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)

Intravenous injections of baclofen have two general dose-dependent effects on phrenic motoneurons in anesthetized cats. Small doses (0.5-1.5 mg/kg) increase the frequency of action potentials recorded from single motoneurons and from the phrenic nerve, whereas large doses (2-10 mg/kg) reduce or abolish action potentials. The increase in frequency produced by small doses is accompanied by membrane depolarization and, in most experiments, by increased input resistance. Large doses hyperpolarize phrenic motoneurons and produce greater increases in input resistance. Extracellular recording during microelectrophoretic application of baclofen reveals only one effect, depression of cell firing, at all effective current strengths. The low dose stimulatory effect of i.v. baclofen is attributed to disinhibition, whereas the depression by large doses is attributed to disfacilitation. During incomplete inhibition by baclofen, CO2 administration further depresses phrenic nerve activity. Bicuculline (100-600 micrograms/kg i.v.) and picrotoxin (900 micrograms/kg i.v.) restore firing depressed by baclofen, whereas strychnine (80-1280 micrograms/kg) does not. 3-Aminopropanesulfonic acid (5-75 mg/kg i.v.) an agonist at gamma-aminobutyric acid-A receptor sites, depresses phrenic nerve activity. It is suggested that the low dose stimulatory effects are related to actions at gamma-aminobutyric acid-B receptors, whereas the high dose depressant effects are related, at least in part, to activation of gamma-aminobutyric acid-A receptors.
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PMID:Biphasic effects of baclofen on phrenic motoneurons: possible involvement of two types of gamma-aminobutyric acid (GABA) receptors. 630 14

A simple procedure is described for rapidly inactivating areas 17 and 18 in the rat by superfusion of the immediately overlying dura mater with chilled, physiological saline solution. Unit recording indicates deep depression of cortical activity within 20 s or less, and equally rapid restoration upon rewarming. Repetition does not appear to be deleterious. During such inactivation of the "visual" cortex (VC) essentially all neurons in the visual portion of the thalamic reticular nucleus (vTRN) are significantly depressed in their background activity and/or in their response to photically or electrically elicited input over the optic tract (Table 1). Activity of neurons in the dorsal portion of the lateral geniculate nucleus (LGNd), on the other hand, is much less likely to be affected, although in occasional neurons the effects should be profound. No evidence of disinhibition was apparent. It is concluded that the vTRN in the rat is highly dependent upon the VC in its activity, and is, thus, likely to be primarily a tool of the VC in the modulation of thalamic events. Extensive work of others shows that the vTRN provides inhibitory input to the LGNd, but in the present experiments the loss of inhibition via this route seems to be balanced by a corresponding loss of general excitatory input when the VC is inactivated.
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PMID:Cryogenic blockade of the visual cortico-thalamic projection in the rat. 632 Dec 21

Variations in the intensity or severity of affective disorders were evaluated relative to perturbations in nocturnal sleep physiology. Individual variations in polygraphic features of the sleep cycle based upon psychopathologic scale ratings were investigated in two constituencies (Ns = 6) for 8 hr during 1-3 consecutive nights. The constituencies consisted of twelve young adult (18-25 years) nonpsychotic unipolar depressed psychiatric patients with a primary affective illness and an age-matched normal healthy control group (N = 8). The severely versus mildly depressed patient subgroups scored significantly higher on the Hamilton, Beck and Zung psychopathologic rating scales, indicating a larger magnitude of depressive symptomatology. The average value for total time asleep was 6.1 hr in severely versus 7.8 hr among the mildly depressed patients and controls. EEG-sleep of the severely versus mildly depressed patients and controls contained significantly less stages 2 and 3. Although total time asleep was almost identical in the mildly depressed constituency compared with controls, patients accumulated significantly more of stages 2 and 3. Both patient subgroups exhibited a significantly shorter REM latency than controls. REM latency was reduced to a significantly lower level in the severely versus mildly depressed patients. A significant decrease of REM cycle duration occurred in the polygraphic sleep recordings of severely depressed patients compared with the age-matched controls. The shortened REM latencies indicate a disinhibition of neural processes that would normally delay appearance of the initial REM episodes during nocturnal sleep. The present study generally extends and confirms finding on nocturnal EEG-sleep disturbances in depression associated with the severity of affective illness, particularly the disrupted REM cycle and shorter REM latency.
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PMID:Individual variations in the sleep of depression. 646 66

The hypothesis that greater perturbations of EEG-sleep architecture and continuity would occur in clinical depression contingent upon epsilon stage shifts was tested. Duration of successive REM cycles was also evaluated in 16 young adult (17-25 years) nonpsychotic unipolar patients with primary depression and eight age-matched normal controls for 8 hr during 1-3 consecutive EEG recording nights (epsilon N = 55). Two subgroups of eight patients were identified whose polysomnograms contained greater than 100 versus less than 100 epsilon sleep stage transitions. As predicted, sleep was shallow and fragmented to a significantly larger extent in depressives with: greater than 100 stage shifts versus, less than 100 transitions, compared with controls. This was reflected by significantly longer delays in falling asleep, more intermittent wakefulness transitions into stage 1, increased epsilon stage shifts, and more transitional stage 1 sleep. The depressed patients with less than 100 stage shifts (versus greater than 100 transitions relative to the controls) accumulated significantly less total sleep (7.0 vs greater than or equal to 7.6 hr), REM time; exhibited fewer REM episodes, and a slower REM cycle. Compared with controls both patient constituencies accumulated less REM time, showed a propensity for shallow NREM sleep reflected by significantly decreased stage 4, and more frequent transition into stage 1. REM time significantly increased progressively during sleep through the fourth cycle in both controls and depressives. The initial REM cycle was significantly longer among patients (N = 16), and the fourth proved to be shorter compared with controls. The longer first REM cycle in primary depression is construed to represent a disinhibition of neural processes that would normally either attenuate or delay this phenomenon. Accordingly, the possibility is raised that REM sleep disinhibition potentiates the mood disturbances and neurovegetative symptoms of endogenous/primary depression.
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PMID:Sleep stage transitions and tonic REM in depression. 651 Dec 12

Zung depression scores were positively related to eye movement density in a sample of 19 noncomplaining young adult males. The subjects were not clinically depressed and had average scores on the Depression Scale of the Minnesota Multiphasic Personality Inventory. There was no relation of Zung depression to rapid eye movement (REM) latency, stage 3 and stage 4 sleep, or REM in the first third of the sleep period. The finding is consistent with the hypothesis of a disinhibition or phase lead of REM sleep phasic events in depression.
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PMID:Increased REM eye movement density in self-rated depression. 657 89

The present survey highlights the rationale for the use of state-dependent biological markers as predictors of clinical course in depression. Cortisol plasma levels after dexamethasone provide such a tool to monitor clinical progress. Since dexamethasone-resistant cortisol gradually returns to normalcy before a complete clinical remission is seen this measure has a possible predictive potential. Moreover, reversion to abnormal dexamethasone responses is prognostically infaust. Though the dexamethasone test has some merits, technical factors (e.g. exclusion criteria, dexamethasone-kinetics) which invalidate test results deserve careful consideration in future studies. Cortisol hypersecretion is considered as a physiological readout of a central disinhibition. This hypothesis is tested applying corticotropin-releasing factor and corticotropin in normal and abnormal DST responders. The data support the validity of the concept which assumes an intact but overactive pituitary-adrenal axis in a depressed subpopulation. A thesis is submitted which places the variety of biological disturbances in depression between two extreme viewpoints. One view considers all biological disturbances as sequelae to one particular dysfunction, e.g. disinhibition of corticosteroid secretion. The opposite view considers the myriad of biological disturbances as a sign of general loss of order, i.e. increased entropy, the precipitating mechanism of which is unknown.
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PMID:Prediction of clinical course by dexamethasone suppression test (DST) response in depressed patients - physiological and clinical construct validity of the DST. 666 28

A sample of college students (70 men and 70 women, each group composed of equal numbers of heavy and light drinkers) completed the Beck Depression Inventory, Form V of the Sensation Seeking Scale, the S-R Inventory of General Trait Anxiousness, the Rosenberg Self-Esteem Scale, as well as seven other measures directly assessing alcohol-related attitudes and behavior. It was hypothesized that heavy drinkers would evidence strong sensation-seeking needs with a specially high need for disinhibition. It was also predicted that heavy-drinking women would display more adjustment problems than other students and would report greater anxiety than men when drinking in situations involving social evaluation or interactions with members of the opposite sex. The first hypothesis was confirmed: heavy drinkers did exhibit strong sensation-seeking needs. However, heavy-drinking women were not characterized by adjustment problems nor did they report greater anxiety in drinking situations. The results suggest that women tend to drink to enhance social pleasures, whereas men expect a greater degree of aggressive arousal and social deviance when drinking.
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PMID:Sex differences in motivations for and effects of drinking among college students. 670 Feb 20

Brain-stem control of inhibitory circuits in the dorsal lateral geniculate nucleus (d.l.g.n.) of the cat was studied with extracellular recordings from functionally identified interneurones and with intracellular recordings from principal cells. Perigeniculate neurones, the recurrent inhibitory interneurones of the d.l.g.n., were inhibited by low-threshold stimulation within a wide bilateral field of the brainstem reticular formation extending from the rostral mesencephalon to the caudal medulla oblongata. The inhibition had a latency of 10-12 ms for stimulation sites in the mesencephalon and a duration of about 100 ms. The brain-stem stimulation evoked large hyperpolarizing potentials in intracellularly recorded perigeniculate neurones, indicating that the effect was due to post-synaptic inhibition. Intrageniculate interneurones, the feed-forward inhibitory interneurones of the d.l.g.n., were inhibited with a similar time course from the same region of the brain stem. Both feed-forward and recurrent inhibitory post-synaptic potentials (i.p.s.p.s) in principal cells were depressed by a preceding stimulation of brain-stem sites effective for the interneurones. The depression had about the same time course as the inhibition of the interneurones and it occurred without a concomitant change in the membrane potential of the recorded principal cells. A small depolarizing potential, with a latency of 10-20 ms, was observed in some principal cells after brain-stem stimulation. The potential reversed polarity when i.p.s.p.s were reversed by current injection into the recorded cell indicating that it was due to disinhibition of the principal cells. The possible neuronal pathway for the inhibition of the d.l.g.n. in interneurones is considered and it is proposed that the effect is mediated by a group of neurones located in the caudal mesencephalon and the rostral pons close to the fibres of the brachium conjunctivum.
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PMID:Inhibition from the brain stem of inhibitory interneurones of the cat's dorsal lateral geniculate nucleus. 670 70

The dexamethasone suppression test (DST) was developed from the neuroendocrine research strategy to provide indirect information about the integrity of the limbic system in patients with endogenous depression (ED). Abnormal test results occur in close temporal relationship to clinical episodes of ED, but not during the intervals between episodes. The neuroendocrine disinhibition revealed by the test is not a trait marker of individuals predisposed to develop ED. A standardized DST procedure has been established and can be applied in outpatient or inpatient routine clinical practice, with good sensitivity (50-65%) and high specificity (96%). The conditional probability principles of interpreting the test results are discussed and the effect of prevalence on the predictive value of the test results is emphasized. The DST should not be used as a screening test for all psychiatric patients but should be reserved for cases where clinical indications for its use are present. These indications include diagnostic confirmation of ED, monitoring the response to treatment, prediction of relapse or new episodes, and possibly prediction of suicide risk in patients with ED. The test may be especially useful in the diagnostic assessment of patients with difficult or confusing presentations of ED such as catatonia, depressive pseudodementia, depression in adolescents or children, "masked" depression, depression complicated by a personality disorder, and schizoaffective depression.
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PMID:Clinical applications of the dexamethasone suppression test for endogenous depression. 703 18

This study examines the utility of the dexamethasone suppression test (DST) in identifying a clinically meaningful subtype of depression. Forty-nine inpatients who met research diagnostic criteria for major depressive disorder underwent DSTs and standard clinical assessments and ratings. Half of those with primary depression showed escape from dexamethasone suppression and are referred to as nonsuppressors, while few of those with secondary depression had this response. Most of the nonsuppressors were rated as having a good response to treatment, while only one third of the suppressors were rated as having a good response to treatment. These data suggest that pituitary adrenal disinhibition as assessed by the DST is selectively associated with primary depression. The DST may be a marker of a depressive subtype with a specific pathophysiology or pathogenesis.
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PMID:Response to dexamethasone and subtype of depression. 719 Mar 79


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