortical system and the pathophysiology of depression. Previously, three studies identified single nucleotide polymorphisms (SNPs) in the FKBP5 gene associated with response to antidepressants, and one study found an association with diagnosis of depression. We selected five markers from the region of interest.

The German MultiCare-study: Patterns of multimorbidity in primary health care - protocol of a prospective cohort study.

Background: Multimorbidity is a highly frequent condition in older people, but well designed longitudinal studies on the impact of multimorbidity on patients and the health care system have been remarkably scarce in numbers until today. Little is known about the long term impact of multimorbidity on the patients' life expectancy, functional status and quality of life as well as health care utilization over time. As a consequence, there is little help for GPs in adjusting care for these patients, even though studies suggest that adhering to present clinical practice guidelines in the care of patients with multimorbidity may have adverse effects.

No association of the Val66Met polymorphism of the brain-derived neurotrophic factor with hippocampal volume in major depression.

Recently, an association of the Val66Met polymorphism of the brain-derived neurotrophic factor with hippocampal volume in patients with major depression has been reported. Here, we aimed at replicating this finding in an independent German sample. We included 79 patients with unipolar major depressive episodes and 84 healthy comparison participants.

Association of major depression with rare functional variants in norepinephrine transporter and serotonin1A receptor genes.

Dysregulations of central noradrenergic and serotonergic neurotransmission have been suggested to contribute to the pathogenesis of neuropsychiatric disorders such as depression. The norepinephrine transporter (NET; SLC6A2) and the serotonin (5-HT)(1A) receptor (5-HT(1A) receptor; HTR1A) play an important role in central nervous monoaminergic homeostasis. As shown previously, variations in the human NET and 5-HT(1A) receptor genes can alter noradrenergic and serotonergic signaling in the brain: a single nucleotide polymorphism (SNP) in the coding region of the NET gene resulting in a F528C substitution increased plasma membrane expression of this NET variant, and a SNP in the human 5-HT(1A) receptor gene leading to the R219L receptor variant almost abolished cellular signal transduction subsequent to receptor activation.

G72 and its association with major depression and neuroticism in large population-based groups from Germany.

Objective: G72 is among the most frequently replicated vulnerability genes for schizophrenia and bipolar disorder. The authors previously found identical haplotypes of markers M23 and M24 to be associated with schizophrenia, bipolar disorder, and panic disorder. Given both the well-recognized familial clustering across these disorders and recent linkage findings implicating the region harboring G72 in the etiology of major depression and panic disorder, we can hypothesize that G72 should also be involved in the etiology of major depression.

Unipolar depression and hippocampal volume: impact of DNA sequence variants of the glucocorticoid receptor gene.

Glucocorticoid receptor (GR) plays a major role in regulation of the hypothalamic-pituitary-adrenocortical (HPA) system; HPA dysregulation represents the most consistent biological pattern of depression. Multiple functional polymorphisms are known for the GR gene, which might influence the development of unipolar depression. Previous studies reported associations to some variants in this gene but not consistently so.

Possible association between genetic variants at the GRIN1 gene and schizophrenia with lifetime history of depressive symptoms in a German sample.

Genetic variation in glutamatergic signalling pathways is believed to play a substantial role in the aetiology of schizophrenia. The N-methyl-D-aspartate receptor subunit gene GRIN1 has been proposed as a candidate gene for schizophrenia. We tested for a potential association between schizophrenia and four single nucleotide polymorphisms (rs4880213, rs11146020, rs6293, and rs10747050) and one microsatellite marker at GRIN1 in a German sample of 354 patients and 323 controls.

No association between genetic variants at the ASCT1 gene and schizophrenia or bipolar disorder in a German sample.

Altered glutamatergic neurotransmission is considered a potential etiological factor of schizophrenia (SCZ) and affective disorders. The gene ASCT1 (SLC1A4) coding for a Na+-dependent neutral aminoacid transporter is a member of the glutamate transporter superfamily and is located on 2p13-14, a region showing linkage to both SCZ and bipolar disorder (BD). ASCT1 can thus be considered a candidate gene for both disorders.

No association between genetic variants at the GRIN1 gene and bipolar disorder in a German sample.

Disturbed glutamatergic neurotransmission has been implicated in the pathogenesis of schizophrenia and bipolar disorder, with the N-methy-D-aspartate receptors being in the focus of research. The NR1 subunit, which is encoded by the gene GRIN1, plays a key role in the functionality of N-methy-D-aspartate receptors. We tested the association between GRIN1 and bipolar disorder in a sample of German descent, consisting of 306 bipolar disorder patients and 319 population-based controls.

Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression.

Background: Previous genetic studies investigating a possible involvement of variations at the brain derived neurotrophic factor (BDNF) gene locus in major depressive disorder (MDD), bipolar affective disorder (BPAD), and schizophrenia have provided inconsistent results.

Methods: We performed single-marker and haplotype analyses using three BDNF polymorphisms in 2,376 individuals (465 MDD, 281 BPAD, 533 schizophrenia, and 1,097 control subjects).

Results: Single-marker analysis did not provide strong evidence for association.

The power of sample size and homogenous sampling: association between the 5-HTTLPR serotonin transporter polymorphism and major depressive disorder.

Background: Several lines of evidence indicate that abnormalities in the functioning of the central serotonergic system are involved in the pathogenesis of affective illness. A 44-base-pair insertion/deletion polymorphism in the 5' regulatory region of the serotonin transporter gene (5-HTTLPR), which influences expression of the serotonin transporter, has been the focus of intensive research since an initial report on an association between 5-HTTLPR and depression-related personality traits. Consistently replicated evidence for an involvement of this polymorphism in the etiology of mood disorders, particularly in major depressive disorder (MDD), remains scant.