Abstract:Expression of the carboxyl-terminal fragment (CT) of the fl-amyloid precursor protein (APP) in transgenic animals has been linked with neurotoxicity. However, it remains to be clarified whether the neurotoxicity is caused by~3-amyloid proteins (A~3s) derived from CT or by CT itself. To study the in vivo neurotoxicity of CT, mice were given a single intracerebroventricular injection of a recombinant 105-amino acid CT (CT1C5; 68.5-685 pmol, intracerebroventricularly), anu changes in behavior and in brain histology were examined. Animals given CT1O5 (410 or 685 pmol, intracerebroventricularly) showed a dose-dependent impairment in the passive avoidance performance, whereas boiled CT1O5 had no effect. CT1O5 (685 pmol, intracerebroventricularly) induced reactive gliosis in neocortex and hippocampus and neurodegeneration in neocortex. These results indicate that centrally administered CT1 05 induces behavioral impairment and neuropathologic changes, suggesting a direct toxic effect of CT1O5 per se. Key Words: Carboxyl-terminal fragment-/3-Amyloid precursor protein-Step-through passive avoidance task-Reactive gliosis-Neuronal degeneration. J. Neurochem. 71, 875-878 (1998).Altered metabolism of the~-amy1oid precursor protein (APP) and subsequent generation of toxic metabolites of APP are postulated to be intimately involved in Alzheimer's disease (AD) (for review, see Selkoe, 1994). Although~3-amyloid proteins (A/3s) aru the most extensively studied toxic fragments of APP, other proteolytic products of APP may also contribute to the pathogenesis of AD. The carboxyl-terminal fragment (CT) of APP is derived from /3-secretase cleavage of APP and contains whole A/I in the amino-terminal portion (for review, see . Expression of CT 100-105 amino acids in length was shown to be toxic to cultured cell lines (Yankner et al., 1989;Fukuchi et a!., 1992), and brain transplants of cells expressing CT cause specific neuropathol~y in vivo . Furthermore, expression of CT 100-104 amino acids in length in transgenic animals (Kammesheidt et al., 1992; Oster-Granite et al., 1996; Nalbantoglu et al., 1997) has been linked with neurotoxicity. However, it is unclear whether this neurotoxicity was caused by CT peptide itself or by A/Is derived from CT, because CT contains whole A/I. We previously reported that direct addition of a recombinant 105-amino acid CT (CT1OS) to the culture medium induced toxicity to primary cultured cortical neurons and PC12 cells (Kim and Suh, 1996). However, the in vivo effect of CT 105 administered centrally on behavior and brain histology has not been investigated so far. Thus, in this study we attempted to examine the potential detrimental effect of CT 105 injected intracerebroventricularly on passive avoidance performance and brain histology. MATERIALS AND METHODS Intracerebroventricular injection of CT1O5The CTIO5 peptide was synthesized and purified as described (Chong et al., 1994). In brief, CTIO5 (Mr 14,242) was purified by a combination of urea solubilization and ion exchange chromatography and...

This case report aimed to describe various psychiatric manifestation and treatment course in a patient with DiGeorge syndrome. Psychiatric symptoms and treatment course in a female patient with DiGeorge syndrome were described. This patient showed psychotic symptoms, mood symptoms, and intellectual disability. As well as various psychiatric symptoms, treatment response and sensitivity of side effect by antipsychotics were different from typical characteristics in psychiatric disorders. This case suggests that the genetic defect in DiGeorge syndrome might have a great association with psychiatric problems and response of antipsychotics.

Background: A long-term follow-up study in patients with amnestic mild cognitive impairment (aMCI) is needed to elucidate the association between regional brain volume and psychopathological mechanisms of Alzheimer’s disease with psychosis (AD + P). Objective: The purpose of this study was to investigate the effect of the thickness of the angular cingulate cortex (ACC) on the risk of AD + P conversion in patients with aMCI. Methods: This was a hospital-based prospective longitudinal study including 174 patients with aMCI. The main outcome measure was time-to-progression from aMCI to AD + P. Subregions of the ACC (rostral ACC, rACC; caudal ACC, cACC) and hippocampus (HC) were measured as regions of interest with magnetic resonance imaging and the Freesurfer analysis at baseline. Survival analysis with time to incident AD + P as an event variable was calculated with Cox proportional hazards models using the subregions of the ACC and HC as a continuous variable. Results: Cox proportional hazard analyses showed that the risk of AD + P was associated with sub-regional ACC thickness but not HC volume: reduced cortical thickness of the left cACC (HR [95%CI], 0.224 [0.087–0.575], p = 0.002), right cACC (HR [95%CI], 0.318 [0.132–0.768], p = 0.011). This association of the cACC with the risk of AD also remained significant when adjusted for HC volume. Conclusion: We found that reduced cortical thickness of the cACC is a predictor of aMCI conversion to AD + P, independent of HC, suggesting that the ACC plays a vital role in the underlying pathogenesis of AD + P.

methods will help individuals manage stressful situations, but they are not all equally efficient at this task. Some methods only can make matters worse. 4 In this reason, it may be important to identify these habitual ways of coping, assess how effectively this will handle stressful situations, and correct them if necessary. 5 Endler and Parker have identified three coping styles: taskoriented, emotion-oriented and avoidance-oriented coping. Task-oriented coping describes task-oriented efforts aimed at solving the problem, cognitively restructuring the problem, or attempts to alter the situation. Emotion-oriented coping describes emotional reactions that are self-oriented, aimed to reduce stress. It includes emotional responses such as selfblaming, getting angry and rumination. Avoidance-oriented coping describes activities and cognitive changes aimed at avoiding stressful situation and alleviate stress. 6 Research indicated that patients with depressions tend to use maladaptive or emotion-oriented strategies. 7,8 Problem solving (task-oriented coping) was related to less depression and emotion discharge (emotion-oriented coping) was asso-