Major Depressive Syndrome Research Articles

CHRM2 gene predisposes to alcohol dependence, drug dependence and affective disorders: results from an extended case–control structured association study

Cholinergic muscarinic 2 receptor (CHRM2) is implicated in memory and cognition, functions impaired in many neuropsychiatric disorders. Wang et al. [Wang, J.C., Hinrichs, A.L., Stock, H., Budde, J., Allen, R., Bertelsen, S., Kwon, J.M., Wu, W., Dick, D.M., Rice, J. et al. (2004) Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome. Hum. Mol. Genet., 13, 1903-1911] reported that variation in CHRM2 gene predisposed to alcohol dependence (AD) and major depressive syndrome. We examined the relationships between variation in CHRM2 and AD, drug dependence (DD) and affective disorders, using a novel extended case-control structured association (SA) method. Six markers at CHRM2 and 38 ancestry-informative markers (AIMs) were genotyped in a sample of 871 subjects, including 333 healthy controls [287 European-Americans (EAs) and 46 African-Americans (AAs)] and 538 AD and/or DD subjects (415 with AD and 346 with DD and 382 EAs and 156 AAs). The same CHRM2 markers were genotyped in a sample of 137 EA subjects with affective disorders. All of the six markers were in Hardy-Weinberg equilibrium in controls, but SNP3 (rs1824024) was in Hardy-Weinberg disequilibrium in the AD and DD groups. Using conventional case-control comparisons, some markers were nominally significantly or suggestively associated with phenotypes before or after controlling for population stratification and admixture effects, but these associations were not significant after multiple test correction. However, regression analysis identified specific alleles, genotypes, haplotypes and diplotypes that were significantly associated with risk for each disorder. We conclude that variation in CHRM2 predisposes to AD, DD and affective disorders. One haplotype block within the 5'-UTR of CHRM2 may be more important for the development of these disorders than other regions. Interaction between two specific alleles within this block and interaction between two specific diplotypes covering this block multiplicatively increased risk for AD and DD. Although interaction between these two diplotypes also increased risk for affective disorders, the magnitude of the increased risk was less than the sum of the individual risks. In addition, a specific diplotype might inversely affect risk for AD and DD and risk for affective disorders.

Neuroanatomic Correlates of Psychopathologic Components of Major Depressive Disorder

The Hamilton Depression Rating Scale (HDRS) is widely used to measure the severity of depression in mood disorders. Total HDRS score correlates with brain metabolism as measured by fludeoxyglucose F 18 ([(18)F]-FDG) positron emission tomography. The HDRS comprises distinct symptom clusters that may be associated with different patterns of regional brain glucose metabolism. To examine associations between HDRS component psychopathologic clusters and resting glucose cerebral metabolism assessed by [(18)F]-FDG positron emission tomography. Patients We evaluated 298 drug-free patients who met the DSM-III-R criteria for major depressive disorder. Five principal components were extracted from the 24-item HDRS for all subjects and ProMax rotated: psychic depression, loss of motivated behavior, psychosis, anxiety, and sleep disturbance. The [(18)F]-FDG scans were acquired in a subgroup of 43 drug-free patients in twelve 5-minute frames. Voxel-level correlation maps were generated with HDRS total and factor scores. Total HDRS score correlated positively with activity in a large bilateral ventral cortical and subcortical region that included limbic, thalamic, and basal ganglia structures. Distinct correlation patterns were found with the 3 individual HDRS factors. Psychic depression correlated positively with metabolism in the cingulate gyrus, thalamus, and basal ganglia. Sleep disturbance correlated positively with metabolism in limbic structures and basal ganglia. Loss of motivated behavior was negatively associated with parietal and superior frontal cortical areas. Different brain regions correlate with discrete symptom components that compose the overall syndrome of major depression. Future studies should extend knowledge about specific regional networks by identifying responsible neurotransmitters related to specific psychopathologic components of mood disorders.

Depression and Mental-Health Service Utilization Among Women in WIC

This exploratory 2003 study of 261 women in WIC addresses depression and mental-health service utilization in six race/ethnic-immigrant/migrant groups and factors amenable to change. Using the PrimeMD-PHQ, island-born Puerto Rican women had the highest prevalence of subthreshold depressive syndrome (27.8%); African American women had the highest prevalence of major depressive syndrome (21.3%); proportionately more White women used mental-health services (41.9%). The odds for major depressive syndrome among those with no one to help with childcare were almost four times greater than those with help. The odds of mental-health service use among those with indirect exposure to mental-health care were four times greater than those without such exposure. Implications for intervention and further research are discussed.

Antipsychotiques et troubles bipolaires

Antipsychotiques et troubles bipolaires

Depressed mood and memory impairment in temporal lobe epilepsy as a function of focus lateralization and localization

Objective Memory disorders and depressed mood are prominent psychological symptoms of temporal lobe epilepsies (TLEs). We examined the interaction of depressive mood and memory as a function of focus localization. Methods One hundred fifty-two TLE patients with right mesial ( n = 37, RTLE-AHS), right lateral ( n = 31, RTLE-LAT), left mesial ( n = 42, LTLE-AHS), and left lateral ( n = 42, LTLE-LAT) lesions and epilepsies underwent comprehensive presurgical evaluation and neuropsychological assessment of mood and memory. Univariate and multivariate analyses of covariance (ANCOVAs) and partial correlation analyses were performed to reveal interactions of depression and memory as a function of focus localization. Results No differences between the study groups were revealed for depression, indicating a general risk of 30% for depressed mood (BDI > 12) in patients with TLE. ANCOVAs revealed significant main effects of focus side (left: verbal learning deficits; right: figural learning deficits) and site (mesial at disadvantage) on learning and memory scores. Correlation analyses revealed interactions between memory and mood only in LTLE-LAT patients. Conclusions Although the data provide evidence that side and site of the epileptogenic region differentially affect material specific memory performance, there was no evidence of a specific temporal target region for depressive mood. In the majority of the patients, depressed mood and memory impairment appeared as independent rather than as related symptoms of TLE. In LTLE-LAT, however, mood was significantly related to verbal and figural memory performance. Epilepsy-driven pathological left temporofrontal circuits are discussed as a prerequisite for the coupling of mood disorders and memory impairment in this specific patient subgroup which is also known from the psychiatric major depression syndrome.

Adjustment to antidepressant utilization rates to account for depression in remission

Conventional estimates of antidepressant (AD) utilization in major depressive syndrome (MDS) have been low, but this may be partially because ongoing AD use by individuals with resolved MDS is not included. Valid estimates of AD utilization should include this ongoing use for MDS, but this is difficult since most surveys do not collect data on the reason for taking ADs. Only a proportion ( f dep ) of the nondepressed (nMDS) population taking ADs does so for depression. Published studies have not reported this proportion, and data required to estimate f dep are not usually available from surveys. The current study was performed to (1) estimate f dep by employing information on past history of depression, and (2) use the estimate to obtain an “adjusted” AD utilization rate, including resolved MDS subjects taking ADs. Data were collected in Calgary in 1998 and 1999 by random-digit dial telephone interview from consenting adults aged 18+ years. MDS was assessed using the Composite International Diagnostic Interview Short Form for Major Depression (CIDI-SFMD). Data were gathered on current medications, past depression, and current chronic physical illness. Of 2,542 respondents, 17.1% had MDS as defined by the CIDI-SFMD. A total of 20.2% of MDS and 3.2% of nMDS subjects were taking ADs. Of nMDS individuals taking ADs, 70.6% reported past depression ( f dep = 70.6%). An “adjusted” AD utilization rate including this group was 28.2%. Physical illnesses that can be treated with ADs affected only 30.0% of nMDS subjects without past depression taking ADs. This study suggests that most individuals without active depression taking ADs do so for depression. AD utilization rates that ignore this group may be unrealistically low. AD use among nMDS subjects without previous depression is probably not primarily for physical illnesses. Limitations include the use of a brief predictive instrument for MDS, and self-report of past depression.

The difference between single and married mothers in the 12-month prevalence of major depressive syndrome, associated factors and mental health service utilization.

Previous studies suggest that single mothers are at a higher risk of major depression and more likely to use mental health services than are married mothers. The objectives of this analysis were to provide estimates of the prevalence of major depressive syndrome among single and married mothers, to investigate the factors which may affect the difference in the prevalence of major depressive syndrome among single and married mothers and to estimate the health care service utilization by single and married mothers. This was a cross-sectional study using the data from the 1996-97 Canadian National Population Health Survey (NPHS). Major depressive syndrome was evaluated using the Composite International Diagnostic Interview-Short Form for major depression. The prevalence of major depressive syndrome was calculated among 3030 single and 10195 married mothers. The effects of demographic, socioeconomic and biological variables on the association between single-mother status and major depressive syndrome were evaluated by stratified analyses. In the NPHS, the difference between single and married mothers in the prevalence of major depressive syndrome was found among women who were between the ages of 25 and 50. The association in this age group depended on race and on whether they had one or more jobs. Education,problem drinking, daily smoking, having one or more long-term medical illnesses, financial hardship and social support did not affect the association between single-mother status and major depressive syndrome. Single mothers were more likely to visit health professionals for mental problems than were married mothers. The difference between single and married mothers in the prevalence of major depression is age-specific. Single mothers who reported having had one or more jobs and who are non-white had an increased risk of having major depressive syndrome, compared to married mothers. Future studies need to replicate the findings of this analysis and investigate why single mothers with ethnic minority backgrounds and those who are working are at high risk of having depressive disorders.

Agitated depression in bipolar I disorder: prevalence, phenomenology, and outcome.

The study aimed to explore how prevalent agitated depression is in bipolar I disorder, whether it represents a mixed state, and whether it differs from nonagitated depression with respect to course and outcome. From 313 bipolar I patients with an index episode of major depression, the authors selected those fulfilling Research Diagnostic Criteria for agitated depression. These 61 patients were compared to 61 randomly recruited bipolar I patients with an index episode of nonagitated depression and 61 randomly recruited bipolar I patients with an index episode of mania regarding demographic, historical, and clinical features. The two depressive groups were also compared regarding time to recovery from the index episode, treatment received for that episode, percentage of time spent in an affective episode during a prospective observation period, and 5-year outcome. Patients with agitated depression were consistently not elated or grandiose, but one-fourth had the cluster of symptoms with racing thoughts, pressured speech, and increased motor activity, and one-fourth had the paranoia-aggression-irritability cluster. Compared to patients with nonagitated depression, they had a longer time to 50% probability of recovery from the index episode, were more likely to receive standard antipsychotic drugs during that episode, and spent more time in an affective episode during the observation period. The occurrence of agitated depression in bipolar I disorder is not rare and has significant prognostic and therapeutic implications. Whether the co-occurrence of a major depressive syndrome with one or two of these symptomatic clusters makes up a "mixed state" remains unclear.

P.1.125 A 20-month, double-blind, maintenance study of lithium versus divalproex monotherapy in bipolar I and II disorder accompanied by rapid cycling

P.1.125 A 20-month, double-blind, maintenance study of lithium versus divalproex monotherapy in bipolar I and II disorder accompanied by rapid cycling

New Diagnostic Tool Validates Alzheimer’s-Syndrome Depression

New Diagnostic Tool Validates Alzheimer’s-Syndrome Depression

The relation of psychogenic excoriation with psychiatric disorders: a comparative study.

Psychogenic excoriation (PE), characterized by excessive scratching or picking of the skin, is not yet recognized as a symptom of a distinct DSM-IV disorder. It is a chronic disorder with a high rate of psychiatric comorbidity. The purpose of this study was to compare patients diagnosed with PE and patients with another dermatological disease in terms of comorbid psychiatric disorders. Thirty-one consecutive subjects were recruited from an outpatient dermatology clinic. The control group was composed of 31 patients with chronic urticaria. All subjects were interviewed using the Structured Clinical Interview for DSM-III-R (SCID-I), Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HARS), and Yale-Brown Obsession and Compulsion Scale (Y-BOCS) and also completed a semistructured questionnaire. Current major depressive syndrome was the most common psychiatric disorder in the PE group. There was a statistically significant difference between the two groups in terms of current major depressive syndrome (PE group 58.1%, control group 6.5%, P<.01). In the PE group, 45.2% of subjects were diagnosed with obsessive compulsive disorder (OCD), while the rate of OCD was only 3.7% in the control group (P <.01). The PE group scored significantly higher on the BDI, HARS, and Y-BOCS. The results of this study point to the close relationship of PE to depression and OCD.

A follow-up study of DSM-III-R generalized anxiety disorder with syndromal and subsyndromal major depression

Objective: The authors examined the long-term outcome of generalized anxiety disorder with depressive symptoms utilizing both categorical and dimensional analyses. Method: Thirty-nine out-patients with a DSM-III-R diagnosis of generalized anxiety disorder (GAD) with depressive symptoms, both with ( n=23) and without ( n=16) syndromal major depression (MD) participated in an 11-week clinical trial. Approximately 18 months after initial screening, these individuals were once again evaluated using a structured diagnostic interview and a battery of rating scales. Results: Three distinct groups were discernible at follow-up. Twenty-three (60%) of the patients remained syndromal for GAD; 10 patients (43%) were in partial remission from GAD; six (15%) were asymptomatic. Of the 23 patients who were syndromal for MD at baseline, 13 (56%) remained syndromal for MD at follow-up. All of the patients who were syndromal for MD at follow-up remained syndromal for GAD as well. Conclusions: Outcomes in this study were quite divergent, though they support the concept of GAD as a chronic illness in most patients, with or without MD. The presence or absence of MD versus subsyndromal depression at baseline appeared to have relatively little impact upon the outcome. Patients with subsyndromal anxiety and depressive symptoms may be at special risk for syndromal disorders over time.

Toward validation of atypical depression in the community: results of the Zurich cohort study

Aims: This paper (1) examines the validity of the atypical subtype of depression in a community-based longitudinal cohort study, (2) presents estimates of the prevalence and sex differences of DSM-IV atypical depression and a newly more broadly defined atypical syndrome in the community and (3) compares the clinical correlates and treatment patterns of those with atypical depression with other depressives. Methods: The Zurich cohort study is comprised of 591 subjects selected from a population-based cohort of young adults representative of the canton of Zurich in Switzerland, who were screened in 1978 with the Symptom Checklist 90-R [L.R. Derogatis (1977)] and followed prospectively with five interviews between 1979 and 1993. Atypical depression was defined on a spectrum ranging from atypical major to minor to atypical depressive symptoms alone. Results: The rate of DSM-IV atypical major depressive episodes in this community is 4.8% and for major atypical depression syndrome is 7.3%. Whereas there was no marked sex difference for nonatypical features, there was a significant female preponderance for DSM-IV and broadly defined atypical depressive subtypes. Systematic investigation of the diagnostic criteria for atypical depression revealed that a nonhierarchical definition of atypical depression with respect to mood reactivity yielded as valid a syndromic definition as the current hierarchy based on mood reactivity as an essential feature. Very high comorbidity (odd ratios>2.0) was found with seasonality, bipolar II, social phobia, binge eating, neurasthenia and sociopathy. Limitations: Atypical depression was not defined à priori, its criteria were derived from two sections of the Zurich interview. Conclusions: Atypical depression has high population prevalence and substantial significance in terms of clinical severity, impairment, and service use. The intriguing finding that the sex difference in depression may be attributed to atypical features of depression will need further investigation. Overall, our data indicate that the atypical subtype of depression is a valid entity based on evidence from such traditional indicators of validity as inclusion criteria and indicators of course. However, there are some problems with discriminatory validity from other disorders. Although comorbidity with these disorders may in part reflect an operational artifact of symptom overlap, further work needs to be done in distinguishing atypical depression from bipolar II.

Postpsychotic depression in schizophrenia patients.

Depression is a frequent comorbidity in the course of schizophrenia and is associated with increased mortality from suicide. Postpsychotic depression is defined as the syndrome of major depression occurring following remission of psychotic symptoms in a person with schizophrenia. Various proposed causes, differential diagnosis, and issues regarding management of postpsychotic depression are discussed.

Psychotic Symptoms and Paranoid Ideation in a Nondemented Population–Based Sample of the Very Old

Psychotic symptoms are reported to be uncommon in the elderly, and may be underrated in traditional epidemiological studies. Psychotic symptoms, physical disorders, disability in daily life, and sensory impairments were assessed using results of psychiatric and physical examinations, key-informant interviews, and medical record reviews in a representative sample of nondemented individuals aged 85 years living in the community or in institutions in Göteborg, Sweden (n = 347). The sample was observed for 3 years regarding psychotic symptoms, mortality, and incident dementia. The prevalence of any psychotic symptom was 10.1% (95% confidence interval [CI], 7.1%-13.7%); hallucinations, 6.9% (95% CI, 4.5%-10.1%); and delusions, 5.5% (95% CI, 3.3%-8.4%). The prevalence of paranoid ideation was 6.9% (95% CI, 4.5%-10.1%). Stepwise logistic regression analyses showed that hallucinations were associated with major depressive syndrome (odds ratio [OR], 3.9; 95% CI, 1.3-11.9), disability in daily life (OR, 5.2; 95% CI, 1.8-14.9), and visual deficits (OR, 3.4; 95% CI, 1.0-11.1). Delusions were associated with disability in daily life (OR, 4.9; 95% CI, 1.8-13.3). Paranoid ideation was associated with visual deficits (OR, 3.6; 95% CI, 1.2-10.5) and myocardial infarction (OR, 4.6; 95% CI, 1.7-12.6). Hallucinations (OR, 3.1; 95% CI, 1.4-6.8), delusions (OR, 2.9; 95% CI, 1.2-6.9), and paranoid ideation (OR, 2.7; 95% CI, 1.2-6.2) were each related to increased incidence of dementia from 85 to 88 years of age. Hallucinations and paranoid ideation were associated with increased 3-year mortality in women but not in men. We found a higher prevalence of psychotic symptoms and paranoid ideation in the elderly than previously reported, and these symptoms were associated with a poor prognosis.

The significance of psychotic features in manic episodes: a report from the NIMH collaborative study

Background: Psychotic features in the context of major depressive syndromes have correlates in symptom severity, acute treatment response and long-term prognosis. Little is known as to whether psychotic features have similar importance when they occur within manic syndromes. Methods: These data derive from a multi-center, long-term follow-up of patients with major affective disorder. Raters conducted follow-up interviews at 6-month intervals for the first 5 years and annually thereafter. A sub-set of probands participated in a family study in which all available, adult, first-degree relatives were interviewed as well. Results: Of 139 who entered the study in an episode of mania, 90 patients had psychotic features. Symptom severity ratings at intake were more severe for this group. Though time to first recovery and time to first relapse did not distinguish the groups, psychotic features were associated with a greater number of weeks ill during follow-up and the strength of this association was similar to that seen for psychotic features within depressed patients described in an earlier publication. Patients with psychotic mania at intake did not differ significantly from those with nonpsychotic mania by response to acute lithium treatment, suicidal behavior during follow-up, or risks for affective disorder among first-degree relatives. Psychotic features within manic syndromes were not associated with high psychosis ratings during follow-up. In contrast, when psychotic features accompanied depressive syndromes, they strongly predicted the number of weeks with psychosis during follow-up, particularly among individuals whose episodes at intake were less acute. Conclusions: As with major depressive syndromes, psychotic features in mania are associated with greater symptom severity and higher morbidity in the long-term. Psychotic features are much less predictive of future psychosis when they occur within a manic syndrome than when they occur within a depressive syndrome.

Immunological differences between patients with major depression and somatization syndrome

There is some evidence that major depression is accompanied by activation of the inflammatory response system (IRS). There is also evidence that proinflammatory cytokines and induction of IRS activation are associated with sickness behavior in experimental animals. However, no research has examined the IRS in somatization disorder. The aim of this study was to examine possible immunological differences between major depression, somatization and healthy controls. We measured the following IRS variables in patients with major depression ( n=36), somatization syndrome (SSI-8; n=37), major depression and somatization ( n=40) and healthy controls ( n=37): interleukin-6 (IL-6); interleukin-1-receptor-antagonist (IL-1RA); plasma soluble interleukin-6 receptor (IL-6R); soluble suppressor/cytotoxic antigen (CD8); leukemia inhibitory factor (LIF-R); and Clara cell protein (CC16), an endogenous anticytokine. Serum CD8 concentrations were significantly increased in patients with major depression compared with concentrations in patients with somatization syndrome, whereas concentrations in normal controls were intermediate between those of the two groups of patients. Serum CC16 was significantly lower in major depression than in healthy controls. The highest CC16 scores were found in patients with somatization syndrome. Somatizing patients have significantly lower serum IL-6 values than normal controls and depressed patients. The present results indicate (1) an activation of the IRS in depression with signs of T-cell activation (increased CD8), monocytic activation (IL-1RA) and a lowered anti-inflammatory capacity of the serum (lower CC16) and (2) an immune alteration in somatizing syndrome, such as monocytic activation (increased IL-1RA) and indicators of lowered T-lymphocytic activity (lowered CD8 and IL-6). These results suggest different immune alterations in somatization syndrome and depression.

THE CLINICAL NEUROPYSCHIATRY OF STROKE: COGNITIVE, BEHAVIOURAL AND EMOTIONAL DISORDERS FOLLOWING VASCULAR BRAIN INJURY.: By Robert G. Robinson. 1998. Cambridge: Cambridge University Press. Price pound60. Pp. 491. ISBN 0-52144-234-6.

Neuropsychiatrists are interested in stroke because of what it might tell us about the neural basis of mental disorder. The stroke lesion is (apparently) neatly localized, and onset is sudden so that it is relatively easy to characterize the course of associated mental abnormality. In this book, Dr Robinson concentrates on his own research in stroke-related psychopathology. His main studies have been in the nature of depression associated with stroke, and his thesis (broadly) is this. Depression is a specific complication of stroke, and it has two different manifestations. The more interesting is the so-called major depressive syndrome—it comes early and persists; it is strongly associated with lesion location; it affects social and intellectual function and it is associated with worse outcomes, including increased mortality. Fortunately …

Glucocorticoids and cognitive function: from physiology to pathophysiology.

This paper reviews the literature on the relationship between glucocorticoids and cognitive functioning, including memory and selective attention. The main body of evidence suggests that hypothalamic-pituitary-adrenal (HPA) axis dysfunction or a state of hypercortisolaemia can be correlated with cognitive deficits specific to the medial temporal lobe declarative memory system. These impairments are discussed in relation to patients with HPA abnormalities, as seen in a significant number of patients with major depression or Cushing's syndrome, and also in relation to healthy volunteers after administration of glucocorticoids. It remains to be seen whether there are differential effects on acquisition, consolidation or retrieval processes. However, it would seem that glucocorticoids have a preferential effect on recall of information as opposed to recognition, possibly because recognition is more automatic.Type 2 glucocorticoid receptors (GRs), which are occupied by cortisol in humans in times of stress, are thought to be responsible for the glucocorticoid-induced memory impairment. GRs alter the feedback of the HPA axis, which in turn disrupts hippocampal functioning. While this can be reversible, animal studies suggest that chronic elevation of glucocorticoid levels can lead to the loss of hippocampal neurons and irreversible decline in declarative memory. Copyright 2001 John Wiley & Sons, Ltd.

Amitriptyline enhances the central component of physiological tremor

OBJECTIVESPostural tremor is a regularly encountered side effect of amitriptyline which can be strong enough to cause discontinuation of therapy. The aim was to characterise amitriptyline induced tremor and to...