Unmedicated Major Depressive Disorder Research Articles

Inhibition-related activity in subgenual cingulate is associated with symptom severity in major depression

Individuals with major depressive disorder (MDD) show impaired inhibitory control over negative thoughts. However, the brain mechanism underlying impaired inhibitory control in MDD has been incompletely described. The objective of this study was to examine brain function during inhibitory and error processing in a unique population of young, healthy, unmedicated MDD individuals. We hypothesized that MDD subjects would show clinically relevant alterations in brain activation in medial prefrontal and anterior cingulate cortex (ACC) during both inhibitory and error processing. Subjects performed an individualized parametric stop-signal task during functional magnetic resonance imaging (fMRI). MDD subjects ( n = 15) met DSM-IV criteria for current MDD. Healthy control (HC) subjects ( n = 16) had no lifetime history of MDD or other psychiatric disorder. The groups were not significantly different in several socio-demographic variables or in behavioral performance. A group by trial difficulty interaction on error-related activation in bilateral inferior frontal gyrus and left supragenual ACC was observed, suggesting a demand-specific failure of this circuitry in MDD. Additionally, a group by trial difficulty interaction on inhibition-related activation in subgenual ACC was observed. Among MDD individuals, inhibition-related subgenual activation correlated with depressive symptom severity, implicating subgenual ACC in inhibitory control processes related to clinical depression.

Resting state corticolimbic connectivity abnormalities in unmedicated bipolar disorder and unipolar depression

This study for the first time investigated resting state corticolimbic connectivity abnormalities in unmedicated bipolar disorder (BD) and compared them with findings in healthy controls and unipolar major depressive disorder (MDD) patient groups. Resting state correlations of low frequency BOLD fluctuations (LFBF) in echoplanar functional magnetic resonance (fMRI) data were acquired from a priori defined regions of interests (ROIs) in the pregenual anterior cingulate cortex (pgACC), dorsomedial thalamus (DMTHAL), pallidostriatum (PST) and amygdala (AMYG), to investigate corticolimbic functional connectivity in unmedicated BD patients in comparison to healthy subjects and MDD patients. Data were acquired from 11 unmedicated BD patients [six manic (BDM) and five depressed (BDD)], and compared with data available from 15 unmedicated MDD and 15 healthy subjects. BD patients had significantly decreased pgACC connectivity to the left and right DMTHAL, similar to findings seen in MDD. Additionally, BD patients had decreased pgACC connectivity with the left and right AMYG as well as the left PST. An exploratory analysis revealed that both BDD and BDM patients had decreased connectivity between the pgACC and DMTHAL. The results of the study indicate a common finding of decreased corticolimbic functional connectivity in different types of mood disorders.

Distinct Profiles of Neurocognitive Function in Unmedicated Unipolar Depression and Bipolar II Depression

Studies have demonstrated neuropsychological deficits across a variety of cognitive domains in depression. Few studies have directly compared depressed subjects with major depressive disorder (MDD) and bipolar disorder (BD), and many are confounded by medication status across subjects. In this study, we compared the performance of unmedicated currently depressed MDD and BD groups on a battery of neuropsychological tests that included measures of risk taking and reflection impulsivity. Twenty-two MDD, seventeen BDII, and 25 healthy control subjects (HC), matched for age and IQ, were assessed on a battery of neuropsychological tests. The depressed groups showed comparable ratings of depression severity and age of illness onset. The MDD group was impaired on tests of spatial working memory and attentional shifting, sampled less information on a test of reflection impulsivity, and was oversensitive to loss trials on a decision-making test. The BDII subjects were generally intact and did not differ significantly from control subjects on any test. These data indicate differing profiles of cognitive impairment in unmedicated depressed MDD versus BDII subjects. Moderately depressed BDII subjects displayed relatively intact cognitive function, whereas MDD subjects demonstrated a broader range of executive impairments. These cognitive deficits in depression were not attributable to current medication status.

HPA axis dysfunction in unmedicated major depressive disorder and its normalization by pharmacotherapy correlates with alteration of neural activity in prefrontal cortex and limbic/paralimbic regions

Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis is one of the most prominent neurobiological findings in major depressive disorder (MDD). The relationship of regional brain metabolism to HPA axis dysfunction in depressed patients, however, is still unclear. In this study, to examine the clinical pharmacotherapeutic effects on HPA axis function and brain metabolism in MDD patients, we performed the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test on 24 antidepressant-free patients with MDD a few days after positron emission tomography (PET) with a radiotracer, [ 18F]-fluorodeoxyglucose (FDG). Moreover, 10 patients who responded to pharmacotherapy were re-tested. 75% of unmedicated MDD patients exhibited a heightened cortisol response to the DEX/CRH test, and thus were defined as non-suppressors. Non-suppressors showed a marked hypometabolism in the medial prefrontal cortex as compared with suppressors. After successful pharmacotherapy, enhanced cortisol responsiveness normalized. Prior to treatment of the unmedicated MDD, a significant hypometabolism in various frontal regions and a significant hypermetabolism in the right hippocampus and parahippocampal gyrus were observed compared with controls. Metabolic activity in treatment responders showed a normalizing pattern in almost all the areas that had been characterized by metabolic abnormality at baseline except for the medial prefrontal cortex. These results indicate that depressed patients remitted with antidepressant treatment were accompanied by resolution of HPA dysregulation and alteration of regional glucose metabolism in the prefrontal cortical, limbic and paralimbic regions.

Anatomical MRI study of corpus callosum in unipolar depression

Previous studies have suggested abnormal cerebral lateralization in major depressive disorder (MDD). Few controlled MRI studies have investigated the corpus callosum (CC), the largest commissura connecting the two cerebral hemispheres, in MDD. This study investigated anatomical abnormalities in the CC and its subdivisions in MDD patients. Twenty-two unmedicated MDD patients and 39 healthy subjects underwent brain magnetic resonance imaging (MRI). Measurements of the CC and its sub-regions were performed with a semi-automated software (NIH Image, version 1.62). ANCOVA with age, gender, and intra-cranial volume (ICV) as covariates showed no significant differences in CC measurements between patients and controls (df = 1,56; p > 0.05). However, patients with familial MDD had a significantly larger middle genu area ( F 1,45 = 4.252; p = 0.045) compared to healthy controls, and significantly larger middle genu ( F 1,13 = 5.366; p = 0.037), anterior splenium ( F 1,13 = 6.27; p = 0.026), and middle splenium areas ( F 1,13 = 4.706; p = 0.049) compared to patients with non-familial MDD. Although preliminary, our findings suggest that anatomical abnormalities in CC may be restricted to patients with familial MDD, with possible enlargement of CC in this particular sub-group. The possible role of callosal abnormalities in the pathogenesis of mood disorders should be further examined.

No psychomotor slowing in fine motor tasks in dysthymia

Introduction Few studies using objective and sensitive measuring techniques have investigated whether psychomotor retardation (PR), an important symptom of a major depressive disorder (MDD), is also present in dysthymic patients. In this study, the following questions were addressed: (1) is PR also prevalent in dysthymia? (2) If so, is the PR cognitive or motor in nature? And (3) does the nature and degree of the PR in patients with dysthymia differ from the PR in MDD patients found in earlier studies? Methods PR was measured by comparing the, digitally recorded, fine motor performance of 20 unmedicated dysthymic inpatients (mean age: 33) and 32 controls on copying and drawing tasks. In addition, the performance of the dysthymic patients was compared to the performance results of 32 unmedicated MDD inpatients collected in an earlier study. Results The dysthymic patients were not slower than the controls in performing the fine motor tasks: neither initiation time (IT) nor movement time (MT) were prolonged. As expected, the MDD patients did show significantly longer ITs and MTs in all tasks compared to the controls. On the clinical Salpêtrière Retardation Rating Scale (SRRS), the dysthymic patients had high scores on mainly subjective cognitive items like concentration and memory complaints. Limitations The dysthymic patients had significantly less severe forms of depression compared to the MDD patients. As dysthymia, by definition, is a less severe form of depression we could not examine whether PR would manifest itself in severely depressed dysthymic patients, as is the case in certain MDD patients. Conclusion In this study, no objective evidence was found for PR in dysthymic patients during fine motor tasks. PR may be used to differentiate between dysthymia and MDD.