Severe Major Depressive Episode Research Articles

Tobacco Consumption Concerns With the Use of CYP1A2 Metabolized Antidepressants

Tobacco Consumption Concerns With the Use of CYP1A2 Metabolized Antidepressants

The role of adiposity in the relationship between serum leptin and severe major depressive episode

AbstractTo assess the role that adiposity plays in the association between leptin and major depressive episode (MDE), we analyzed the data of 1046 men and 1359 women aged 20–39 years, who completed an interview and had blood collected as a part of the National Health and Nutrition Examination Survey (NHANES) between 1991 and 1994. Waist-hip ratio (WHR) was used as an indicator of adiposity. MDE was assessed with the Diagnostic Interview Schedule. For normal-WHR women, the prevalence of MDE was reversely associated with leptin levels, 13.7(4.4)%, 12.2(4.0)% and 2.3(1.8)% respectively for lower, interquartile, and upper quartile. For abnormal-WHR women, the prevalence of MDE was positively associated with leptin, 6.1(2.3)%, 9.1(2.4)% and 20.0 (3.8) respectively for the three leptin levels. Compared to women with lower quartile of leptin, the odds ratio of MDE for women with upper quartile was 0.09 (0.01–0.98) for normal-WHR women but 4.35 (1.55–12.2) for abnormal-WHR women. No moderating effects were observed among men. Using BMI in place of WHR revealed similar findings. The association between MDE and leptin is moderated by adiposity. High leptin levels are associated with low odds of MDE among women with normal adiposity but high odds among women with abnormal adiposity.

The Suicidal State between “the Wish to Die” and “an Urge to Die”

From the standpoint of existential analysis, the present article compares the psycho-dynamics of the suicidal states examined hereby, where the first case is diagnosed as a “Major depressive episode. Borderline personality disorder” and the second case as “Severe major depressive episode, with psychotic elements”. In the first case, the suicidal state was based on the association between the second motivation (“to enjoy life”) and the third motivation (“to be myself”), and the suicidal act was a “false” one. In the second case, the suicidal state resulted from the second motivation (“to enjoy life”) and the first motivation (“being able to be”), and it was a “real” suicidal act.

Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes.

The neuroinflammatory hypothesis of major depressive disorder is supported by several main findings. First, in humans and animals, activation of the immune system causes sickness behaviors that present during a major depressive episode (MDE), such as low mood, anhedonia, anorexia, and weight loss. Second, peripheral markers of inflammation are frequently reported in major depressive disorder. Third, neuroinflammatory illnesses are associated with high rates of MDEs. However, a fundamental limitation of the neuroinflammatory hypothesis is a paucity of evidence of brain inflammation during MDE. Translocator protein density measured by distribution volume (TSPO VT) is increased in activated microglia, an important aspect of neuroinflammation. To determine whether TSPO VT is elevated in the prefrontal cortex, anterior cingulate cortex (ACC), and insula in patients with MDE secondary to major depressive disorder. Case-control study in a tertiary care psychiatric hospital from May 1, 2010, through February 1, 2014. Twenty patients with MDE secondary to major depressive disorder and 20 healthy control participants underwent positron emission tomography with fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA). Patients with MDE were medication free for at least 6 weeks. All participants were otherwise healthy and nonsmokers. Values of TSPO VT in the prefrontal cortex, ACC, and insula. In MDE, TSPO VT was significantly elevated in all brain regions examined (multivariate analysis of variance, F15,23 = 4.5 [P = .001]). The magnitude of TSPO VT elevation was 26% in the prefrontal cortex (mean [SD] TSPO VT, 12.5 [3.6] in patients with MDE and 10.0 [2.4] in controls), 32% in the ACC (mean [SD] TSPO VT, 12.3 [3.5] in patients with MDE and 9.3 [2.2] in controls), and 33% in the insula (mean [SD] TSPO VT, 12.9 [3.7] in patients with MDE and 9.7 [2.3] in controls). In MDE, greater TSPO VT in the ACC correlated with greater depression severity (r = 0.63 [P = .005]). This finding provides the most compelling evidence to date of brain inflammation, and more specifically microglial activation, in MDE. This finding is important for improving treatment because it implies that therapeutics that reduce microglial activation should be promising for MDE. The correlation between higher ACC TSPO VT and the severity of MDE is consistent with the concept that neuroinflammation in specific regions may contribute to sickness behaviors that overlap with the symptoms of MDE.

Longitudinal Monitoring of the Serotonin Transporter Gene Expression to Assess Major Depressive Episode Evolution

Background: Mood disorders are frequently characterized by uncertain prognosis and studying mRNA expression variations in blood cells represents a promising avenue of identifying biomarkers for mood disorders. State-dependent gene expression variations have been described during a major depressive episode (MDE), in particular for SLC6A4 mRNA, but how this transcript varies in relation to MDE evolution remains unclear. In this study, we prospectively assessed time trends of SCL6A4 mRNA expression in responder and nonresponder patients. Methods: We examined SLC6A4 mRNA expression in blood samples from 13 patients treated for severe MDE and their matched controls by reverse transcription and quantitative PCR. All subjects were followed for 30 weeks. Patients were classified as either responders or nonresponders based on improvement of depression according to the 17-item Hamilton Depression Rating Scale. Using a longitudinal design, we ascertained mRNA expression at baseline, 2, 8, and 30 weeks and compared mRNA expression between responder and nonresponder patients, and matched controls. Results: We observed a decrease of SLC6A4 mRNA expression in responder patients across a 30-week follow-up, while nonresponder patients exhibited up-regulated SLC6A4 mRNA. Conclusion: Peripheral SLC6A4 mRNA expression could serve as a biomarker for monitoring and follow-up during an MDE and may help to more appropriately select individualized treatments.

Troubles dissociatifs et troubles affectifs

The phenomenology of dissociative disorders may be complex and sometimes confusing. We describe here two cases who were initially misdiagnosed. The first case concerned a 61 year-old woman, who was initially diagnosed as an isolated dissociative fugue and was actually suffering from severe major depressive episode. The second case concerned a 55 year-old man, who was suffering from type I bipolar disorder and polyvascular disease, and was initially diagnosed as dissociative fugue in a mooddestabilization context, while it was finally a stroke. Yet dissociative disorders as affective disorder comorbidity are relatively unknown. We made a review on this topic. Dissociative disorders are often studied through psycho-trauma issues. Litterature is rare on affective illness comorbid with dissociative disorders, but highlight the link between bipolar and dissociative disorders. The later comorbidity often refers to an early onset subtype with also comorbid panic and depersonalization-derealization disorder. Besides, unipolar patients suffering from dissociative symptoms have more often cyclothymic affective temperament. Despite the limits of such studies dissociative symptoms-BD association seems to correspond to a clinical reality and further works on this topic may be warranted.

Prevalence and clinical correlates of co-occurring insomnia and hypersomnia symptoms in depression

BackgroundThe aim was to examine the prevalence and consequences of co-occurring insomnia and hypersomnia symptoms in depressed adults drawn from a representative sample of the U.S. population. MethodData from 687 National Comorbidity Survey Replication (NCS-R) respondents meeting criteria for a major depressive episode (MDE) in the past year were included. Respondents completed clinical interviews that assessed 12-month DSM-IV disorders, impairment, mental health treatment, and depressive symptom severity. Outcomes were compared between respondents who experienced insomnia symptoms-only (N=404), hypersomnia symptoms-only (N=44), both insomnia and hypersomnia symptoms (N=184) and no sleep problems (N=55) during an MDE. ResultsInsomnia and hypersomnia symptoms co-occurred in 27.7% of respondents with past-year MDEs, most frequently in bipolar spectrum disorders and major depressive disorder with dysthymia. Similar to the insomnia-only group, respondents with co-occurring sleep disturbances had more severe depression, and higher rates of past-year impulse control disorders and suicide planning. Similar to the hypersomnia-only group, respondents with co-occurring sleep disturbances had higher rates of past-year drug use disorders and suicide attempts. Compared to the insomnia-only and no sleep problem groups, respondents with both sleep disturbances were more frequently in mental health treatment, seeing a general practitioner, and taking antidepressants. LimitationsThe NCS-R is cross-sectional and did not evaluate sleep disorder diagnoses. ConclusionsCo-occurring insomnia and hypersomnia symptoms were associated with a more severe MDE. Further research is warranted to more fully understand the joint presentation of insomnia and hypersomnia in depression.

Converging translational evidence for the involvement of the serotonin 2A receptor gene in major depressive disorder.

An association between serotonin 2A receptor (5-HT2AR), encoded by HTR2A gene, and major depressive disorder (MDD) has been suggested. Here, we combined preclinical and ecological clinical approaches to explore the impact of impaired 5-HT2AR-mediated transmission on MDD or anxio-depressive-like phenotype in mice. Htr2a knock-out mice (Htr2a(-/-)) and wild-type mice were compared for the ability of chronic corticosterone to elicit some anxio-depressive-like phenotype in three behavioral paradigms (elevated plus maze, tail suspension test and splash test). Accordingly, two single nucleotide polymorphisms of the HTR2A gene (rs6314 ie His452Tyr and rs6313 ie 102C/T), which specific allelic variants may decrease 5-HT2AR-mediated transmission (as in Htr2a(-/-)mice), were studied in a sample of 485 Caucasian patients with MDD. In response to chronic corticosterone exposure, Htr2a(-/-) mice displayed more pronounced anxiodepressive-like phenotype than wild-type mice, as shown by a significant higher "emotionality score" (p<0.01). In patients, the C allele of rs6313 was more frequent in depressed patients (p=0.019) and was also associated with a more severe major depressive episode (p=0.03). This translational and ecological study involving constitutive Htr2a(-/-) knock-out mice and related SNPs in depressed patients suggests that a lower neurotransmission at the 5-HT2AR may favor the susceptibility and severity of MDE. It also suggests that specific allelic variants of the rs6313 and rs6314 may reduce 5-HT2AR-mediated transmission.

Agomelatine in the treatment of depressive disorders in clinical practice: multicenter observational CHRONOS study.

BackgroundCHRONOS was a large naturalistic study designed to evaluate the effectiveness and safety of agomelatine in the management of patients with major depression in routine clinical practice.MethodsPatients (n=6,276) with a moderate or severe major depressive episode without psychotic symptoms were treated initially as outpatients (80.2%) or in psychiatric facilities (19.8%) in 54 regions of the Russian Federation. Patients received a flexible-dosing regimen of agomelatine 25 mg or 50 mg once daily for 8 weeks, with frequent study visits (weeks 1, 2, 3, 4, 6, and 8).ResultsPatients (mean age 44 years, 72.6% female) showed progressive improvement on the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score from 22±6.9 at baseline to 4.7±4.7 at week 8 (P<0.0001). The proportion of responders (HAMD-17 decrease of ≥50%) was 90.1% and the proportion of remitters (HAMD-17 <7) was 79.1% at week 8. All individual HAMD-17 item scores improved rapidly, and the change relative to baseline was significant (P<0.0001) at week 1 and at each subsequent visit in all cases. There were corresponding rapid improvements in Clinical Global Impression Severity and Improvement scores. In the subgroup of patients with more severe illness (HAMD-17 ≥21 at baseline; n=3,478), the proportions of responders and remitters were 92.4% and 72.8%, respectively, at week 8.ConclusionAgomelatine was effective and well tolerated in a large sample of depressed patients in an observational treatment setting, and showed a rapid onset of benefit across all HAMD-17 items.

An attentional scope model of rumination.

Rumination, defined as repetitive thinking about negative information, has been found to lead to serious maladaptive consequences, including longer and more severe episodes of major depression. In this review, we present and discuss research findings motivated by the formulation that individual differences in cognitive processes that control how information is processed influence the likelihood that thoughts will become repetitive and negative. Several studies have demonstrated that a tendency to ruminate (i.e., trait rumination) is related to difficulties updating working memory (WM) and disengaging from and forgetting no-longer-relevant information. Other investigators have documented that trait rumination is also associated with an enhanced ability to ignore distracting information and with more stable maintenance of task-relevant information. In contrast to trait rumination, a state of rumination has been found to be related to widespread deficits in cognitive control. In this article, we discuss how the current accounts of control functioning cannot explain this pattern of anomalous control functioning. To explain these findings, including unexpected and contradictory results, we present an attentional scope model of rumination that posits that a constricted array of thoughts, percepts, and actions that are activated in WM or available for selection from long-term memory affects the control functioning of trait ruminators. This model explains, at a cognitive level, why rumination is particularly likely to arise when individuals are in a negative mood state; it also accounts for a number of findings outside of the rumination-control literature and generates several novel predictions.

Efficacy and safety of generic escitalopram versus Lexapro in the treatment of major depression: a multicenter double-blinded randomized controlled trial.

BackgroundDepression is an increasingly important public health problem in China, but only a small minority of patients with this condition receive treatment. One of the reasons for low treatment rates is the relatively high cost of imported antidepressant medications.AimCompare the efficacy and safety of the generic form of the selective serotonin re-uptake inhibitory (SSRI) antidepressant escitalopram to the proprietary form of escitalopram (Lexapro) in the treatment of major depression.MethodsA multicenter double-blinded randomized controlled trial enrolled 260 patients with depression and randomly assigned them to receive eight weeks of treatment with either generic escitalopram (n=130) or Lexapro (n=130). Efficacy was assessed by the Hamilton rating scale for depression (HAMD-17). Safety was assessed by evaluating adverse events reported by patients, regularly recording vital signs, and conducting laboratory tests and electrocardiograms.ResultsThere were 35 (27%) dropouts during the 8 weeks of treatment in the generic escitalopram group and 32 (25%) in the Lexapro group. In the intention-to-treat analysis (i.e., including all patients) the mean (s.d.) drop in the HAMD total score at the end of the 8th week of treatment was 13.9 (8.2) in the generic escitalopram group and 14.3 (8.1) in the Lexapro group (t=0.44, p=0.664). The proportions of patients responsive to treatment (i.e., >50% drop in total HAMD score) were 69% and 67% in the generic escitalopram group and Lexapro group, respectively (χ2=0.16, df=1, p=0.690; and the proportions that achieved remission (i.e., final HAMD <7) were 51% and 49% (χ2=0.06, df=1, p=0.804). The most frequently reported adverse events were dry mouth (12.3%), nausea (9.2 %) and dizziness (6.2%) in the generic escitalopram group and nausea (10.8%), fainting (7.7%) and drowsiness (6.9%) in the Lexapro group. During the first 35 days of treatment, one suicide and two suicide attempts occurred in the generic escitalopram group and one suicide occurred in the Lexapro group (Fisher exact test, p=0.314).ConclusionGeneric escitalopram is as effective and safe as Lexapro in the initial treatment of patients with moderate to severe episodes of major depression who seek treatment in the outpatient departments of psychiatric hospitals in China. Careful monitoring of the risk of suicidal events is an essential component of the treatment of depressed patients.Trial registrationNCT00866593 (clinical.trails.gov)

952 – A population-based longitudinal study on work environment and major depressive disorder

To investigate the relationships between work environmental factors and the risk of major depressive disorder (MDD) over one year and to identify factors associated with the outcomes of individuals with MDD. We conducted a population-based longitudinal study of employees who were randomly selected in Alberta (n = 4239). MDD was assessed using the World Health Organization's Composite International Diagnostic Interview - Auto 2.1. The one-year incidence of MDD was 3.6% (95% CI: 2.8%-4.6%) overall. It was 2.9% (95% CI: 1.9% - 4.2%) in men and 4.5% (95% CI: 3.3% - 6.2%) in women. The relationships between work environmental factors and MDD differed by sex. In men, high job strain increased the risk of MDD in those who worked 35-40 hours per week; job insecurity and family-work conflict were predictive of MDD. Women who worked 35-40 hours, who reported job insecurity, high effort-reward imbalance and work-family conflict were at higher risk of MDD. Long working hours, negative thinking and having comorbid social phobia were predictive of MDD. Perceived work-family conflict, severity of major depressive episode and symptom of depressed mood were significantly associated with recurrence of MDD. Job strain, effort-reward imbalance, job insecurity and work-family conflicts are important risk factors for the onset of MDD, and should be targets of primary prevention. However, these work environmental factors appear to operate differently in men and in women. Clinical and psychosocial factors are important in the prognosis of MDD. The factors associated with persistence and recurrence of MDD may be different.

1848 – From gene expression variation to definition of biomarkers in depression

Several studies examined gene expression variations in depressive patients compared to control subjects in post-mortem samples as well as in fresh peripheral tissues. Our aim has been investigate gene expression variations during Major Depressive Episode (MDE) in peripheral blood mononuclear cells (PBMCs). We collected PBMCs from two different cohorts of severe MDE patients (n=11 and n=13) and compared gene expression between patients and matched-control subjects. Moreover, in a 64 weeks prospective study, we had the opportunity to investigate what happens when a healthy subject gets his first MDE. We analysed gene expression variations accross time in both patients and controls and used both pan-genomic microarray and RT-qPCR strategies for RNA quantification. Finally, to compare gene expression variations in blood tissue and in post-mortem, we benefited from transcriptome databases to reanalyze, with uniform filtering and quantification procedures, gene expression in a large set of samples collected from other groups. We found several genes whose expression vary significantly between patient and control subjects as well as between the severe acute MDE phase and the following therapeutic response or remission phases occuring several weeks and months later, respectively. Beyond then, both well-known candidate genes, such as 5HTT, TPH1 or NRG1, and new genes (HIST1E1, PPT1) could be proposed for biomarkers development in MDE. Our results demonstrate that gene expression variation in PBMCs could be relevant as biomarkers for depression. The convergence of our data and other studies will be discussed as well as the comparability between brain and blood gene expression.

The bipolar–depressive continuum in the National Epidemiologic Survey on Alcohol and Related Conditions

To the Editor: We thank Dr. Weinstock and colleagues for noting our recent article on differences in depressive episodes in major depressive disorder (MDD), bipolar I disorder (BD-I), and bipolar II disorder (BD-II) analyzing data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (1). In our study we documented the existence of a linear trend in the severity of major depressive episodes: highest for BD-I, followed by BD-II, and lastly by MDD. As Dr. Weinstock and colleagues point out, our conclusions converge with those of their studies (2, 3) and with those from other groups whose work also draws on NESARC data (4). It is reassuring that the conclusions of our studies converge despite addressing two complementary but rather different questions. Dr. Weinstock’s analyses focused on the differences in probability of DSM-IV depression symptom endorsement after adjusting for disorder severity across unipolar and bipolar depressive disorders (2, 3). By contrast, because we were interested in the nosological question of whether different mood disorders arrayed along a dimension, we decided to move beyond symptoms and examined the existence of linear trends in BD-I, BD-II, or MDD across a broad range of variables, including sociodemographic characteristics, clinical characteristics, and lifetime treatment patterns. Our results, which remained significant when stratifying the analyses by gender and by race/ethnicity, strongly supported the existence of a spectrum of severity. Our analyses were also complementary regarding sampling selection. Dr. Weinstock’s group included individuals based on endorsement of lifetime depressed mood and/or anhedonia regardless of whether they met DSM-IV criteria for MDD, BD-I, or BD-II. Consistent with the focus of our analyses, we used DSM-IV diagnoses as inclusion criteria, as we were interested in contributing data to the discussion of the DSM-5 mood disorders classification. Despite these differences in sampling selection, our conclusions pointed in the same direction. The adjustment for other covariates was also complementary in the analyses conducted by the two groups. To adjust for the severity of depressive symptomatology when comparing symptom differences between bipolar and unipolar depression, Dr. Weinstock’s group relied on item response theory methods. As our focus was broader, we were concerned about the effect of other potential confounders beyond severity of depression, including unmeasured confounders. Therefore, in addition to adjusting for number of symptoms of depression, we adjusted for the Short Form Health Survey–12, a global reliable and valid impairment measure in population surveys that takes into account the severity of depression as well as the impact of other disorders (5). Finally, our analyses were complementary in the statistical approach to multiple comparisons. Dr. Weinstock and colleagues used the Benjamini–Hochberg correction. They raise the concern that, because we did not apply a similar correction to our analyses, our analyses run the risk of inflating type I error. Because we conducted 290 comparisons at an α = 0.05, we could expect 290 × 0.05 = 14.5 to be significant simply by chance. We found that 192 were. A test of binomial proportions indicates that the probability of having at least 192 significant tests out of 290 is approximately 1 in 10000000. Therefore, our pattern of results is highly unlikely to be due to chance. We believe that, overall, the findings of these groups of studies consistently suggest the existence of a continuum of depressive clinical syndromes that would be better characterized by dimensional approaches. In this regard, severity is being considered for inclusion as a specifier in upcoming diagnostic classifications (6). We eagerly await studies with epidemiological, clinical or biological data that may contribute to clarify the structure of mood disorders.

Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode

To date, it remains impossible to guarantee that short-term treatment given to a patient suffering from a major depressive episode (MDE) will improve long-term efficacy. Objective biological measurements and biomarkers that could help in predicting the clinical evolution of MDE are still warranted. To better understand the reason nearly half of MDE patients respond poorly to current antidepressive treatments, we examined the gene expression profile of peripheral blood samples collected from 16 severe MDE patients and 13 matched controls. Using a naturalistic and longitudinal design, we ascertained mRNA and microRNA (miRNA) expression at baseline, 2 and 8 weeks later. On a genome-wide scale, we detected transcripts with roles in various biological processes as significantly dysregulated between MDE patients and controls, notably those involved in nucleotide binding and chromatin assembly. We also established putative interactions between dysregulated mRNAs and miRNAs that may contribute to MDE physiopathology. We selected a set of mRNA candidates for quantitative reverse transcriptase PCR (RT-qPCR) to validate that the transcriptional signatures observed in responders is different from nonresponders. Furthermore, we identified a combination of four mRNAs (PPT1, TNF, IL1B and HIST1H1E) that could be predictive of treatment response. Altogether, these results highlight the importance of studies investigating the tight relationship between peripheral transcriptional changes and the dynamic clinical progression of MDE patients to provide biomarkers of MDE evolution and prognosis.

Depression in bipolar disorder versus major depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions

To compare the clinical features and course of major depressive episodes (MDEs) occurring in subjects with bipolar I disorder (BD-I), bipolar II disorder (BD-II), and major depressive disorder (MDD). Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (2001-2002), a nationally representative face-to-face survey of more than 43000 adults in the USA, including 5695 subjects with lifetime MDD, 935 with BD-I and lifetime MDE, and 494 with BD-II and lifetime MDE. Differences on sociodemographic characteristics and clinical features, course, and treatment patterns of MDE were analyzed. Most depressive symptoms, family psychiatric history, anxiety disorders, alcohol and drug use disorders, and personality disorders were more frequent-and number of depressive symptoms per MDE was higher-among subjects with BD-I, followed by BD-II, and MDD. BD-I individuals experienced a higher number of lifetime MDEs, had a poorer quality of life, and received significantly more treatment for MDE than BD-II and MDD subjects. Individuals with BD-I and BD-II experienced their first mood episode about ten years earlier than those with MDD (21.2, 20.5, and 30.4 years, respectively). Our results support the existence of a spectrum of severity of MDE, with highest severity for BD-I, followed by BD-II and MDD, suggesting the utility of dimensional assessments in current categorical classifications.

CLINICAL PREDICTORS OF FAMILIAL DEPRESSION IN HAN CHINESE WOMEN

BackgroundA number of clinical features potentially reflect an individual's familial vulnerability to major depression (MD), including early age at onset, recurrence, impairment, episode duration, and the number and pattern of depressive symptoms. However, these results are drawn from studies that have exclusively examined individuals from a European ethnic background. We investigated which clinical features of depressive illness index familial vulnerability in Han Chinese females with MD.MethodsWe used lifetime MD and associated clinical features assessed at personal interview in 1,970 Han Chinese women with DSM-IV MD between 30–60 years of age. Odds Ratios were calculated by logistic regression.ResultsIndividuals with a high familial risk for MD are characterized by severe episodes of MD without known precipitants (such as stress life events) and are less likely to feel irritable/angry or anxious/nervous.ConclusionsThe association between family history of MD and the lack of a precipitating stressor, traditionally a characteristic of endogenous or biological depression, may reflect the association seen in other samples between recurrent MD and a positive family history. The symptomatic associations we have seen may reflect a familial predisposition to other dimensions of psychopathology, such as externalizing disorders or anxiety states. Depression and Anxiety 0:1–6, 2011. © 2011 Wiley-Liss, Inc.

The inter‐rater reliability of the Japanese version of the Inventory of Depressive Symptomatology, Clinician version

The Inventory of Depressive Symptomatology, clinician version (IDS‐C), was developed by Rush et al. to evaluate the severity of major depressive episodes. The aim of the present study was to establish the inter‐rater reliability of the Japanese version of the IDS‐C. A total of 16 subjects with DSM‐IV major depressive episode were evaluated. Two psychiatrists, who had completed a training session for evaluating the IDS‐C before starting this reliability study, attended systematic interview sessions with each subject to evaluate the IDS‐C independently, using the Japanese version of the structured interview guide for combined rating of the IDS‐C and the Hamilton Depression Rating Scale. The severity of the 30 IDS‐C items assessed by the two raters ranged from 0 to 4 for 27 items and from 0 to 3 for 3 items. The analysis of variance intra‐class correlation inter‐rater reliability values for the individual scale items ranged from 0.874 to 1.000. The present results suggest that the Japanese version of the IDS‐C is a potentially useful rating instrument with high inter‐rater reliability for measuring the severity of depressive symptoms in the hands of psychiatrists with sufficient evaluation training.

Case of isolated adrenocorticotropic hormone deficiency mimicking major depressive disorder

ISOLATED ADRENOCORTICOTROPIC HORMONE (ACTH) deficiency is a rare pituitary disorder characterized by decreased secretion of ACTH, but not of the other hormones of the anterior pituitary and causes secondary adrenal insufficiency.1 Since isolated ACTH deficiency gradually and latently develops and shows non-specific symptoms, it is easily misdiagnosed. We report a case of middle-aged-onset isolated ACTH deficiency that showed a severe major depressive episode. A 62-year-old man was admitted to our hospital due to suicidal behavior. He did not have any previous history of neuropsychiatric or endocrine disorders. From 6 months before the admission, he complained of mild general fatigue, depressed mood, loss of pleasure, psychomotor retardation, insomnia, decrease in appetite, and weight loss. He was diagnosed as having major depressive disorder. A dose of 100 mg/day of sertraline did not relieve him of his depressive symptoms at all. At the time of admission, he was fully conscious and showed a severe major depressive episode with suicidal ideas. He did not show any symptoms suggestive of atypical depression or chronic fatigue syndrome, such as hypersomnia, lead paralysis, mood reactivity, rejection sensitivity, muscle pain, lymph node swelling, and fever. Magnetic resonance imaging of his brain did not show any structural abnormality, including an empty sella. Blood test revealed anemia (red blood cell count, 3.24 × 106/µL; hemoglobin, 10.0 mg/dL) and hyponatremia (117 mEq/L). Thyroid function studies were consistent with hypothyroidism: thyroid-stimulating hormone (TSH), 49.8 µIU/mL (normal range, 0.6–5.1); fT3, 2.45 pg/mL (2.47–4.34); and fT4, 0.71 ng/dL (0.97–1.79). Rheumatoid factor and antinuclear, antithyroglobulin, anti-thyroid peroxidase, TSH-receptor, and antipituitary antibodies were negative. Both serum ACTH (<2.0 pg/mL; normal range, 7.2–63.3) and cortisol (0.2 µg; 3.7–19.4) were extremely low, whereas aldosterone (61.6 pg/mL; 38.9–307.0) was within normal range. Neither ACTH nor cortisol responded to corticotrophin-releasing hormone stimulation test, showing that he suffered from secondary adrenocortical insufficiency. Thyrotropin-releasing hormone test, gonadotrophin-releasing hormone test, and growth hormone-releasing hormone test showed normal responses, revealing that his secondary adrenocortical insufficiency was caused by isolated ACTH insufficiency. We discontinued sertraline and started to administer him 5 mg/day of hydrocortisone. Three days later, his symptoms mimicking major depressive episode were dramatically resolved. As in our case, isolated ACTH deficiency may be comorbid with primary hypothyroidism although the mechanism of the coexistence is unknown.2 However, the comorbid hypothyroidism did not seem to induce his depressive state as hypothyroidism was recovered 4 months after rapid relief of his psychiatric state. Relationships between glucocorticoid function and symptoms mimicking major depressive episodes are complex but might reflect insufficient glucocorticoid signaling. Some major depressive episodes might be associated with the insufficient glucocorticoid signaling by decrease of glucocorticoid production or decrease of sensitivity of glucocorticoid receptors.3 Our case suggests that isolated ACTH deficiency should be added into a differential diagnostic list of major depressive disorder. The patient gave the authors informed consent to publish this letter.

Main Features of Prevalence and Severity of Major Depressive Episode in Romania

Main Features of Prevalence and Severity of Major Depressive Episode in Romania