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)

In 28 patients with primary depression, relationships were sought between rating scores on the Montgomery-Asberg Depression Rating Scale and the concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) in cerebrospinal fluid (CSF). Among the single items in the rating scale, reported sadness correlated negatively with HMPG. No other significant relationships were found in the total group of patients. However, in subgroups with low or high concentrations of monoamine metabolites, several significant relationships were found, such as a negative correlation between inner tension and concentration difficulties, respectively, and 5-HIAA in the low-HMPG subgroup. Curvilinear relationships were found between pessimistic thoughts and 5-HIAA in the high-5-HIAA subgroup and between apparent sadness and 5-HIAA in the low-HMPG subgroup. Suicidal thoughts tended to correlate in a curvilinear way with the ratio of HMPG/5-HIAA in the low-HVA and the high-HMPG subgroups, but the curves were mirrored. The results indicate that relationships between clinical symptoms and monoamine metabolite homeostasis in CSF are qualitatively and quantitatively different in defined high-and low-monoamine subgroups of depressed patients.
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PMID:Relationships between clinical symptoms and monoamine metabolite concentrations in biochemically defined subgroups of depressed patients. 246 3

Effects of the neurotoxin para-chloroamphetamine (PCA) on sex differences in passive avoidance were studied. Seven days prior to passive avoidance training and testing, male and female rats were injected with PCA (5 mg/kg) or physiological saline (SAL). Treatment effects on brain monoamines levels were evaluated in brains collected shortly after the passive avoidance test. Compared to SAL-treated control groups PCA severely reduced both serotonin (5-HT) and 5-hydroxyindole-acetic acid (5-HIAA) in the frontal cortex of males and females. Levels of dopamine (DA) and homovanillic acid (HVA) in the frontal cortex were not affected. These data are indicative of a strong and selective depression of the central 5-HT activity. PCA- and SAL-treated male and female rats were trained and tested in a two-compartment step-through passive avoidance apparatus. Sex differences in passive avoidance were clearly observed in the SAL-treated control groups; a higher number of males did not enter either compartment within the maximum test duration. After PCA treatment sex differences in passive avoidance were abolished, mainly resulting from an increase in the number of PCA-males reentering. Irrespective of sex or treatment subjects seldom failed to choose the nonshock compartment when entering during the passive avoidance test, indicating that disturbance of memory or learning cannot explain for the present results. Rather, the data are discussed in terms of a sex-specific role of central 5-HT in punishment-induced behavioral suppression.
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PMID:Sex differences in passive avoidance depend on the integrity of the central serotonergic system. 246 88

1. Focal cortical freezing lesions in rats caused a widespread decrease in local cerebral glucose utilization (LCGU) in cortical areas of the lesioned hemisphere and this was interpreted as reflecting a depression of cortical activity (Pappius 1981). Cortical serotonin (5-HT) metabolism was increased throughout the lesioned hemisphere (Pappius and Dadoun 1987). To find if these changes in the serotonergic system are of functional importance and mediate the observed changes in LCGU, the effects of inhibition of 5-HT synthesis with p-chlorophenylalanine (PCPA) on cerebral metabolism and indoleamine content in injured brain were studied (Pappius et al. 1988). PCPA decreased 5-HT levels in the cortical and raphe areas of both intact and injured brain in a dose dependent manner. At doses of PCPA ineffective on LCGU (50 and 100 mg/kg) brain trauma still resulted in increased 5-HT metabolism. PCPA at doses which selectively ameliorated the depression of cortical LCGU in the lesioned hemisphere (200 and 300 mg/kg) completely prevented changes in 5-HT and 5-hydroxyindoleacetic acid seen following traumatization in untreated animals. These results provide evidence that decreased LCGU in lesioned brain is due to an activation of the serotonergic system. The data are thus in agreement with a postulated inhibitory role of serotonin in the cerebral cortex, and its involvement in functional alterations associated with injury.
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PMID:Involvement of indoleamines in functional disturbances after brain injury. 247 86

5-Hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations and 5-HT turnover (5-HIAA/5-HT) were determined in 6 brain regions from 19 suicide victims in whom a retrospective diagnosis of depression was established, and 19 age- and sex-matched control subjects. Thirteen of the suicides were free of psychoactive drugs at the time of death; 5 were receiving antidepressant drugs. 5-HT, 5-HIAA and 5-HT turnover did not differ significantly between the total, drug-free and antidepressant-treated suicides and controls in frontal and temporal cortex, caudate and hippocampus. 5-HIAA concentration was significantly higher in amygdala of drug-free suicides than controls, whereas 5-HT and 5-HT turnover did not differ. 5-HT concentration was significantly lower in putamen of the total and antidepressant-treated suicides and a similar reduction was also apparent in the drug-free suicides. 5-HT turnover in putamen was significantly higher in the total and drug-free suicides compared to controls. 5-HT and 5-HIAA concentrations in putamen were significantly lower in drug-free suicides who died by non-violent means than in those who died by violent means. Differences between controls and suicides could not be attributed to age, sex or postmortem delay. These results offer no support for the view that 5-HT turnover is reduced in depressed subjects who commit suicide.
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PMID:Serotonin concentrations and turnover in brains of depressed suicides. 247 56

Dementia and depression in patients with Parkinson's disease have been reported separately, but their prevalence is controversial. This study examines the coexistence of these two problems and suggests a common underlying biochemical system. We examined these two entities by retrospective chart review and cerebrospinal fluid biochemistry. We found a prevalence of 10.9% for dementia, 51% for depression, and 5.4% for coincident depression and dementia. In a prospective study of patients with Parkinson's disease we found a continuum of cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. Patients who were either depressed or demented had lower concentrations of this metabolite than other patients with Parkinson's disease, but patients who were depressed and demented had the lowest levels. These results suggest that the coexistence of dementia and depression represents a unique clinical entity in Parkinson's disease. The serotonergic system may be involved in depression and dementia because evidence of a cumulative effect on this biochemical system is present.
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PMID:Coexisting dementia and depression in Parkinson's disease. 248 Jan 3

Alcoholism is a multifaceted medicosocial problem. Recent literature discusses a common dyad, alcoholism and anxiety. Both disorders are interdigitated with the brain amine serotonin (5-hydroxytryptamine, 5-HT). Direct 5-HT activation reportedly attenuates alcohol consumption, whereas depletion enhances use patterns. Acute alcohol consumption has also been associated with a transient rise, albeit eventual diminished 5-HT turnover. A variety of 5-HT models have confirmed this observation, e.g., reduced platelet 5-HT content, uptake, and cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid. Such altered characteristics of 5-HT secondary to chronic alcohol use may explain the frequent morbidity of anxiety and/or depression. Acute alcohol consumption is also associated with accumulation of the 5-HT aldehyde derivative 5-hydroxymethtryptoline. Thus, alcohol may induce the in vivo formation of aldehydes, e.g., beta-carbolines, that themselves possess high lipophilicity and psychotropic activity. Future investigation into 5-HT-specific pharmacologic probes in alcoholism will be interesting. Preliminary research has consistently demonstrated that 5-HT-enhancing agents (e.g., zimelidine or fluvoxamine) decrease alcohol consumption, preference, and short-term memory decrements. Thus, 5-HT appears to represent at least one common denominator for a spectrum of behavioral disorders including anxiety and alcoholism.
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PMID:Serotonin and alcohol: interrelationships. 256 40

To evaluate the neurotransmitter actions of lithium without the confounding biochemical abnormalities associated with affective disorders, Li was given to 12 hospitalized healthy young men. After a 600-mg loading dose, subjects were placed on "therapeutic" Li doses averaging 1225 +/- 300 mg for 1 wk, reaching steady-state plasma levels of 0.82 +/- 0.17 mEq/l. Cardiovascular function at rest and diastolic blood pressure and pulse on standing were not altered by Li. Average baseline plasma norepinephrine (NE) concentration in the supine position (1.07 +/- 0.50 pmol/ml) did not change after 1 wk of Li dosing (1.16 +/- 0.57 pmol/ml). There was similar variability, without mean change, in plasma NE increments after orthostatic challenge and in plasma 3-methoxy-4-hydroxyphenylglycol concentrations before and during Li dosing. Urine volume was stable throughout the week of drug dosing, during which daily NE excretion was constant. In contrast to earlier data obtained in patients with depression receiving Li, there were no Li-related decrements in average whole-body NE or dopamine turnover. Mean daily urinary excretion rates of serotonin and its major metabolite 5-hydroxyindoleacetic acid did not change throughout the study. Our and other studies suggest that Li has a corrective action in patients with depression and hypothesized neurotransmitter abnormalities, but Li does not affect individuals without affective disorders.
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PMID:Differences in lithium effects in depressed and healthy subjects. 257 6

Magnesium and calcium concentrations were measured in the cerebrospinal fluid (CSF) of 15 neurological controls and 41 psychiatric patients suffering from major depression (n = 16), schizophrenic disorder (n = 15), or adjustment disorder (n = 10). All subjects were women 19-67 years of age and free from drugs at the time of the study. CSF was evaluated for 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and cortisol (CS) levels, and all patients received a dexamethasone suppression test (DST) following lumbar puncture. CSF calcium levels did not differ among groups, although we found a trend toward higher mean levels in both depression and schizophrenia. By contrast, CSF magnesium was found to be significantly lower in both depression and adjustment disorder; if, however, patients who had made suicide attempts were excluded, the difference became insignificant. Patients who had made suicide attempts (by using either violent or nonviolent means) had significantly lower mean CSF magnesium level irrespective of the diagnosis. CSF calcium did not correlate with magnesium, 5-HIAA, HVA, CS, global severity, therapeutic response, or DST, but CSF magnesium correlated significantly with CSF 5-HIAA, especially after correcting for age and body height. Both variables seemed to be primarily related to recorded suicide attempts, but decreased magnesium was not limited to violent cases.
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PMID:Cerebrospinal fluid magnesium and calcium related to amine metabolites, diagnosis, and suicide attempts. 257 29

The effects of amitriptyline (AMI) or imipramine (IMI) on levels of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) (the major brain metabolites of the neurotransmitters norepinephrine [NE], serotonin [5-HT], and dopamine [DA]) in cerebrospinal fluid were determined in 66 subjects with unipolar and bipolar depression. There were significant reductions in MHPG and 5-HIAA levels for the depressed group taken as a whole, but levels of HVA did not change significantly. The changes were similar when subjects were grouped as treated with AMI and IMI and with unipolar and bipolar depression. Reductions in MHPG and 5-HIAA levels were greater in women than in men. In all subjects with depression and in those treated with AMI and IMI, amine metabolite changes did not differ significantly between those who had a positive clinical response to drug therapy and those who did not. Responders with bipolar depression had smaller reductions in MHPG levels than did responders with unipolar depression. The similar effects of AMI and IMI on MHPG and 5-HIAA differ from the dissimilar effects of the two drugs on NE and 5-HT amine uptake systems reported in animal and in in vitro studies. Results provide conclusive evidence of the effects of AMI and IMI on noradrenergic and serotonergic (but not dopaminergic) systems in patients with depression.
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PMID:Effects of amitriptyline and imipramine on brain amine neurotransmitter metabolites in cerebrospinal fluid. 257 12

Various irregularities in serotonin (5-HT) function have been postulated as causes of affective disorders. Serotonin has been related to many of the major symptoms of depression, e.g. mood, appetite, sleep, activity, and cognitive dysfunction. Interference with 5-HT synthesis or storage has been shown to induce depression in vulnerable individuals. Decreased levels of 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid, decreased plasma tryptophan, low tryptophan neutral amino acid ratio, abnormalities in serotonergic function indicated by neuroendocrine challenge tests and various platelet measures, have been reported in depressed patients. Concentrations of 5-HIAA, the major metabolite of 5-HT in plasma, were found to be significantly negatively correlated with severity of depression as measured by the Hamilton Rating Scale for Depression score and specific depressive symptoms, despite the fact that plasma 5-HIAA is largely peripheral in origin. Blood platelets, which have been suggested as models for serotonergic nerve terminals, have a significantly decreased number of 5-HT uptake sites and 3H-imipramine binding sites in depressed patients. Antidepressant drugs may act, in part, by enhancing serotonergic activity. The serotonergic deficit may occur at any of several levels: diminished availability of precursor, impaired activity of tryptophan hydroxylase, abnormalities in 5-HT release or uptake, 5-HT receptor abnormalities or interactions with other neurotransmitters.
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PMID:Serotonergic dysfunction in depression. 269 37


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