Involvement of BDNF receptor TrkB in spatial memory formation

The N-methyl-D-aspartate (NMDA) receptors are involved in long-term potentiation (LTP), and are phosphorylated by several tyrosine kinases including a Src-family tyrosine kinase Fyn. Brain-derived neurotrophic factor (BDNF) is a neurotrophin, which also enhances hippocampal synaptic transmission and efficacy by increasing NMDA receptor activity. Here, we show that Fyn is a key molecule linking the BDNF receptor TrkB with NMDA receptors, which play an important role in spatial memory formation in a radial arm maze. Spatial learning induced phosphorylation of TrkB, Fyn, and NR2B, but not NR2A, in the hippocampus. Fyn was coimmunoprecipitated with TrkB and NR2B, and this association was increased in well-trained rats compared with control animals. Continuous intracerebroventricular infusion of PP2, a tyrosine kinase inhibitor, in rats delayed memory acquisition in the radial arm maze, but PP2-treated animals reached the same level of learning as the controls. The phosphorylation of Fyn and NR2B, but not TrkB, was diminished by PP2 treatment. Our findings suggest the importance of interaction between BDNF/TrkB signaling and NMDA receptors for spatial memory in the hippocampus.     

Aha! Insight experience correlates with solution activation in the right hemisphere

In one experiment, we tested for an association between semantic activation in the right hemisphere (RH) and left hemisphere (LH) and the Aha! experience when people recognize solutions to insight-like problems. The compound remote associate problems used in this experiment sometimes evoke an Aha! experience and sometimes do not. On each trial, participants (N = 44) attempted to solve these problems and, after 7 sec, named a target word, made a solution decision, and rated their insight experience of recognizing the solution. As in prior studies, the participants demonstrated more solution priming for solutions presented to the left visual field-RH (lvf-RH) than for solutions presented to the right visual field-LH (rvf-LH). As was predicted, following unsolved problems the participants showed greater priming for solutions that they rated as evoking an insight experience on the subsequent solution decision than for solutions that did not evoke an insight experience. This association was stronger for solutions presented to the lvf-RH than for those presented to the rvf-LH. These results tie the subjective experience of insight to an objective measure-semantic priming-and suggest that people have an Aha! experience in part because they already had semantic activation that could lead them to recognize the solution quickly. We believe semantic activation in both hemispheres cooperatively contributes to problem solving, but weak solution activation that contributes to the Aha! experience is more likely to occur in the RH than in the LH.     

The neuroendocrinology of posttraumatic stress disorder: new directions

Studies of the hypothalamic-pituitary-adrenal (HPA) axis in persons with posttraumatic stress disorder (PTSD) have produced variable findings. This review focuses on the factors likely to have affected the outcome of these studies, including population characteristics and experimental design. Also discussed is a possible role for the adrenal neurosteroid dehydroepiandrosterone (DHEA) as a mediator of HPA axis adaptation to extreme stress and the psychiatric symptoms associated with PTSD. The antiglucocorticoid properties of DHEA may contribute to an upregulation of HPA axis responses as well as mitigate possible deleterious effects of high cortisol levels on the brain in some PTSD subpopulations. The neuromodulatory effects of DHEA and its metabolite DHEAS at gamma-aminobutyric acid and N-methyl-D-aspartate receptors in the brain may contribute to psychiatric symptoms associated with PTSD. The possible importance of other neurohormone systems in modulating HPA axis and symptom responses to traumatic stress is also discussed. Understanding the complex interactions of these stress-responsive neurosteroid and peptide systems may help explain the variability in patterns of HPA axis adaptation, brain changes, and psychiatric symptoms observed in PTSD and lead to better targeting of preventive and therapeutic interventions.     

Emerging therapeutics for Alzheimer's disease: an avenue of hope

Emerging therapies for Alzheimer's disease offer hope to patients and their caregivers. Future treatments will probably include combination approaches with agents that modify amyloid processing, deposition, and clearance. One example, the AD vaccine, reduced amyloid burden and changed behavior in animal models of AD, but the human trial was halted when several subjects developed brain inflammation. Anti-inflammatory agents have epidemiologic support, but clinical trials have been disappointing, possibly related to inadequate study with anti-inflammatory agents that modify amyloid processing. Agents that target known cardiovascular risk factors, such as hypercholesterolemia, hypertension, and insulin resistance, have epidemiologic, preclinical, and clinical evidence to warrant further investigation. Heavy metal chelators, antioxidants, neurotrophic factors, glutaminergic modulators, and agents that modify hyperphosphorylation of Tau are other approaches in research and development.     

Methylphenidate-induced obsessive-compulsive symptoms in an elderly man

An 82-year-old man with treatment-resistant depression and early Alzheimer's disease was started on methylphenidate. Significant obsessive-compulsive behavior ensued but diminished over several weeks when methylphenidate was replaced by fluvoxamine. The patient had no prior psychiatric history, but he had a sister with obsessive-compulsive disorder. It appears that methylphenidate precipitated the patient's pathological behavior.     

New lessons from knockout mice: The role of serotonin during development and its possible contribution to the origins of neuropsychiatric disorders

Serotonin (5-HT) modulates numerous processes in the central nervous system that are relevant to neuropsychiatric function and dysfunction. It exerts significant effects on anxiety, mood, impulsivity, sleep, ingestive behavior, reward systems, and psychosis. Serotonergic dysfunction has been implicated in several psychiatric conditions but efforts to more clearly understand the mechanisms of this influence have been hampered by the complexity of this system at the receptor level. There are at least 14 distinct receptors that mediate the effects of 5-HT as well as several enzymes that control its synthesis and metabolism. Pharmacologic agents that target specific receptors have provided clues regarding the function of these receptors in the human brain. 5-HT is also an important modulator of neural development and several groups have employed a genetic strategy relevant to behavior. Several inactivation mutations of specific 5-HT receptors have been generated producing interesting behavioral phenotypes related to anxiety, depression, drug abuse, psychosis, and cognition. In many cases, knockout mice have been used to confirm what has already been suspected based on pharmacologic studies. In other instances, mutations have demonstrated new functions of serotonergic genes in development and behavior.     

Topiramate in the preventive treatment of episodic migraine: a combined analysis from pilot,double-blind,placebo-controlled trials

The safety and efficacy of medications for preventive treatment of migraine is the subject of current concern and investigation in health care. Two single-center, double-blind, placebo-controlled studies were conducted to evaluate the efficacy and safety of topiramate for migraine prophylaxis. Seventy patients with a diagnosis of migraine were randomly assigned to topiramate-treated and placebo groups. The studies consisted of a 4-week baseline phase, a 6-8 week titration, and 8-12 weeks of maintenance. Topiramate was titrated from an initial dose of 25 mg/day to a target dose of 100 mg BID. The primary efficacy measure, the mean 28-day migraine frequency, was lower in topiramate-treated patients than in the placebo group (3.2 versus 3.8, P=.001). Similarly, topiramate treatment resulted in a significantly greater mean reduction in migraine frequency than did placebo (1.55 versus 0.47, P=.001) and a significantly higher responder rate (35.3% versus 8.3%, P=.008). Paresthesia was the most common side effect reported with topiramate treatment. Other topiramate-associated adverse events included altered taste, memory impairment, diarrhea, and appetite suppression/weight loss. The rates of discontinuation were similar for the topiramate group (n=10) and the placebo group (n=8). These results suggest that topiramate is effective and well tolerated in the preventive treatment of migraine headaches.     

I don't think that's what really happened: the effect of cross-examination on the accuracy of children's reports

In the courtroom, child witnesses must undergo cross-examination. Prior research has shown that children change their original testimony under cross-examination, but the effect of these changes on the accuracy of children's testimony is unknown. The authors examined the effect of cross-examination on the accuracy of 5- and 6-year-old children's (N=46) reports of a contrived event. Consistent with prior research, children made changes to their original responses during cross-examination. Furthermore, these changes occurred irrespective of original accuracy. Finally, prior exposure to misleading information did not affect children's responses to cross-examination. Even children with no prior exposure to misinformation altered their original responses, decreasing their ultimate levels of accuracy. These findings demonstrate that cross-examination style questioning is inappropriate for young children.     

Stereotype development in Andalusian children

Social psychologists have shown a profound interest in intergroup relationships, but there are very few papers focusing on the developmental aspects that explain the psychological mechanisms involved in the construction of group and cultural identity. Our research aims to explore how the self-categorization of Andalusian children evolves. We tried to assess the degree to which they self-identify as Andalusian, Spanish, and European, and how this identification changes with age. We were also interested in the affective evaluation of different groups (French, Italian, English, German, Spanish, Catalonian, and Andalusian) made by Andalusian children. Furthermore, we analyzed the relationship between self-categorization and the evaluation of these groups. Results show that the development of national (autonomous community) identity in these children is influenced by their cognitive development, as well as by the relationships among the regional communities of Spain and the relationships between Spain and other countries. The peculiarity of Andalusians as a group is that they assume both identities: Spanish and Andalusian, from a very early age. In-group favoritism is an extended phenomenon at all ages, and Andalusian children have a negative stereotype of the other Spanish groups and other European communities.