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)

We report here the first direct functional evidence of an increase in the tonic activation of postsynaptic 5-HT1A receptors by antidepressant treatments. Because 5-HT1A receptor activation hyperpolarizes and inhibits CA3 pyramidal neurons in the dorsal hippocampus, we determined, using in vivo extracellular recording, whether the selective 5-HT1A receptor antagonist WAY 100635 could disinhibit these neurons. Unexpectedly, no disinhibition could be detected in controls. However, after long-term treatment with the tricyclic antidepressant imipramine, the selective 5-HT reuptake inhibitor paroxetine, the reversible monoamine oxidase-A inhibitor befloxatone, the alpha2-adrenergic antagonist mirtazapine, or the 5-HT1A receptor agonist gepirone or multiple electroconvulsive shock (ECS) administration, WAY 100635 markedly increased (60-200%) the firing activity of CA3 pyramidal neurons. Such a disinhibition was absent in rats treated with the nonantidepressant drug chlorpromazine, in rats receiving only one ECS, or in rats receiving multiple ECSs in combination with an intrahippocampal pertussis toxin treatment to inactivate Gi/o-coupled 5-HT1A receptors. These data indicate that such antidepressant treatments, acting on entirely different primary targets, might alleviate depression by enhancing the tonic activation of forebrain postsynaptic 5-HT1A receptors.
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PMID:Long-term antidepressant treatments result in a tonic activation of forebrain 5-HT1A receptors. 982 68

The aim of the present study was to document behavioral disturbances in dementia patients in a sample not specifically referred to a clinic. Ninety patients with dementia in a community were studied in relation to the behavioral and psychiatric manifestations as perceived by their caregivers. They were categorized into two subgroups based on severity of the illness, namely mild and moderate-severe, for the purpose of comparison. There were 68 patients with Alzheimer disease, 10 with vascular dementia, and the remaining 12 formed a miscellaneous group.The frequency of the following behaviors in relation to the severity of the dementia were assessed: aggression, physical violence, wandering, incontinence, disinhibition, binge-eating, hallucinations, delusions, and depression. The most common behavioral change was aggression (59%), followed by wandering (27%), delusions (22%), and incontinence (18%). Aggression caused the most distress to the caregiver. There was a higher incidence of wandering, incontinence (p= 0.009), and persecutory delusions (p=0.02) in the moderate severe group. A significantly higher proportion of the moderate-severe group required further care and intervention (p=0.04). This study is probably one of the rare nonclinical surveys on this subject.
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PMID:Behavioral and psychiatric manifestations in dementia patients in a community: caregiver burden and outcome. 987 61

Tonic muscle nociceptive discharge evoked chemically from the foot extensor digitorum brevis muscle in man produces a depression of Ia excitation and Ib inhibition of the soleus (Sol) motoneurones (Mns). The possibility that both these changes partly result from presynaptic inhibition of Ia fibres projecting to Sol Mns and to interneurones mediating group I non-reciprocal inhibition is tested. Convergence of Ia fibres on these interneurones was deduced from evidence that reducing the excitatory effect of the extensor Ia fibres (by potentiation of their presynaptic inhibition) resulted in Ib disinhibition. Nociceptive-induced potentiation of Ia presynaptic inhibition was deduced from the following congruent results obtained by two independent methods: (1) depression of heteronymous Ia monosynaptic facilitation of the quadriceps muscle to Sol Mns; (2) potentiation of presynaptic inhibition of Sol Ia fibres evoked by mechanical activation of the tibialis anterior primary spindle afferents. It is concluded that nociceptive volleys arising from dorsal foot muscles facilitate the activity of interneurones intercalated in pathways responsible for presynaptic inhibition of Sol Ia fibres. It is also proposed that the same Ia presynaptic inhibition depresses the excitability of interneurones mediating group I non-reciprocal inhibition, thus resulting in Ib disinhibition of Sol Mns.
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PMID:Presynaptic excitability changes of group Ia fibres to muscle nociceptive stimulation in humans. 991 33

Migraine sufferers have abnormal cerebral information processing and personality disorders, post-traumatic headache sufferers also have some personality changes. We therefore, studied intensity dependence of auditory evoked potentials, Plutchik-van Praag's depression inventory, Zuckerman's sensation seeking scales and Zuckerman-Kuhlman's personality questionnaire in patients suffering from migraine without aura (n = 26) and chronic post-traumatic headaches (n = 26) as well as in healthy volunteers (n = 30). The migraine group showed significantly increased neuroticism-anxiety than controls, increased intensity dependence of N1-P2, and decreased thrill and adventure score compared with the controls and post-traumatic headaches. The post-traumatic headache had significantly increased depression compared with the controls, and increased disinhibition compared with the controls and migraines. This study demonstrates that the two headache types have different neurophysiological and personality traits. The pronounced intensity dependence of N1-P2 suggests a cortical potentiation response, together with a decreased thrill and adventure seeking, favor a lower serotonergic innervation in migraine. While the elevated disinhibition and depression, as consequences, may be linked with the wide cortical neuronal/axonal degeneration in post-traumatic headache.
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PMID:Auditory evoked potentials and multiple personality measures in migraine and post-traumatic headaches. 1006 69

This study identified predictors of weight gain versus continued maintenance among individuals already successful at long-term weight loss. Weight, behavior, and psychological information was collected on entry into the study and 1 year later. Thirty-five percent gained weight over the year of follow-up, and 59% maintained their weight losses. Risk factors for weight regain included more recent weight losses (less than 2 years vs. 2 years or more), larger weight losses (greater than 30% of maximum weight vs. less than 30%), and higher levels of depression, dietary disinhibition, and binge eating levels at entry into the registry. Over the year of follow-up, gainers reported greater decreases in energy expenditure and greater increases in percentage of calories from fat. Gainers also reported greater decreases in restraint and increases in hunger, dietary disinhibition, and binge eating. This study suggests that several years of successful weight maintenance increase the probability of future weight maintenance and that weight regain is due at least in part to failure to maintain behavior changes.
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PMID:What predicts weight regain in a group of successful weight losers? . 1022 27

Mood disorders constitute a significant clinical problem in patients with a wide range of neurodegenerative disorders. This article reviews recent empirical studies examining depression, anxiety, and mania/disinhibition in patients with focal lesions (stroke), primary subcortical degeneration (Parkinson's disease), and primary cortical degeneration (Alzheimer's disease). Although each neuropsychiatric condition has unique clinical correlates, several common themes can be identified and include similarities in prevalence, neuroanatomic substrate, neurochemistry, and treatment response. Depression, for example, is associated with frontal lobe (primarily left hemisphere) dysfunction in stroke, Parkinson's disease, and Alzheimer's disease, whereas mania and dishinhibition are associated with dysfunction of ventral frontal and ventral temporal structures in both stroke and Alzheimer's disease. These similarities across distinctly different neuropathological conditions can provide important validation of fundamental neuroanatomical, as well as possible psychosocial pathways for the development of mood syndromes in neurological disease. The study of neuropsychiatric syndromes represents an important but relatively understudied area of research, that may ultimately help to illuminate the causes and specific treatments of these important clinical disorders.
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PMID:Mood Disorders in Neurodegenerative Diseases. 1032 Apr 30

Exogenous application of agonists at the kainate subtype of glutamate receptors has been shown to depress evoked monosynaptic inhibition by gamma-aminobutyric acid (GABA)ergic interneurons in the hippocampus. This observation has led to the hypothesis that synaptic release of endogenous glutamate might have a disinhibitory effect on neuronal circuits, in addition to depolarizing neurons via postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, and N-methyl-D-aspartic acid (NMDA) receptors. It is not known, however, if glutamate released from excitatory neurons has the same kainate receptor-mediated effect on monosynaptic inhibitory transmission as exogenous agonist application. Indeed, the recent demonstration that excitatory synaptic signals elicited in interneurons are partly mediated by kainate receptors suggests that these receptors may have a pro- rather than disinhibitory role. Here, we examine the effect of synaptically released glutamate on monosynaptic inhibitory signaling. In the presence of antagonists to AMPA and NMDA receptors, brief bursts of activity in glutamatergic afferent fibers reduce GABAergic transmission. This depression of inhibition is reversibly abolished by blocking kainate receptors. It persists when GABA(B) receptors are blocked and is enhanced by blocking metabotropic glutamate receptors, possibly explained by presynaptic regulation of glutamate release from excitatory afferents by metabotropic autoreceptors. We conclude that the net kainate receptor-mediated effect of synaptically released glutamate is to reduce monosynaptic inhibition. Since this form of disinhibition may contribute to seizure initiation, kainate receptors may constitute an important target for anticonvulsant drug development.
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PMID:Synaptically released glutamate reduces gamma-aminobutyric acid (GABA)ergic inhibition in the hippocampus via kainate receptors. 1044 97

Information on personality, on anxiety and depression and on several aspects of religion was collected in 1974 Dutch families consisting of adolescent and young adult twins and their parents. Analyses of these data showed that differences between individuals in religious upbringing, in religious affiliation and in participation in church activities are not influenced by genetic factors. The familial resemblance for different aspects of religion is high, but can be explained entirely by environmental influences common to family members. Shared genes do not contribute to familial resemblances in religion. The absence of genetic influences on variation in several dimensions of religion is in contrast to findings of genetic influences on a large number of other traits that were studied in these twin families. Differences in religious background are associated with differences in personality, especially in Sensation Seeking. Subjects with a religious upbringing, who are currently religious and who engage in church activities score lower on the scales of the Sensation Seeking Questionnaire. The most pronounced effect is on the Disinhibition scale. The resemblances between twins for the Disinhibition scale differ according to their religious upbringing. Receiving a religious upbringing seems to reduce the influence of genetic factors on Disinhibition, especially in males.
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PMID:A religious upbringing reduces the influence of genetic factors on disinhibition: evidence for interaction between genotype and environment on personality. 1048 Jul 46

Earlier behavioural studies have shown that the expression of the immediate-early gene c-fos, as visualized by the immunohistochemical detection of Fos, in the inferior olive (IO) correlated closely with expression in related areas of the cerebellar nuclei. It has been speculated that the expression of c-fos within the cerebellar nuclei may be induced by enhanced spiking activity of the immunopositive neurons in the inferior olive. Two potential mechanisms may play a role in this process: a direct induction by way of the collaterals of the olivary climbing fibres to the cerebellar nuclei, or indirectly, by climbing fibre activity-induced depression of mossy fibre-parallel fibre-induced simple spike frequency of the Purkinje cells resulting in a subsequent disinhibition of the related parts of the cerebellar nuclei. In an attempt to distinguish between these possible mechanisms, we analysed Fos immunoreactivity in the olivocerebellar system of wild-type mice and in the mutant mouse Lurcher which lacks Purkinje cells. The tremorgenic agent harmaline, which is known to induce enhanced and rhythmic firing of olivary neurons was given intraperitoneally to anaesthetized mice of both genotypes. Harmaline application coincides with the induction of Fos-immunoreactive neurons in most areas of the IO in both wild-type and Lurcher mice. Both types of mice also showed enhanced expression in the larger neurons of the cerebellar nuclei. However, in the smaller, GABAergic nucleo-olivary neurons, increased c-fos expression was only observed in the wild-type mice. We conclude that: (i) increased olivary activity indeed may result in increased c-Fos expression in related areas of the cerebellar nuclei; (ii) because the indirect mode of induction is not operative in Lurcher mice, the olivary collateral innervation of the cerebellar nuclei is sufficient for c-fos induction in the larger nucleobulbar neurons in Lurcher and potentially also in wild-type mice; however (iii) for the nucleo-olivary cells an intact cerebellar cortical input is necessary to evoke increased expression of c-fos following harmaline application.
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PMID:Inferior olivary-induced expression of Fos-like immunoreactivity in the cerebellar nuclei of wild-type and Lurcher mice. 1058 70

Long-term potentiation (LTP) and long-term depression (LTD) are two main forms of activity-dependent synaptic plasticity that have been extensively studied as the putative mechanisms underlying learning and memory. Current studies have demonstrated that prior synaptic activity can influence the subsequent induction of LTP and LTD at Schaffer collateral-CA1 synapses. Here, we show that prior short-term synaptic disinhibition induced by type A gamma-aminobutyric acid (GABA) receptor antagonist picrotoxin exhibited a facilitation of LTP induction and an inhibition of LTD induction. This effect lasted between 10 and 30 min after washout of picrotoxin and was specifically inhibited by the L-type voltage-operated Ca2+ channel (VOCC) blocker nimodipine, but not by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphopentanoic acid (D-APV). Moreover, this picrotoxin-induced priming effect was mimicked by forskolin, an activator of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), and was blocked by the adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536) and the PKA inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS). It was also found that following picrotoxin application, CA1 neurons have a higher probability of synchronous discharge in response to a population of excitatory postsynaptic potential (EPSP) of fixed slope (EPSP/spike potentiation). However, picrotoxin treatment did not significantly affect paired-pulse facilitation (PPF). These findings suggest that a brief of GABAergic disinhibition can act as a priming stimulus for the subsequent induction of LTP and LTD at Schaffer collateral-CA1 synapses. The increase in Ca2+ influx through L-type VOCCs in turn triggering a cAMP/PKA signalling pathway is a possible molecular mechanism underlying this priming effect.
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PMID:Prior short-term synaptic disinhibition facilitates long-term potentiation and suppresses long-term depression at CA1 hippocampal synapses. 1058 94


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