Female Major Depressive Disorder Patients Research Articles

Ventilatory inefficiency in major depressive disorder: A potential adjunct for cardiac risk stratification in depressive disorders?

Background Cardiopulmonary exercise testing (CPET) provides insights into ventilatory, cardiac and metabolic dysfunction in heart and lung diseases and might play a role in cardiac risk stratification in major depressive disorder (MDD). Objective The VE/VCO 2-slope indicates ventilatory efficiency and has been applied to stratify the cardiac risk in heart failure (HF). Therefore, the current study was conducted to evaluate and classify ventilatory efficiency and its relationship to physical fitness and disease severity in MDD. Methods Exhaustive incremental exercise testing was completed by 15 female MDD patients and pair matched controls. The ventilatory threshold (VT) and the VE/VCO 2-slope were assessed. Statistical analyses were conducted by means of MANOVAs and follow-up univariate ANOVAs. Results In patients with MDD, significant different relative work rates and oxygen uptakes at the VT in comparison to healthy controls were observed. Furthermore, we found an increased VE/VCO 2-slope in depressed patients. We additionally report an inverse relationship between the VE/VCO 2-slope and peak power output as well as peak oxygen uptake solely in patients. We did not observe any association of assessed parameters with disease severity. Conclusion CPET measures indicate ventilatory inefficiency in patients with MDD. The elevated VE/VCO 2-slope indicates that patients with MDD need to ventilate significantly more to a given amount of developing CO 2. Further investigations are needed to verify the application of the ventilatory classification system to stratify cardiovascular risk in depressive disorder.

Gender-Specific Association of Galanin Polymorphisms with HPA-Axis Dysregulation, Symptom Severity, and Antidepressant Treatment Response

Galanin (GAL) is an estrogen-inducible neuropeptide, highly expressed in brain regions reported to be involved in regulation of mood and anxiety. GAL possibly has a direct modulatory effect on hypothalamic-pituitary-adrenal (HPA)-axis regulation. Recent data from pharmacological and genetic studies indicate a significant function of GAL in stress-related disorders. By using a tag SNP approach covering the locus encoding preprogalanin (PPGAL), earlier findings of female-specific associations of polymorphisms in this locus with panic disorder were expanded to a larger sample of 268 outpatients with anxiety disorders (ADs). Within a larger sample of 541 inpatients with major depressive disorder (MDD), we then tested associations of one PPGAL tag SNP with specific depression symptom clusters and HPA-axis activity assessed by the combined dexamethasone-suppression/CRH-stimulation test both at inpatient admission and discharge (n=298). Gender specificity as well as dependence of the association on levels of circulating estrogens was analyzed. Genotyping revealed high linkage disequilibrium in the promoter area of the PPGAL gene, which includes several estrogen-response elements. Confirming earlier results, rs948854, tagging this promoter region, was associated with more severe anxiety pathology in female AD patients, but not in males. In premenopausal female MDD patients, the same allele of rs948854 was associated with more severe vegetative but not cognitive depressive symptoms at discharge and worse treatment response on antidepressant medication. Furthermore, this allele was associated with higher HPA-axis activity at admission. No significant case-control associations could be observed. However, because of power limitations of both patient samples, small effects cannot be excluded. The reported associations in independent samples of AD and MDD support an estrogen-dependent function of GAL in pathophysiology of anxiety and depression, affecting response to antidepressant treatment.

Normal metabolite levels in the left dorsolateral prefrontal cortex of unmedicated major depressive disorder patients: A single voxel 1H spectroscopy study

Few proton magnetic resonance spectroscopy ( 1H spectroscopy) studies have investigated the dorsolateral prefrontal cortex (DLPFC), a key region in the pathophysiology of major depressive disorder (MDD). We used 1H spectroscopy to verify whether MDD patients differ from healthy controls (HC) in metabolite levels in this brain area. Thirty-seven unmedicated DSM-IV MDD patients were compared with 40 HC. Subjects underwent a short echo-time 1H spectroscopy examination at 1.5 T, with an 8-cm 3 single voxel placed in the left DLPFC. Reliable absolute metabolite levels of N-acetyl aspartate (NAA), phosphocreatine plus creatine (PCr+Cr), choline-containing compounds (GPC+PC), myo-inositol, glutamate plus glutamine (Glu + Gln), and glutamate were obtained using the unsuppressed water signal as an internal reference. Metabolite levels in the left DLPFC did not statistically differ between MDD patients and HC. We found an interaction between gender and diagnosis on PCr+Cr levels. Male MDD patients presented lower levels of PCr+Cr than male HC, and female MDD patients presented higher levels of PCr+Cr than female HC. Moreover, length of illness was inversely correlated with NAA levels. These findings suggest that there is not an effect of diagnosis on the left DLPFC neurochemistry. Possible effects of gender on PCr+Cr levels of MDD patients need to be further investigated.

Dissociation of performance parameters at the IAT requires specific exercise recommendations for depressed patients

Aerobic exercise training is considered an adequate complementary treatment strategy for major depressive disorder (MDD). However, there is a need for comparative methodological investigations to determine the appropriate exercise intensity for these patients. The study compared submaximal exercise intensity determination with those derived from maximal parameters such as percentages of heart rate reserve (HRR), maximal heart rate (HR(max)) and peak oxygen uptake (VO(2peak)) of patients and controls. An exhaustive incremental bicycle exercise test was completed by 15 female MDD patients and matched controls. The individual anaerobic lactate threshold (IAT) as a gold standard to determine individual aerobic exercise intensity was assessed according to Stegmann and coworkers. Exercise intensities at 70 and 85% of HR(max), 70 and 85% of HRR and 50 to 80% of VO(2peak) were compared to the IAT. Patients suffering from MDD switched earlier to anaerobic metabolism than matched healthy controls. But interestingly, the level of self-rated perceived exertion, concentration of lactate, respiratory exchange ratio and heart rate at the IAT level revealed no significant difference between both groups. Due to a growing number of clinical aerobic exercise treatments in depressive disorders exercise intensities >70% of (a) HR(max), (b) HRR, (c) VO(2peak) should be amended by the IAT and Borg scale measurements to avoid over challenging as well as increased anaerobic metabolism.

Hippocampus, glucocorticoids and neurocognitive functions in patients with first-episode major depressive disorders

The aim of this study was to determine whether there was any relationship between hippocampal volume, and glucocorticoid regulation, and cognitive dysfunctions in drug-naïve major depressive disorder (MDD) patients during their first episode. Twenty drug-free female MDD patients in their first episode and 15 healthy females as control subjects were included in the study. All subjects underwent 3.0 Tesla (T) magnetic resonance imaging (MRI), comprehensive neuropsychological testing and dexamethasone suppression tests (DST). The volumes of the right and left hippocampus of the patients were found to be significantly smaller than those of the controls. Patients were found to have significantly lower scores on measures of attention, working memory, psychomotor speed, executive functions, and visual and verbal memory fields. The performance of the patients only in the recollection memory and memory of reward-associated rules were positively correlated with hippocampal volumes. The volumes of the left and right hippocampus did not correlate with basal or post-dexamethasone cortisol levels. Our findings indicate that depressed patients have smaller hippocampi even in the earlier phase of their illness. Further research efforts are needed to explain the mechanisms that are responsible for the small hippocampus in depressed patients.

Neuropsychological and hypothalamic–pituitary-axis function in female patients with melancholic and non-melancholic depression

Executive function deficits in depression implicate involvement of frontal-striatal circuits. However, studies of hypothalamic-pituitary-axis (HPA) function suggest that stress-related brain changes of hippocampus may also implicate prefrontal-hippocampal circuits, which may explain the profile of both executive dysfunction and memory deficits. In this study we examined the performance of patients with major depressive disorder (MDD) on tasks of memory and executive function in relation to melancholic features and to cortisol levels. Our hypothesis was that raised cortisol levels in melancholic patients would correlate with these deficits. Forty female MDD patients, 20 having melancholic features (MEL vs. Non-MEL), and 20 sex-age- and education-matched normal controls were investigated using the Cambridge neuropsychological test automated battery (CANTAB), to assess memory (paired associative learning, PAL; short-term recognition memory, SRM) and executive (intradimensional/extradimensional set-shifting, ID/ED; Stockings of Cambridge, SOC) functions. Plasma and salivary cortisol levels were measured. The MDD patients performed worse than controls on PAL and both executive tasks. The MEL group differed from controls on all tests, and differed from the non-MEL only at the ED stage of the ID/ED task. Patient cortisol levels were within the normal range and did not correlate with neuropsychological performance for any group. MDD patients showed neuropsychological deficits on tasks of executive function and memory, supporting the model of frontal-temporal dysfunction. MEL vs. non-MEL performed worse overall and demonstrated a qualitative difference in set shifting, perhaps implicating more extensive prefrontal involvement. Cortisol levels did not correlate with depression severity or the observed deficits.

Selective Deficits in the Omega-3 Fatty Acid Docosahexaenoic Acid in the Postmortem Orbitofrontal Cortex of Patients with Major Depressive Disorder

Epidemiological surveys and peripheral tissue (red blood cells/plasma) fatty acid composition studies suggest that omega-3 fatty acid deficiency is associated with major depressive disorder (MDD) and suicide. It was hypothesized that patients with MDD would exhibit lower frontal cortical concentrations of docosahexaenoic acid (DHA), the principal omega-3 fatty acid in brain, relative to normal controls. We determined the total fatty acid composition of postmortem orbitofrontal cortex (Brodmann's Area 10) from patients with DSM-IV-defined MDD (n = 15) and age-matched normal controls (n = 27) by gas chromatography. After correction for multiple comparisons, the omega-3 fatty acid DHA was the only fatty acid that was significantly different (-22%) in the postmortem orbitofrontal cortex of MDD patients relative to normal controls. Deficits in DHA concentrations were greater in female MDD patients (-32%) than in male MDD patients (-16%), and could not be wholly attributed to lifestyle factors or postmortem tissue variables. These results demonstrate a selective deficit in the omega-3 fatty acid DHA in the orbitofrontal cortex of patients with MDD. This finding adds to a growing body of evidence implicating omega-3 fatty acid deficiency as well as the orbitofrontal cortex in the pathophysiology and potentially pathogenesis of MDD.

Alteration in Estrogen Receptor α mRNA Levels in Frontal Cortex and Hippocampus of Patients with Major Mental Illness

Gender differences have been described in major mental illnesses (MMI). The dorsolateral prefrontal cortex (DLPFC) and hippocampus are estrogen-sensitive brain regions structurally and functionally altered in patients with MMI. We hypothesized that gender-specific alterations in DLPFC and hippocampus estrogen receptor alpha (ERalpha) mRNA levels may exist in MMI patients. We used Northern blot analysis to survey the expression of ERalpha mRNA transcripts in brain and body, detected by our human ERalpha riboprobe and in situ hybridization, to examine the expression pattern and quantify ERalpha mRNA levels in DLPFC and anterior hippocampus of patients with major depressive disorder (MDD), schizophrenia, and bipolar disorder compared with normal control subjects. Northern blotting revealed brain-region-specific differences in expression levels of a 5 kb ERalpha mRNA transcript. By in situ hybridization, ERalpha mRNA was detected in all layers of DLPFC and all hippocampal subfields in all subjects. We detected greater DLPFC ERalpha mRNA expression in male compared with female MDD subjects and reduced ERalpha mRNA levels in the dentate gyrus of schizophrenics compared with control subjects. Our results suggest that alterations in ERalpha mRNA levels exist in distinct telencephalic regions in male and female MDD patients, and in both genders in schizophrenia.