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)

Although the FDA recommends imipramine hydrochloride (IMI) only for temporary relief of symptoms of enuresis nocturna (EN), the drug has been applied to a number of other pediatric situations, including the Hyperkinetic Syndrome (HS), childhood depression, somnambulism and pavor nocturnus, school phobia, petit mal epilepsy, allergies, autism, encorpresis and head-banging. We have reviewed the literature, with particular attention to the pharmacokinetics of IMI in children, and its putative mechanisms of action. The drug probably works through a number of different actions, and the futher delineation of these will be of considerable heuristic value. We review the toxic effects of IMI treatment and IMI poisoning in children, and the pediatric literature concerning other antidepressant drugs and lithium carbonate (Li).
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PMID:Imipramine and children: a review and some speculations about the mechanism of drug action. 40 23

Comparative effects of anticonvulsant drugs on the thalamocortical system were analyzed quantitatively. Paired stimuli were delivered to the ventrolateral thalamus with evoked responses recorded from the ipsilateral sensorimotor cortex in the cat. Threshold and excitability profiles were developed with an on-line computer. Effects of phenytoin and diazepam were generally similar, with depression of excitability and slight elevation of thresholds. Ethosuximide produced a pronounced pair-interval dependent effect of unchanged or increased excitability and lowered threshold at shorter intervals, with depressed excitability and raised threshold at longer intervals. These data demonstrate a marked difference in effect of the petit mal and grand mal agents tested and suggest a basis for the effectiveness of ethosuximide in controlling 3-per-second repetitive activity.
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PMID:Effects of antiepileptic drugs on thalamocortical excitability. 41 19

Neuropeptides represent a new class of compounds with important implications for the understanding of the mechanisms and treatment of epileptic disorders. Several systems of peptide modulators--in particular the opioid-like peptides, vasopressin, somatostatin, thyrotropin-releasing hormone (TRH) and ACTH--have partially demonstrated endogenous roles in some forms of epilepsy. Seizures and stressful situations may release endogenous opioid peptides and mediate postictal depression and postictal seizure refractoriness. Vasopressin is believed to increase susceptibility to convulsions and may be involved in the pathogenesis of febrile convulsions. Derangements in TRH regulation may lower thresholds for seizure expression by regulating arousal systems; however, some TRH analogs have proven to be effective anticonvulsants. Long-term alterations in somatostatin regulation could be components of focal epilepsies. ACTH is particularly useful in the treatment of infantile spasms. Pharmacological effects of these and other peptides have potentials for defining new classes of anticonvulsants. Cholecystokinin (CCK) and its analogs, the opioid peptides beta-endorphin and FK33824, TRH analogs, and several dipeptides exhibit potent anticonvulsant properties in chemical, electroshock, and genetic model screens. Convulsant actions of CRF, somatostatin, TRH, vasopressin, and high doses of endorphin or enkephalins may provide new tools to study regulatory mechanisms of cerebral excitability. The enkephalin epileptogenic effect is being developed as a predictive tool for new anti-petit mal anticonvulsants. Advances in molecular biology have identified the genes of particular peptide families. A concept has developed that the large propeptide precursors, coded by these genes, whose processing leads to functional peptide formation and release, regulate peptidergic humoral responses to external stimuli. This idea may have particular application in the understanding of the genetic basis of some seizure states. Techniques for amplification of mRNA expression have identified specific neuronal proteins and peptides. Knowledge of protein and propeptide structural cleavage sites has suggested previously unknown candidates for modular systems in epileptic states. Technological advances in automated peptide sequencing and synthesis have allowed the development of metabolically resistant analogs and antagonist peptides. The anticonvulsant potencies of CCK, TRH, and opioid peptides have been defined more clearly with these methods.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuropeptides: anticonvulsant and convulsant mechanisms in epileptic model systems and in humans. 287 23

Four patients with primary generalized or true petit mal epilepsy were studied with positron emission tomography using [18F]fluorodeoxyglucose (FDG). FDG studies were carried out during 10 minutes of hyperventilation before and again after medical control of spontaneous absences. Before seizures were controlled all 4 patients demonstrated frequent bilaterally synchronous three-per-second spike-and-wave discharges associated with altered consciousness. After spontaneous seizures were controlled, hyperventilation produced only electroencephalographic slowing without clinical symptoms in 3; the fourth patient had absences less frequently. Patterns of local cerebral metabolic rate for glucose (CMRGlc) were normal and identical for ictal and interictal scans; there was, however, a 2.5- to 3.5-fold diffuse ictal increase in global CMRGlc evident when ictal studies were compared with hyperventilation control studies in which no seizures occurred. The CMRGlc was similar in the two scans obtained from the patient who had absences during both studies. No anatomical substrate of petit mal epilepsy was identified. The CMRGlc in these patients during petit mal absences was higher than that recorded in other patients during partial or generalized convulsive seizures. This difference may reflect the fact that petit mal absences are not associated with postictal depression.
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PMID:Local cerebral metabolic rate for glucose during petit mal absences. 391 36

The effects of gamma-hydroxybutyrate (GHB) upon sleep wakefulness patterns and quantified nuchal muscle activity were examined in the rabbit in a dose-response paradigm (25-1,000 mg/kg). Relative to control (saline) values, there was no facilitation of sleep onset or epileptogenic activity at any of the dosages studied. However, at the higher GHB concentrations, slow wave sleep and tonic muscle activity were enhanced and a high amplitude, slow activity was superimposed on background EEG patterns. The highest concentration of GHB (1,000 mg/kg) was associated with depression of motor activity. An enhancement of paradoxical sleep observed at lower GHB levels in other species occurred in attenuated form in the rabbit. The results indicate dose-related effects on both sleep and motor activation in the rabbit, but the absence of seizure activity for the concentrations of GHB studied.
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PMID:EEG and behavioral effects of gamma-hydroxybutyrate in the rabbit. 713 75

Levels of mRNA for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and the tyrosine kinase receptors trkB and trkC have been studied using in situ hybridization in the rat brain after topical application of KCl to the cortical surface (which induces spreading depression). Repeated episodes of spreading depression during 2 h caused a rapid and marked increase of BDNF mRNA levels in deep and, in particular, superficial cortical layers of the ipsilateral hemisphere (to 213 and 417% of control, respectively). Maximal levels were reached within 2 h after the cessation of spreading depression and at 24 h BDNF mRNA expression had returned to control values. Levels of BDNF mRNA were unaffected in the hippocampus, in areas outside the cerebral cortex and in the contralateral hemisphere. Furthermore, no change of the expression of mRNA for NGF, NT-3, trkC or the full length trkB receptor was detected at any time point. However, at 2 h after spreading depression there was an increased level (150% of control) in superficial cortical layers of mRNA hybridizing to an oligonucleotide probe detecting both truncated receptors lacking the tyrosine kinase domain and full length trkB receptors. Also one single episode of spreading depression gave rise to a significant increase of cortical BDNF mRNA levels (to 207% of control), which was attenuated (by 61%) after administration of the competitive NMDA receptor antagonist CGS 19755. The results provide evidence that mild brain insults associated with glutamate release and elevated intracellular calcium, such as spreading depression, also in the absence of seizure activity can lead to activation of the BDNF gene in cortical neurons.
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PMID:Rapid increase of BDNF mRNA levels in cortical neurons following spreading depression: regulation by glutamatergic mechanisms independent of seizure activity. 823 31

In a rat model of generalized absence epilepsies (Genetic Absence Epilepsy Rats from Strasbourg, GAERS), multiunit activity was recorded simultaneously at different sites of the thalamocortical system under neurolept anaesthesia (fentanyl-droperidol). Under these conditions, bilaterally synchronized spike-and-wave-discharges (SWDs) occurred spontaneously on the electroencephalogram (EEG) that were in principle identical to those reported earlier from unanaesthetized preparations. The generation of SWDs on the EEG was associated with spike-concurrent, rhythmic burst-like activity in (mono-)synaptically connected regions of specific (somatosensory) thalamic regions and layers IVN of the somatosensory cortex, and the reticular thalamic nucleus. Precursor activity was typically recorded in cortical units, concomitant with 'embryonic' SW seizures on the EEG, before the paroxysm was evident on the gross EEG and in the thalamus. On average, SWD-correlated activity in layers IVN of the somatosensory cortex started significantly earlier than correlated burst-like firing in reticular and in ventrobasal thalamic neurons. Cellular peak firing in thalamus and cortex during bilaterally synchronized SWDs was related to the spike component on the gross EEG with the temporal rank order ventroposteromedial > ventrolateral > or = ventroposterolateral thalamic > > rostral reticular thalamic nuclei > or = cortex (layers IVN) = caudal reticular thalamic nucleus. A spike-related depression and wave-related increase in firing was recorded in anteroventral ventrolateral thalamic areas, presumably reflecting their peculiar anatomical arrangement within the thalamus. These results from an in vivo preparation with intact synaptic connections that spontaneously produces SWDs indicate that SWDs spread within the thalamocortical network, involving short and long delays. The order of concurrent rhythmic firing observed in thalamocortical circuits during SW seizures are supportive of the hypothesis that the processes of rhythmogenesis recruit local thalamic networks, while cortical mechanisms appear to synchronize rhythmic activities on a larger spatiotemporal scale, thereby providing an important contribution to the generalization of epileptiform activity and expression of SWDs on the EEG.
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PMID:Relations between cortical and thalamic cellular activities during absence seizures in rats. 975 78

In this paper the author aims to evaluate theories of onset conditions both before psychological and before somatic symptoms by the first ever clinical-quantitative assessment of their preconditions, and then to compare these preconditions with Freud (1926) and with other theories of symptom formation. The seven cases in the sample were the only cases of recorded psychotherapy or psychoanalysis, each with recurrent symptoms in segments of sessions before symptoms versus segments of sessions before controls (with no symptoms) that were suitable for 'the symptom-context method'. The recurrent psychological symptom cases were: momentary forgettings, depressive shifts, and phobic feelings and behaviours; the recurrent somatic symptoms were stomach ulcer pains, migraine headaches, absence (petit mal) episodes and premature ventricular contractions (PVC) of the heart. Independent ratings of pre-symptom segments versus pre-control segments showed significant differences in all seven cases. Many emotional state qualities differentiating the pre-symptom from the pre-control segments were similar across cases. These were, in rank order, hopelessness, lack of control, anxiety, feeling blocked, helplessness, concern about 'supplies', depression, hostility to therapist, guilt, involvement with therapist, separation concern and hostility to others. For example, hopelessness significantly differentiated pre-symptom versus pre-control for all seven cases. For the first time, samples of segments of sessions before recurrent symptoms have been both clinically and quantitatively compared with segments without symptoms. Brief segments before recurrent symptoms showed significantly more of certain qualities than brief segments before controls where no symptoms appeared. These qualities led to the author's revised symptom-context theory of symptom formation and then to a comparison with five classical theories of symptom formation.
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PMID:The only clinical and quantitative study since Freud of the preconditions for recurrent symptoms during psychotherapy and psychoanalysis. 1180 87

Clinical features of 47 cases of temporal lobe epilepsy are analyzed and treatment of this disorder is outlined. Twenty-four per cent of all cases of epilepsy seen by one of the authors over a two-year period were of this type. Fifteen of these 47 patients had a history of birth injury. Care must be taken to distinguish the symptoms of temporal lobe epilepsy from those of acute anxiety or hysteria and to differentiate the short-lived temporal lobe attack from centrencephalic petit mal.Interictal personality disturbances were identified in 11 of 24 persons with temporal lobe epilepsy, four of 35 with focal epilepsy from all other areas, and one of 17 with centrencephalic epilepsy. Personality deviations most frequently encountered were irritability, aggressiveness, bouts of depression, paranoid tendencies and exhibitionism. Medical or surgical treatment often improves the personality abnormalities concomitantly with control of seizures.
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PMID:TEMPORAL LOBE EPILEPSY: A CLINICAL STUDY OF 47 CASES. 1422 3

That 3alpha-hydroxy-5alpha/beta-pregnane steroids (GABA steroids) have modulatory effects on the GABA-A receptor is well known. In behavioral studies in animals high exogenous dosages give concentrations not usually reached in the brain under physiological conditions. Animal and human studies show that GABA-A receptor-positive modulators like barbiturates, benzodiazepines, alcohol, and allopregnanolone have a bimodal effect. In pharmacological concentrations they are CNS depressants, anesthetic, antiepileptic, and anxiolytic. In low dosages and concentrations, reached endogenously, they can induce adverse emotional reactions in up to 20% of individuals. GABA steroids can also induce tolerance to themselves and similar substances, and rebound occurs at withdrawal. Menstrual cycle-linked disorders can be understood by the concept that they are caused by the action of endogenously produced GABA-steroids through three mechanisms: (a) direct action, (b) tolerance induction, and (c) withdrawal effect. Examples of symptoms and disorders caused by the direct action of GABA steroids are sedation, memory and learning disturbance, clumsiness, increased appetite, worsening of petit mal epilepsy, negative mood as tension, irritability and depression during hormone treatments, and the premenstrual dysphoric disorder (PMDD). A continuous exposure to GABA steroids causes tolerance, and women with PMDD are less sensitive to GABA-A modulators. A malfunctioning GABA-A receptor system is related to stress sensitivity, concentration difficulties, loss of impulse control, irritability, anxiety, and depression. An example of withdrawal effect is "catamenial epilepsy," when seizures increase during menstruation after the withdrawal of GABA steroids. Similar phenomena occur at stress since the adrenals produce GABA steroids during stress.
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PMID:Pathogenesis in menstrual cycle-linked CNS disorders. 1499 39


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