Cerebrospinal Fluid Somatostatin Research Articles

Somatostatin and Neuropeptide Y in Cerebrospinal Fluid: Correlations With Amyloid Peptides Aβ1-42 and Tau Proteins in Elderly Patients With Mild Cognitive Impairment.

A combination of low cerebrospinal fluid (CSF) Amyloid β1–42 (Aβ1–42) and high Total-Tau (T-Tau) and Phosphorylated-Tau (P-Tau) occurs at a prodromal stage of Alzheimer’s disease (AD) and recent findings suggest that network abnormalities and interneurons dysfunction contribute to cognitive deficits. Somatostatin (SOM) and Neuropeptide Y (NPY) are two neuropeptides which are expressed in GABAergic interneurons with different fates in AD the former only being markedly affected. The aim of this study was to analyze CSF SOM, NPY and CSF Aβ1–42; T-Tau, P-Tau relationships in 43 elderly mild cognitively impairment (MCI) participants from the Biomarker of AmyLoïd pepTide and AlZheimer’s disease Risk (BALTAZAR) cohort. In these samples, CSF SOM and CSF Aβ1–42 on the one hand, and CSF NPY and CSF T-Tau and P-Tau on the other hand are positively correlated. CSF SOM and NPY concentrations should be further investigated to determine if they can stand for early AD biomarkers.Clinical Trial Registration: www.ClinicalTrials.gov, identifier #NCT01315639.

Low CSF somatostatin associated with response to nimodipine in patents with affective illness

Background: In patients with depression, treatment with nimodipine has been shown to increase cerebrospinal fluid (CSF) somatostatin (SRIF) and ameliorate baseline global cerebral hypometabolism. This study was conducted to assess whether a low baseline level of CSF SRIF was associated with response to nimodipine treatment. Methods: Twenty-one depressed patients underwent lumbar puncture for analysis of CSF somatostatin-like immunoreactivity (SRIF-LI) during a medication-free period and after at least 6 weeks of nimodipine monotherapy. Twenty-five healthy control subjects were utilized as a comparison group. Clinical improvement was assessed using the Clinical Global Impression Scale for Bipolar Illness. Results: As predicted, baseline CSF SRIF-LI was significantly lower in eventual nimodipine responders (33.1 ± 2.8 pg/mol) compared to eventual nonresponders [41.9 ± 2.6 pg/mL; t(19) = 1.98, p = .03, one-tailed]. Conclusions: Low baseline CSF somatostatin in depression may be associated with response to nimodipine, which in turn may be related to the ability of nimodipine to increase CSF somatostatin.

A follow up study of suicide attempters: Increase of CSF–somatostatin but no change in CSF–CRH

Concentrations of somatostatin and corticotrophin releasing hormone (CRH), measured in cerebrospinal fluid (CSF) have been reported to be low in suicidal patients with major depressive disorder (MDD). Often have MDD patients in general, high CSF–CRH and low CSF–somatostatin concentrations, which both seem to normalise with clinical recovery. The present study was designed to look for CSF–CRH and CSF–somatostatin alterations along with clinical changes in patients studied repeatedly after a suicide attempt. Sixteen patients with different diagnoses, initially inpatients after a suicide attempt (baseline), participated. Lumbar punctures and ratings according to the Suicidal Assessment Scale (SUAS) and the Montgomery–Asberg Depression Rating Scale (MADRS) were performed while patients were drug-free (baseline) and after a median of 7 (5 to 9) months. At follow up MADRS- and SUAS-scores were significantly decreased ( P<0.05), whereas CSF–somatostatin was significantly increased ( P=0.013) and CSF–CRH had not changed significantly. Thus, the patients showed long-lasting low CSF–CRH concentrations, in spite of changed CSF–somatostatin concentrations and clinical amelioration.

Cerebrospinal fluid somatostatin levels in febrile seizures and epilepsy in children

We analysed the level of cerebrospinal fluid (CSF) somatostatin in children with febrile seizures and epilepsy. In the febrile seizure group (n = 23), the somatostatin level was 83.9 ± 11.2 pg/ml, which was significantly higher than that of age-matched controls. CSF samples obtained within 3 h of the last seizure had higher somatostatin levels (106.1 ± 12.4 pg/ml;n = 14) than did the CSF obtained after 3 h (49.4 ± 15.6 pg/ml;n = 9). The mean somatostatin level in the epilepsy group was 35.3 ± 4.3 pg/ml (n = 34), and was distributed as follows: 27.6 ± 3.6 pg/ml in the idiopathic generalized epilepsy group (n = 16), 44.0 ± 9.4 pg/ml in the symptomatic generalized epilepsy group (n = 13), and 37.2 ± 10.1 pg/ml in the partial epilepsy group (n = 5). The levels in each group were significantly higher than those in age-matched controls. Somatostatin is a hypothalamic tetradecapeptide with excitatory effects on neurons in children with febrile seizures and epilepsy. The finding that patients with convulsive disease had elevated levels of CSF somatostatin suggests that somatostatin release is somehow related to seizure activity. It remains to be determined whether this is due to increased release from over-active excitatory neurons or leakage from damaged or anoxic neurons, secondary to seizure activity.

Cerebrospinal fluid somatostatin, mood, and cognition in multiple sclerosis

Background: Cerebrospinal fluid (CSF) somatostatin (SS) levels have been shown to be decreased in multiple sclerosis (MS) during relapse as well as in disorders characterized by depression or cognitive impairment. Since MS is often associated with depression and cognitive impairment, we examined both the effect of course of illness on CSF SS as well as the variance in SS attributable to associated features (e.g., depression or cognitive impairment).Methods: Fifteen patients with chronic progressive MS participating in a 2-year cyclosporine trial underwent lumbar punctures for CSF SS at baseline and at 12 and 24 months. Additionally, patients were evaluated by neuropsychological testing, and physical disability and mood ratings. Baseline CSF SS levels were also obtained in a group of control subjects (n = 10).Results: At baseline, CSF SS levels were lower in MS patients than control subjects (p < .001). Decreaed CSF SS at 24 months was correlated with decreased cognitive performance on several measures and was best and significantly predicted by cognitive deterioration at 24 months.Conclusions: Our data support those from previous studies that found lower levels of CSF SS in MS during relapse and suggest that changes in CSF SS are related to the process responsible for diminished cognitive function in MS.

Cerebrospinal fluid somatostatin in West syndrome: changes in response to combined treatment with high-dose pyridoxal phosphate and low-dose corticotropin

Eighteen children with West syndrome (5–11 months of age) were selected to receive an oral dose of pyridoxal phosphate, (20–50 mg/kg) for 14 d. Seizures disappeared in one patient. The remaining 17 patients were treated with 0.01 mg/kg synthesized corticotropin intramuscularly for 2 weeks as an additional therapy. Seizures disappeared in all 17 patients within a few days after initiation of the corticotropin. Levels of somatostatin in the cerebrospinal fluid were as follows: 61.0 ± 10.7 pg/ml before therapy, 34.2 ± 6.4 pg/ml during pyridoxal phosphate therapy, and 26.8 ± 4.2 pg/ml after 2 weeks corticotropin therapy. Somatostatin levels in untreated patients were higher (p < 0.05) than those of age-matched controls (35.7 ± 11.8 pg/ml) and decreased (p < 0.05) after pyridoxal phosphate treatment. Somatostatin is a hypothalamic tetradecapeptide with excitatory effects on neurons and pyridoxal phosphate might subclinicaly influence neuronal excitation.

Role of serotonin in obsessive-compulsive disorder

Serotonin may play a role in the pathophysiology of obsessive-compulsive disorder (OCD) because of the anti-obsessional effect of selective serotonin reuptake inhibitors (SSRIs). The literature is reviewed on knowledge of the role of serotonergic neurons in brain function, studies on monoamine metabolites in cerebrospinal fluid (CSF), various stress neuropeptides, neuroendocrine and behavioural challenge after administration of direct and indirect serotomimetic compounds, and neuroanatomical data on brain circuits organising behaviour. In most of the OCD cases analysed, CSF 5-hydroxyindoleacetic acid and homovanillic acid concentrations do not significantly differ from age-corrected controls. However, a relationship appears to exist between pre-treatment levels of these metabolites and clinical response to drugs acting on the serotonin transporter. Abnormalities in CSF arginine vasopressin, corticotropin-releasing hormone, oxytocin and somatostatin levels have been reported in OCD. Long-term treatment with high-doses of clomipramine, fluvoxamine, and fluoxetine tend to correct these neuropeptide abnormalities. We hypothesise that continuous treatment with SSRIs alters serotonin turnover and neuropeptide expression patterns in OCD-entertaining functional forebrain/midbrain circuits.

Cerebrospinal fluid concentrations of corticotropin-releasing hormone, vasopressin, and somatostatin in depressed patients and healthy controls: Response to amitriptyline treatment

The effect of amitriptyline upon hypothalamic-pituitary-adrenal [HPA]-system-regulating neuropeptides (corticotropin-releasing hormone [CRH], vasopressin, somatostatin) was studied in a group of depressed elderly patients and controls. A first lumbar puncture was performed in 37 depressed in-patients. This was followed by a 6-week medication phase with amitriptyline. Upon its completion a second cerebrospinal fluid (CSF) sample was obtained in 18 of these 37 patients. In 25 healthy controls a first lumbar puncture was done eleven of these individuals agreed to take 75 mg/d amitriptyline for 6 weeks and to participate in the follow-up CSF study. Within the group of depressed patients amitriptyline led to a significant decrease of CSF CRH in treatment responders only (F1, 16 = 5.2; P < 0.02). Also, in normal controls CSF CRH concentration tended to decrease with amitriptyline treatment (t-test; P < 0.09). No effects of amitriptyline upon vasopressin or somatostatin were observed. In normal controls (r = 0.4; P < 0.02) and in patients (r = 0.4; P < 0.03) age correlated positively with baseline CSF somatostatin. A trend for CSF CRH to increase with aging was found only in controls (r = 0.3; P < 0.09); patients did not show a significant association here. Finally, CSF neuropeptide concentration at baseline did not differ between the group of depressed patients and healthy controls. Our study corroborates the evolving concept that antidepressants effect various components of the HPA system with the net result of a reduction in its activity. In addition, we found CSF CRH and CSF somatostatin concentrations to be better reflections of age than of depression and, finally, that during aging and during depression the HPA system changes in similar directions.

Nimodipine increases CSF somatostatin in affectively ill patients

Preliminary evidence suggests that nimodipine, an L-type calcium channel blocker, is effective in treating some patients with rapidly cycling affective disorders and some phases of Alzheimer's disease, i.e., two syndromes associated with transient or permanent reductions in cerebrospinal fluid (CSF) somatostatin, respectively. CSF somatostatin (SRIF) was measured in 14 affectively ill patients while they were medication-free and during chronic nimodipine treatment. CSF somatostatin significantly increased in patients during active nimodipine treatment compared with ones in the medication-free state. The current findings raise the possibility that nimodipine-induced increases in CSF somatostatin could potentially contribute to its spectrum of efficacy on neuropsychiatric disorders associated with cognitive or affective impairment. Further clinical and preclinical studies are indicated to elucidate the potential mechanisms involved in the elevation of CSF SRIF, whether it is reflected in regional changes in brain, and its possible relevance to nimodipine's clinical actions.

Nimodipine Increases CSF Somatostatin in Affectively Ill Patients

Preliminary evidence suggests that nimodipine, an L-type calcium channel blocker, is effective in treating some patients with rapidly cycling affective disorders and some phases of Alzheimer's disease, i.e., two syndromes associated with transient or permanent reductions in cerebrospinal fluid (CSF) somatostatin, respectively. CSF somatostatin (SRIF) was measured in 14 affectively ill patients while they were medication-free and during chronic nimodipine treatment. CSF somatostatin significantly increased in patients during active nimodipine treatment compared with ones in the medication-free state. The current findings raise the possibility that nimodipine-induced increases in CSF somatostatin could potentially contribute to its spectrum of efficacy on neuropsychiatric disorders associated with cognitive or affective impairment. Further clinical and preclinical studies are indicated to elucidate the potential mechanisms involved in the elevation of CSF SRIF, whether it is reflected in regional changes in brain, and its possible relevance to nimodipine's clinical actions.

Cerebrospinal fluid somatostatin concentrations in schizophrenia and schizoaffective disorder: the effects of antipsychotic treatment

The authors examined the effects of antipsychotic treatment on cerebrospinal fluid somatostatin like immunoreactivity (CSF SLI) in 14 schizophrenic and 3 schizoaffective patients. There was a modest but significant increase in CSF SLI in 13 out of the 14 schizophrenic patients. In addition, there was a significant positive correlation between duration of treatment and post-treatment CSF SLI concentrations. No differential response was noted in patients also treated with the anticholinergic benztropine.

A long-term follow-up study of cerebrospinal fluid somatostatin in delirium.

Cerebrospinal fluid somatostatin-like immunoreactivity (CSF SLI) was determined for elderly delirious patients during the acute stage and after 1- and 4-year follow-up periods, and the SLI levels were compared with age-equivalent controls. As a whole group, and also when the group was subdivided according to the severity of cognitive decline at the acute stage, type of delirium or the central nervous system disease, delirious patients showed significant reduction of SLI as compared with the controls. In the follow-up, we observed a further reduction of CSF SLI together with significant correlations in the second, third and fourth samples between SLI levels and Mini-Mental State Examination scores. Our results suggest a role for somatostatinergic dysfunction in the genesis of some symptoms of delirium, and this dysfunction may be linked to the long-term prognosis of delirious patients.

Alterations in plasma and cerebrospinal fluid levels of neuropeptides in idiopathic senile anorexia.

Plasma and cerebrospinal fluid (CSF) concentrations of three well-known satiety neuropeptides, cholecystokinin (CCK), somatostatin and calcitonin gene-related peptide (CGRP), along with two powerful orexigenic neuropeptides, neuropeptide Y (NPY) and beta-endorphin have been measured in elderly persons with idiopathic anorexia and normal weight healthy subjects in a similar age range. Plasma and CSF immunoreactivity levels of the two main fractions of CCK (CCK8s and CCK33) after being separated by HPLC were measured by a radioimmunoassay (RIA) developed in our laboratory, whereas the other neuropeptides were assayed by commercially available RIA kits. Elderly underweight anorectic patients had significantly lower levels of beta-endorphin but increased concentrations of NPY in both plasma and CSF when compared to controls. In addition to significantly higher levels of CCK8s but not CCK33 in plasma, we found a trend to higher CSF concentrations of CCK8s and a positive correlation between the body mass index and either beta-endorphin (r = 0.58, P < 0.05) or CCK8s (r = 0.69, P < 0.01) concentrations in CSF in the anorectic group. CSF somatostatin concentrations were decreased significantly, but plasma somatostatin levels and plasma and CSF concentrations of CGRP were similar in senile anorectics and controls. Treatment of five anorectic patients with megestrol acetate, 480 mg daily for 6 months, reversed only the decrease in CSF beta-endorphin levels but did not normalize the body weight or the fat body mass. On the basis of our findings, we hypothesize that a decrease in CSF beta-endorphin concentration along with a rise in plasma levels of CCK8s might be accounted for the primary anorexia of aging.

CSF somatostatin in Alzheimer's disease and major depression: Relationship to hypothalamic-pituitary-adrenal axis and clinical measures

Patients with Alzheimer's disease (AD) and major depression have been shown to have overlapping clinical symptoms and biological markers, including decreased concentrations of cerebrospinal fluid (CSF) somatostatin-like immunoreactivity (SLI), which may be related to alterations in the hypothalamic-pituitary-adrenal axis activity. As in prior studies, we found that CSF SLI was significantly decreased in a group of AD patients ( N = 49) and a group of elderly patients with major depression ( N = 18), as compared with 13 age-matched controls ( F[2, 77] = 12.9, p < .001). In the present study, CSF SLI and CSF corticotropin-releasing factor correlated significantly within the group of AD patients ( r = 0.49, p < .0004) and almost attained significance in the depressed patients ( r = 0.47, p < .07). CSF SLI correlated significantly with urinary free cortisol within each patient group ( r = −0.51, p < .03). Clinical measures of dementia severity and depression did not consistently correlate with CSF SLI in either patient group.

Somatostatin concentrations in cerebrospinal fluid and brain tissue of patients with refractory epilepsy.

The somatostatin concentrations of cerebrospinal fluid (CSF) and brain tissue in 16 refractory epileptic patients were measured simultaneously by a radioimmunoassay (RIA) method. An increased level of somatostatin was found in the epileptic foci of cerebral cortex, determined by the cortical EEG. There were significant differences among the epileptic foci (75.58 +/- 6.58 pg/mg wet wt, +/- SEM), nonfocal tissues (37.04 +/- 6.55 pg/mg), and normal tissues of control patients (47.69 +/- 10.12 pg/mg), p < 0.001 and p < 0.05, respectively. The somatostatin concentrations of CSF in 11 epileptic patients were determined before (257.78 +/- 19.11 pg/mL) and after (178.36 +/- 8.78 pg/mL) the removal of epileptic focal area, and a dramatic decrease of the CSF somatostatin concentration after operation was detected (p < 0.01). We also found that the somatostatin level of cerebral scar induced by head injury in cases of posttraumatic epilepsy was highest (106.39 +/- 12.41 pg/mg). The results suggested that the surgical removal of the epileptic focal area in refractory epileptic patients may reduce the increased central somatostatin level, which could play an important part in the pathophysiological process of refractory epilepsy.

CSF corticotropin-releasing hormone and somatostatin in major depression: response to antidepressant treatment and relapse

Immunoreactive corticotropin-releasing hormone (CRH) and somatostatin (SRIF) were measured in the cerebrospinal fluid (CSF) of 24 female in-patients, suffering from DSM-III-R major depression, both before and after antidepressant treatment. In the total group there were no significant differences between pre- and post-treatment CSF-CRH and SRIF concentrations despite satisfactory clinical improvement in each patient. However, there was a significant post-treatment reduction of the CSF-CRH concentration in the 15 patients who remained depression-free for at least 6 months following treatment, in contrast to the tendency for elevation in those 9 subjects who relapsed within 6 months. CSF-SRIF showed no similar pattern. High, or even increasing, CSF-CRH concentration during antidepressant treatment may indicate lack of normalization of an underlying process in major depression despite symptomatic improvement and predicted early relapse.

Somatostatin-like immunoreactivity in CSF of schizophrenic patients during haloperidol treatment

Reduction of somatostatin-like immunoreactivity (SLI) has been demonstrated in discrete brain areas as well as in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease and Parkinson's disease (Beai and Martin 1986). A less widespread and severe decrease of SLI in the frontal cortex (Broadmann's area 12) (Nemeroff et al 1983) and hippocampus (Fetrier et al 1983) has also been found in schizophrenic patients. In contrast, results of CSF studies are not as consistent; there are reports on normal (Gerner and Yamada et al 1982), increased (Gerner et al 1984), and reduced (Bissette et al 1986; Reinikainen et al 1990) CSF SLI concentrations in schizophrenia. Because CSF somatostatin seems also to be low in numerous other diseases, the question arises as to whether the changes in CSF reflect primary alterations or secondary effects, for example, to drug treatment. The purpc, se of the present study was to determine whether controversial CSF findings in schizophrenia could be explained by treatment with neuroleptic medication. Firstly, SLI in CSF was detemfined from 17 chronic schizophrenic

Somatostatin and cognitive functions in Alzheimer's disease — the relationship of cerebrospinal fluid somatostatin increase with clinical response to tetrahydroaminoacridine

We studied the effect of tetrahydroaminoacridine (THA) on cerebrospinal fluid somatostatin-like immunoreactivity (CSF-SLI) in probable Alzheimer disease (AD) patients (n = 20) who took part in an open THA treatment trial. The maintenance dose (100 mg/day) was continued for 4 weeks. Samples of CSF were obtained before treatment and at the end of the treatment period. The CSF-SLI increased significantly (P = 0.01) in the responders for the treatment (increase of the Mini-Mental State Examination score greater than or equal to 3; n = 11), while the non-responders (n = 9) showed a significant decrease of CSF-SLI (P = 0.003). The change of CSF-SLI had also a significant correlation (P = 0.001) with neuropsychological performance. We conclude that the effects of of THA on the CSF-SLI may be due to presynaptic cholinergic or direct somatostatinergic stimulation.

Somatostatin cerebrospinal fluid levels in dementia

Somatostatin levels were measured in cerebrospinal fluid of patients with Alzheimer's disease, multi-infarct dementia and normal pressure hydrocephalus and compared with levels from a normal control group. All pathological groups showed a statistically significant decrease of somatostatin with respect to the control group, but no significant differences were found amongst them. A negative correlation was found between the Mini Mental State Test and the somatostatin levels in Alzheimer's disease patients but not in the other groups. Our results confirm that the lower levels of somatostatin in cerebrospinal fluid are not specific to Alzheimer's disease and indicate that the decrease found in all the groups is probably the result of neuronal destruction or damage in the diseases examined.

CSF monoamine metabolites and somatostatin in Alzheimer's disease and major depression

Decreased cerebrospinal fluid (CSF), somatostatinlike immunoreactivity (SLI) and alterations in the CSF monamine metabolites 3-methoxy-4-hydroxyphenylethylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) have been reported in patients with probable Alzheimer's disease (AD) and in patients with major depression. In this study, we found CSF SLI to be significantly lower in a large group of AD patients n = 60) and in a group of age-matched patients with major depression (n = 18) as compared with normal controls (n = 12). Mean CSF, MHPG, 5-HIAA, andHVA levels were not significantly different among diagnostic groups. Within a group of “depressed” AD patients, CSF levels of 5-HIAA showed a significant positive correlation (p = 0.03) with CSF SLI; a similar relationship was found within the group of patients with major depression. Further exploration of the relationship between the somatostatin and serotonin systems may provide clues as to how neuropeptides interact with monoamine neurotransmitters and what role they have in depression.