Endogenous Depression Research Articles

What do general practitioners think depression is? A taxonomy of distress and depression for general practice

To create a taxonomy of distress and depression for use in primary care, that mirrors the thinking and practice of experienced general practitioners. Qualitative study, using an ethnomethodological approach, with observation of videotaped routine GP-patient consultations and in-depth interviews with GPs. The study was conducted in metropolitan Melbourne in 2005. Fourteen GPs conducted 36 patient consultations where depression was a focus; nine GPs participated in in-depth interviews to elicit details of how they recognised and diagnosed depression in their patients. GPs consider distress and depression in three steps. In the first step, a change in a group of symptoms and signs is observed (eg, facial expression, loss of drive). The second step categorises the syndrome according to whether or not there is an identifiable environmental cause (reactive or "endogenous"), with the final step categorising the reactive syndromes according to their most prominent symptoms: either anxiety and worry, or helplessness and hopelessness. The resulting taxonomy includes: endogenous depression (a chronic and perhaps characterological depression characterised by a lack of interest and motivation); anxious depressive reaction (stress or worry); and hopeless depressive reaction (demoralisation). This simple and parsimonious taxonomy has validity based on its derivation from within the primary care setting.

Expert Opinion: Migraine, Psychiatric Comorbidities, and Treatment

A 28-year-old woman has had migraine withoutaura since the age of 13 with attacks now occurringabout4timespermonthwithaninconsistentresponseto triptans. In addition, she has had recurring endog-enous depression for 3 years treated with paroxetinelastoveroneyearagowithsomehelp.Herdepressionis currently mild.There is no history to suggest hypo-maniaormania.Shehasbeenfrequentlyanxiousforafew years as well, worrying about everything, whichcan cause difficulty falling asleep. Her mother has ahistoryofmajordepressionandmigraine.Hersisterisbeing treated for migraine and bipolar disease.

A suicidal risk in patients with neurotic and endogenous depressions

A suicidal risk in patients with neurotic and endogenous depressions

Management of treatment-resistant depression without ECT (author's transl)

Intravenous infusions of clomipramine and maprotiline, preceded by a five-day tranquilising regimen with a neuroleptic drug, were given to 177 patients with treatment-resistant depression. During the treatment period of 10-20 days the patients were given one infusion daily followed by both antidepressants taken orally. The neuroleptic drug was given at night, from the start of the infusion phase to the end of hospitalisation. After four weeks 66% of the endogenous depressions and 53% of the exhaustion depressions had completely regressed. In patients who failed to respond the infusion regimen can be repeated, if necessary with nomifensin (Alival) instead of clomipramine (Anafranil) and maprotiline (Ludiomil) in order to achieve the desired improvement without ECT. In addition to careful diagnosis, a prerequisite for likely success in the management of treatment-resistant depression is the combination of drug administration with adequate psychotherapeutic and physiotherapeutic measures. The infusion regimen is relatively easy to undertake, can also be used on an out-patient basis and could be the treatment of choice in the future, not only for treatment-resistant depressions but also for patients whose depressive state requires rapidly effective antidepressive measures.

Psychotic Depression

Psychotic Depression

IFN-induced depression in HCV patients and endogenous depression is associated with an enhanced sensitivity to IFN-alpha

IFN-induced depression in HCV patients and endogenous depression is associated with an enhanced sensitivity to IFN-alpha

Post-stroke depression

Post-stroke depression (PSD) is among the most common emotional disorders afflicting stroke sufferers. Approximately one third of stroke survivors experience an early or later onset of depression. PSD impedes the rehabilitation and recovery process, jeopardizes quality of life and increases mortality. Diagnosis of PSD is challenging in the acute and chronic aftermath. Therefore, it often remains unrecognized and/or undertreated. The interaction between depression and stroke is very complex and the pathophysiological mechanisms have not as yet been fully elucidated, although an interaction between anatomical and psychosocial factors may be important in PSD development. Neurochemical changes and clinical findings are similar to endogenous depression. PSD is potentially treatable, although no conclusive benefits of antidepressant agents and nonpharmacological interventions have been observed. The efficacy of preventive strategies in PSD remains essentially undetermined.

Neonatal clomipramine induced endogenous depression in rats is associated with learning impairment in adulthood

Clinical studies show cognitive impairment in depression. However, the neural substrates underlying these remain elusive. Hence, we have examined the effect of neonatal clomipramine treatment on cognition in adulthood. The neonatal clomipramine treated rats displayed a profound impairment in partially baited 8-arm radial maze task. This work provides a novel perspective into neural basis of depression associated cognitive changes and help in development of therapeutic strategies to treat depression related memory dysfunctions.

Non‐equivalence of growth arrest induced by predation risk or food limitation: context‐dependent compensatory growth in anuran tadpoles

1. To gain insight into the evolution of compensatory growth, we studied the growth patterns of anuran (Rana temporaria) larvae following either a period of exogenous growth depression (food restriction) or a period of endogenous depression (exposure to predators). We also investigated the potential deferred costs that larval compensatory growth could impose on post-metamorphic individuals. 2. Food-deprived larvae exhibited full compensatory growth in response to reduced growth rates caused by food limitation, and the growth trajectories of low- and high-rations tadpoles converged before the onset of metamorphosis. 3. According to our predictions, individuals exposed to larval predators did not show growth compensation following predator removal despite undergoing a significant reduction in growth rate associated with low activity levels. 4. Jumping ability of individuals exposed to predators during only 20 days from the commencement of the larval phase was equivalent to that of non-exposed animals, and greater than the jumping capacity of those maintained with predators until the time of metamorphosis. This pattern was consistent with the pattern observed for variation in relative leg length. 5. These results support the suggestion that submaximum and compensatory growth could have evolved to minimize the overall growth/mortality costs in environments with high spatiotemporal variation in predation intensity.

The diagnosis of art: melancholy and the Portrait of Dr Gachet

Dr Paul Gachet (1828-1909), born in Lille, studied medicine in Paris and Montpellier, and wrote a thesis entitled Etude sur la melancolie.1 In 1858, he returned to Paris to practise as a doctor and moved to Auvers-sur-Oise in 1872. There he befriended many painters, including Cezanne (who painted The House of Dr Gachet), Daubigny, Guillaumin, and Pissarro. Gachet himself became an artist, signing his works ‘P van Ryssel’. Vincent van Gogh (1853-1890) moved to Auvers on 20 May 1890, after leaving the asylum at St-Remy. He made three portraits of Gachet, an etching (May 1890) and two paintings (June 1890)—the second, for Gachet himself to keep, a near copy of the first.2 The best known of these, Portrait of Dr Gachet (oil on canvas, 67× 56 cm, location unknown), shows the doctor with his head propped on his right hand; his elbow rests on a table next to a purple foxglove and two books, Germinie Lacerteux (1865) and Manette Salomon (1867), both by the Goncourt brothers, Edmond and Jules. The portrait is profoundly melancholic: the colours are mostly heavy and oppressive; the two novels are depressing in content—Germinie Lacerteux is about a young servant who lives a debauched life and dies miserably in the workhouse and Manette Salomon describes the lives of four more or less unsuccessful painters. Gachet is palpably depressed—his head-in-hand pose is classical,2 as is his facial expression. Van Gogh wrote that Gachet's face was ‘grief-hardened’; ‘... he certainly seems to be suffering [nervous trouble] as seriously as I’, and ‘he is sicker than I am’. But van Gogh saw himself going beyond the doctor's individual melancholy to a more general state. As he wrote to Gauguin, ‘I have a portrait of Dr Gachet with the heart-broken expression of our time’. And to his brother Theo: ‘I had to paint [him] like that to convey how much expression and passion there is in modern heads.. .that is how one ought to paint many portraits’. And what is the foxglove doing in the painting? Some have suggested that it is the badge of the physician2—a role that it plays nowhere else in art. Others have suggested that Gachet treated van Gogh's seizures with digitalis. It has even been suggested that digitalis toxicity may have accounted for van Gogh's love of yellow,3 which does not bear scrutiny.4 But in the 19th century, digitalis was used to treat some psychiatric problems, including delirium tremens and mania, and it was also sometimes used to raise the spirits. According to William Withering's son: ‘... women of the poorer class in Derbyshire... drink large draughts of Foxglove tea, as a cheap means of obtaining the pleasures or the forgetfulness of intoxication’.5 Van Gogh described Gachet's foxglove as being ‘of sombre purple hue’. Perhaps he included it as another symbol of melancholy. But why was Gachet melancholic? Was it endogenous depression? Or was it the symptom of some physical illness? In the painting, his hands are slightly pigmented, albeit paler than his sunburnt face, and his nails are completely pale. Could he have had Addison's disease? Alas for this hypothesis, van Gogh's painting is impressionistic, not realistic; a contemporary photograph of Gachet shows that he had a fuller face than van Gogh portrayed; his hands are not seen. In fact, the portrait of Gachet is more like van Gogh himself or his brother, Theo, than Gachet. And indeed Gachet had asked van Gogh to paint it in the style of one of his self portraits. Perhaps Gachet was, like van Gogh, addicted to absinthe.6 We encourage further speculation.

Patient Predictors of Response to Psychotherapy and Pharmacotherapy: Findings in the NIMH Treatment of Depression Collaborative Research Program

Objective: The authors investigated patient characteristics predictive of treatment response in the National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program. Method: Two hundred thirty-nine outpatients with major depressive disorder according to the Research Diagnostic Criteria entered a 16-week multicenter clinical trial and were randomly assigned to interpersonal psychotherapy, cognitive-behavior therapy, imipramine with clinical management, or placebo with clinical management. Pretreatment sociodemographic features, diagnosis, course of illness, function, personality, and symptoms were studied to identify patient predictors of depression severity (measured with the Hamilton Rating Scale for Depression) and complete response (measured with the Hamilton scale and the Beck Depression Inventory). Results: One hundred sixty-two patients completed the entire 16-week trial. Six patient characteristics, in addition to depression severity previously reported, predicted outcome across all treatments: social dysfunction, cognitive dysfunction, expectation of improvement, endogenous depression, double depression, and duration of current episode. Significant patient predictors of differential treatment outcome were identified. 1) Low social dysfunction predicted superior response to interpersonal psychotherapy. 2) Low cognitive dysfunction predicted superior response to cognitive-behavior therapy and to imipramine. 3) High work dysfunction predicted superior response to imipramine. 4) High depression severity and impairment of function predicted superior response to imipramine and to interpersonal psychotherapy. Conclusions: The results demonstrate the relevance of patient characteristics, including social, cognitive, and work function, for prediction of the outcome of major depressive disorder. They provide indirect evidence of treatment specificity by identifying characteristics responsive to different modalities, which may be of value in the selection of patients for alternative treatments.

Endogenous Activation of Adenosine A1 Receptors, but Not P2X Receptors, During High-Frequency Synaptic Transmission at the Calyx of Held

Activation of presynaptic receptors plays an important role in modulation of transmission at many synapses, particularly during high-frequency trains of stimulation. Adenosine-triphosphate (ATP) is coreleased with several neurotransmitters and acts at presynaptic sites to reduce transmitter release; such presynaptic P2X receptors occur at inhibitory and excitatory terminals in the medial nucleus of the trapezoid body (MNTB). We have investigated the mechanism of purinergic modulation during high-frequency repetitive stimulation at the calyx of Held synapse. Suppression of calyceal excitatory postsynaptic currents (EPSCs) by ATP and ATPgammaS (100 microM) was mimicked by adenosine application and was blocked by DPCPX (10 microM), indicating mediation by adenosine A1 receptors. DPCPX enhanced EPSC amplitudes during high-frequency synaptic stimulation, suggesting that adenosine has a physiological role in modulating transmission at the calyx. The Luciferin-Luciferase method was used to probe for endogenous ATP release (at 37 degrees C), but no release was detected. Blockers of ectonucleotidases also had no effect on endogenous synaptic depression, suggesting that it is adenosine acting on A1 receptors, rather than degradation of released ATP, which accounts for presynaptic purinergic suppression of synaptic transmission during physiological stimulus trains at this glutamatergic synapse.

Neonatal citalopram exposure produces lasting changes in behavior which are reversed by adult imipramine treatment

Neonatal exposure to antidepressants, including selective serotonin reuptake inhibitors such as citalopram, induces behavioral disturbances which persist in mature rats. These disturbances have been proposed to model the symptoms of endogenous depression. However, to date there is scant evidence for the predictive validity of any of these behaviors in response to adult antidepressant treatments. In order to directly assess the predictive validity of the early antidepressant exposure paradigm, the present study examined whether the behavioral abnormalities observed in adult animals exposed as neonates to citalopram can be reversed by adult antidepressant treatment with the prototypic antidepressant, imipramine. As noted earlier, neonatal citalopram exposure robustly increased locomotor activity and impaired male sexual behavior in adult rats. These behavioral changes were reversed following chronic adult imipramine treatment. No such reversal was observed in handled, saline treated rats. The present data support the hypothesis that some of the lasting behavioral abnormalities induced by early antidepressant exposure are sensitive to clinically relevant antidepressant treatments thus adding a measure of predictive validity to this paradigm as a model of these depressive symptoms.

Carbon dioxide exhalation temporarily increases during electroconvulsive therapy

Electroconvulsive therapy induces hypermetabolism and elevates oxygen and energy demands, while more carbon dioxide is produced than usual. The purpose of the present study was to determine the elevated carbon dioxide exhalation and the adequate ventilation volume during electroconvulsive therapy. Carbon dioxide exhalation during an electrically induced seizure was continuously monitored by capnography and spirography in 15 patients with endogenous depression. A laryngeal mask airway was used to measure the airway gas flow. Data were collected during a total of 80 electroconvulsive therapy trials. The carbon dioxide exhalation at 1 min after electrical stimulation was higher than the control value (2.8 +/- 0.4 versus 2.3 +/- 0.3 ml.min(-1).kg(-1), mean +/- SD; P < 0.05). The ventilation volume was increased for 3 min after the electrical stimulation to maintain the end-tidal carbon dioxide partial pressure at 35-40 mmHg. The results showed that increasing the ventilation volume by approximately 20% may be necessary to compensate for the increased carbon dioxide exhalation during electroconvulsive therapy.

There is a gender difference in the relationship between metabolic syndrome and oxidative stress among Japanese

Neurobiological mechanisms invoking the release of endogenous opioids and depression of stress hormone release are believed to be the basis of acupuncture analgesia. This study compared plasma β-endorphin and cortisol levels with self assessment scores of intensity of pain, before and after 10 days of electro-acupuncture treatment in patients suffering from chronic pain as a result of osteoarthritis knees. Forty patients of either sex over 40 years with primary osteoarthritis knee were recruited into a single-blinded, sham-controlled study. For electro-acupuncture group the points were selected according to the Traditional Chinese Medicine Meridian Theory. In the sham group needles were inserted at random points away from true acupoints and no current was passed. Both groups were treated for 10 days with one session every day lasting for 20–25 min. Pre- and post-treatment Western Ontario and McMaster Universities (WOMAC) index of osteoarthritis knee and Visual Analogue Scale (VAS) for pain were recorded and blood samples were taken for the measurement of plasma cortisol and β-endorphin levels. Following electro-acupuncture treatment there was a significant improvement in WOMAC index and VAS (p = 0.001), a significant rise in plasma β-endorphin (p = 0.001), and a significant fall in plasma cortisol (p = 0.016). In conclusion electro-acupuncture resulted in an improvement in pain, stiffness and disability. Of clinical importance is that an improvement in objective measures of pain and stress/pain associated biomarkers was shown above that of a sham treatment; hence demonstrating acupuncture associated physiological changes beyond that of the placebo effects.

Long-term depression in the sensorimotor cortex induced by repeated delivery of 10 Hz trains in vivo

Memory consolidation in the neocortex is thought to be mediated in part by bi-directional modifications of synaptic strength. The sensorimotor cortex shows marked spontaneous activity near 10 Hz during both waking and sleep in the form of electroencephalographic spindle waves, and is also sensitive to electrical activation of inputs at 10 Hz. Induction of long-term synaptic depression in corpus callosum inputs to layer V of the sensorimotor cortex of the awake, adult rat requires repeated low-frequency stimulation over many days. To determine if 10 Hz stimulation may facilitate the induction of long-term depression, we compared the amounts of long-term depression induced by conventional 1 Hz trains, repeated delivery of 450 pairs of stimulation pulses using a 100 ms interpulse interval, and 45 short, 2 s, 10 Hz trains. Each pattern was delivered daily for 10 days and was matched for total duration and number of pulses. Changes in synaptic responses were assessed by monitoring field potentials evoked by stimulation of the corpus callosum. A facilitation of synaptic responses in layer V was observed during delivery of both paired-pulse trains and 10 Hz trains. There was no significant difference in long-term depression induced by 1 Hz stimulation and repeated paired-pulse stimulation, but 10 Hz trains induced significantly greater long-term depression than 1 Hz trains in both the early monosynaptic and late polysynaptic field potential components. The effectiveness of short 10 Hz trains for the induction of long-term depression suggests that synchronous population activity at frequencies near 10 Hz such as spindle waves may contribute to endogenous synaptic depression in sensorimotor cortex.

Assembling the Emotions

Endogenous depression is highly correlated with low levels of serotonin in the central nervous system. Does this imply or suggest that this sort of depressionjust isthis neurochemical deficit? Scorning such an inference, Antonio Damasio writes:If feeling happy or sad … corresponds in part to the cognitive modes under which your thoughts are operating, then the explanation also requires that the chemical acts on the circuits which generate and manipulate [such thoughts]. Which means that reducing depression to a statement about the availability of serotonin or norepinephrine in general- a popular statement in the days and age of Prozac- is unacceptably rude (1995, 161).Damasio's thought is that depression isessentiallya modification of how we perceive the world, reason about it, and make decisions about how to act in it - in other words, that it is essentially cognitive. A reduced level of serotonin might cause the said modification, but no adequate account of depression would identify the malady with its cause. A proper account would minimally need to say how cognitive processing is affected by a reduced level of serotonin.

Multiple Intracerebral Hemorrhages following Electroconvulsive Therapy

Electroconvulsive therapy is the most effective treatment for endogenous depression. Possible adverse effects include confusion, memory loss, headache, hypotension, and tachycardia. We describe a 22-year-old woman treated for unconsciousness four hours after electroconvulsive therapy. She had no history of recent head trauma, hypertension or cerebrovascular symptoms. Complete blood count, platelet count, prothrombin and partial thromboplastin time were normal. Multiple intracerebral hemorrhages were seen on computed tomography. This unusual finding has not been reported previously.

Toward Holistic, Compassionate, Professional Care: Using a Cultural Lens to Examine the Practice of Contemporary Psychotherapy in the West*

The author describes work undertaken in New Delhi with two young Indian women and their families from 1995 to 1999. Both presented with depression and suicidal ideation. One was severely cerebral palsied, the other was diagnosed with endogenous depression. As an integrative therapist, the author looks at her work from several perspectives. The debates highlighted here focus on the optimal usefulness of each of these perspectives in different situations, both the benefits and the limits and the very limits of contemporary psychotherapy itself. The author uses a cultural lens to explore the use of the self of the therapist and issues around boundaries, continuity, ethics, and compassion in psychotherapy.

Behavioural and neurochemical effects induced by chronic mild stress applied to two different rat strains

Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in rats that resembles some of the symptoms of endogenous depression in humans. In the present study, CMS-induced behavioural responses along with neurochemical alterations in dopaminergic and serotonergic function in prefrontal cortex, striatum, hypothalamus and hippocampus were examined following treatment with imipramine in Wistar and Sprague–Dawley rats. The CMS procedure lasted 7 weeks in total. Once per week, a 1-h preference test for 1% sucrose solution was conducted. Treatment with imipramine (10 mg/kg i.p., once daily) commenced after experimental week 3. CMS induced significant reductions in absolute and relative sucrose intake and sucrose preference in both rat strains but their temporal pattern was different especially during the weeks 0–3. These effects were reversed by IMI. An increase in the dopaminergic and a decrease in the serotonergic activity were observed in the prefrontal cortex in both rat strains following CMS. A decrease in the striatal dopaminergic activity and an increased hippocampal serotonergic activity were also seen in both rat strains following CMS. In Wistar rats, dopaminergic and serotonergic activities were enhanced in the hypothalamus whereas in Sprague–Dawley rats no such stress-induced changes were observed. Notably, the clear decrease in sucrose consumption observed in stressed Wistar rats could be directly associated with a respective increase in the dopaminergic hypothalamic activity. Chronic treatment with imipramine normalized all neurochemical alterations induced by CMS. Our results suggest that a specific and regionally differentiated serotonin–dopamine interaction is directly related to the observed stress-induced anhedonia.