Copidosoma floridanum (Hymenoptera: Encyrtidae) Rapidly Alters Production of Soldier Embryos in Response to Competition.

Most social insects are free living and produce castes that develop in response to extrinsic environmental cues. Caste-forming polyembryonic insects, in contrast, are all endoparasitoids that form social groups inside the bodies of host insects. The best studied polyembryonic wasp is Copidosoma floridanum (Ashmead), which produces ∼3,000 clonal offspring that develop into two castes named reproductive and soldier larvae. Caste determination in this species is mediated by whether or not embryos inherit primary germ cells (PGCs). Prior results showed that C. floridanum increases the proportion of female soldier larvae it produces per host in response to other parasitoids like Microplitis demolitor. Here we show that caste ratio shifts occur through increased formation of embryos lacking PGCs. Our results further indicated that increased soldier production was a specific response to multiparasitism elicited by the chorion of M. demolitor eggs.

Morphogenetic mechanisms of coelom formation in the direct-developing sea urchin Heliocidaris erythrogramma.

Indirect development via a feeding pluteus larva represents the ancestral mode of sea urchin development. However, some sea urchin species exhibit a derived form of development, called direct development, in which features of the feeding larva are replaced by accelerated development of the adult. A major difference between these two developmental modes is the timing of the formation of the left coelom and initiation of adult development. These processes occur much earlier in developmental and absolute time in direct developers and may be underlain by changes in morphogenetic processes. In this study, we explore whether differences in the cellular mechanisms responsible for the development of the left coelom and adult structures are associated with the change in the timing of their formation in the direct-developing sea urchin Heliocidaris erythrogramma. We present evidence that left coelom formation in H. erythrogramma, which differs in major aspects of coelom formation in indirect developers, is not a result of cell division. Further, we demonstrate that subsequent development of adult structures requires cell division.

Nodal expression and heterochrony in the evolution of dorsal-ventral and left-right axes formation in the direct-developing sea urchin Heliocidaris erythrogramma.

To understand the role of body axes in the evolution of larval form, we use the two sea urchins in the genus Heliocidaris, which have distinctly different larval morphologies. Heliocidaris tuberculata is an indirect-developing sea urchin, which forms a pluteus larva, whereas its sister species, Heliocidaris erythrogramma, exhibits direct development and forms a nonfeeding, ovoid larva. Changes along all three larval axes underlie the differences in larval form associated with each developmental mode. Nodal signaling has recently been implicated as important in establishing the dorsal-ventral (D-V) and left-right (L-R) axes in the indirect-developing sea urchin Paracentrotus lividus. However, because of changes in morphology and timing of morphogenetic events associated with the D-V and L-R axes, respectively, in H. erythrogramma, it was unclear whether nodal played the same roles during direct development. We show that the expression patterns and functions of nodal during H. erythrogramma development are similar to its roles in indirect-developing sea urchins in both D-V and L-R axes formation. However, there are profound changes in gene expression downstream of nodal signaling along the D-V axis and major heterochronies in the execution of the function of nodal along the L-R axis. These highly modified events are linked to the dramatic modifications of larval morphology that have occurred during the evolution of direct development in H. erythrogramma.

Lithium, arginine vasopressin and the dex/CRH test in mood disordered patients.

The impact of lithium on arginine vasopressin (AVP) release has implications for our understanding of the pathophysiology and treatment of mood disorders and for the interpretation of neuroendocrine studies. In this secondary analysis of neuroendocrine, data from 23 patients with chronic major depressive disorder, 41 patients with bipolar disorder and 18 healthy controls, we examine the relationship between lithium therapy, AVP levels and the cortisol response to the dexamethasone/corticotropin-releasing hormone (dex/CRH) test. These data demonstrate that patients taking lithium have elevated post-dexamethasone AVP levels compared to both healthy controls and patients not on lithium.

Plasma cortisol-dehydroepiandrosterone (DHEA) ratios in schizophrenia and bipolar disorder.

Hypercortisolaemia is a feature of many severe psychiatric illnesses and has been suggested to be both a causal and exacerbating factor of clinical symptoms and neurocognitive impairment. The adrenal steroid dehydroepiandrosterone (DHEA) has antiglucocorticoid properties that may have regulatory effects on glucocorticoid action in the brain. However, there is a paucity of data on these steroids and their ratio in schizophrenia and bipolar disorder. We therefore sought to assess cortisol and DHEA levels and the cortisol-DHEA ratio in patients with schizophrenia (n=20) and bipolar disorder (n=20), on stable medication for a minimum of 6 weeks, and healthy age- and sex-matched control subjects (n=20). Steroid levels were measured from plasma samples collected at 30 min intervals from 1:00 p.m. to 4:00 p.m. Cortisol levels were found to be significantly elevated in both patient groups compared with controls. DHEA levels were elevated in schizophrenic patients compared with bipolar patients and controls, but there was no evidence of a difference in the cortisol-DHEA ratio of the groups. These data suggest that afternoon hypercortisolaemia is evident in symptomatic bipolar and schizophrenic patients compared to controls. However, an elevation in DHEA levels may represent a specific endocrine marker in schizophrenia.

The dex/CRH test--is it better than the DST?

The dexamethasone suppression test (DST), frequently abnormal in mood disorder patients, is considered to measure glucocorticoid receptor-mediated negative feedback. We examined the hypothesis that the, apparently more sensitive, dexamethasone/corticotrophin-releasing-hormone (dex/CRH) test unveils subtle hypothalamic-pituitary-adrenal axis disturbance not detected by the DST in 82 patients with mood disorders and 28 controls. There was a close correlation between the cortisol responses on the two tests (r(s)=0.73, p<0.0005). However, ROC analysis revealed that the dex/CRH test had better diagnostic performance than the DST (p=0.031). The sensitivity of delta cortisol (from the dex/CRH) was 61.9% and the specificity 71.4%. The sensitivity of 1500 h cortisol (the DST) was 66.6% and the specificity was 47.6%. This suggests that the two tests measure common pathology but that the dex/CRH test has better diagnostic utility.

Effects of adjunctive mifepristone (RU-486) administration on neurocognitive function and symptoms in schizophrenia.

BACKGROUND: It has been suggested that hypercortisolemia may cause or exacerbate both neurocognitive impairment and symptoms in schizophrenia. We hypothesized that antiglucocorticoid treatments, particularly glucocorticoid receptor (GR) antagonists, would improve neurocognitive functioning and clinical symptoms in this disorder. METHOD: Twenty patients with schizophrenia were treated with 600 mg/day of the GR-antagonist mifepristone (RU-486) or placebo for 1 week in a double-blind, crossover design. Neurocognitive function was evaluated at baseline and 2 weeks after each treatment. Neuroendocrine profiling was performed at these times and also immediately after each treatment. Symptoms were evaluated weekly. RESULTS: Mifepristone administration resulted in a temporary two- to threefold increase in plasma cortisol levels (p < .0001). No significant effects were observed on any measure of neurocognitive function, including the primary outcome measures of spatial working memory and declarative memory. Minor changes in symptoms occurred in both arms of the study and were indicative of a general improvement over time, irrespective of treatment. CONCLUSIONS: In contrast to our earlier report of positive effects in bipolar disorder, these data suggest that the GR-antagonist mifepristone has no effect on neurocognitive function or symptoms in this group of patients with schizophrenia. Future studies in schizophrenia should examine patients with demonstrable hypothalmic-pituitary-adrenal axis dysfunction.

Elevated prolactin responses to L-tryptophan infusion in medication-free depressed patients.

RATIONALE: Several previous neuroendocrine studies have demonstrated reduced 5-HT1A receptor function in major depressive disorder (MDD). However, hypercortisolaemia or previous drug treatment may have been significant confounds. OBJECTIVES: To replicate previous studies in subjects with MDD who had been drug free for at least 8 weeks and to relate the findings to measures of HPA axis function. METHODS: Hormonal responses to l-tryptophan infusion were measured in patients with MDD (n=20) and healthy controls (n=20). Basal salivary cortisol and DHEA were also profiled. RESULTS: No attenuation of 5-HT1A receptor-dependent neuroendocrine responses (growth hormone, prolactin) was observed in patients with MDD. The prolactin response to l-tryptophan was significantly greater in MDD patients than in healthy controls (P=0.008). There was a significant negative correlation between prolactin response and basal salivary cortisol secretion over the 3 days prior to the test. CONCLUSIONS: These data do not support previous findings of reduced 5-HT1A function in MDD and suggest that hypercortisolaemia or psychotropic medication may have accounted for the attenuation. Basal cortisol, DHEA and the cortiso l-DHEA ratio did not differ between patients and controls, and all patients were psychotropic medication-free. The greater prolactin response to l-tryptophan infusion in depressed subjects may be the result of an increase in dopamine receptor sensitivity, secondary to reduced dopamine levels.

Effect of sub-chronic hydrocortisone on responses to amphetamine in normal male volunteers.

RATIONALE: Enhancement of dopamine (DA) release by corticosteroids may be of aetiological importance in substance misuse. OBJECTIVES: To examine the effect of sub-chronic administration of hydrocortisone on the response to amphetamine in healthy male volunteers. METHODS: Following baseline assessment, 20 volunteers were pretreated for 7 days with 20 mg of hydrocortisone or placebo at 0800 hours and 2000 hours in a double-blind, random order, cross-over design prior to receiving 0.15 mg/kg metamphetamine intravenously. Blood samples for cortisol and prolactin were taken every 15 min. Subjects also underwent tests of neuropsychological function including sustained attention using the rapid visual information processing test (RVIP), which has been shown to be sensitive to changes in DA function. RESULTS: Metamphetamine produced a substantial reduction in prolactin levels, and increased subjective mood ratings of "mind-race" and "buzz". Sub-chronic hydrocortisone administration had no effect on these neuroendocrine responses, subjective mood changes or neurocognitive performance on a task of sustained attention (RVIP). CONCLUSIONS: Despite measurable changes in neuroendocrine and affective functioning in response to metamphetamine, pretreatment with hydrocortisone did not significantly affect any of the variables measured. This suggests that this model of DA function is not affected by this regimen of corticosteroid administration.

A randomized trial to examine the effect of mifepristone on neuropsychological performance and mood in patients with bipolar depression.

BACKGROUND: Deficits in neuropsychological performance are found in patients with bipolar disorder and represent a potential treatment target for novel therapeutic strategies. We have previously demonstrated a beneficial effect on spatial working memory (SWM) of treatment for 1 week with the progesterone and glucocorticoid receptor antagonist mifepristone, evident 2 weeks after the cessation of treatment. METHODS: We examined the longer-term efficacy of 600 mg/day of mifepristone as an adjunctive treatment, for 1 week, in a placebo-controlled, randomized, double-blind trial in 60 patients with bipolar depression, with SWM as the primary outcome measure. A comparator group of healthy control subjects was also recruited. RESULTS: At baseline, neuropsychological performance of patients was impaired, but hypothalamic-pituitary-adrenal axis function did not differ from that of control subjects. Mifepristone treatment was associated with a time-limited increase in cortisol awakening response and with a sustained improvement in SWM performance, which was evident 7 weeks after the cessation of treatment. The magnitude of this neuropsychological response was predicted by the magnitude of the cortisol response to mifepristone. The response occurred in the absence of a significant improvement in depressed mood. CONCLUSIONS: These data accord with the findings of animal studies and demonstrate that brief treatment with mifepristone is associated with a sustained improvement in SWM, an effect that might be mediated by a persistent enhancement in hippocampal mineralocorticoid receptor function.