Endogenous Depression Research Articles

Attributional biases, paranoia, and depression in early psychosis

Attributional biases to externalize blame for negative events (externalizing bias) and to target other people for blame (personalizing bias) may constitute a vulnerability to psychosis. However, most research to date has only examined attributional biases in chronic patients. We examined attributional style, paranoia, and depression in early psychosis patients to assess the primacy of attributional biases in psychosis. A quasi-experimental design was adopted to compare the attributional style of patients and controls. Correlates of attributional style were also examined. Early psychosis patients and age- and gender-matched healthy controls completed the 'Internal, Personal and Situational Attributions Questionnaire'. Paranoid tendencies, suspiciousness, and depression were also assessed in both groups, while severity of current symptoms was assessed in patients. A high proportion of patients had persecutory delusions. These patients, however, did not differ from controls in externalizing or personalizing bias. Whereas suspiciousness and persecutory delusions in patients associated with externalizing bias, no bias measures associated with paranoid tendencies in either patients or controls. Counter to the pattern seen for endogenous depression, depression in patients was associated with an increased tendency to attribute events to self and a decreased tendency to attribute events to circumstances. These preliminary findings raise doubts about the primacy of attributional biases in psychosis. The novel findings with regard to depression warrant further investigation and suggest that young people, who develop depression after the onset of psychosis, may experience a need to re-establish a sense of personal control over life events that appear unpredictable.

EEG correlates and possible predictors of the efficacy of the treatment of endogenous depression

An analysis of EEG spectral power values and of quantitative clinical scores of depressive conditions has been carried out in dynamics of treatment in 40 patients with endogenous depression with the main goal to study neurophysiologic correlates and to search possible predictors of therapeutic outcome. The reduction of depressive symptoms by the end of the treatment course was associated with EEG signs of improvement of brain functional state. Significant correlations have been revealed between the EEG narrow-band spectral power values and clinical scores. As well, significant correlations have been revealed between some initial (before beginning of treatment) EEG parameters and quantitative clinical scores at the stage of remission establishing. The values of EEG beta-1 and beta-2 spectral power appeared to be such predictors, while initially larger values of EEG beta activity spectral power were associated with higher pronounce of residual depressive symptoms after the treatment course. The data obtained allow to justify basic views on brain mechanisms of various aspects of depressive disorders, and to reveal possible neurophysiological predictors of efficacy of treatment of endogenous depression.

Insulin Versus Glucagon Crosstalk

Plasma glucose level depends on the peripheral intra-islet crosstalk between A cells (glucagon) + B-cells (insulin) and D-cells (somatostatin). Gastrointestinal hormones (secretin, CCK-PZ, gastrin, and serotonin) modulate the glucose- and amino acids-induced secretions of insulin and glucagon, respectively. Serotonin (5-HT) arose from the enterochromaffin cells during postprandial periods excites basal but inhibits excited B-cells. Serotonin excites adrenal glands that release adrenaline (Ad) + dopamine (DA). The former is positively correlated with hyperglycemia, whereas DA antagonizes this effect. Noradrenaline (NA) released from both sympathetic nerves and adrenal glands modulates the Ad release from this latter and excites A-cells. Thus, NA attenuates the hyperglycemic effects triggered by Ad. Dopamine released from both sources, adrenal glands and peripheral sympathetic nerves, antagonizes Ad-induced hyperglycemia plus the NA-triggered glucagon secretion. Both plasma insulin and glucagon cross the blood-brain barrier and excite A5(NA) and C1(Ad) neurons, respectively. C1 (Ad) neurons send excitatory drives to both islet A-cells and adrenal glands. Both central nervous system A5(NA) and C1(Ad) nuclei interchange inhibitory axons. Predominance of the former redounds in hyperinsulinism plus hypoglycemia, whereas the latter axis is responsible for hyperglucagonemia + hyperglycemia. In addition, the dorsal raphe serotonergic and the median raphe serotonergic nuclei interchange excitatory axons with the C1 (Ad) and the A5(NA) neurons, respectively. Hence, the former binomial axis (responsible for uncoping stress) is positively correlated with the hyperglycemic syndrome, whereas the A5(NA) + median raphe serotonergic binomial is correlated with hypoglycemia. Hence, the insulin resistance disorder should be underlain by the overactivity of both axes simultaneously. The above pathophysiological mechanisms are consistent with the successful neuropharmacological manipulations addressed to treat these neuroendocrine syndromes. Finally, one of the showiest findings derived from our research work arises from the unbalance between the DA versus 5-HT circulating parameters demonstrating that absolute predominance of the former is always paralleled by hypoglycemia (endogenous depression syndrome), whereas the opposite profile is registered in mammals affected by hyperglycemia (dysthymic depression and uncoping stress syndromes).

Melancholia: A Distinct Entity?

As the debates about the future shape of the Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition, continue, a review of one of the liveliest arguments, about melancholia as a diagnostic category in its own right, appears timely.In A Case for Reprising and Redefining Melancholia, Dr Gordon Parker1 argues persuasively for melancholia being positioned as a separate, independent subtype of depression. He points out that the diagnosis of melancholic can be delineated with relative precision, and that it has important clinical consequences in favouring biological therapy (drug and electroconvulsive) above psychotherapy, and broad-spectrum antidepressants (ADs) over narrow-action selective serotonin reuptake inhibitors. Conversely, and disconcertingly, the current accretion of varied depressive syndromes under only one diagnostic umbrella precludes both targeted treatments and more productive research of the different entities.When Dr Parker1 reminds us of the limitations to current, unitary, severity-based grouping of depressions, it is hard not to agree with his argument for a separate melancholic category. The DSM symptom-based diagnoses have a century-old, historical foundation and have served satisfactorily for shorthand communication among mental health professionals and for administrative purposes. However, for what is now really needed and missing, both in practice and in research advancement, the current classification has fundamental limitations. As Dr Parker points out, when we now ask for a diagnosis helpful in selecting effective treatment, informing about prognosis and advancing research of the underpinnings, we leave empty-handed.To be fair, DSM-1II was a step forward, compared with its predecessors, which were based largely on speculative theories. Nevertheless, stressing reproducibility without accompanying validity of mood disorder diagnoses created entities that are inadequately demarcated and highly heterogeneous. The current mood disorder categories neither serve the clinical need for guidance in treatment nor inform psychobiological research.Dr Parker's metaphor of major breathlessness standing for major depression1· p m is indeed instructive: it shows how in other areas of medicine these nonspecific entities would not stand as acceptable or valid constructs of disease. One can think of many similar examples from medicine where a seemingly reproducible but abundantly heterogeneous and invalid diagnostic construct would not survive.Of course, a dispute about the classification of depressions is not new. Dr Parker revives another question that raged a few decades ago: Is there 1 large unitary or 2 distinctly binary depressions (for example, endogenous depression and reactive and (or) neurotic depression1· p 286). Amusingly, he points out that the binary model of low mood was already mentioned by St Paul in the Bible. Dr Parker spent a long time searching for the right answer2·5 and discovered that the solution depends on methodology: eliminating nonspecific symptoms leads unavoidably to 2 types of depression; 2 distinct categories that had been employed in clinical practice for decades. Despite this evidence, a unitarian view was introduced in DSM-III and the International Classification of Diseases, 10th Revision, with clinical varying merely dimensionally. This approach has been consolidated during the past 3 decades - long outlasting its expiry date.While dissatisfied, Dr Parker1 does not favour a return to the old binary categories; he proposes a new revision delineating melancholia from a group of other, nonmelancholic depressions. And he supports his argument by the utility and validity of his revision and recommends concentrated studies to improve melancholia's clinical distinction. It may be worth mentioning that similar arguments about the limitations of DSM approach can be made not only about depressive disorders but also about the bipolar spectrum. …

Quantum Nature of Winter Depression

Depression is a disease that concerns a growing group of people: children, youth, adult and the elderly. Statistics indicate that 5 up to 20% of the population of the globe suffer from it. Women suffer from this disease four times more often than men. Depression is such a mental state in which the patient has a deep sense of meaninglessness of life and sees the world in the gloomy colors. Such a person is depressed, their mood affects the job, interpersonal relationships, and learning process. They have a feeling of hopelessness, worthlessness, pessimism and sadness. In many cases patients suffering from depression contemplate or attempt suicide. They cannot notice the solution of their problems. Moreover, they cannot imagine their future, if they were stopped in time. For such people only the past and their past failures matter. Time stopped for them. In addition to endogenous depression, there is also autumn-winter depression, which is a seasonal disease. The first symptoms appear in early autumn. The improvement of the patients’ mental health is observed from February whereas the next symptoms of the disease appear spontaneously in March and April. Winter depression is caused by a prolonged night in autumn and winter and this fact results in the prolonged synthesis of melatonin by the pineal gland, which affects the development of depression.

2777 – Mechanisms of suicidogenesis in different variants of depressive disorders

The aim of the study was to investigate clinical-psychopathological and pathopsychological peculiarities of suicidal behavior in patients with endogenous and exogenous depressions in order to develop principles of differential therapy and prevention for these patients. Depressed patients with suicidal behavior (120 persons; main group) and without one (30 persons; control group) were examined with clinical-psychopathological, psychodiagnostic and psychometric methods. Combined psychogenias prevailed among factors of psychic traumatization (loneliness - 44.2%, job dissatisfaction - 28.3%, worsening of well-being - 24.2%, and loss of job - 23.3%). In a clinical picture there was predominance of anxious (50.8%) and somatic-autonomous (46.6%) variants of the syndrome, less often asthenic (24.2%) and melancholic (22.5%), and rarely obsessive (5.8%) and tearful (5.0%) variants were pointed out. In the patient of the control group asthenic (76.6%) and adynamic (56.6%) variants of depressive syndrome were prevailed. Patients of the main group with endogenous depressions more often had anxious (70.0%), melancholic (45.0%), and senesthopathic (31.6%) variants; patients with exogenous depressions had somatic-autonomous (65.0%) and asthenic (43.3%) variants. A differential system for crisis therapy and prevention of suicidal behavior in depressions was developed. It included pharmacotherapy and psychotherapy (in three stages: rational psychotherapy for a crisis support, group psychotherapy for a crisis intervention, cognitive-behavioral therapy for prevention). This system had a higher therapeutic efficacy as compared with methods used traditionally (recovery - 59.5% vs. 35.1% (p

An end to depression in primary care?

I enjoyed Moscrop’s essay.1 As a GP Trainee in the early 70s with an interest in the psychological I was taught to distinguish between endogenous depression (no evident trigger, serious, chronic, more likely to respond to antidepressants) and reactive depression (for example, triggered by bereavement, relationship breakdown, or job loss, and less likely to respond to antidepressants). Inspired by the works of Michael Balint and Colin Murray Parks I tried to offer a listening ear to troubled patients in long appointments at the end of normal surgery times. There were inevitable disappointments, such as the newly-widowed lady who came to see me weekly over several months who plaintively asked on her last visit ‘So am I not getting any pills?’ An early addition to my Patient’s Unmet Needs list.

Interaction between the BDNF gene Val/66/Met polymorphism and morning cortisol levels as a predictor of depression in adult women

Common genetic variants, such as the brain-derived neurotrophic factor (BDNF) Val/66/Met polymorphism (rs6265), are known to interact with environmental factors such as early adversity to increase the risk of subsequent major depression. Much less is known about how they interact with individual differences in cortisol, although these also represent a risk for major depression. To determine whether this BDNF variant moderated the risk represented by higher levels of morning salivary cortisol in adult women. We recruited 279 premenopausal women who were at high risk of major depressive disorder because of either negative self-evaluation, unsupportive core relationship or chronic subclinical symptoms of depression or anxiety. Morning salivary cortisol was measured daily for up to 10 days at entry. Participants were followed up for about 12 months by telephone calls at 3-4 monthly intervals. Major depression and severe life events were assessed through interviews at baseline and follow-up; DNA was obtained from the saliva. There were 53 onsets (19%) of depressive episodes during follow-up. There was a significant U-shaped relationship between adjusted morning cortisol levels at baseline and the probability of depression onset during follow-up. In total, 51% experienced at least one severe life event/difficulty, and this strongly predicted subsequent onsets of depressive episodes. The BDNF Val/66/Met genotype was not directly associated with onsets of depression or with cortisol levels, but there was significant interaction between Val/66/Met and cortisol: the association between baseline cortisol and depression was limited to those with the Val/66/Val variant. There was no interaction between life events and either this BDNF polymorphism or cortisol levels. Morning salivary cortisol interacts with the BDNF Val/66/Met polymorphism in predicting new depressive episodes. This paper adds to the evidence that single gene polymorphisms interact with endogenous factors to predict depression.

Depression – The Global Crisis

Byline: M. Reddy With the backdrop, Depression - The global crisis, as the theme for the year 2012-2013, this is an attempt to compile some clinical pearls, a few loud thoughts, lingering dilemmas, myriad questions, current challenges, research questions, and tomorrow's optimism! WHO - Depression will be the second most common cause of disability by 2020, and the first by 2040! Sadness may be adaptive, in the evolutionary sense, by permitting withdrawal to conserve inner resources or signal the need for support from significant others. Hippocrates (460-357 BC) described melancholia. The first English text entirely devoted to affective illness was Robert Burton's Anatomy of Melancholia published in 1621…. described causeless melancholia. Sartorius, in 2001, predicted the prevalence of depressive disorders would increase in the years to come, citing various reasons. Did it really increase in the last decade? The international consortium of psychiatric epidemiology interviewed 37,000 adults in 10 countries (USA, South America, Europe, and Asia) using WHO composite international diagnostic interview and found the lifetime prevalence of depression for adults varied from 3% in Japan (the country ravaged by the series of war, earthquakes, tsunamis, economic slowdown, and with high rates of suicide) to 16.9% in USA. Fashion of the day will be to dismiss this difference due to methodological issues. Probing into the reasons for this striking difference in these two developed countries may offer useful insights, data invaluable for primary prevention of depression in the population . Depression is a risk factor for type II diabetes mellitus, and cardio vascular and cerebrovascular disorders, and a bidirectional positive association has been assumed. Depression is an independent risk factor, and the mediating factor could be hyper cortisolism / Dysregulation of HPA axis. DSM IV TR makes no provision for family history and history of past episodes. In clinical practice, these factors would strongly weigh in diagnosis of depression. episodes of behavioral abnormality - consider always the diagnosis of mood disorder as the first choice. Recurrent schizophrenia is described, but is an uncommon presentation. Is MDD with psychosis mostly misdiagnosed as schizophrenia? One-third of depressive patients fulfill the diagnostic criteria for a personality disorder, most commonly of obsessive-compulsive personality. 40% of patients with depressive disorders have anxiety disorders/alcohol abuse as co-morbidity. Kraeplin believed that no more than 5% of patients with mood disorders have chronicity, whereas the current figures show chronicity going up to 30% - ? Reasons Akiskal et al ., in 1978 - reported that in a 3-year follow-up of 100 patients diagnosed with neurotic depression, 18 developed bipolarity, 36 had revised diagnosis of endogenous depression, and 42 showed episodic course…. The classification into endogenous - reactive subtypes seems to be passe and mood disorders are best conceptualized as endoreactive, unitary model of Major Depressive Disorder (MDD) . The increasing clinical diagnosis of depressive disorders should not be dismissed as mere therapeutic fad. External validating strategies, such as genetic and prospective follow-up studies, buttress the broadened concept. In dysthymic and cyclothymic disorders, representing milder forms/intense temperamental instability, impairment is not due to the severity of mood disturbance per se , but to the cumulative impact of the dysregulation beginning in the early years and continuing unabated or intermittently over long periods. The sub-threshold conditions appear to be fertile terrain for interpersonal conflicts and post-affective pathological character development that may ravage the lives of patients and their families. …

ROLE OF HEMOSTATIC DISORDERS IN PNEUMONIA PROGRESS IN ACUTE PERIOD OF BURN DISEASE

Pneumonia is not only the most frequent complication of burn patients, but also one of the leading causes of deaths as a result of this pathology. We have studied the system of hemocoagulation, endogenous anticoagulants and fibrinolysis in 136 patients with severe burns; in 69 patients, the burn disease was complicated by pneumonia and in 67 patients, it was not observed. Based on the totality of the laboratory tests results, it has been shown that pneumonia progress in the acute period of the burn disease was accompanied by high procoagulant activity, reduced levels of endogenous anticoagulants, fibrinolysis depression and moderate thrombocytopenia, severe hepatorenal failure indicating progress of the disseminated intravascular coagulation syndrome (DIC). Progress of acute DIC syndrome from 2 to 6 days after a burn can be not only an indirect evidence of pneumonia, but also can precede its clinical picture.

Lithium and tricyclic antidepressant-induced delirium presenting with prominent dyspraxia: case report

Long-term treatment with lithium has been associated with mild cognitive impairment, mental slowing and memory impairment [Cookson, 1997]. Neurological complications such as muscle weakness, drowsiness, ataxia, confusion and dysarthria can be late signs of lithium toxicity [Tyrer, 1996], but idiosyncratic cases have also been reported [McGovern, 1983; Brown and Rosen, 1992]. In one such case, McGovern described an elderly female patient, with a history of endogenous depression, who developed tremor, vertigo, ataxia and dysphasia, following the initiation of lithium within normal therapeutic serum levels [McGovern, 1983]. In addition, Brown and colleagues described the case of a 64-year-old woman with a 25-year history of schizoaffective disorder who developed delirium following treatment with lithium, also within the therapeutic serum level [Brown and Rosen, 1992]. Tricyclic antidepressants can also cause neurological side effects such as confusion, impaired memory and paresthesia [Joint Formulary Committee, 2011]. Although, there are no case reports of dyspraxia associated with tricyclic antidepressants when used alone in the literature. However, there is an increased risk of toxicity when tricyclic antidepressants are used in combination with lithium. Worrall and colleagues published a case describing slowly developing constructional dyspraxia and mild dysphasia in a 50-year-old female patient with a 2-year history of endogenous depression [Worrall and Gillham, 1983]. After responding to a combination of lithium and amitriptyline for 14 months, she began to complain of difficulties in finding words in conversation and of memory impairment. These problems resolved completely when the lithium was stopped and amitriptyline continued. In our report, we describe a case of delirium presenting with prominent dyspraxia at therapeutic lithium serum levels, following several years of uneventful lithium administration, but within 3 months of the addition of clomipramine. The case described above [Worrall and Gillham, 1983] improved when lithium was stopped but this presentation resolved when clomipramine was withdrawn. This suggests that an idiosyncratic interaction between tricyclic antidepressants and lithium can cause delirium with dyspraxia.

Serum cortisol concentration in patients with major depression after treatment with fluoxetine

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and elevated cortisol levels is characteristic of the pathophysiology of major depressive disorder (MDD). The aim of this study was to determine whether increased plasma cortisol levels appear in patients with major depression and if effective antidepressant treatment by fluoxetine leads to regulation of cortisol level. This aim was realized by describing and validation of methods of determining fluoxetine and cortisol in serum and searching for correlation between their concentrations in patients with endogenous depression, the therapeutic effect as assessed in Hamilton Depression Rating Scale (HDRS), age and sex of patients. Plasma cortisol and fluoxetine levels were measured using high performance liquid chromatography (HPLC) methods with applying Shimadzu chromatograph with UV detection. Plasma cortisol and fluoxetine levels were measured at time zero (before therapy) and after 6h, 24h, 2, 4, 6 and 8weeks of fluoxetine administration in patients with major depression qualified for therapeutic drug monitoring (TDM). The study included 21 patients (14 women, 7 men; mean age 29–75years) and 24 healthy comparison subjects. The patients had a mean score on the 21-item HDRS. As the effect of fluoxetine administration the decrease of the level of cortisol was observed in patients who responded to the therapy (the reduction of points in HDRS scale in at least 50%). The validation parameters of HPLC method of fluoxetine and cortisol determination indicate the possibility of applying them for determination of both: the level of concentration of the drug in therapeutic drug monitoring and the level of cortisol in serum of patients with endogenous depression.

Long term follow up of suicide in a clinically depressed community sample

The purpose of this study was to examine how sex differences in suicide rates unfolded in a long-term follow up of patients who had been diagnosed with major depression. Patients who were diagnosed with major depression in the Chichester/Salisbury Catchment Area Study were followed for 49 years. Recorded deaths from suicide were compared with rates that were predicted from historical data on suicide mortality rates from 1960 onwards. An overall suicide rate of 3.4% was found in the present sample. Sixteen women and three men died from suicide. Women's suicide rates were significantly higher than the level predicted based on general population trends. Men showed a barely non-significant trend in the same direction. The diagnosis of clinical depression was associated more strongly with increased risk for suicide among women compared with men. Of the female suicides, 13 had been diagnosed with endogenous depression. While suicide rates are significantly higher for men in the general population, and for depressed patients of both sexes, the depression may be a particularly strong predictor of suicide risk among women. The dataset does not provide information about processes that mediate the relationship between depression and suicide mortality.

Evidence‐based electroconvulsive therapy

Evidence‐based electroconvulsive therapy

Increased plasma norepinephrine concentration in psychotic depression

We previously found psychotic depression (PSDEP) to have positively correlating plasma norepinephrine (NE) and vasopressin (AVP) concentrations. Since central noradrenergic activity and plasma NE concentration are highly correlated, this suggests an increased noradrenergic activation of the hypothalamus-pituitary-adrenal axis. We hypothesize the increased release of NE in PSDEP to be an associated mechanism. To test this hypothesis we analyzed the relation between plasma NE and PSDEP in a comparison with non-psychotically depressed patients. Potentially confounding variables were, among others, melancholia and two better validated subcategories in the field of melancholia and endogenous depression, three global dimensions of psychopathology - Emotional Dysregulation, Retardation and Anxiety - smoking habit, and different types of psychotropic and particularly antidepressant treatment. The data from nine patients with PSDEP and 69 patients with non-PSDEP were reanalysed. Analysis of covariance controlling for the effects of tricyclic antidepressant treatment (≥100 mg) and smoking habit showed that PSDEP had an increased concentration of plasma NE. The previously found correlation between plasma NE and AVP was still present after correcting for the effects of confounding variables. The results suggest an increased activity of the sympathetic nervous system in PSDEP that may act as a specific mechanism for increased vasopressinergic activation. This supports the view of PSDEP as a distinct subcategory of major depression.

P-1046 - Endogenous depression through the model of informational levels of psychic

Along the time, there were several attempts to explain the etiopathogenic model of endogenous depression. Each time, there was a fragmented view of a complex determined nosological entity influenced by the different paradigms that were shared by different authors. Adepts of organic theory of depression have overestimated the contribution of biological factors, psychoanalysts have based their paradigm of depression exclusively on unconscious processes of psychic, behaviorists have highlighted just the classical and operational conditioning processes of depressive behaviors and the cognitivists have built their paradigm based on consciousness psychic processes as dysfunctional beliefs and cognitive distortions. Unlike the aforementioned paradigms, we developed a new model of the informational levels of psychic that is more comprehensive and can better explain one of the most complex disorder as is depression. Also, our model makes understandable connections between the biological level of depression up to the level represented by noosphere of inter-human communications.

Electroconvulsive Therapy and Melancholia

It has long been lore in the electroconvulsive therapy (ECT) field that melancholic depression is particularly responsive to ECT, whereas nonmelancholic depressions are less so. Early large case series in the 1940s and 1950s, while using now outdated diagnostic nosologies, did provide some hints to the particular efficacy of what later on would be considered melancholic or endogenous depression. The first systematic studies of this subject in the 1950s and 1960s seemed to confirm the superior response of endogenous depression to ECT. However, with the advent of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, and the first criterion set specifically labeled "melancholia," most modern series of studies have failed to find an association of melancholic symptoms with ECT response. Several problems both with the definition of melancholia and the modern methods of diagnosis and outcome assessment are hypothesized to be at the root of the negative findings of modern studies. Suggestions for future ECT/melancholia studies are offered.

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.

Increased expression of the Vesicular Glutamate Transporter-1 (VGLUT1) in the prefrontal cortex correlates with differential vulnerability to chronic stress in various mouse strains: Effects of fluoxetine and MK-801

Major depression is a chronic psychiatric illness that is highly prevalent and disabling. The available medications are ineffective for many patients suggesting that differents molecular pathways could be specifically altered in the unresponsive patients. Recently, the glutamatergic system has emerged as a target in the research on depression and acute NMDA receptor blockade has been shown to produce strong antidepressant effects. We have studied the adaptations of four mice strains (C57BL/6, DBA/2, C3H and BALB/c) to a chronic unpredictable stress protocol, a widely used model of depression in rodents. BALB/c mice displayed strikingly different behavioral and neurochemical adaptations compared to the other strains tested, suggesting that different molecular pathways are involved in their specific vulnerability. They became hyperactive during the dark period, anhedonic-like and displayed no alterations in the tail suspension test (TST). After chronic stress, only the BALB/c displayed an increased frontocortical VGLUT1 expression which is suggestive of a dysregulation of their prefrontal glutamatergic system, and no BDNF mRNA alteration, although the acute stress modulation of this mRNA is similar to the other strains. Chronic administration of an antagonist of NMDA receptors, MK-801, induced antidepressant-like effects in the TST for stressed BALB/c, but was ineffective for the hyperactivity and anhedonia-like behavior, in contrast to fluoxetine. Chronic MK-801 was totally inactive on the behavior of stressed C57BL/6 mice. MK-801, but not fluoxetine, inhibited the VGLUT1 prefrontal increase in BALB/c. Fluoxetine increased VGLUT1 and BDNF mRNA expression in the hippocampus of the C57BL/6 but not in the BALB/c strain, suggesting a different reactivity in-between strain to both stress and antidepressant. Interestingly enough, the BDNF or VGLUT1 increase is not necessary to reverse the stress induced behavioral alterations in our experimental settings. This observation supports the conclusion that BDNF and VGLUT1 are depressive state markers, but not involved in its etiology.Finally, there is a substantial similarity between the phenotypes that are observed in the BALB/c mice and endogenous depression in humans, as well as between C57BL/6 mice and atypical depression. To have a better understanding of the variability of depression etiologies in human, and the implication of the glutamatergic system, it may be suggested that future animal studies in the mouse would systematically compare the two strains BALB/c and C57BL/6 for the identification of relevant biological mechanisms.This article is part of a special Issue entitled ‘Anxiety and Depression’.

Diurnal trend in EEG interhemispheric asymmetry in endogenous depressions

A trend in EEG interhemispheric asymmetry was studied in patients with endogenous depressions in morning and evening hours. In the morning, the spectral power of alpha rhythm particularly in the occipital cortical regions, proved to be higher than that in the evening. In the morning, the interhemispheric differences in the power of occipital alpha rhythm were leveled off while in the evening there was normalization of interhemispheric balance with the higher power of alpha rhythm in the right occipital region. Analysis of the mean coherence (mean Coh) of alpha rhythm in individual cortical regions revealed that the patients with endogenous depression had higher readings mainly in the parietal and central regions of both hemispheres and in the right temporal regions in the morning than in the evening. The occipital and posttemporal regions showed an inverse trend in the mean Coh - it was lower in the morning than in the evening.