Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These studies explore the distribution of putative neuroactive peptides in the human olfactory bulb. Localization of synaptophysin-, serotonin-, cholecystokinin-, substance P-, and somatostatin-like staining was examined by immunocytochemical protocols. The results provide new insights into the composition and laminar segregation of subpopulations of neurons and neuronal processes in the human olfactory bulb. The prominent synaptophysin-like immunoreactivity observed in the glomeruli of the human olfactory bulb is consistent with the notion that the density of synapses, and hence the density of synaptic vesicles, is highest in the glomeruli. Serotonin-like immunoreactivity suggested a variable innervation of glomeruli ranging from a dense tangled ball of fibers within the glomerulus to a sparse innervation by a single immunoreactive fiber. There was no evidence of serotonin-like immunoreactive cell bodies in either the olfactory bulb proper, anterior olfactory nucleus, or proximal regions of the lateral olfactory tract. Cholecystokinin-like immunoreactivity was limited to fibers found largely in the juxtaglomerular region of the glomerular layer. In the deeper layers of the olfactory bulb, cholecystokinin-like immunoreactive fibers did not show any of branching or arborization that was evident in the juxtaglomerular region. Substance P-like immunoreactivity was seen in varicose fibers distributed in all of the human olfactory bulb laminae. In addition, stained multipolar neurons were found in the area of the anterior olfactory nucleus. Somatostatin-like immunoreactivity was similar to that of substance P in that a plexus of stained fibers was found in all laminae of the olfactory bulb. Also, somatostatin-like immunoreactive cell bodies were found in the area of the anterior olfactory nucleus. However, as compared to substance P, somatostatin had a less dense plexus of immunoreactive fibers in the olfactory bulb. These results increase our understanding of the fundamental organization of the human olfactory system. The current data, coupled with prior studies, provide a foundation from which to study the cellular pathology of diseases with known olfactory system sequelae such as Alzheimer's, Parkinson's, and schizophrenia.
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PMID:Immunohistochemical analyses of the human olfactory bulb. 769 Mar 71

The hypothesis that increased central cholinergic neurotransmitter function may be present in schizophrenic illness and may underlie negative symptoms was tested using a neuroendocrine challenge approach. The cholinergic challenge used was the anticholinesterase pyridostigmine, thought to cause the release of growth hormone (GH) from the anterior pituitary by diminishing inhibitory somatostatin tone. Eleven patients, six neuroleptic-naive and five neuroleptic-free, satisfying DSM-III-R criteria for schizophrenia and 11 matched controls took part. Subjects received pyridostigmine (120 mg orally) and blood was sampled at 0, 60, 90, 120, and 180 min for GH estimation. Peak GH responses were significantly increased in the schizophrenic group compared to controls. There was no relationship between individual peak GH values and negative symptom ratings (Scale for the Assessment of Negative Symptoms). Neither could a relationship be established between other aspects of psychopathology or dyskinesias and GH responses. An increased pyridostigmine/GH response is also found in affective disorders and could be related to nonspecific symptoms common to all these diagnostic groups. This study suggests that schizophrenia may be associated with increased cholinergic neurotransmitter function but the relationship between this cholinergic dysfunction and schizophrenia may involve psychopathology not specific to schizophrenia.
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PMID:Growth hormone responses to pyridostigmine in schizophrenia: evidence for cholinergic dysfunction. 783 22

An apparent seasonal or circannual rhythm in the hypothalamic content of CRF, TRH, neurotensin, and neuromedin N has been observed in 12 separate monthly coherts (n = 10@ or 130 total) adult, male Sprague-Dawley rats obtained at the same time each month from a single commercial supplier and held under constant (12:12) photoperiod conditions since birth. Both annual and 4-month (terannual) harmonics can be statistically discerned in these apparent rhythms, which exhibit cycles containing concentration changes up to 3-fold the lowest levels across the year (CRF increases 390%, TRH increases 173%, neurotensin increases 136%, and neuromedin N increases 150%). Hypothalamic somatostatin did not exhibit these statistically significant robust rhythms nor did any peptide in regions outside the hypothalamus. These data indicate that a mechanism allowing enhanced or diminished physiological availability of these regulatory neuropeptides at different times of the year may exist and may display distinct cycles even in the absence of normal photoperiod cues. Possible regulatory responses of pituitary receptor populations for these hypothalamic peptides must be considered. As certain of these neuropeptides also appear to be altered in the cerebrospinal fluid of patients with major depression or schizophrenia, similar hypothalamic cyclic changes may underly psychiatric symptoms with seasonal periodicity.
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PMID:Apparent seasonal rhythms in hypothalamic neuropeptides in rats without photoperiod changes. 783 96

A radioimmunoassay procedure was used to determine levels of somatostatin-like immunoreactivity in cerebrospinal fluid obtained from 9 schizophrenic patients, 7 patients with other psychiatric disorders, and 10 nonpsychiatric surgical controls. There were no significant differences in mean somatostatin baseline levels between the schizophrenic, nonschizophrenic, and surgical patients. The concentration remained almost unaltered after 4 weeks of zuclopenthixol treatment in the schizophrenia group and following various neuroleptic, antidepressant, and anxiolytic medications in the nonschizophrenic patients despite a significant decrease of overt psychopathology assessed by the Brief Psychiatric Rating Scale.
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PMID:Somatostatin in the cerebrospinal fluid of schizophrenic patients before and after neuroleptic drug treatment. 809 31

The concentrations of neuropeptide Y (NPY) and somatostatin (SS) have been said to be altered in the brain and cerebrospinal fluid of schizophrenic patients. This alteration could result from the neuroleptic treatment. Therefore, it is of interest to evaluate effects of long-term treatment with neuroleptics on the peptide concentrations in the brain. Haloperidol (HPD) is one of the most frequently used neuroleptics for the treatment of schizophrenia. We determined regional brain levels of NPY and SS following HPD administration in the rat. A single intraperitoneal injection of HPD, at a dose of 1 mg/kg, did not affect peptide levels in the brain regions studied. Four weeks after an intramuscular deposit injection of HPD decanoate, 50 mg/kg, NPY concentrations were increased in a number of areas of the cerebral cortex. SS content was also significantly increased in the lateral prefrontal cortex and anterior cingulate cortex. Both peptide levels were decreased in the striatum. These results suggest that the reduction found in these peptides' levels in the cerebral cortex of the brain from schizophrenic patients may not be the consequence of HPD treatment and that these peptides' levels might be increased in the cerebral cortex of the brain of schizophrenic patients following the treatment with HPD.
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PMID:Increases in cortical neuropeptide Y and somatostatin concentrations following haloperidol-depot treatment in rats. 853 77

Neuropeptide concentrations were determined in the postmortem cerebral cortex from 19 cognitive-impaired schizophrenics, 4 normal elderly subjects, 4 multi-infarct dementia (MID) cases, and 13 Alzheimer's disease (AD) patients. Only AD patients met criteria for AD. The normal elderly and MID cases were combined into one control group. Somatostatin concentrations were reduced in both schizophrenia and AD. Neuropeptide Y concentrations were reduced only in schizophrenia, and corticotropin-releasing hormone concentrations were primarily reduced in AD. Concentrations of vasoactive intestinal polypeptide and cholecystokinin also were reduced in schizophrenia, although not as profoundly as somatostatin or neuropeptide Y. In AD, cholecystokinin and vasoactive intestinal peptide were unchanged. Neuropeptide deficits in schizophrenics were more pronounced in the temporal and frontal lobes than in the occipital lobe. The mechanisms underlying these deficits in schizophrenia and AD are likely distinct. In schizophrenia, a common neural element, perhaps the cerebral cortical gaba-aminobutyric acid (GABA)-containing neuron, may underlie these deficits.
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PMID:Neuropeptide deficits in schizophrenia vs. Alzheimer's disease cerebral cortex. 871 4

In this article, recent information from neuropathological studies in humans and behavioural and electrophysiological/pharmacological studies in rats is used to examine the hypothesis that the subiculum, the major output region of the hippocampal formation, may contain sites of action for novel antipsychotic drugs. In the first section, the possible interactions between subicular neurons and the sites at which existing antipsychotic drugs act are discussed. These include the interaction implied by convergence of subicular and dopaminergic inputs to the nucleus accumbens. The second section concentrates upon subicular involvement in animal behaviours that are thought to be relevant to schizophrenia, which, in rats, include Latent inhibition and Pre-pulse inhibition of Acoustic Startle. Involvement of the subiculum in the neuropathology of schizophrenia is discussed in the third section. However, few neuropathological studies comment specifically on the subiculum. Those which suggest involvement tend to be recent and, as yet, have not all been replicated. Finally, there is discussion of the possibility that the subiculum contains chemical sites at which drugs could act specifically to produce appropriate physiological effects. Potential sites include, but are not necessarily restricted to, particular ion channels in electrophysiologically defined subclasses of subicular pyramidal neurons, the receptors for neuromodulatory peptides such as somatostatin and cholecystokinin, and the enzyme nitric oxide synthase. It is concluded that a wide range of clinical and basic neuroscience disciplines has provided evidence which, especially when viewed as a whole, is consistent with the hypothesis that the subiculum is a potential site of action for novel antipsychotic drugs.
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PMID:The subiculum: a potential site of action for novel antipsychotic drugs? 915 31

Somatostatin is a neuropeptide that has been shown to interact with dopamine. Low concentrations of cysteamine selectively depletes somatostatin and has been used to investigate the role of endogenous somatostatin in lieu of an available selective receptor antagonist. We examined the effects of various doses of subcutaneous cysteamine on baseline and amphetamine-disrupted sensorimotor gating as measured by prepulse inhibition of the acoustic startle reflex. Cysteamine in doses ranging from 50-300 mg/kg reversed decreases in PPI induced by systemic injections of amphetamine (2 mg/kg). Cysteamine had no effect on the amplitude of the acoustic startle reflex itself. The results lend further support to a somatostatin-dopamine interaction within the brain in which endogenous somatostatin facilitates dopaminergic activity. These findings also suggest that endogenous somatostatin might play a significant role in regulation of sensorimotor gating deficits. This has clinical implications as deficient prepulse inhibition is recorded in humans suffering from neuropsychiatric conditions such as schizophrenia.
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PMID:Cysteamine blocks amphetamine-induced deficits in sensorimotor gating. 932 60

Neuropeptides: corticotropin releasing factor (CRF), neuropeptide Y (NPY) and somatostatin (STS) have been associated with depression and anxiety, while neurotensin (NT), calcitonin gene-related peptide (CGRP) and tachykinins [neurokinin A (NKA) and substance P (SP)] are presumed to also play a role in the function of the dopaminergic system. Moreover, investigations in the past decade have shown that psychotomimetics and antipsychotic drugs as well as lithium affect brain synthesis, tissue concentrations, and release of some neuropeptides. In view of the above, experiments were carried out to explore whether changes in neuropeptides constitute one of the mechanisms of action of electroconvulsive treatment (ECT). Human cerebrospinal fluid (CSF) was studied before and after ECT, and brains from healthy and models of depression rats were investigated in electroconvulsive stimuli (ECS)-treated and sham-treated animals. The major findings were that a series of ECTs, in parallel to clinical recovery, increased CSF concentrations of NPY-like immunoreactivity (-LI), STS-LI, and CRF-LI, and in one study endothelin-LI. A series of ECS, but not a single treatment, reproducibly elevated concentrations of NPY-LI, NKA-LI, and STS-LI--but not NT-LI, SP-LI, galanin-LI, or CGRP-LI--in hippocampus, frontal cortex, and occipital cortex. No changes were measured in other regions, e.g., striatum. NPY and STS mRNAs were also increased indicating that ECS affects peptide synthesis. Generalized seizures induced by, e.g., kainic acid or pentylenetetrazole, had similar effects on neuropeptides. The changes persisted for at least 1 week after the last treatment. Pretreatment with compounds reducing seizures, such as benzodiazepines and MK-801; had no effect on magnitude of neuropeptide changes although the seizure duration was decreased by > 50%. On the basis of these findings, it is suggested that neuropeptides are involved in ECT's mechanisms of action. Since ECT is therapeutically efficient in both schizophrenia and depression and, taking into account that antipsychotic drugs and psychotomimetics as well as lithium selectively affect some neuropeptides, it is hypothesized that distinct combinations of neuropeptide and monoamine changes in selected neuronal populations constitute the underpinnings of ECT's effects on specific disease symptoms, conceivably independent of diagnosis.
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PMID:Neuropeptides and electroconvulsive treatment. 1018 19

The purpose of this review is to indicate the role insulin plays in normal brain neurophysiology, together with the role insulin may play in the regulation of regional cerebral blood flow (rCBF). The relationship between sustained elevation of the inflammatory cytokines and brain insulin dysregulation, with respect to the serious mental disorders, is also discussed. It has been observed that, as the inflammatory cytokines increase, they exert a synergistic influence on insulin and somatostatin, by initially increasing and then decreasing insulin secretion. In the brain, increased levels of insulin result in increased glucose utilization and over-stimulation of the autonomic nervous system (ANS), while the inhibition of insulin secretion results in decreased glucose utilization and dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis. It will further be argued that these alterations in brain insulin influence rCBF in the serious mental disorders such as schizophrenia and the affective disorders. It is hypothesized that insulin regulates rCBF either directly, or indirectly via GLUT4 in the hypothalamus now considered the glucose-sensing, insulin-sensing mechanism of the brain and the body. Thus, we shall propose that insulin plays an important role in normal neurophysiology and that sustained elevation of the inflammatory cytokines dysregulates insulin secretion, rCBF, ANS and the HPA-axis in serious mental disorders.
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PMID:The role of brain insulin in the neurophysiology of serious mental disorders: review. 1036 77


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