Alterations in cerebrospinal fluid concentrations of somatostatinlike immunore-activity in neuropsychiatric disorders

Archives of General Psychiatry (Impact Factor: 14.48). 01/1987; 43(12):1148-51.
Source: PubMed

ABSTRACT The concentration of somatostatinlike immunoreactivity in cerebrospinal fluid (CSF) from normal, healthy volunteers (n = 10) and patients with DSM-III diagnoses of major depression (n = 17), schizophrenia (n = 11), or dementia (n = 29) was measured by a sensitive and specific radioimmunoassay. Statistically significant decreases in CSF concentrations of somatostatinlike immunoreactivity were seen in all three patient populations when compared with controls. These findings confirm previous reports of decreased concentrations of somatostatinlike immunoreactivity in the CSF of patients with depression and dementia and extend this observation to patients with schizophrenia as well. These findings are concordant with the view that reductions in somatostatinlike immunoreactivity concentrations are associated with diseases in which cognitive function is disturbed.

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Available from: Charles B Nemeroff, Sep 28, 2015
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    • "Schizophrenia is a neuropsychiatric disorder characterized by positive (e.g., hallucination), negative symptoms (e.g., emotional blunting, apathy) and cognitive symptoms. Somatostatin deficits in schizophrenia are demonstrated by a reduction of CSF somatostatin (Bissette et al., 1986; Reinikainen et al., 1990), decreased somatostatin gene expression in the dlPFC (Morris et al., 2008; Guillozet-Bongaarts et al., 2013), and decreased number and density of somatostatin-expressing neurons in the hippocampus (Konradi et al., 2011a), caudal entorhinal cortex and parasubiculum (Wang et al., 2011). Changes in somatostatin are also identified in bipolar disorder, which is clinically characterized by fluctuating mood. "
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    ABSTRACT: Our knowledge of the pathophysiology of affect dysregulation has progressively increased, but the pharmacological treatments remain inadequate. Here, we summarize the current literature on deficits in somatostatin, an inhibitory modulatory neuropeptide, in major depression and other neurological disorders that also include mood disturbances. We focus on direct evidence in the human postmortem brain, and review rodent genetic and pharmacological studies probing the role of the somatostatin system in relation to mood. We also briefly go over pharmacological developments targeting the somatostatin system in peripheral organs and discuss the challenges of targeting the brain somatostatin system. Finally, the fact that somatostatin deficits are frequently observed across neurological disorders suggests a selective cellular vulnerability of somatostatin-expressing neurons. Potential cell intrinsic factors mediating those changes are discussed, including nitric oxide induced oxidative stress, mitochondrial dysfunction, high inflammatory response, high demand for neurotrophic environment, and overall aging processes. Together, based on the co-localization of somatostatin with gamma-aminobutyric acid (GABA), its presence in dendritic-targeting GABA neuron subtypes, and its temporal-specific function, we discuss the possibility that deficits in somatostatin play a central role in cortical local inhibitory circuit deficits leading to abnormal corticolimbic network activity and clinical mood symptoms across neurological disorders.
    Frontiers in Pharmacology 09/2013; 4:110. DOI:10.3389/fphar.2013.00110 · 3.80 Impact Factor
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    • "A limited number of studies have linked depression or the effect of antidepressants with the activity of the SRIF system. Cerebrospinal fluid (CSF) SRIF-like immunoreactivity (SRIF-LI) levels have been shown consistently to be reduced in patients with major depression and to be normalized during recovery (Bissette et al, 1986; Rubinow, 1986; Pazzaglia et al, 1995). Interestingly, Gerner and Yamada (1982) reported significant reductions in SRIF levels in the CSF of depressed patients, whereas increased levels were observed in patients with mania, a finding that was not observed by others (Rubinow et al, 1983). "
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    ABSTRACT: This study investigated how the administration (acute and chronic) of the antidepressants citalopram and desmethylimipramine (DMI) influences somatostatin (somatotropin release inhibitory factor, SRIF) levels and SRIF receptor density (sst(1-5)) in rat brain. Animals received either of the following treatments: (1) saline for 21 days (control group), (2) saline for 20 days and citalopram or DMI for 1 day (citalopram or DMI acute groups), (3) citalopram or DMI for 21 days (citalopram or DMI chronic groups). Somatostatin levels were determined by radioimmunoassay. [(125)I]LTT SRIF-28 binding in the absence (labeling of sst(1-5)) or presence of 3 nM MK678 (labeling of sst(1/4)) and [(125)I]Tyr(3) octreotide (labeling of sst(2/5)) binding with subsequent autoradiography was performed in brains of rats treated with both antidepressants. Somatostatin levels were increased after citalopram, but not DMI administration, in the caudate-putamen, hippocampus, nucleus accumbens, and prefrontal cortex. Autoradiography studies illustrated a significant decrease in receptor density in the superficial and deep layers of frontal cortex (sst(2)), as well as a significant increase in the CA1 (sst(1/4)) hippocampal field in brains of chronically citalopram-treated animals. DMI administration increased sst(1/4) receptors levels in the CA1 hippocampal region. These results suggest that citalopram and to a lesser extent DMI influence the function of the somatostatin system in brain regions involved in the emotional, motivational, and cognitive aspects of behavior.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2008; 34(4):952-63. DOI:10.1038/npp.2008.133 · 7.05 Impact Factor
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    • "However, the specificity of this finding is somewhat weakened by the intermediate mea~ values of the CSF peptides in the delirium subgroup (Table 3). It is also difficult to explain why CSF SRIF appeared to be uniformly normal in this population, in contrast to other findings (Bissette et al 1986). One possibility is the longer duration of illness in this study, although the relationship between dementia and central SRIF metabolism is far from clear (Sagar et al 1984; WaUin et al 1991). "
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    ABSTRACT: Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH) and somatostatin (SRIF) were measured in 77 female inpatients with moderate to extreme dementia and in 17 elderly female controls. Both multi-infarct (MID) and Alzheimer-type (SDAT) demented patients had equally elevated CSF CRH and TRH but not SRIF levels as compared with the controls. This elevation was, however, not seen in patients with simple dementia while it was most prominent in those exhibiting marked depressive symptoms. It is concluded that depression rather than dementia itself may be associated with CSF CRH and TRH elevation in elderly patients with cognitive impairment.
    Biological Psychiatry 10/1992; 32(5):452-6. DOI:10.1016/0006-3223(92)90132-J · 10.26 Impact Factor
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