Responses to stressors serve to adjust physiology and behavior to increase short-term survival at the potential expense of increasing susceptibility to disease over the long term. We show that glucagon-like peptide-1 (7-36) amide (GLP-1) increases levels of the stress-activated hormones ACTH and corticosterone when administered directly into the rat brain and increases levels of anxiety as measured by the elevated plus maze. The endocrine response is preferentially activated by GLP-1 administration in the paraventricular nucleus of the hypothalamus, whereas the anxiety response is preferentially activated by administration in the central nucleus of the amygdala. Furthermore, GLP-1 antagonists block increases in stress hormones associated with the toxin LiCl and both the endocrine and anxiety responses to vertical heights. Although diverse neural circuits must necessarily process disparate stressors, the current data implicate a role for the GLP-1 system as a critical mediator of multiple stress responses.

No abstract

SUMMARYObjective: Seizures are common in individuals with duplications of chromosome 15q11.2-q13 (Dup15q). The goal of this study was to examine the phenotypes and treatments of seizures in Dup15q in a large population. Methods: A detailed electronic survey was conducted through the Dup15q Alliance containing comprehensive questions regarding seizures and their treatments in Dup15q.Results: There were 95 responses from Dup15q families. For the 83 with idic(15), 63% were reported to have seizures, of which 81% had multiple seizure types and 42% had infantile spasms. Other common seizure types were tonic-clonic, atonic, myoclonic, and focal. Only 3 of 12 individuals with int dup(15) had seizures. Broad spectrum antiepileptic drugs (AEDs) were the most effective medications, but carbamazepine and oxcarbazepine were also effective, although typical benzodiazepines were relatively ineffective. There was a 24% response rate (>90% seizure reduction) to the first AED tried. For those with infantile spasms, adrenocorticotropic hormone (ACTH) was more effective than vigabatrin. Significance: This is the largest study assessing seizures in Duplication 15q syndrome, but because this was a questionnaire-based study with a low return rate, it is susceptible to bias. Seizures are common in idic(15) and typically difficult to control, often presenting with infantile spasms and progressing to a Lennox-Gastaut-type syndrome. Seizures in those with int dup(15) are less common, with a frequency similar to the general autism population. In addition to broad spectrum AED, medications such as carbamazepine and oxcarbazepine are also relatively effective in controlling seizures in this population, suggesting a possible multifocal etiology, which may also explain the high rate of infantile spasms. Our small sample suggests a relative lack of efficacy of vigabatrin and other c-aminobutyric acid (GABA)ergic medications, such as typical benzodiazepines, which may be attributable to abnormal GABAergic transmission resulting from the duplication of a cluster of GABAb3 receptor genes in the 15q11.2-13 region.

The link between movement abnormalities and psychotic disorders is presumed to reflect common neural mechanisms that influence both motor functions and vulnerability to psychosis. The prodromal period leading to psychotic disorders represents both a viable point for intervention and a developmental period that, if studied, could shed light on etiology; however, no published studies have examined the temporal progression of this link. A group with high levels of prodromal symptomatology (i.e., adolescents with schizotypal personality disorder [SPD]; n = 42) and both psychiatric controls (with other personality disorders or conduct disorder [OD]; n = 30) and nonpsychiatric controls ([NC]; n = 49) were recruited. Videotapes of structured psychiatric interviews were coded for movement abnormalities by raters blind to participants' diagnostic status, and follow-up assessments were conducted 1 year later. Controlling for psychotropic medications, the authors found that adolescents with SPD exhibited significantly more motor abnormalities in the face and upper body than did OD and NC controls. At baseline, movement abnormalities were positively correlated with the severity of positive, negative, and total prodromal symptoms. Within the SPD group, baseline movement abnormalities predicted symptom severity 1 year later. Movement abnormalities represent an early risk indicator that may be predictive of later symptom severity and potentially of psychosis onset.

No abstract

Dysfunction in the neuronal nicotinic acetylcholine receptor (nAChR) system has been implicated in the pathophysiology of schizophrenia, and it has been postulated that treatments that increase nAChR activity may improve symptoms of the disorder. We investigated the effects of the acetylcholinesterase inhibitor and allosteric nAChR modulator, galantamine, on cognitive performance and clinical symptoms when added to a stable antipsychotic medication regimen in nonsmoking outpatients with schizophrenia in a double-blind, placebo-controlled, parallel-group design. Participants were randomized to receive either galantamine (n=10) up to 32 mg/day or identical placebo (n=10) for 8 weeks and completed a cognitive battery at baseline and week 8 and clinical scales at baseline, week 4 and week 8. The primary outcome measure was attentional performance as measured by the d' measure in the Continuous Performance Test - Identical Pairs (CPT-IP) Version. Contrary to our hypothesis, galantamine treatment was associated with inferior performance on the CPT-IP, on the three-card Stroop task, and on the Letter-Number Span task without reordering. Galantamine had no effect on clinical symptoms. In summary, galantamine treatment, at a dose of 32 mg/day, was well tolerated but was not effective as an adjunctive treatment for cognitive deficits in stable nonsmokers with schizophrenia.

In patients with severe ICA stenosis, additional stratification of stroke risk may be possible based on the presence of carotid wall enhancement on CTA-SI. Patients with carotid wall enhancement are more likely to be symptomatic, compared to those with either calcified plaque or no enhancement.

Corticotropin-releasing hormone (CRH) is a 41 amino acid neuropeptide which plays an important role in the stress response in the hypothalamus. We describe the development of an immortalized hypothalamic cell line which expresses CRH. We hypothesized that this cell line would possess the relevant characteristics of parvocellular CRH-expressing neurones such as glucocorticoid receptor (GR) expression and vasopressin (VP) coexpression. For production of hypothalamic cells, embryonic day 19 rat pup hypothalami were dissected and dissociated into tissue culture dishes. They were immortalized by retrovirus-mediated transfer of the SV40 large T antigen gene at 3 days of culture and then screened for expression of CRH following dilution cloning. One cell line was chosen (IVB) which exhibited CRH-like immunoreactivity (CRH-LI) and expressed CRH, VP and CRH 1 receptor RNA via the reverse transcriptase-polymerase chain reaction. In addition, the cell line expressed the neuronal marker, microtubule-associated protein-2. We veri®ed that the CRH-LI from IVB cell lysates coeluted with CRH standard via reversed-phase high-performance liquid chromatography (HPLC). Furthermore, oxidation of the lysate converted its HPLC pro®le to that identical with oxidized CRH standard. In addition, IVB cells exhibited high af®nity binding to CRH. Incubation of IVB cells with CRH lead to increases in cAMP levels and protein kinase A activity in a concentration-dependent manner. Incubation of IVB cells with CRH also resulted in increases in phospho-cyclic-AMP response element binding protein (CREB) imunostaining as detected by immunocytochemical analysis. Finally, CRH treatment of IVB cell lines has been linked to CREB-mediated gene expression as determined via the PathDetect CREB trans-reporting system. The characteristics of IVB cells, such as CRH and VP coexpression, GR expression and a biologically active CRH-R1-mediated signalling pathway, suggest that this neuronal cell line may serve as model of parvocellular CRH neurones.Corticotropin-releasing hormone (CRH) is a 41 amino acid containing neuropeptide which coordinates the neuroendocrine, behavioural, autonomic and immune responses to stress (1, 2). It is secreted from the hypothalamus and acts on pituitary corticotrophs to enhance secretion of adrenocorticotropic hormone (ACTH) and other pro-opiomelanocortin products. ACTH, in turn, stimulates glucocorticoid synthesis and secretion in the adrenal cortex. CRH containing parvocellular neurones coexpress vasopressin (VP) and are subject to negative feedback by glucocorticoids following stressful conditions (3).The cellular effects of CRH are mediated by high-af®nity receptors (4±7). In addition to the anterior and intermediate lobes of the pituitary (8), CRH receptors are located in a wide variety of locations in the central nervous system (CNS), including the parvocellular neurones of the paraventricular nucleus where they are induced by stress (9). There are two CRH receptor types.