Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 55-year-old man presented with a 5-year history of Parkinson's disease and a 6-month history of major depression. The patient's depressive symptoms responded to treatment with fluvoxamine, a selective and potent serotonin reuptake inhibitor. Tryptophan depletion testing, which acutely lowers central serotonin levels, caused a brief exacerbation of the depressive illness, which resolved upon tryptophan repletion. Serotonergic dysfunction may be an etiologic factor in depression that occurs in Parkinson's disease.
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PMID:Serotonergic dysfunction in depression associated with Parkinson's disease. 835 Oct 31

1. Experiments were performed on the brain stem-spinal cord preparation of newborn rats, in which the phrenic and hypoglossal nerves continue to show rhythmic respiratory activity in vitro, in order to compare the effects of serotonin (5-HT) on both activities and to analyse the mechanisms responsible for the depression by 5-HT of the hypoglossal activity. 2. Under control conditions, simultaneous recordings of the inspiratory discharges of hypoglossal and cervical roots showed that the two bursts did not start simultaneously and had different patterns (time-to-peak and peak values); this suggests that both pools of motoneurons did not share the same central drive(s). 3. Adding 5-HT and related agents to the bathing medium delayed and depressed the hypoglossal inspiratory discharge via activation of 5-HT2 receptors since these effects were elicited by 5-HT2 agonists (alpha-methyl-5-HT and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-HCl (DOI)) but not by 5-HT1 agonists (RU 24969 and (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (8-OH-DPAT)). The 5-HT depression of the hypoglossal discharge was prevented by applying a pretreatment with a specific 5-HT2 antagonist (ketanserin). Parallel to the hypoglossal discharge decrease, 5-HT elicited a permanent cervical root discharge along with a persistent inspiratory bursting. Adding the 5-HT precursor L-tryptophan to the bathing medium depressed the hypoglossal (XII) discharge without affecting the cervical one. 4. Local application of 5-HT within the hypoglossal motor nucleus decreased the hypoglossal output, revealing that the 5-HT depression of the hypoglossal discharge was at least partly mediated by the 5-HT effects at the level of the motoneurons. Local application of 5-HT within the cervical motor nucleus elicited a permanent firing in the cervical root with a persistent inspiratory bursting. 5. Intracellular analysis confirmed the existence of differences in central respiratory drive between cervical and hypoglossal motoneurons under control conditions, as well as differences in response to 5-HT. All the hypoglossal motoneurons became silent under 5-HT bathing, and showed no change in the input membrane resistance, a moderate depolarization, and a delayed central respiratory drive with a decreased amplitude. The cervical motoneurons became more active during inspiration, despite a decrease in the amplitude of the central respiratory drive, which was compensated for by a large depolarization and an increased input membrane resistance. Some cervical motoneurons even fired at a low rate during expiration.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Compared effects of serotonin on cervical and hypoglossal inspiratory activities: an in vitro study in the newborn rat. 140 27

The effects of depletion of the serotonin precursor, L-tryptophan, on the threshold and tolerance to cold pressor pain, and the analgesic effect of morphine (10 mg intramuscularly), were tested in a double blind trial on human volunteers. Effects on mood were also assessed using the Profile of Mood States and the Addiction Research Center Inventory (ARCI) Scales. To deplete tryptophan, subjects were fed a tryptophan-deficient amino acid mixture 4.5 h before morphine was administered. Controls received the mixture with tryptophan, which is equivalent to a nutritionally balanced protein. The tryptophan-deficient meal reduced plasma tryptophan more than 70% but had no effect on threshold or tolerance to cold pressor pain. After morphine, tolerance to cold pressor pain increased in controls. Tryptophan depletion abolished this analgesic effect. Pain threshold was not altered by morphine. In subjects with normal tryptophan, the analgesic effect of morphine was predicted by the level of plasma morphine-6-glucuronide, but not by the level of morphine. Morphine increased scores on the LSD scale of the ARCI, but had no effect on other measures of mood. Tryptophan depletion also failed to alter mood in these subjects, who had unusually low depression scores before tryptophan depletion.
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PMID:Acute tryptophan depletion blocks morphine analgesia in the cold-pressor test in humans. 141 Jan 47

Serotonergic mechanisms have been implicated in the pathophysiology of depression and in the neuropharmacology of antidepressant treatment. One measure of central serotonergic function is the prolactin (PRL) response to IV L-tryptophan (L-TRP). We used the L-TRP test to assess the role of serotonin in the mechanism of action of lithium augmentation in refractory major depression. Twenty-six patients with antidepressant-refractory major depression each received three L-TRP tests (after 2 weeks of placebo, after 4 weeks of active primary antidepressant, and after 1 week of lithium augmentation). Primary antidepressant treatment did not increase the PRL response, but lithium augmentation resulted in a statistically significant increase in PRL response as compared to both placebo pretreatment (P less than 0.04) and antidepressant treatment alone (P less than 0.025). This study supports a role for serotonergic mechanisms in the action of lithium augmentation.
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PMID:Serotonergic function during lithium augmentation of refractory depression. 141 Jan 50

Neurological dysfunction, seizures and brain atrophy occur in a broad spectrum of acute and chronic neurological diseases. In certain instances, over-stimulation of N-methyl-D-aspartate receptors has been implicated. Quinolinic acid (QUIN) is an endogenous N-methyl-D-aspartate receptor agonist synthesized from L-tryptophan via the kynurenine pathway and thereby has the potential of mediating N-methyl-D-aspartate neuronal damage and dysfunction. Conversely, the related metabolite, kynurenic acid, is an antagonist of N-methyl-D-aspartate receptors and could modulate the neurotoxic effects of QUIN as well as disrupt excitatory amino acid neurotransmission. In the present study, markedly increased concentrations of QUIN were found in both lumbar cerebrospinal fluid (CSF) and post-mortem brain tissue of patients with inflammatory diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicaemia) independent of breakdown of the blood-brain barrier. The concentrations of kynurenic acid were also increased, but generally to a lesser degree than the increases in QUIN. In contrast, no increases in CSF QUIN were found in chronic neurodegenerative disorders, depression or myoclonic seizure disorders, while CSF kynurenic acid concentrations were significantly lower in Huntington's disease and Alzheimer's disease. In inflammatory disease patients, proportional increases in CSF L-kynurenine and reduced L-tryptophan accompanied the increases in CSF QUIN and kynurenic acid. These responses are consistent with induction of indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway which converts L-tryptophan to kynurenic acid and QUIN. Indeed, increases in both indoleamine-2,3-dioxygenase activity and QUIN concentrations were observed in the cerebral cortex of macaques infected with retrovirus, particularly those with local inflammatory lesions. Correlations between CSF QUIN, kynurenic acid and L-kynurenine with markers of immune stimulation (neopterin, white blood cell counts and IgG levels) indicate a relationship between accelerated kynurenine pathway metabolism and the degree of intracerebral immune stimulation. We conclude that inflammatory diseases are associated with accumulation of QUIN, kynurenic acid and L-kynurenine within the central nervous system, but that the available data do not support a role for QUIN in the aetiology of Huntington's disease or Alzheimer's disease. In conjunction with our previous reports that CSF QUIN concentrations are correlated to objective measures of neuropsychological deficits in HIV-1-infected patients, we hypothesize that QUIN and kynurenic acid are mediators of neuronal dysfunction and nerve cell death in inflammatory diseases. Therefore, strategies to attenuate the neurological effects of kynurenine pathway metabolites or attenuate the rate of their synthesis offer new approaches to therapy.
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PMID:Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. 142 88

Because of the limitations in efficacy and safety of the older tricyclic antidepressants (TCA) and monoamine oxidase inhibitors (MAOI) a number of new approaches have been made in recent years to the treatment of depression to obtain more effective, more rapidly acting, better tolerated and safer drugs. One tactic has been to develop compounds with greater neuropharmacological selectivity in inhibiting the neuronal reuptake of 5-HT. Most of these are as effective as TCA but with fewer side-effects and greater safety. Another development has been 'reversible' MAOI which reduce the risk of interaction with tyramine-containing foods. For resistant depression the addition of lithium (and/or tryptophan) may be effective, possibly through promoting 5-HT neurotransmission. Continuous treatment with a selective 5-HT reuptake inhibitor can reduce the relapse rate in patients with recurrent depression. Unfortunately, these new approaches, despite their advantages in terms of side-effects and safety, have thus far not proved to be more effective or faster acting than the standard TCA. That remains a challenge for the future.
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PMID:New aspects in the treatment of depression. 143 Oct 20

At least three categories of atypical depression have been described. The hysteroid dysphoria is characterized by repeated episodes of depressed mood in response to feeling rejected, and a craving for sweets and chocolate. Two other issues are characterized by a cyclical occurrence of changes of mood and appetite, i.e., the late luteal phase dysphoric disorder (DSM-III-R, appendix), or "the premenstrual syndrome" (PMS), and the major depression with seasonal pattern (DSM-III-R), or seasonal affective disorder (SAD). The reactive mood changes are frequently accompanied by features as hypersomnia, lethargy and increased appetite, particularly with a preference for carbohydrates. Central serotonin pathways participate in the regulation of mood and behavioural impulsivity, and modulate eating patterns qualitatively and quantitatively. Depressives with PMS og SAD benefit, in general, from treatments with serotonin potentiating drugs, suggesting that brain serotonin plays a role in the pathophysiology. Ingestion of carbohydrates increases the plasma ratio of tryptophan to other large neutral amino acids in man and animal, and the serotonin synthesis in the rat brain. Based on these findings it has been suggested that the excessive carbohydrate intake by patients with PMS and SAD reflects a self-medication that temporarily relieves the vegetative symptoms via an increased central serotonergic activity.
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PMID:Serotonin, carbohydrates, and atypical depression. 148 May 61

In a previous paper evidence was presented to show that Helicobacter-induced chronic gastritis is the probable cause of most chronic hypochlorhydria. In this article evidence is presented for the clinical relevance of reduced stomach acid secretion. Reduced mineral absorption is fairly well documented and has sound theoretical support from basic chemistry. Impaired digestion of protein has been suggested by a few studies. Small intestinal bacterial overgrowth in hypochlorhydria probably leads to putrefactive breakdown of the metobolically useful products of protein digestion, thereby reducing their availability for certain essential pathways. The possible lowering of tryptophan, tyrosine, and phenylalanine in the blood may be a precipitating factor in depression in hypochlorhydric patients. In reduced or absent stomach acid secretion a constellation of gastrointestinal symptoms has been consistently observed and reported by clinicians in the past, and treatment of the hypochlorhydria with hydrochloric acid or its substitutes has often been observed to be effective in reducing these symptoms.
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PMID:The clinical importance of hypochlorhydria (a consequence of chronic Helicobacter infection): its possible etiological role in mineral and amino acid malabsorption, depression, and other syndromes. 149 27

The authors briefly review studies of the efficacy of potent serotonin reuptake inhibitors (SRIs) (e.g., clomipramine, fluvoxamine) in obsessive compulsive disorder (OCD) and compare the use of antidepressants in the treatment of depression and OCD. They propose an algorithm for those patients with OCD who fail to respond to an adequate trial with a potent SRI and discuss the promise and limitations of adding tryptophan, fenfluramine, lithium, buspirone, or a neuroleptic to ongoing SRI therapy. Other biological approaches (e.g., ECT, psychosurgery) are considered in terms of their narrowly defined roles in the treatment of patients with SRI-resistant OCD.
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PMID:Pharmacotherapy of obsessive compulsive disorder. 153 62

The possible role of amino acid availability and a functional hypothalamic-pituitary-adrenal axis in the mood disturbances often reported in postpartum women and in users of the oral contraceptive was examined by measuring amino acids and doing a dexamethasone suppression test. Plasma cortisol, tryptophan, tyrosine, their competing amino acids in brain uptake (CAA), and the effect of 1mg dexamethasone were determined in 10 women taking oral contraceptives, 31 women 3 days postpartum, and 9 controls. The pill contained 30 mcg ethinyl estradiol and .075 mg gestodene (2 women), and 30 mg ethinyl estradiol and .15 mg desogestrel (8 women). The subject also took self-rating mood scales: Zung Depression, Zung Anxiety, Beck Depression and State Anxiety Inventory. Cortisol was significantly higher in postpartum women and pill users than in normal controls. Tryptophan, valine, isoleucine and leucine were lower in postpartum women. Tyrosine and tyrosine CAA were lower in postpartum women and pill users. 80% of the postpartum group had negative dexamethasone suppression tests, i.e., cortisol 5 mcg/dl 24 hours after 1 mg dexamethasone. After dexamethasone valine was significantly higher and tryptophan/CAA and tyrosine/CAA ratios were lower, as a result of slightly lower tryptophan and tyrosine and slightly higher CAAs. Furthermore, effects on the amino acid ratios were only evident in women exhibiting dexamethasone suppression. There was a significant negative correlation between depression and anxiety scores and the tryptophan/CAA ratio. The results indicated first that the dexamethasone suppression test is an invalid marker for major depression, and also that availability of the amino acid precursors of brain neurotransmitters may affect mood in the puerperium.
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PMID:Disturbances in dexamethasone suppression test and lower availability of L-tryptophan and tyrosine in early puerperium and in women under contraceptive therapy. 156 Apr 30


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