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.     

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.     

Detecting recurrent major depressive disorder within primary care rapidly and reliably using short questionnaire measures

Background

Major depressive disorder (MDD) is often a chronic disorder with relapses usually detected and managed in primary care using a validated depression symptom questionnaire. However, for individuals with recurrent depression the choice of which questionnaire to use and whether a shorter measure could suffice is not established.

Aim

To compare the nine-item Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory, and the Hospital Anxiety and Depression Scale against shorter PHQ-derived measures for detecting episodes of DSM-IV major depression in primary care patients with recurrent MDD.

Design and setting

Diagnostic accuracy study of adults with recurrent depression in primary care predominantly from Wales

Method

Scores on each of the depression questionnaire measures were compared with the results of a semi-structured clinical diagnostic interview using Receiver Operating Characteristic curve analysis for 337 adults with recurrent MDD.

Results

Concurrent questionnaire and interview data were available for 272 participants. The one-month prevalence rate of depression was 22.2%. The area under the curve (AUC) and positive predictive value (PPV) at the derived optimal cut-off value for the three longer questionnaires were comparable (AUC = 0.86–0.90, PPV = 49.4–58.4%) but the AUC for the PHQ-9 was significantly greater than for the PHQ-2. However, by supplementing the PHQ-2 score with items on problems concentrating and feeling slowed down or restless, the AUC (0.91) and the PPV (55.3%) were comparable with those for the PHQ-9.

Conclusion

A novel four-item PHQ-based questionnaire measure of depression performs equivalently to three longer depression questionnaires in identifying depression relapse in patients with recurrent MDD.     

Differentiating major depressive disorder in youths with attention deficit hyperactivity disorder

BACKGROUND: Youths with attention deficit hyperactivity disorders (ADHD) frequently have comorbid major depressive disorders (MDD) sharing overlapping symptoms. Our objective was to examine which depressive symptoms best discriminate MDD among youths with ADHD. METHODS: One-hundred-eleven youths with ADHD (5.2-17.8 years old) and their parents completed interviews with the K-SADS-PL and respective versions of the child or the parent Mood and Feelings Questionnaire (MFQ-C, MFQ-P). Controlling for group differences, logistic regression was used to calculate odds ratios reflecting the accuracy with which various depressive symptoms on the MFQ-C or MFQ-P discriminated MDD. Stepwise logistic regression then identified depressive symptoms that best discriminated the groups with and without MDD, using cross-validated misclassification rate as the criterion. RESULTS: Symptoms that discriminated youths with MDD (n=18) from those without MDD (n=93) were 4 of 6 mood/anhedonia symptoms, all 14 depressed cognition symptoms, and only 3 of 11 physical/vegetative symptoms. Mild irritability, miserable/unhappy moods, and symptoms related to sleep, appetite, energy levels and concentration did not discriminate MDD. A stepwise logistic regression correctly classified 89% of the comorbid MDD subjects, with only age, anhedonia at school, thoughts about killing self, thoughts that bad things would happen, and talking more slowly remaining in the final model. LIMITATIONS: Results of this study may not generalize to community samples because subjects were drawn largely from a university-based outpatient psychiatric clinic. CONCLUSIONS: These findings stress the importance of social withdrawal, anhedonia, depressive cognitions, suicidal thoughts, and psychomotor retardation when trying to identify MDD among ADHD youths.     

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.     

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.     

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.     

Treatment approaches to major depressive disorder relapse. Part 1: dose increase

OBJECTIVE: Although continuing antidepressant treatment after patients have responded to medication has been shown to greatly reduce the risk of relapse, this risk is not eliminated. A number of theories have been proposed to account for this apparent loss of efficacy. A common initial approach to managing relapse is to increase the dose of antidepressant. We prospectively evaluated the likelihood of response to increasing the fluoxetine doses in patients relapsing during a long-term efficacy study of two fluoxetine dosing regimens. METHOD: Patients meeting the DSM-IV criteria for major depressive disorder with modified HAMD17 scores > or =18 and CGI-severity scores > or =4 were treated for 13 weeks with open-label 20 mg/day fluoxetine in a multicenter US study. Responders (n = 501) were randomized to 20 mg fluoxetine daily, placebo, or 90 mg enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. If the patients relapsed during the continuation phase, they were offered a 25-week optional rescue treatment phase during which the study medication dose was increased as follows: (1) patients on placebo had treatment with fluoxetine 20 mg/day reinitiated, (2) patients on fluoxetine 20 mg/day had their dose increased to 40 mg/day, and (3) patients on a 90-mg weekly dose had their dose increased to 90 mg twice a week. The results of the rescue phase for the latter two groups who relapsed while on continuation treatment with fluoxetine are reported. Response was defined as a 50% reduction in the modified HAMD17 score since time of relapse and a CGI-severity score < or =2. Additional efficacy analyses included HAMD and CGI-severity changes from baseline to endpoint. Safety measures included assessment of treatment-emergent adverse events, vital signs, and laboratory measures. RESULTS: Overall, patients relapsing during the continuation treatment responded to an increased dose (57% of the 40-mg-daily group and 72% of the enteric-coated 90-mg-twice-weekly group). Mean modified HAMD17 scores decreased from a mean of approximately 20 to below 8 and were maintained for up to 6 months in the responders. Thirty-five percent of patients either did not respond or initially responded but again relapsed after augmentation of medication. CONCLUSIONS: The patients relapsing after initially responding to fluoxetine can benefit from an increase in fluoxetine dose. These results also generally support increasing dose as a first-line treatment strategy for a patient who has relapsed while taking a previously effective dose of an antidepressant. Increasing enteric-coated fluoxetine 90 mg once weekly to twice weekly appeared to be as well-tolerated and effective in restoring response as increasing a daily fluoxetine dose from 20 to 40 mg.     

Prepulse inhibition in patients with non-psychotic major depressive disorder

BACKGROUND: Prepulse inhibition (PPI) of the startle response is a measure of sensorimotor gating. PPI deficits have been reported in schizophrenia and in patients characterized by a known dysfunction in the cortico-striato-pallido-thalamic (CSPT) brain substrates that regulate PPI. Patients with Major Depressive Disorder (MDD) are also thought to have impairment in the CSPT circuitry as they are characterized by clinical gating deficits. Therefore, we assessed PPI in non-psychotic MDD patients and compared their results to schizophrenia patients and non-patients. METHOD: PPI was assessed in 19 non-psychotic hospitalized MDD patients and compared to 14 hospitalized patients with schizophrenia and 13 archival normal comparison subjects. RESULTS: MDD patients had PPI levels that were significantly higher than schizophrenia patients. The MDD subjects had PPI levels that were lower than non-patients but these differences were not statistically significant. CONCLUSIONS: MDD patients without psychosis do not exhibit PPI deficits comparable to schizophrenia patients. However, the MDD patients demonstrated a non-significant tendency towards lower PPI than the non-patients. Our results replicate previous findings that PPI deficits are found in acutely hospitalized schizophrenia patients, even when treated with atypical antipsychotic medication. Future studies with psychotic MDD patients are necessary to fully understand the relationship between MDD, psychosis, symptom severity and PPI.     

Interleukin-1beta and tumor necrosis factor-alpha in children with major depressive disorder or dysthymia

BACKGROUND: Immune function is altered in adult depressed patients. The aim of our study was to see whether or not cytokine secretion is impaired at a very young phase of development of depressive disorders, possibly being pathogenetically involved in their course. METHODS: Basal plasma concentrations of interleukin-1beta (Il-1beta) and tumor necrosis factor-alpha (TNF-alpha) were measured radioimmunologically in 22 drug-free children-adolescents, 11 with recurrent major depressive disorders (MDD) and 11 with dysthymia (DYS), and in 11 psychophysically healthy age-sex matched controls. Depression was monitored using the Poznanski Rating Scale and Anxiety with the Reynold Rating Scale. RESULTS: Il-1beta levels were not significantly different in MDD from controls and significantly higher than normal in DYS subjects. TNF-alpha levels were not significantly different in MDD patients from controls and significantly lower than normal in DYS patients. Cytokine concentrations were correlated with anxious and depressive symptomatology in MDD but not in DYS patients. CONCLUSIONS: There is a cytokine pathology in depressive disorders of obscure etiopathogenetical significance.     

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.     

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.     

Categoric overgeneral autobiographical memory in adolescents with major depressive disorder

BACKGROUND: Categoric, overgeneral autobiographical memory is more common in depressed adults than controls and predicts persistence of depression. This cross-sectional study investigated whether, compared with non-depressed psychiatric cases and community controls, first episode major depressive disorder (MDD) in adolescents is associated with categoric overgeneral memory retrieval. METHODS: Ninety-six clinically referred adolescents (aged 12-17 years) with MDD, 26 non-depressed psychiatric cases and a sample of 33 community controls were recruited. All subjects were assessed using the Kiddie-Schedule for Schizophrenia and Affective Disorders, and completed Williams' cued Autobiographical Memory Test and the Mood and Feelings Questionnaire. Hamilton Depression Rating Scales were completed with MDD subjects, as an index of depression severity. RESULTS: Adolescents with current first episode MDD retrieved more categoric overgeneral memories than controls, but not than non-depressed psychiatric cases. Adolescents in full remission from a recent episode of MDD retrieved more categoric memories to positive cues than controls. Categoric memory in MDD was related to observer-rated and self-reported severity, but not to the pattern of co-morbid diagnoses. There were negative correlations between IQ and categoric memories in both clinical cases and controls. A positive correlation between categoric memory to negative cues and self-reported depressive symptoms was found in clinical cases (but not controls). CONCLUSIONS: In adolescents, increased categoric overgeneral memory is associated with, but not specific to first episode MDD. Positive categoric memories are also increased in fully remitted MDD as compared to controls.     

Somatic symptoms in outpatients with major depressive disorder treated with fluoxetine

Among patients with major depressive disorder (MDD), physical and somatic symptoms are associated with a high degree of disability and healthcare utilization. However, little is known regarding the treatment of these symptoms with standard pharmacotherapy. To measure somatic symptoms of depression, the authors administered The Symptom Questionnaire (Kellner) before and after 8 weeks of open-label treatment with fluoxetine, 20 mg/day, in 170 MDD outpatients (mean age: 40.4 years). Somatic symptom scores decreased significantly after fluoxetine treatment. The degree of reduction in somatic symptoms was significantly and positively correlated with the degree of improvement in depressive symptoms as measured by the 17-item Hamilton Rating Scale for Depression (Ham-D). Somatic symptom scores at baseline did not predict the degree of reduction in Ham-D scores during treatment. However, fluoxetine-remitters had significantly lower somatic symptom scores at end-point than responders who did not remit. Taken together, these findings suggest that developing treatment strategies that successfully target somatic symptoms of depression may further improve the ability to treat depression to remission.     

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.