Untreated Major Depression Research Articles

Reduced amygdala volume in newly admitted psychiatric in-patients with unipolar major depression

Structural neuroimaging studies investigating amygdala volumes in patients suffering from major depression have yielded variable results. Discrepant findings across studies may be attributable in part to heterogeneity with respect to antidepressant medication and to lack of adequate control for the effects of total brain volume and age. Here, 24 unipolar depressed in-patients newly admitted to a psychiatric unit and 14 healthy control participants matched for age, gender, and years of education underwent quantitative magnetic resonance imaging (MRI) toward the end of a one-week washout period. Saliva cortisol was measured at 08.00 and at 16.00 h in patients during washout. Absolute amygdala volumes were significantly reduced in the patient group (by 13% in left amygdala and 12% in right amygdala). The effect of reduced amygdala volumes in patients remained significant after correction for brain volume (BV) and age. Furthermore, amygdala volume measurements in the patient sample showed a significant inverse relationship to the number of preceding depressive episodes. In patients, severity of disease (baseline HAMD scores) and baseline cortisol levels were not related to amygdala volume. This study of a sample of unmedicated depressed in-patients adds to the small, yet growing, body of evidence linking untreated major depression to reduced amygdala volume.

Detecting and Evaluating Depression Among Elderly Patients in Home Health

Among home health patients, depression is a debilitating and treatable psychiatric condition that often remains undiagnosed and reduces quality of life, social interactions, daily functioning, and treatment adherence. Untreated major depression increases functional decline; costly medical, emergency, and mental health visits; and reliance on disability or welfare. In the worst case, many patients decide that life is not worth living and attempt suicide. Screening and careful assessment are the keys to the detection and evaluation of depression. Scant literature exists to guide the evaluation and management of depressive disorders in home care. This article illustrates the evaluation and management of depression. The home care provider is in a key position to detect, evaluate, and intervene with depression and monitor its complications such as suicide risk. Evaluating depression is a professional nursing responsibility requiring judgment and the ability to understand subtle dynamics of loss, hopelessness, and emotional pain.

Modafinil Treatment for Fatigue in HIV+ Patients

Fatigue is widespread among human immunodeficiency virus-positive (HIV+) patients, yet few studies have assessed effective treatments. The authors conducted a pilot study to evaluate the efficacy of modafinil for fatigue in this clinical population. Response was evaluated after a 4-week open-label trial. Data were collected from February 2003 through January 2004. Responders were offered 8 additional weeks of modafinil. Inclusion criteria included written approval from the primary care physician, clinically significant fatigue, current use of anti-retroviral medications, and the absence of treatable medical conditions known to cause fatigue. Exclusion criteria included untreated major depression and current substance abuse. Major outcome measures were the Fatigue Severity Scale, Chalder Fatigue Scale, Hamilton Rating Scale for Depression, Beck Depression Inventory, and neuropsychological tests assessing verbal memory, speed of processing, and executive function. Immunologic and virologic measures were performed at baseline and week 4 to assess safety of treatment. All 30 patients who enrolled completed 4 weeks of treatment; 24 (80%) were rated as responders. Responders showed statistically significant improvement on all measures of fatigue, depressive symptoms, and executive function, while nonresponders did not. Mean values of CD4 cell count and HIV RNA viral load did not change. The most common side effect was headache, followed by irritability and feeling "hyper." This pilot study shows encouraging results for modafinil in alleviation of fatigue in HIV+ patients. In addition, depressive symptoms were substantially reduced. Improvements on measures of verbal memory and executive function were significant, but in the absence of a placebo control, the magnitude of effect due to practice cannot be determined.

A longitudinal population-based study of treated and untreated major depression.

Few studies have investigated the factors associated with different outcomes in individuals with major depressive episode (MDE) in relation to mental health service utilization. This study was to, in depressed individuals who used and did not use mental health services, 1) compare the demographic, psychosocial, and clinical characteristics; 2) estimate the risk of MDE in a 6-year follow-up period; and 3) identify the factors associated with the persistence/recurrence of MDE. This was a population- based longitudinal analysis. Participants included the longitudinal cohort of the Canadian National Population Health Survey who reported MDE at the baseline survey (n = 609). MDE was measured by the Composite International Diagnostic Interview-Short Form for Major Depression. In the 6-year follow-up period, 49.8% of participants with treated depression developed subsequent MDE; 28.7% of those with untreated depression reported MDE. Multivariate analyses showed that, among those who reported the use of mental health services, childhood and adulthood traumatic events and functional impairment were related to the recurrence of MDE. Among those who did not use mental health services, reported negative life events and the severity of depressive symptoms were predictive of recurrent MDE. The risk of the recurrence of MDE and associated factors differ in mental health service users and nonusers. Future studies need to confirm these results and to identify service barriers for those who do not use the services and who are at a high risk of MDE.

Working memory dysfunction in major depression: an event-related potential study

Objectives: To study working memory function in untreated major depression using a digit probe identification and matching task. Methods: We compared behavioural performance and event-related potentials during processing of the Sternberg working memory task in 14 depressed patients and 14 healthy matched control subjects. Results: Patients made more mistakes than controls as the memory load was increased from one to 5 digits and had significantly slower reaction times at all levels of memory load. The patients' event-related potentials (ERPs) differed significantly from controls. Pathological changes were similar for auditory and visual presentation. Surface negative activity in the 157–210 ms section of the waveform was reduced for all levels of memory load, suggesting abnormal sensory/perceptual processing in the modality-specific association cortices, possibly due to a failure of selective attention mechanisms. In the 375–840 ms epoch, the patients' responses showed large amplitude sustained negative activity, maximal at Cz and a reduced late positive wave. The large prolonged negativity in the patients' ERPs suggests activation of additional neuronal assemblies than those normally participating in the task. This could reflect either compensatory mechanism or dysfunction of inhibitory systems. These changes were sensitive to memory load, suggesting that they reflect alterations of memory-related processes. Conclusions: This study provides objective evidence that major depression significantly affects working memory. The ERP changes in depression could be accounted for by dysfunction of the central executive control of working memory.

Platelet serotonin functions in untreated major depression

The uptake of [ 14C]5-HT, [ 3H]paroxetine and [ 3H]LSD binding was determined in platelets from 30 untreated patients with major depression and compared with corresponding variables from 30 healthy age-, sex- and season-matched control subjects. The maximum velocity ( V max) for the 5-HT uptake was significantly decreased in patients ( P=0.014) compared to control subjects. Depressed women had significantly lower V max than female control subjects. In men, V max did not differ between patients and control subjects. V max was significantly lower in male inpatients compared with male outpatients ( P=0.05). The density ( B max) of 5-HT uptake sites was found to be significantly increased in patients ( P<0.05) compared to control subjects and male patients had significantly higher B max than male control subjects, but there was no difference between female control subjects and female patients. No significant difference was found in B max of 5-HT 2-receptors between patients and control subjects. A positive correlation was found between B max of 5-HT 2-uptake sites and the degree of anxiety and between B max of 5-HT 2 receptors and MADRS scores. B max of 5-HT 2-receptors was positively correlated with the degree of suicidality. The results in the present study indicate that there may be a gender difference in serotonergic dysfunction in depression.

Platelet serotonergic indices in major depression: up-regulation of 5-HT 2A receptors unchanged by antidepressant treatment

This study examined, in the largest sample of major depressives reported so far, platelet serotonergic parameters (5-HT uptake, [ 3H]paroxetine binding and 5-HT 2A receptors measured by [ 3H]LSD binding) in 60 antidepressant-free depressed patients and 40 age- and gender-matched control subjects before treatment, and in 45 major depression patients during treatment with antidepressants. We found that, at baseline, the density ( B max) of 5-HT 2A receptors was significantly higher (by 39%) in depressed patients than in controls. Suicidal patients had significantly higher B max values than controls or non-suicidal patients. The rate of serotonin uptake ( V max), but not the uptake at a single concentration, was significantly higher in depressed patients, particularly in females. There was no significant difference between the K d or B maxof [ 3H]paroxetine binding in control and depressed subjects. Treatment with antidepressant drugs of different pharmacological profile had no significant effect on the density of 5-HT 2A receptors, nor did the receptor number predict the response to treatment. The affinity of serotonin uptake site for 5-HT and [ 3H]paroxetine significantly decreased during treatment with antidepressants, particularly SSRIs. Suppression of 5-HT uptake correlated with decreases in Hamilton depression (HAMD) scores. Our data suggest that the increased density of platelet 5-HT 2A receptors may be associated with untreated major depression in antidepressantfree depressed patients, in particular those with suicidal thoughts. The persistence after antidepressant treatment and clinical improvement would suggest that up-regulation of 5-HT 2A receptors is a trait rather than state phenomenon. Correlation of 5-HT uptake suppression with decreases in HAMD scores suggests that serotonin uptake inhibition is a relevant factor in antidepressant drug effect and clinical improvement.

The use of psychiatric services before imprisonment: a survey and case register linkage of sentenced prisoners in Melbourne.

Information about contact with psychiatric services before imprisonment was obtained for a stratified random sample of sentenced prisoners, who were not receiving prison psychiatric care, in Melbourne's three metropolitan prisons. The sample of 158 men and 31 women was matched with the longitudinal person-linked records of state psychiatric service use in the Victorian Psychiatric Case Register (VPCR). Records of contact with the state services were found for 54 men (34%) and 19 women (61%), including records of in-patient treatment for 25 men (16%) and 15 women (48%). For 64% of individuals with a positive match, the case-note diagnoses were substance use disorders only. Diagnoses of psychotic disorders were recorded for four prisoners, and mood disorders for another six. In addition, clinicians conducted standardized diagnostic interviews and enquired about treatment and personal history. A further 24 prisoners reported specialist psychiatric treatment outside the state treatment sector. This study links the findings from an interview survey of psychiatric morbidity in prisoners with the records available in the VPCR, and emphasizes a number of matters important to the public health. The high rates of previous treatment for substance abuse disorders, the apparent pool of prisoners with largely untreated major depression, and the service needs of those with chronic psychotic disorders are discussed.

Hidden severe psychiatric morbidity in sentenced prisoners: an Australian study

The aim of this survey was to estimate the prevalence of severe mental disorders in a representative sample of sentenced prisoners. The subjects were selected as a random sample of sentenced prisoners in Melbourne's three metropolitan prisons. Interviews were conducted with 158 men and 31 women. Clinicians used the Structured Clinical Interview for DSM-III-R (SCID) to diagnose psychotic, affective, and substance use disorders. Six prisoners (3%) received current diagnoses of psychotic disorders, and 23 (12%) were diagnosed as having current mood disorders, mainly major depression. A lifetime diagnosis of at least one mental disorder each was made for 82% of the respondents, and in 26% more than one lifetime disorder was diagnosed. Sixty-nine percent received lifetime diagnoses of dependence on or abuse of alcohol, other psychoactive substances, or a combination of these. These findings do not indicate a large-scale shift of deinstitutionalized psychotically ill people from mental hospitals to prisons. They do, however, highlight the diversion into the corrections system of substance-dependent people and the apparent pool of prisoners with largely untreated major depression.

Nocturnal Serum Thyrotropin (TSH) Surge and the TSH Response to TSH-Releasing Hormone: Dissociated Behavior in Untreated Depressives*

TSH secretion, with particular regard to the nocturnal surge of the hormone, was evaluated in 15 women (age range, 35-66 yr; mean, 50 yr) with untreated major endogenous depression and 15 healthy women (age range, 32-67 yr; mean, 53 yr) using an ultrasensitive assay. Mean morning (0830 h) TSH values did not differ in the 2 groups (1.3 +/- 02 mU/L in depressives and 1.4 +/- 0.1 mU/L in controls), whereas mean nighttime (2400-0200 h) values were significantly reduced in depressives (1.5 +/- 0.3 vs. 3.1 +/- 0.3 mU/L; P less than 0.0005). At variance with the control group, morning and nighttime TSH values did not differ in the depressives. The nocturnal serum TSH surge was abolished in 14 of 15 depressed patients. The mean peak TSH value after TRH was slightly yet significantly lower in the depressives. Patients with subnormal (less than 0.4 mU/L) TSH values in the morning had a serum TSH increase after TRH less than 2 mU/L in 5 of 6 cases and a lack of the nocturnal TSH surge in 6 of 6. Among the 9 patients with normal TSH values in the morning, the nocturnal serum TSH surge was lost in 8 of 9, whereas the response to TRH was normal in all. The depressives, at variance with other reports, showed significantly lower values of total and free thyroid hormones. Mean serum sex hormone-binding globulin (SHBG) and ferritin were also significantly reduced. In conclusion, major endogenous depression is associated with a major impairment of TSH secretion, which baseline TSH measurements in the morning and the evaluation of the TSH response to TRH may not reveal. In this regard, the loss of the nocturnal serum TSH rise would appear to be a more sensitive indicator of hypothalamus-pituitary-thyroid axis alterations in depressives than the TRH test, which is commonly used in the evaluation of these patients. The lack of the nocturnal TSH surge may be responsible for the reduced thyroid hormone secretion and supports the case for some degree of central hypothyroidism in endogenous depression.