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

Cushing's disorder and depression present overlapping although not identical psychological symptomatology. In turn, a subset of patients with affective disorders present with hypercortisolemia and disturbances, specifically disinhibition, of the hypothalamic hypophysio adrenal axis (HHAA). Memory disturbances, in particular, biasing toward negative contents, overlapping sleep abnormalities (marked reduction of stages 3 and 4) increased fatigue and loss of energy, attentional deficits and irritability, are just part of the common symptomatology presented by patients with both Cushing's disorder and depression. All of these behavioral manifestations are known to be affected by adrenal steroid hormones. There is consensus that hippocampal structures are a main target for adrenal steroid hormones; hence, these neural regions are some of the most likely mediators of the effects of corticoadrenal steroids on behavior. This paper proposes that an imbalance of adrenal steroids and their metabolites may play a fundamental role in the psychophysiopathology of Cushing's and depressive disorders. The imbalance of these hormones, especially at limbic sites, could distort mood and memory content affecting cognition based on recollection and present experiences. Reestablishing an adrenal balance could therefore be considered as a therapeutic aid in a subset of depressive disorders.
 ...
PMID:Effects of adrenal cortex hormones on limbic structures: some experimental and clinical correlations related to depression. 846 Dec 80

Cognitive and noncognitive psychiatric symptoms were systematically evaluated in 21 patients with Alzheimer's disease by using the Neurobehavioral Rating Scale. Regional cerebral metabolic activity was measured in each patient by [18F]fluorodeoxyglucose PET. Significant correlations emerged between global cortical metabolic activity and the Agitation/Disinhibition factor score, Cognition factor score, and total score. Relationships between noncognitive symptoms and metabolic activity were regionally specific, with significant correlations between Agitation/Disinhibition factor score and metabolism in the frontal and temporal lobes, between Psychosis factor score and metabolism in the frontal lobe, and between Anxiety/Depression factor score and metabolism in the parietal lobe. These results suggest that psychiatric symptoms are fundamental expressions of the cortical dysfunction of Alzheimer's disease.
 ...
PMID:The relationship between psychiatric symptoms and regional cortical metabolism in Alzheimer's disease. 855 51

Paired-pulse field responses were recorded from the granule cell layer of the dentate gyrus in brain slices from temporal lobe epileptic patients. Paired-pulse depression (PPD) was examined using perforant path stimulation of low to moderate intensity at an inter-stimulus interval (ISI) of 20 ms. The paired-pulse ratio (PS2/PS1) was expressed as the population spike amplitude of the second response (PS2) relative to that of the first response (PS1). Representative tissue response from each patient biopsy were divided into two groups that were significantly different based on the magnitude of the highest paired-pulse ratio recorded for each biopsy specimen: the strong paired-pulse depression group (PS2/PS1 = 0.12 +/- 0.03; n = 15) and the weak paired-pulse depression group (PS2/PS1 = 0.68 +/- 0.06; n = 13). Paired-pulse ratios from the strong PPD group were relatively independent of stimulus intensity, whereas, PPD was dependent on stimulus intensity in the weak PPD group; i.e., PPD was greatest at the lowest intensity and reached a plateau at higher intensities. Bicuculline (20 microM) and low concentrations of baclofen (0.1-0.2 microM) reduced paired-pulse depression in the strong PPD group, but did not significantly change the paired-pulse ratio in the weak PPD group. Paired-pulse facilitation was observed in some cases after inhibition was blocked pharmacologically. The number of population spikes was increased in the presence of bicuculline but was unchanged by baclofen. In the strong PPD group, baclofen significantly altered the EPSP-population spike (E-S) relationship by increasing the slope of the relationship for the second response, without having an effect on the slope of the first response. Baclofen had no effect on the E-S relationship of either response in the weak PPD group. The data are consistent with (1) less inhibition in the weak PPD group compared to the strong PPD group, (2) reduction of feedback inhibition in the strong PPD group by bicuculline and by low concentrations of baclofen, and (3) the occurrence of paired-pulse facilitation when inhibition was pharmacologically reduced in the dentate gyrus of temporal lobe epileptic patients. The results are also consistent with the presence of GABAB receptors on human inhibitory interneurons that, when activated by baclofen, result in disinhibition of granule cells through feedback circuits. Although inhibition may be compromised in some epileptic human biopsy specimens, the presence of strong inhibition in other patients' biopsy material suggest the re-evaluation of the role of inhibition in epilepsy.
 ...
PMID:Effects of bicuculline and baclofen on paired-pulse depression in the dentate gyrus of epileptic patients. 855 27

Frontal-subcortical circuits provide a comprehensive framework for understanding the anatomy, biochemistry, and pharmacology of behavior. The three principal behaviorally relevant circuits originate in the dorsolateral prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex, respectively. Circuit-specific marker behaviors associated with each circuit are executive dysfunction (dorsolateral prefrontal-subcortical circuit), disinhibition and OCD (orbitofrontal-subcortical circuit), and apathy (medial frontal-subcortical circuit). Environmental dependency is common to all prefrontal-subcortical syndromes and may reflect disruption of working memory. Depression, mania, and psychosis are mediated by structures involved in prefrontal-subcortical circuits and are circuit-related but not circuit-specific behaviors. The actions of PCP, LSD, serotonergic antidepressants, anxiolytics, sedative-hypnotics, antipsychotic agents, and ethanol may all be partially or primarily mediated through transmitter systems and receptor effects expressed through frontal-subcortical circuits.
 ...
PMID:Anatomic and behavioral aspects of frontal-subcortical circuits. 859 19

These findings support the hypothesis that a frontal-subcortical abnormality is necessary to produce symptoms of depression (e.g., mood-related signs, behavioral disturbances, neurovegetative signs) in dementia. Behavioral disturbances (e.g., disinhibition, agitation, social withdrawal) were more likely to occur in FLTD than in AD or SCD.
 ...
PMID:Symptoms of depression in Alzheimer's disease, frontal lobe-type dementia, and subcortical dementia. 859 40

1. The ability of 5-hydroxytryptophan, 5-HT2 receptor antagonists and typical and atypical neuroleptic agents to modify behavioural responding to aversive situations was investigated in the mouse light/dark test and rat social interaction. 2. The administration of 5-hydroxytryptophan inhibited rat social interaction and the exploratory behaviour of mice in the light/dark test. 3. The 5-HT2 receptor antagonists, ketanserin, ritanserin, MDL11939, methysergide and RP62203, the neuroleptic agents, spiperone, haloperidol and benperidol, and the atypical neuroleptic agent, clozapine, when administered alone failed to modify mouse or rat behaviour. In contrast, when administered alone, sulpiride in rats and mice and thioridazine in rats disinhibited behaviour. 4. Methysergide, RP62203, ketanserin, ritanserin and MDL11939 antagonized the inhibitory effects of 5-hydroxytryptophan or reversed the inhibitory effects to one of disinhibition. 5. Low doses of spiperone (but not haloperidol or benperidol) also antagonized the inhibitory effects of 5-hydroxytryptophan in the rat but not the mouse. Higher doses of the three neuroleptic agents caused locomotor depression in both rats and mice which obscured any specific changes in behavioural responding to the aversive situations. 6. The disinhibitory profile of sulpiride in both mice and rats and thioridazine in rats was evident during their interaction with 5-hydroxytryptophan. Thioridazine in the mouse and clozapine in rats and mice also reversed the inhibitory effects of 5-hydroxytryptophan to one of disinhibition. 7. In summary, we present evidence that the atypical neuroleptic agents, thioridazine and clozapine, with their known affinity for the 5-HT2 receptors, can mimic the actions of reference 5-HT2 receptor antagonists to antagonize the inhibitory effects of 5-hydroxytryptophan in rodent models of anxiety. The results are intepreted in terms of drug action on different 5-HT2 and other 5-HT receptor subtypes. In addition, thioridazine and sulpiride have disinhibitory effects in their own right which remain to be explained.
 ...
PMID:Behavioural interactions between 5-hydroxytryptophan, neuroleptic agents and 5-HT receptor antagonists in modifying rodent responding to aversive situations. 868 Jul 34

Interactions of physical, emotional, cognitive and behavioural impairments after severe closed head injury (CHI) remain poorly understood. A 47-year-old man was referred to our department 13 months after a severe CHI. He demonstrated severe left hemiplegia and disabling orthopaedic complications (left hip infectious arthritis, after surgical treatment for heterotopic ossification). His hip was blocked and extremely painful. He was totally dependent for daily-life activities (Functional Independence Measure (FIM) score = 18). Moreover he exhibited severe cognitive and behavioural troubles, which had been stable for many months beforehand, e.g. complete disorientation for time and place, major memory disorders, agitation, anxiety, depression, irritability, disinhibition, aggressiveness and lack of initiative. Pain disappeared within a few weeks after treatment. Progressively, functional improvement occurred (sitting position, transfers, walking between parallel bars). The FIM score increased to 63. Aggressiveness, irritability and agitation disappeared. Surprisingly, neuropsychological assessment demonstrated parallel improvement of cognitive functions, especially in regard to orientation, and to a lesser degree attention and memory. Such an observation should encourage use of active treatment of physical disabilities, even in patients presenting with an apparently poor cognitive prognosis at a late stage of severe CHI.
 ...
PMID:Late cognitive and behavioural improvement following treatment of disabling orthopaedic complications of a severe closed head injury. 869 16

An abnormal electrophysiological response in brain slices of the dentate gyrus from biopsy material from patients surgically treated for intractable epilepsy (46/57), exhibited characteristics similar to the physiological hallmark of epilepsy, the paroxysmal discharge, a prolonged (30-600 ms) and often large amplitude field potential. The most striking feature of the prolonged response to a single perforant path stimulus was a predominantly biphasic field potential (23/46 cases). The biphasic response was characterized by a negative field potential of substantial duration exceeding 180 ms which followed an initial shorter duration positive field potential. Multiple population spikes occurred during both phases of the response. During a 1 Hz stimulus train applied to the perforant path, the magnitude and duration of the negative component of the field response was significantly increased. Approximately half of the cases (Group 1; 30/57) exhibited potentiation of the biphasic response, while the remaining cases (Group 2; 27/57) exhibited no negative field component during 1 Hz stimulation trains. This repetitive stimulation, in general, increased the area of the field response in a large majority of cases (44/57) regardless of the sign of the field potential. The number of population spikes following 1 Hz stimulation increased significantly for cases in both groups, although the increase was greater for those in Group 1 than in Group 2. Paired pulse depression (20 ms ISI) was reduced in cases that exhibited potentiated biphasic responses during 1 Hz stimulation (Group 1) in comparison to cases that exhibited no negative field potentials (Group 2). Paired pulse depression at a 200 ms ISI was not significantly different between the groups. During a single stimulus, bicuculline disinhibition (20 microM) resulted in either a prolonged positive or biphasic field potential. Intracellularly recorded responses to single perforant path stimuli also exhibited prolonged and large depolarizations that were comparable in time course to the duration of field potentials recorded in the same area whether generated in the absence or presence of bicuculline. The prolonged field potential after bicuculline was reduced by APV (20 microM). We suggest that the prolonged field response, whether biphasic or monophasic when generated by either 1 Hz stimulation or bicuculline disinhibition, may be due directly or indirectly to an increase in membrane depolarization mediated by activation of the NMDA receptor.
 ...
PMID:Prolonged field potentials evoked by 1 Hz stimulation in the dentate gyrus of temporal lobe epileptic human brain slices. 879 93

Clinical and preclinical studies provide convincing evidence for persistent neurological/psychiatric impairments and possible neuronal degeneration associated with chronic cocaine/stimulant abuse. These impairments include multifocal and global cerebral ischemia, cerebral hemorrhages, infarctions, optic neuropathy, cerebral atrophy, cognitive impairments, and mood and movement disorders. These findings may encourage the placement of stimulant addiction into the category of organic brain disorders. Functional and microanatomical anomalies in the frontal and temporal cortex as well as other brain regions may be responsible for certain aspects of phenomenology and neuropsychopathology that are characteristic of stimulant polydrug addictions. These may include broad spectrum of deficits in cognition, motivation, and insight; behavioral disinhibition; attention deficits; emotional instability; impulsiveness; aggressiveness; depression; anhedonia; and persistent movement disorders. Although it is still debated whether the hypofrontality and other brain anomalies observed in stimulant abusers are a consequence or an antecedent of drug abuse, this debate seems purely academic and irrelevant with respect to the importance of compensating for these deficits in the development of treatment strategies. The neuropsychiatric impairments accompanying stimulant abuse may contribute to the very high rate of relapse in addicts that can take place after long periods (years) of abstinence. It is possible that the neurological deficits present in stimulant addicts, whether they are primary or secondary to stimulant abuse, are responsible for perpetual drug abuse which may be a form of self-medication (Weiss et al. 1991, 1992). In this context, addiction to stimulants, once fully developed, may represent a true biological dependency on drugs that temporarily compensate for existing neurological deficits. The concept of self-medication by drug addicts is supported by major theories of biological psychiatry. While a majority of drug addicts are polydrug users, there seems to be a preference for a particular type of drug among different populations of addicts. Addicts who experience distress, anxious dysphoria, and turbulent anger prefer the calming actions of opiates, whereas addicts with preceding attention deficit disorder, depression, or bipolar disorder often prefer stimulants (Khantzian 1985). Figure 1 presents conceptual relationships between brain damage and cocaine/stimulant abuse. More clinical studies are needed to establish unequivocally the epidemiological relationships between preexisting neurological deficits-resulting either from genetic, developmental, traumatic, or neurotoxic factors- and vulnerability to drug addictions. Nonetheless, deducing from the results of preclinical studies, it is conceivable that individuals with neurological deficits associated with attention deficit disorder, developmental neuroanatomical abnormalities, lead poisoning, alcoholism, posttraumatic brain lesions, and PTSD may be more vulnerable to stimulant addiction. This notion has significant empirical support as preclinical studies have shown that animals with lesioned prefrontal cortex became supersensitive to cocaine (Schenk et al. 1991) and animals with lesions at the amygdala, VTA, or raphe nuclei manifest more rapid acquisition of amphetamine self-administration than control rats (Deminiere et al. 1989). The above arguments, postulating neuropathology as an intrinsic component of stimulant addiction, should be taken into consideration with the caveat that the clinical manifestations of the disease are heterogenous and addicts may express varying stages and degrees of the disease as determined by environmental and genetic factors. Therefore, it is likely that stimulant addicts who have less advanced neuropathology may recover spontaneously after detoxification with proper nutritional and psychotherapeutic support if they can sustain abstinence. (ABSTR
 ...
PMID:Cocaine addiction as a neurological disorder: implications for treatment. 880 51

1. Using simple animal tests, "behavioural" and "biochemical" aspects of depression, anxiolysis, disinhibition, psychostimulation and sedation were investigated in mice using a variety of antidepressant drugs. 2. Dothiepin and mianserin (16 and 32 mg/kg), fluoxetine (32 and 64 mg/kg), maprotiline and imipramine (16, 32 and 64 mg/kg) and viloxazine (16 mg/kg) significantly potentiated mortality following acute administration with yohimbine. 3. Dothiepin and imipramine (32 mg/kg), fluoxetine (16 and 32 mg/kg), viloxazine (8 and 16 mg/kg), maprotiline (32 mg/kg) and mianserin (32 mg/kg) reduced immobility time in the forced swimming test. 4. In the black and white box, dothiepin (32 mg/kg) significantly increased the time spent in the bright compartment: Fluoxetine (8 and 16 mg/kg) significantly increased the number of crossings between compartments, an effect indicative of desinhibition. 5. It can be concluded that dothiepin possesses both antidepressant and anxiolytic properties in these animal models. The present procedure is useful not only for the screening of compounds that may possess antidepressant properties, but is also of value in determining other properties that may contribute to the overall clinical efficacy of the drugs.
 ...
PMID:A schematic representation of the psychopharmacological profile of antidepressants. 900 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>