Positive association between the GABRA5 gene and unipolar recurrent major depression

The authors describe a case with double perinatal survival of a monoamniotic twin pregnancy and give a survey on the literature regarding this rare and riskful kind of twinning. The importance of accurate antenatal diagnosis, intensive fetal surveillance and operative delivery is discussed.     

Relative memory deficits in recurrent versus first-episode major depression on a word-list learning task.

Although memory deficits are associated with major depressive disorder, few studies have identified which patient characteristics predict impairment. Because recurrent depression appears related to more severe cerebral dysfunction, the present study tested whether recurrent depressed individuals have worse memory function than first-episode depressed individuals. Two groups of young-adult, nonpsychotic, depressed inpatients (20 single episode [SE] and 46 recurrent episode [RE]) were administered the California Verbal Learning Test within a broader battery of neuropsychological tests. The groups were equivalent in age, education, estimated IQ, severity of depression, and demographic composition. The RE group demonstrated memory deficits relative to both the SE group and published norms, but no other significant difference was found across the battery. Data indicate that abnormal memory performance is associated with recurrent depression, whereas memory deficits are not prominent in first-episode depressed individuals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Seasonal influence on platelet 5-HT levels in patients with recurrent major depression and schizophrenia

The influence of seasons on platelet serotonin (5-HT) concentration was determined in 88 unipolar depressed and 117 schizophrenic male inpatients, and 90 normal male controls. Platelet 5-HT concentrations showed moderate, but insignificant intragroup seasonal variations in healthy controls and in the groups of depressed (psychotic and nonpsychotic) and schizophrenic (positive and negative) patients. In spring, platelet 5-HT concentrations were higher in schizophrenic patients than in normal controls or in depressed patients, while in other seasons platelet 5-HT concentrations were not significantly different between the groups. Higher platelet 5-HT concentrations were detected in psychotic when compared to nonpsychotic depressed patients in summer, fall, and winter. Increased platelet 5-HT concentrations observed in schizophrenic patients with positive symptoms clearly separated these patients from patients with negative schizophrenia, especially in spring, summer, and fall. Our results indicate the necessity to match patients with regard to the season of the sampling, and to divide depressed and schizophrenic patients into subtypes.     

Implications of failing to achieve successful long-term maintenance treatment of recurrent unipolar major depression

This is a review article that describes current data, issues, and controversies regarding long-term maintenance treatment of depression. The authors suggest that the issues represent a public health crisis. This paper will identify the need, from both a health-care and economic perspective, for more research on the efficacy of maintenance treatment for this pernicious and lifelong disorder. Data will be reviewed on the natural course of unipolar depression, focusing on clinical predictors that increase the risk of a relapse or recurrence. This review will include new data from the National Institute of Mental Health Collaborative Depression Study. Failing to achieve adequate maintenance treatment for unipolar recurrent major depression has psychopathological and psychosocial consequences, decreasing work productivity and the quality of a person's life. Published double-blind placebo-controlled studies on continuation treatment of major depression will be reviewed. The two competed double-blind placebo-controlled long-term maintenance studies of recurrent unipolar major depression will be discussed in detail. Despite the positive findings from research done to date, there remain many unresolved questions relating to the maintenance treatment of recurrent unipolar major depression, and the need for research in this area is critical. The paper concludes with recommendations for long-term maintenance treatment of unipolar major depression.     

The hypothalamic-pituitary-thyroid axis in major depression

We investigated the capacity of several thyroid-axis measures to distinguish between depressed and control subjects and determined whether these variables were related to antidepressant treatment response. We studied 105 subjects who fulfilled the DSM-III-R criteria for a current major depressive episode and 41 volunteers with no current mental disorder. The following thyroid-axis variables were measured: difference between T4 levels at 09.00 hours and 13.00 hours; baseline TSH; maximal TSH response to 400 micrograms TRH (delta max TSH); and presence of a blunted delta max TSH. The T4 difference variable alone distinguished between depressed and control subjects. In multivariate analyses, T4 difference and delta max TSH were independently related to antidepressant-treatment outcome, and predicted a modest proportion (14%) of the variance in outcome. The relationship between these two variables and treatment outcome was particularly strong in depressed male subjects who were receiving desipramine, for whom they accounted for 36% of the variance in treatment outcome. The T4 difference variable both distinguished between depressed and control subjects and was related to treatment outcome. Although this finding requires replication, it is consistent with other reports of the usefulness of thyroid-axis indices measured at different times of day in depressed patients.     

Frontostriatal deficits in unipolar major depression

Recent accounts of major depression have tended to focus on dysfunction of frontothalamic-striatal reentrant circuits as a possible source of the disorder. Evidence of frontostriatal involvement in unipolar major depression from lesion and neuropsychological studies, and functional and structural imaging studies is examined. The high incidence of depressive symptomatology following left frontal and basal ganglia lesions implicate these as possible sites of dysfunction. Neuropsychological evidence indicates similar deficits in patients with major depression, perhaps with dorsolateral prefrontal deficits most prominent. Structural imaging studies report frontal and basal ganglia (BG) abnormalities particularly in cases of late-age onset depression. Resting state functional imaging studies show deficits in dorsolateral, anterior cingulate (medial frontal), and BG structures. Activation imaging studies show less consistent evidence of dorsolateral deficit, while anterior cingulate deficit is more consistently demonstrated. Variability in findings across studies may reflect differences between subtypes of depression and differences in methodology. Possible involvement of the BG in the psychomotor retardation of depression is examined. It is concluded that, while there is evidence of frontostriatal deficit in major depression, the exact nature of such deficits is uncertain. Issues such as component vs. system dysfunction need to be addressed.     

Hypothyroidism and hyperthyroidism in major depression revisited

BACKGROUND: The aim of our study was to evaluate the prevalence of thyroid abnormalities among depressed outpatients and to examine the response to treatment of those subjects with relatively low or high thyroid hormone levels. METHOD: Outpatients (N = 200) 18 to 65 years of age who met DSM-III-R criteria for major depression were screened for the presence of thyroid abnormalities using a number of thyroid indices. Of these patients, 166 were then treated openly with the antidepressant fluoxetine for 12 weeks. We assessed whether patients with relatively low or high thyroid hormone levels had a different response to treatment compared with other patients. The 17-item Hamilton Rating Scale for Depression (HAM-D-17) was administered during the study to assess changes in depressive symptoms. Thyroid function was assessed by measuring T3, T4, free T4 index (FT4I), T3 uptake (T3U), and serum thyroid-stimulating hormone (TSH) levels. RESULTS: No clinical cases of hyperthyroidism or hypothyroidism were detected. Of the patients examined, 5 (2.6%) had slightly elevated TSH levels (range, 4.7-8.2); none of these had T4 or FT4I levels below the normal range. Subnormal levels of T4 or FT4I were found in 1 subject (0.5%). T3 and T3U levels were below the normal range in a larger number of patients (7.6% and 15.0% respectively), but only 1 of these patients had elevated TSH levels. None of the patients had levels of TSH below the normal range, and only 3 subjects (1.5%) had T4 levels above the normal range. No relationship was found between response rate (assessed as either change in HAM-D-17 score or as remission of depressive symptoms with a HAM-D-17 score < or = 7 for 3 consecutive weeks) and each of the thyroid tests, even after adjusting for baseline severity of depression. CONCLUSION: In depressed outpatients, it appears that hypothyroidism and hyperthyroidism are extremely uncommon and that the presence of subtle thyroid function abnormalities does not have an impact on treatment outcome.     

Inadequacy of antidepressant treatment for patients with major depression who are at risk for suicidal behavior

Microscopic evaluation of all adult tonsillar specimens has been considered essential despite the low incidence of unsuspected pathologic conditions. We evaluate whether routine histologic examination of clinically benign adult tonsillar specimens is indicated. We retrospectively reviewed pathology results from all tonsillectomies performed on patients ages 18 years or older at our institution from 1989 through 1996. Three groups were created on the basis of indications for tonsillectomy: (1) routine tonsillectomies for benign disease, (2) asymmetric tonsils, and (3) search for unknown primary lesions. Demographic data and pathologic findings in each group were analyzed. In 1280 tonsillectomies performed for benign disease there were no malignancies (0%) and 32 cases (2.50%) with clinically unsuspected benign pathologic conditions. In 31 cases of tonsillar asymmetry, two cases with malignant lymphoma (6.5%) and three cases with benign pathology (9.7%) were identified. In nine patients with squamous cell carcinoma metastatic to the neck, two occult primary lesions were identified in the ipsilateral tonsil. Our results suggest that histologic evaluation of adult tonsils removed for benign disease may be clinically unnecessary. The elimination of microscopic examination of tonsils removed from patients whose clinical presentation is entirely consistent with benign disease poses minimal risk of missing clinically significant pathologic conditions. Substantial costs for negative examinations may be avoided.     

Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine

We recently reported that fluoxetine or paroxetine, two selective serotonin reuptake inhibitors (SSRIs), when administered to rats, increase the brain content of the neurosteroid 3alpha-hydroxy-5alpha-pregnane-20-one (3alpha5alpha-ALLO) without altering the brain content of other neurosteroids. ALLO (3alpha5alpha and 3alpha5beta isomers) binds with high affinity to various gamma-aminobutyric acid (GABA) receptor A subtypes and facilitates the action of GABA at these receptors. We hypothesized that the increase of ALLO brain content induced by treatment with SSRIs could contribute to alleviating the anxiety and dysphoria associated with the symptomatology of major unipolar depression. We measured ALLO content in four cisternal-lumbar fractions of cerebrospinal fluid (CSF) before and 8-10 weeks after treatment with fluoxetine or fluvoxamine in 15 patients with unipolar major depression. The concentration of ALLO ( approximately 40 fmol/ml in each CSF fraction of three control subjects) was about 60% lower in patients with major unipolar depression. However, in the same patients, fluoxetine or fluvoxamine treatment normalized the CSF ALLO content. Moreover, a statistically significant correlation (r = 0.58; P < 0.023; n = 15) existed between symptomatology improvement (Hamilton Rating Scale for Depression scores) and the increase in CSF ALLO after fluoxetine or fluvoxamine treatment. The CSF content of PREG and PROG remained unaltered after treatment and failed to correlate with the SSRI-induced increase of CSF ALLO. The normalization of CSF ALLO content in depressed patients appears to be sufficient to mediate the anxiolytic and antidysphoric actions of fluoxetine or fluvoxamine via its positive allosteric modulation of GABA type A receptors.     

Autobiographical memory in the euthymic phase of recurrent depression.

The authors investigated autobiographical memory specificity in subjects who formerly had depression. In 122 euthymic patients with at least two previous major depressive episodes, memory specificity was significantly impaired compared to matched control participants but not related to residual symptoms and illness characteristics, was not differentially affected by cognitive therapy, and was also not predictive of relapse/recurrence during the 2-year follow-up. However, memory specificity was associated with age, education, and immediate and delayed memory recall. The results suggest that memory specificity may reflect a global cognitive impairment that remains in patients who (formerly) had depression but does not constitute a trait marker for vulnerability for relapse/recurrence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of major depression symptoms in multiple sclerosis patients

Retrospective review of affective disturbances in 238 patients with multiple sclerosis (MS) seen over a 6-month period revealed: 1) 51 patients (22%) received pharmacologic treatment for depressive symptoms during or within 4 years of the study period, and 17 (7%) received treatment for rapid mood swings; 2) among the 51 depressed patients, response rate to medication was extremely high; 3) relapse of depressive symptomatology after discontinuation of medication was also high (17/29); 4) first episodes of major depression frequently occurred during periods of MS progression or exacerbation, but first episodes also occurred during periods of relative clinical stability; 5) suicidal ideation was common (12 patients), but only 1 patient had a history of attempted suicide; and 6) side effects were tolerable in most patients.     

Benchmarks for psychotherapy efficacy in adult major depression.

This study estimates pretreatment-posttreatment effect size benchmarks for the treatment of major depression in adults that may be useful in evaluating psychotherapy effectiveness in clinical practice. Treatment efficacy benchmarks for major depression were derived for 3 different types of outcome measures: the Hamilton Rating Scale for Depression (M. A. Hamilton, 1960, 1967), the Beck Depression Inventory (A. T. Beck, 1978; A. T. Beck & R. A. Steer, 1987), and an aggregation of low reactivity-low specificity measures. These benchmarks were further refined for 3 conditions: treatment completers, intent-to-treat samples, and natural history (wait-list) conditions. The study confirmed significant effects of outcome measure reactivity and specificity on the pretreatment-posttreatment effect sizes. The authors provide practical guidance in using these benchmarks to assess treatment effectiveness in clinical settings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alcohol consumption and major depression in the Canadian population

OBJECTIVE: Various clinical studies have documented associations between alcohol consumption and depressive disorders. In some circumstances, alcohol ingestion may cause or worsen depression, whereas in other circumstances the direction of causal effect may be reversed. The objective of this study was to evaluate associations between alcohol consumption and major depression in the Canadian population. METHOD: Data from the Canadian National Population Health Survey (NPHS) were analyzed. This survey, conducted by Statistics Canada in 1994, used a probability sample of 17,626 subjects. The NPHS included measures of alcohol ingestion and a diagnostic screen for major depression (Composite International Diagnostic Interview [CIDI] Short Form). RESULTS: Subjects reporting any drinking in the year preceding the interview were more likely to have experienced an episode of major depression during that time than subjects reporting no drinking. Subjects reporting maximal ingestions of 5 or more drinks (and especially 10 or more drinks) on at least 1 occasion during the preceding year were also at greater risk of major depression than nondrinking subjects or subjects reporting smaller maximal ingestions. Neither the average amount consumed daily nor the frequency of drinking was associated with major depression. CONCLUSIONS: In the general population, there is no simple relationship between the quantity or frequency of alcohol consumption and the prevalence of major depression. Any drinking and maximal consumption on 1 occasion, however, are related to the prevalence of major depression. Further research is needed to delineate causal mechanisms so that clinical and public-health interventions can be formulated.     

Personality disorders in adolescents with major depression, substance abuse disorders, and coexisting major depression and substance use disorders.

This study examined the presence of personality disorders in adolescent inpatients with major depression (MDD; n?=?45), substance use disorders (SUD; n?=?27), or both disorders combined (MDD-SUD; n?=?42). A consecutive series of patients were given structured diagnostic interviews for Axes I and II disorders. The groups did not differ with regard to age, gender, ethnicity, socioeconomic status, psychiatric history, or global assessment of functioning. Borderline personality disorder was diagnosed more frequently in the MDD-SUD group than in the MDD or SUD groups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mindfulness-based cognitive therapy to prevent relapse in recurrent depression.

For people at risk of depressive relapse, mindfulness-based cognitive therapy (MBCT) has an additive benefit to usual care (H. F. Coelho, P. H. Canter, & E. Ernst, 2007). This study asked if, among patients with recurrent depression who are treated with antidepressant medication (ADM), MBCT is comparable to treatment with maintenance ADM (m-ADM) in (a) depressive relapse prevention, (b) key secondary outcomes, and (c) cost effectiveness. The study design was a parallel 2-group randomized controlled trial comparing those on m-ADM (N = 62) with those receiving MBCT plus support to taper/discontinue antidepressants (N = 61). Relapse/recurrence rates over 15-month follow-ups in MBCT were 47%, compared with 60% in the m-ADM group (hazard ratio = 0.63; 95% confidence interval: 0.39 to 1.04). MBCT was more effective than m-ADM in reducing residual depressive symptoms and psychiatric comorbidity and in improving quality of life in the physical and psychological domains. There was no difference in average annual cost between the 2 groups. Rates of ADM usage in the MBCT group was significantly reduced, and 46 patients (75%) completely discontinued their ADM. For patients treated with ADM, MBCT may provide an alternative approach for relapse prevention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological function in young patients with unipolar major depression

BACKGROUND: While neuropsychological studies have consistently reported impaired cognition in elderly patients with unipolar depression, studies of cognitive function in younger patients with depression have produced equivocal results. The aim of this study was to examine the presence and nature of cognitive deficits in young patients with depression. METHODS: Neuropsychological function was assessed in 20 young patients with unipolar depression, in comparison to 20 age-, education- and IQ- matched controls. Subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were employed, as this battery has proved sensitive to deficits in middle-aged and elderly patients with depression. RESULTS: The patients were not impaired for short-term memory capacity, spatial working memory, planning ability, cognitive speed, delayed matching to sample or recognition memory. Compared to controls, the patients showed impaired subsequent movement latencies on the Tower of London task, suggesting deficits in the ability to sustain motor responses in depression. The depression group were also impaired on the task of attentional set shifting, requiring more trials to criterion at the intradimensional stage of the task and being more likely to fail the task at the extradimensional shift stage than controls. Further analysis indicated that half of the depression group failed to complete all stages of the set shifting task. These patients were more likely to have required in-patient hospitalization at some time during their illness. CONCLUSIONS: These results indicate that there are specific cognitive deficits in young patients with depression and that their presence may be related to a history of hospitalization.