Suicidal ideation and depressive symptoms in an urban post-partum maternity setting: a retrospective cohort study.

BACKGROUND: Fifteen percent of women worldwide experience depression in the perinatal period. Suicide is now one of the leading causes of maternal mortality in developed countries. Internationally, many healthcare systems screen post-natal women for depressive symptoms and suicidal ideation to facilitate early assessment and intervention. To our knowledge, no Irish data exists on the prevalence of suicidal ideation in this cohort. AIMS: To evaluate the prevalence of suicidal ideation and depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) in post-natal women attending a large Dublin maternity hospital. METHODS: A retrospective cohort study was conducted. Women were randomly selected by delivery date over a 6 month period. Demographic and medical information was collected from their booking visit and discharge summary data. EPDS results at discharge post-partum were examined. RESULTS: Data was collected on 643 women. Post-partum, 19 women (3.4%) had experienced suicidal ideation in the previous 7 days. Just over half of these women also had high EPDS scores (>12). Overall, 29 women (5.2%) screened positive for depression (EPDS score > 12). CONCLUSIONS: The rate of suicidal ideation is in line with the published international data and emphasises the need for all clinicians to inquire about such thoughts. Training of midwifery and obstetric staff is required. Maternity units should have a policy on the management of suicidal ideation and risk. The prevalence of depressive symptoms post-partum was comparatively low in our study. This could suggest that antenatal screening and early intervention, which are integral parts of the perinatal mental health service, are effective. However, due to limitations of the study, it could also reflect an under-representation of depressive symptom burden in this cohort.

Survey of distribution of substance P, vasoactive intestinal polypeptide, cholecystokinin, neurotensin, Met-enkephalin, bombesin and PHI in the spinal cord of cat, dog, sloth and monkey.

Levels of substance P (sP), peptide-histidine-isoleucine (PHI), vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), neurotensin (NT), bombesin (BOM) and methionine-enkephalin (Met-Enk) like immunoreactivity were measured in cat, dog, primate and sloth cervical, thoracic, lumbar and sacral dorsal and ventral horns and dorsal root ganglia. The levels of peptides in the cat sacral cord and the principal peaks of immunoreactivity on a 10-60% acetonitrile gradient on a C18 reverse phase high performance liquid chromatography (HPLC) were sP (sP1-11: 369 ng/g), PHI (PHI: 271 ng/g), VIP (VIP1-28: 210 ng/g), Met-Enk (Met1-5 and extended forms: 257 ng/g), BOM (BOM1-10 and GRP1-27: 20 ng/g), CCK (CCK-8: 15 ng/g) and NT (NT1-13: 10 ng/g). Consideration of the rostrocaudal levels revealed an approximately even distribution with the exception of VIP and PHI which showed sacral/cervical ratios of 79 and 63. For sP, Met-Enk and BOM dorsal/ventral ratios were greater than 1 at all spinal levels. For VIP, PHI and CCK these ratios were greater than 1 only in the sacral cord. Dorsal root ganglion (DRG) levels of sP, VIP, PHI were readily measurable in single ganglia and covaried with the respective levels in the dorsal cord. Pooled samples of spinal ganglia and the trigeminal ganglia revealed that the relative levels of peptide immunoreactivity were: sP (25 ng/g); VIP (26 ng/g); PHI (28 ng/g); Met-Enk (6 ng/g); CCK (2 ng/g); NT (1 ng/g); and BOM (1 ng/g).

Identification and distribution of immunoreactive peptide YY in the human, canine, and murine gastrointestinal tracts: species-related antibody recognition differences.

A radioimmunoassay using two antisera (antibody 80 and antibody 213) from rabbits immunized with porcine peptide YY has been characterized for both sensitivity and specificity. To determine the distribution of peptide YY in the gut, fresh tissue specimens from the human and canine gut were separated into mucosal-submucosal and muscularis externa layers by microdissection. These tissues and transmural specimens from murine gut were acid-extracted and neutralized, followed by radioimmunoassay using each antiserum. Immunoreactive peptide YY in canine and murine gut was present in similar concentration and distribution using each antiserum, with highest concentrations in the mucosal-submucosal layer of the descending colon. Using antibody 213, immunoreactive peptide YY throughout the human gut was measured only at the lower detection limit of the radioimmunoassay. By contrast, using antibody 80, peptide YY in human gut was present in a distribution similar to canine and murine gut. Using antibody 80, one major immunoreactive species was identified with C18 reverse-phase high-performance liquid chromatography in extracts of human, canine, and murine colon. These results suggest species-related antibody recognition differences. The similar concentrations of peptide YY in canine and murine gut determined with the two antisera are consistent with the hypothesis that the amino acid sequences of canine and murine peptide YY are similar to porcine peptide YY. Using antibody 213, the low concentrations of immunoreactive peptide YY found in human gut are consistent with the hypothesis that human and porcine peptide YY have different amino acid sequences. Antisera prepared by immunization with porcine PYY must therefore be carefully characterized prior to studies using human sera or human tissue extracts.

Distribution, quantitation, and origin of immunoreactive neuropeptide Y in the human gastrointestinal tract.

A radioimmunoassay for measurement of immunoreactive neuropeptide Y has been developed using antiserum from a rabbit (221) immunized with porcine neuropeptide Y. Antibody 221 has been characterized for both sensitivity and specificity. To determine the distribution of neuropeptide Y in the human gastrointestinal tract, fresh tissue specimens were separated by microdissection into the muscularis externa and the mucosa-submucosa. To examine the origin of neuropeptide Y in human colon, specimens of aganglionic and ganglionic colon were obtained from patients with Hirschsprung's disease. Immunoreactive neuropeptide Y in human gut was present in highest concentrations in the muscularis externa of the stomach and in lowest concentrations in the muscularis externa of the ileum and descending colon. Neuropeptide Y in the stomach was present in higher concentrations in the muscularis externa than in the mucosa-submucosa, but in the descending colon there were lower concentrations of neuropeptide Y in the muscularis externa than in the mucosa-submucosa. In Hirschsprung's disease, concentrations of neuropeptide Y were increased in aganglionic colon in both the muscularis externa and the mucosa-submucosa, compared to corresponding layers from proximal ganglionic colon. Extracts of the gastric muscularis externa and the colonic mucosa-submucosa were separated by C18 reverse-phase high-performance liquid chromatography. One major immunoreactive species was identified by radioimmunoassay which eluted in a position similar to synthetic human neuropeptide Y. These results demonstrated both regional and layer differences in concentrations of neuropeptide Y in human gut. Increased concentrations of neuropeptide Y in aganglionic colon from Hirschsprung's disease most likely result from enlargement of neuropeptide Y-containing extrinsic nerve fibers in both the mucosa-submucosa and the muscularis externa.

Distribution of neuropeptide Y in the spinal cords of cat, dog, rat, man and pig.

Regional distribution of neuropeptide Y (NPY) in spinal cord, dorsal root ganglia (DRG) and peripheral nerves was quantitated in rat, cat, dog, pig, and man. Spinal cords were harvested post mortem and dissected into regions or individual segments. A further dissection into dorsal and ventral horns was carried out, and DRG were harvested in all species except rat. Tissues were extracted into boiling 0.1 M HCl, and NPY was measured by radioimmunoassay using a specific antibody and I125-labeled NPY. Highest concentrations of NPY were consistently found in the dorsal horn of the lumbo-sacral cord (200-800 ng/g). DRG concentrations, in contrast, were routinely low or undetectable. Sciatic nerve concentrations in rat and pig were considerable. High performance liquid chromatography (HPLC) confirmed that the NPY immunoreactivity measured in dorsal horns of each species coeluted with authentic NPY (1-36) as a single peak.

Characterization of neuropeptides extracted from canine intestine.

Quantitative determination of neuropeptides in biologic tissues by radioimmunoassay requires both an efficient extraction of neuropeptides as well as maintenance of immunochemical reactivity. Vasoactive intestinal peptide, substance P, and met5-enkephalin were chosen for this study because they are neuropeptides which appear to be involved in multiple physiologic systems. Since all three neuropeptides have a methionine residue within their amino acid sequence, oxidation of methionine to methionine-sulfoxide during the extraction process could diminish their immunochemical reactivity. Multiple factors that might be important in extracting these neuropeptides from canine intestine, including pH of the solvent, tissue homogenization, heating, and addition of enzyme inhibitors, were examined. Concentrations of vasoactive intestinal peptide-like immunoreactivity and substance P-like immunoreactivity were significantly higher in acidic solvents, and tissue homogenization appeared to increase the concentrations of these two neuropeptides. Substance P-like immunoreactivity was increased by heating after tissue homogenization, suggesting heat-induced denaturation of tissue enzymes liberated by homogenization. Separation of acidic tissue extracts by high performance liquid chromatography followed by radioimmunoassay for all three neuropeptides revealed minor acid-induced oxidation of substance P. These results should be useful for planning the extraction of these three neuropeptides from other tissues.

Neuronal cholecystokinin-like immunoreactivity is postprandially released from primate hypothalamus.

By use of the push-pull perfusion technique, release of neuronal cholecystokinin-like immunoreactivity (CCK-LI) from hypothalamus of owl monkeys was investigated in relation to an intragastric meal. In overnight fasted, halothane-anesthetized owl monkeys, levels of CCK-LI in the hypothalamic push-pull perfusate were below assay sensitivity (less than 4 pg/30 min). After intragastric administration of a carbohydrate/amino acid meal, however, a 10-fold increase in CCK-LI release (51 +/- 7 pg/30 min) was observed in 5 out of 15 perfusion sites during the first postprandial 30 min. During the subsequent two 30-min intervals, release of CCK-LI was still increased with 32 +/- 5 pg/30 min and 15 +/- 6 pg/30 min, respectively. Thereafter, CCK-LI release was below assay sensitivity again. Addition of 40 mM potassium chloride (KCl) to the perfusion solution, which causes neuronal depolarization, resulted in a second increase in CCK-LI release of 56 +/- 7 pg/30 min which was comparable to the meal-induced release. All sites that exhibited an increase in CCK-LI were located in the anterolateral aspect of the hypothalamus. In experiments without meal-induced release, KCl did not have any effect on CCK-LI in perfusate, suggesting that these particular sites did not contain CCK-releasing terminals. High performance liquid chromatography (HPLC) identified the C-terminal octapeptide of CCK (CCK-8) as the predominant molecular form of CCK within the owl monkey hypothalamus. No gastrin-17 was present.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical relevance of regulatory gastrointestinal peptides.

The application of radioimmunoassay of insulin, C-peptide, gastrin, glucagon, vasoactive intestinal polypeptides (VIP), somatostatin, human pancreatic polypeptides (hPP), substance P and neurotensin to detect endocrine tumors of the pancreas and other organ systems is undoubtedly important in the clinical management of patients suspected of having tumors that secrete these hormones. Radioimmunoassays of the above gut peptides have certain degrees of specificity and sensitivity; however, there are several factors that need to be considered in the interpretation of results since heterogeneity of molecular forms does occur and the varied radioimmunoassay techniques use different antibodies that may yield different results. It is, therefore, important that each laboratory establish its own normal values, determine the molecular species that each assay is detecting, and also determine the false positivity of the methodology. The same endocrine tumor may contain and secrete several detectable peptides, but the syndrome may relate to only one peptide. Although the simultaneous measurement of multiple peptides in patients with benign gastrointestinal disease has yielded information that contributes to our understanding of the complexities of gut neuroendocrine interaction, the pathophysiological role of gut peptides and their clinical relevance need further evaluation.

Abnormalities of fasting serum concentrations of peptide YY in the idiopathic inflammatory bowel diseases.

Peptide YY has been localized within human ileocolonic endocrine cells and may contribute to the regulation of gastric secretion and gastric emptying in man. Since our previous studies had shown decreased colonic concentrations of peptide YY in the idiopathic inflammatory bowel diseases, a specific radioimmunoassay was used to measure fasting serum concentrations of peptide YY in healthy controls and in patients with adenocarcinoma of the rectum, idiopathic chronic active liver disease and hepatic cirrhosis, ulcerative colitis, and Crohn's disease. In healthy controls and in patients with adenocarcinoma of the rectum, serum concentrations of peptide YY ranged from 50 to 260 pg/ml. Serum concentrations of peptide YY in patients with hepatic cirrhosis ranged from 59 to 717 pg/ml. Serum concentrations of peptide YY in patients with ulcerative colitis were similar to healthy controls. In patients with Crohn's disease, serum concentrations of peptide YY were less than 50 pg/ml in three patients who had had a previous proctocolectomy, and were more than 260 pg/ml in 14 patients who had had previous resection of more than 48 cm of ileum or presently had symptomatic Crohn's disease subsequently requiring surgical resection of a total of more than 75 cm of ileum. These results suggest that most circulating peptide YY is released from the colorectal region. Hepatic cirrhosis, previous ileal resection, and symptomatic Crohn's disease were associated with elevation of fasting serum peptide YY. The mechanism of increased fasting serum peptide YY in patients with Crohn's disease could be the loss of an ileal inhibitory factor or possibly an increased release of colonic peptide YY in response to fat malabsorption. The effect of alteration of serum peptide YY concentrations on the pathophysiology of Crohn's disease is yet unknown.

Peptide YY concentrations in normal ileum and colon and in idiopathic inflammatory bowel disease.

Concentrations of the candidate endocrine and paracrine peptide, peptide YY, were measured by specific radioimmunoassay in tissue extracts prepared from normal ileum, normal colon, Crohn's disease, and ulcerative colitis. In both the ascending and descending colon, there were significantly decreased mean concentrations of peptide YY in Crohn's colitis and ulcerative colitis, compared to mean concentrations in normal colon. There was no age-related decrease of concentrations of peptide YY in normal colon. The decrease in concentrations of peptide YY in colon obtained from patients with inflammatory bowel disease did not appear related either to the duration of the clinical symptoms of the disease or to the severity of colonic inflammation. Further studies of the physiological function of peptide YY in man are needed to determine whether these findings might be useful in understanding a component of the pathophysiology of idiopathic inflammatory bowel disease.

Release of hypothalamic cholecystokinin in cats: effects of nutrient and volume loading.

Systemic cholecystokinin (CCK) suppresses food intake in various species and has therefore been proposed to act as a satiety factor. Because CCK is also present in the hypothalamus and furthermore meets neurotransmitter criteria, the hypothesis was tested whether CCK participates in the transmission of satiety messages at the lateral hypothalamic (LH) level. The results of this study demonstrate that in halothane-anesthetized cats, neurons located in the LH will indeed release CCK-like material after a carbohydrate-protein meal in a time-dependent fashion. This release, as water loads demonstrate, is most likely due to volumetric distension rather than to the nutrient content. The releasable CCK does not originate from peripheral sources, since intravenously infused CCK octapeptide (CCK-8) does not appear in the perfusate. The release occurs only in discrete neurons and is not universal to CCK-releasing systems within the LH, and also, CCK-releasing systems are not present at all locations. The molecular form of CCK in feline hypothalamus is the COOH-terminal octapeptide (CCK-8) as shown by high-performance liquid chromatography. No gastrin-17 is present. CCK-8 is also the predominant form found in meal-induced as well as in KCl-induced CCK released from hypothalamic neurons. These results suggest a correlated role for hypothalamic CCK in the termination of food intake.

Neural isolation of the jejunoileum. Effect on tissue morphometry, mucosal disaccharidase activity, and tissue peptide content.

The aim of this study was to determine the effects of a model of intestinal extrinsic denervation on mucosal structure and function. Six dogs underwent in situ neural isolation of the jejunoileum (Group 2); six other dogs served as operated controls (Group 1), and five nonoperated dogs were naive controls (Group 3). Thirty-centimeter segments of proximal jejunum and distal ileum were excised before (time zero) and at 2 weeks and 8 weeks postoperatively in Groups 1 and 2, while similar regions were removed at time zero in Group 3. Tissues were analyzed for morphology with quantitative morphometry, mucosal disaccharidase activities (sucrase, maltase, and lactase), and tissue content of selected regulatory peptides in transmural, mucosa/submucosa, and muscularis regions. In situ neural isolation had no significant or consistent effects on morphology/morphometry or on mucosal disaccharidase activities. Tissue content of neuropeptide Y decreased markedly (P < 0.002) in all layers of the jejunal and ileal walls, but tissue content of vasoactive inhibitory polypeptide, substance P, cholecystokinin, neurotensin, met-enkephalin, neurokinin A, somatostatin, and calcitonin gene-related peptide demonstrated only minor changes. The physiologic effects of intestinal transplantation (extrinsic denervation and disruption of intrinsic, enteric neural continuity, and lymphatic drainage) have little effect on morphology, mucosal disaccharidase activity, and tissue content of most regulatory peptides. How these minor alterations might affect enteric function, however, needs to be investigated.

Adrenomedullary secretion of DOPA, catecholamines, catechol metabolites, and neuropeptides.

Catecholamines and their metabolites have been proposed as markers of sympathetic nervous system stimulation. However, the adrenal medulla is a rich source of catecholamines and catecholamine metabolites and may play a significant role in plasma levels of these compounds. In addition to adrenal catecholamine metabolite efflux, the role of the catecholamine precursor 3,4-dihydroxyphenylalanine (DOPA) has not been fully evaluated. The simultaneous effluxes of catecholamines, metabolites, DOPA, and neuropeptides were measured in perfusates from isolated dog adrenals. The relative abundance of compounds detected consistently during unstimulated conditions was epinephrine >> norepinephrine > 3,4-dihydroxyphenylglycol > metanephrine > normetanephrine > dopamine > 3,4-dihydroxyphenylacetic acid > 3-methoxy-4-hydroxyphenylglycol > or = DOPA >> [Met]enkephalin >> neuropeptide Y. Effluxes of analytes were not affected by cocaine and the ratios of catecholamines to metabolites increased dramatically with carbachol stimulation, consistent with negligible reuptake into adrenal cells. Thus, most of the 3,4-dihydroxyphenylglycol is expected to be derived from epinephrine and norepinephrine subsequent to translocation from chromaffin vesicles into the cytosol. The efflux of DOPA increased dramatically during stimulation with 30 microM carbachol in a calcium-dependent manner. Efflux of DOPA during the initial stabilization period of the perfusion preparation declined exponentially, in parallel with the effluxes of the catecholamines and neuropeptides but not with metabolites. Evoked release of DOPA was Ca2+-dependent. These data suggest that DOPA can be stored and released exocytotically from chromaffin granules.