Abnormal size of the amygdala predicts impaired emotional memory in major depressive disorder

BACKGROUND: Amygdala and hippocampus show significant structural abnormalities in major depressive disorder (MDD). Individuals with MDD have difficulties in emotional memory. A relationship between emotional memory deficits and structural abnormalities of amygdala and hippocampus in MDD has been proposed but not shown, yet. METHODS: The current study assessed memory for emotional faces in 21 young women with recent-onset MDD and 23 matched control subjects. All subjects underwent structural magnetic resonance imaging (3D-MRI) and a clinical and neuropsychological assessment. RESULTS: Depressive subjects had significantly enlarged amygdala size and significantly reduced hippocampal size compared with controls. Depressive subjects were significantly impaired in learning emotional facial expressions, with deficits being most pronounced for fearful, surprised and disgusted faces. Depressive subjects with amygdala volumes 1 SD or more above the mean of control subjects showed the strongest impairments. Correlation analyses revealed that larger left amygdala volumes were significantly related to worse memory performance and to higher anxiety scores of depressive subjects. Smaller left hippocampal volumes of depressive subjects were related to higher anxiety scores as well. LIMITATIONS: All MDD subjects were taking antidepressant medication at the time of the study. Longitudinal studies are needed to clarify whether the behavioral and/or volumetric abnormalities of MDD subjects can be attributed to medication or MDD or both. CONCLUSIONS: It might be speculated that amygdala enlargement in young MDD subjects is correlated with amygdalar over-activation and resolves with antidepressant treatment, as was shown for amygdalar over-activation.     

Association study of corticotropin-releasing hormone receptor1 gene polymorphisms and antidepressant response in major depressive disorders

Hypothalamic-pituitary-adrenal (HPA) axis appears to play a key role in the pathogenesis of major depressive disorders (MDD). Treatment of certain selective serotonin reuptake inhibitors (SSRIs) has been shown to reduce the activity of corticotropin-releasing hormone (CRH) neurons and may contribute to their therapeutic action. It has been proposed that the downregulation of CRH activity is final and common step of antidepressant treatment. In this study, we tested whether the polymorphisms of three sites (rs1876828, rs242939 and rs242941) in corticotropin-releasing hormone receptor1 (CRHR1) gene are related to 6 weeks fluoxetine antidepressant effect in 127 Han Chinese patients with MDD. The results show that the rs242941 G/G genotype and homozygous GAG haplotype of the three single-nucleotide polymorphisms (SNPs) are associated with fluoxetine therapeutic response in MDD patients of high-anxiety (HA). The results support the idea that the CRHR1 gene is likely to be involved in the antidepressant response in MDD.     

Autobiographical memories in major depressive disorder

The objective of this research was to study the relation between the processing and recall of information in major depressive disorder. An autobiographical memory task was applied to 42 subjects with a diagnosis of major depressive disorder, 28 subjects with a diagnosis of panic disorder and 51 subjects without any psychological disorder. We used clinical scales for the evaluation of depression and anxiety. The results of the three groups, and both assessment periods of depressed subjects, were compared. The results indicate the existence, in severely depressed subjects, of a bias in processing and recalling negative information. We associate this situation to the existence of negative contents in self-schemas and processing and recall of information consistent with these schema contents. Based on the obtained results, we consider that the onset and maintenance of depression is more related to the information encoding and recall processes, controlled by the self's negative schemas, than with negative thoughts.     

RSA fluctuation in major depressive disorder

Cardiac vagal control, as measured by indices of respiratory sinus arrhythmia (RSA), has been investigated as a marker of impaired self-regulation in mental disorders, including depression. Past work in depressed samples has focused on deficits in resting RSA levels, with mixed results. This study tested the hypothesis that depression involves abnormal RSA fluctuation. RSA was measured in depressed and healthy control participants during rest and during two reactivity tasks, each followed by a recovery period. Relative to controls, depressed persons exhibited lower resting RSA levels as well as less RSA fluctuation, primarily evidenced by a lack of task-related vagal suppression. Group differences in RSA fluctuation were not accounted for by differences in physical health or respiration, whereas group differences in resting RSA level did not survive covariate analyses. Depression may involve multiple deficits in cardiac vagal control.     

Interpersonal profiles in major depressive disorder

Although patients with mood disorders report interpersonal difficulties in addition to depression or anxiety, few studies have examined interpersonal patterns in those patients. Here the authors' goals were to (a) identify the interpersonal pattern in patients with major depressive disorder (MDD), (b) determine interpersonal differences between subgroups of MDD patients, and (c) examine the interpersonal patterns of comorbid MDD patients. One- hundred forty-one MDD adults participated in an ongoing randomized clinical trial of treatments for depression. Interpersonal profiles revealed that MDD patients were significantly more distressed by interpersonal problems than normative samples. Furthermore, MDD patients with depressive personality disorder reported more interpersonal distress than MDD-only patients report and were more likely to have interpersonal problems related to dominance and control than submissiveness.     

Regional brain responses to serotonin in major depressive disorder

BACKGROUND: Positron Emission Tomography (PET) studies have reported altered resting regional brain glucose metabolism in mood disorders. This study examines the relationship of such changes to serotonin system abnormalities associated with depression. METHODS: Thirteen male medication free subjects who were inpatients with a DSM-IIIR major depressive disorder and seven healthy male subjects underwent an [18F]-fluorodeoxyglucose (18FDG) PET scan on consecutive days. Three hours prior to 18FDG subjects received single blind placebo or fenfluramine. Comparisons of voxel level regional glucose metabolic rate responses (rCMRglu) between groups in the two states were performed with SPM99. RESULTS: Unlike healthy male subjects who have significant increases in rCMRglu in prefrontal and parietal cortical regions after receiving fenfluramine, depressed male subjects have no significant increases in rCMRglu. CONCLUSIONS: Blunted increases in rCMRglu in response to fenfluramine in prefrontal and parietal cortex are consistent with our previous pilot study and the indoleamine hypothesis of depression. Differences in specific brain regions affected between this study and previous studies may be attributable to gender differences.     

Physical anhedonia in major depressive disorder.

Physical anhedonia, evaluated by the score on the physical anhedonia scale (PAS) of Chapman et al. [J. Abnorm. Psychol. 4 374-382 (1976)] was studied in 61 patients, who met RDC criteria for major depressive disorder and in 61 normal subjects. The depressed patients scored significantly higher than the normal group and presented a continuous distribution. Physical anhedonia of depressed patients seems related to the severity of the depression and does not appear to identify a qualitatively distinct subgroup.     

Delayed mood transitions in major depressive disorder

The hypothesis defended here is that the process of mood-normalizing transitions fails in a significant proportion of patients suffering from major depressive disorder. Such a failure is largely unrelated to the psychological content. Evidence for the hypothesis is provided by the highly variable and unpredictable time-courses of the depressive episodes.     

Cerebellar vermis volume in major depressive disorder

The vermis is located in the midline of the cerebellum and is involved in the regulation of affect and cognitive processes. Although changes in vermis size have been reported in several psychiatric disorders such as schizophrenia and bipolar disorder, no volumetric studies have been conducted on samples of patients with major depressive disorder (MDD). One-hundred and five adult subjects were recruited: 35 patients who were presenting for first treatment (FT; 22 females), 35 patients with known previous treatment (PT; 22 females), and 35 healthy controls (NC; 22 females), matched for age and gender. We compared the volumes of the total vermis, the anterior lobe (V1), the superior–posterior lobe (V2), and the inferior–posterior lobe (V3), among these study groups. Anterior vermis (V1) was larger in patients with MDD with a long history of antidepressant treatment compared to healthy controls. This finding was evident only in men [F(2, 36) = 9.23, p = .001]. Patients in the FT group did not differ from healthy controls in any vermian region. We found no correlations between vermian subregional volumes and clinical variables such as illness duration or age at onset of illness. We speculate that the larger anterior vermis volumes might arise from abnormalities in connectivity or as compensatory responses to the prefrontal dysfunction noted in patients with MDD but confirmation of this hypothesis awaits further studies.     

Prodromal symptoms in primary major depressive disorder

Prodromal symptomatology was investigated, by means of a modified version of Paykel's Clinical Interview for Depression, in 15 outpatients at their first episode of primary major depressive disorder. Compared to normals, generalized anxiety and irritability were significantly more frequent. Impaired work and interests, fatigue, initial and delayed insomnia were also reported. Four patients who relapsed upon discontinuation of antidepressant treatment displayed the same prodromal symptomatology as in the initial episode.     

Fluoxetine in tricyclic refractory major depressive disorder

Data regarding open-label treatment with fluoxetine following failure to respond to tricyclic antidepressants (TCAs) or intolerance of TCA side effects, suggest a response rate between 51.4% and 62.1%, depending on the definition of TCA refractoriness employed. Double-blind study of this issue would extend these findings. Fluoxetine is well tolerated in patients unable to tolerate TCAs. Within this population, more than 80% of patients unable to tolerate TCAs found fluoxetine acceptable. Fluoxetine, as an alternative to polypharmaceutical augmentation, may represent a logical choice as the next step in therapy for a patient who has initially been treated with a TCA and has proven refractory or intolerant.     

Serum lipid concentrations in Croatian veterans with post-traumatic stress disorder,post-traumatic stress disorder comorbid with major depressive disorder,or major depressive disorder

The aim of this study was to assess eventual differences in serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, LDL-C/HDL-C ratio between veterans with combat-related post-traumatic stress disorder (PTSD) only or comorbid with major depressive disorder (MDD), veterans with combat experiences with MDD, and healthy control group. PTSD and/ or MDD were diagnose according to structured clinical interview based on DSM-IV criteria. Additional criteria to diagnose PTSD were Clinician Administered PTSD Scale (CAPS), and to diagnose MDD Montgomery-Asberg Depression Rating Scale (MADRAS). Serum lipid concentrations were determined by using the enzyme-assay method. Veterans with combat-related PTSD as well as veterans with combat-related PTSD comorbid with MDD showed significantly higher concentrations of cholesterol (F=9.858, p<0.01), triglycerides (F=10.112, p<0.01), LDL-C (F=11.145, p<0.01), and LDL-C/HDL-C ratio (F=8.346, p<0.01) vs. veterans with MDD or healthy control group. Contrary healthy control group and veterans with MDD showed significantly higher concentrations of HDL-C (F=8.421, p<0.01), vs. veterans with PTSD or PTSD comorbid with MDD. In conclusion, there are no differences in serum lipid concentrations between veterans with combat-related PTSD and PTSD comorbid with MDD, but they have higher lipid concentrations than veterans with MDD or healthy control subjects.     

Increased bone remodeling in first-episode major depressive disorder

OBJECTIVE: Bone mineral density is decreased in patients with depressive disorder. This study evaluated biochemical bone remodeling markers in patients having their first depressive episode who had not taken psychotropic medications to evaluate possible pathogenic mechanisms implicated in the loss of bone mineral density in early states of this illness. METHODS: Serum osteocalcin, parathyroid hormone, bone alkaline phosphatase, telopeptide, collagen type I C-terminal propeptide, cross-laps, and 25-hydroxyvitamin D levels were measured in 19 depressive patients and 19 age-matched healthy women. In addition, serum cortisol and interleukin-6 were determined. Patients were assessed with the Schedules for Clinical Assessment in Neuropsychiatry interview and met criteria for a single depressive episode. RESULTS: Depressed patients had increased levels of osteocalcin (p = .003), an osteoblastic marker; telopeptide (p = .01), an osteoclastic marker; and cross-laps (p = .000), another osteoclastic marker. Parathyroid hormone was lower in patients (p = .02), whereas the rest of the markers were comparable between patients and healthy control subjects. Serum cortisol was higher in depressed patients than in control subjects (p = .003), but cortisolemia and interleukin-6 did not show any relationship with bone markers in patients. Clinical severity of the illness and weight loss due to depression in patients did not correlate with bone remodeling markers. CONCLUSIONS: These data suggest that an increase in bone remodeling not due to vitamin D deficiency induces a release of calcium from bone and inhibition of parathyroid hormone secretion.     

Automaticity in anxiety disorders and major depressive disorder

In this paper we examine the nature of automatic cognitive processing in anxiety disorders and Major Depressive Disorder (MDD). Rather than viewing automaticity as a unitary construct, we follow a social cognition perspective (Bargh, 1994) that argues for four theoretically independent features of automaticity: unconscious (processing of emotional stimuli occurs outside awareness), efficient (processing emotional meaning uses minimal attentional resources), unintentional (no goal is needed to engage in processing emotional meaning), and uncontrollable (limited ability to avoid, alter or terminate processing emotional stimuli). Our review of the literature suggests that most anxiety disorders are characterized by uncontrollable, and likely also unconscious and unintentional, biased processing of threat-relevant information. In contrast, MDD is most clearly typified by uncontrollable, but not unconscious or unintentional, processing of negative information. For the anxiety disorders and for MDD, there is no sufficient evidence to draw firm conclusions about efficiency of processing, though early indications are that neither anxiety disorders nor MDD are characterized by this feature. Clinical and theoretical implications of these findings are discussed and directions for future research are offered. In particular, it is clear that paradigms that more directly delineate the different features of automaticity are required to gain a more comprehensive and systematic understanding of the importance of automatic processing in emotion dysregulation.