ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19.

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3-5 years from onset. Familial ALS (FALS) comprises 5%-10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis. We identified a Japanese family affected by late-onset, autosomal-dominant ALS in which mutations in genes known to be associated with FALS were excluded. A whole- genome sequencing and parametric linkage analysis under the assumption of an autosomal-dominant mode of inheritance with incomplete penetrance revealed the mutation c.2780G>A (p. Arg927Gln) in ERBB4. An extensive mutational analysis revealed the same mutation in a Canadian individual with familial ALS and a de novo mutation, c.3823C>T (p. Arg1275Trp), in a Japanese simplex case. These amino acid substitutions involve amino acids highly conserved among species, are predicted as probably damaging, and are located within a tyrosine kinase domain (p. Arg927Gln) or a C-terminal domain (p. Arg1275Trp), both of which mediate essential functions of ErbB4 as a receptor tyrosine kinase. Functional analysis revealed that these mutations led to a reduced autophosphorylation of ErbB4 upon neuregulin-1 (NRG-1) stimulation. Clinical presentations of the individuals with mutations were characterized by the involvement of both upper and lower motor neurons, a lack of obvious cognitive dysfunction, and relatively slow progression. This study indicates that disruption of the neuregulin-ErbB4 pathway is involved in the pathogenesis of ALS and potentially paves the way for the development of innovative therapeutic strategies such using NRGs or their agonists to upregulate ErbB4 functions.

[Group reminiscence therapy for Japanese elderly community].

This study examined the effectiveness of group reminiscence therapy in a Japanese elderly community. The relationship between the effectiveness of reminiscence therapy and styles of daily reminiscence was also examined. Participants (Two men and 46 women, mean age = 81.9 years) were recruited from a welfare center of a community. The reminiscence group and the control group consisted of 22 and 26 participants, respectively. They completed the assessment of anxiety and insomnia, depression, integrity, life satisfaction, and self-esteem before and after the intervention and in the 12-week follow-up. Participants in the reminiscence group took eight one-hour weekly sessions. Results showed that the reminiscence group showed improvement in life satisfaction after the intervention. Results also revealed that the frequency of daily reminiscence positively correlated with self-esteem at the posttest, suggesting that older adults reminiscing frequently may improve self-esteem when they participate in reminiscence therapy. The results suggested the potential value of group reminiscence therapy for Japanese elders.

[Interpersonal intolerance of ambiguity, interpersonal life events, and mental health].

This study examined in the interpersonal context whether interactions of intolerance of ambiguity and positive as well as negative life events in a diathesis-stress model predicted changes in mental health. College students, 236 men and women, completed a questionnaire of Revised Interpersonal Intolerance of Ambiguity (IIAS-R), Stress Response, and Happiness scales. They completed one and a half months later another questionnaire of Interpersonal Life Event, Stress Response, and Happiness scales. Hierarchical regression analyses showed that for men interaction terms of IIAS-R's Friend scores with a negative life event score significantly predicted an increase in stress response. For women, interaction terms of IIAS-R's Stranger scores with a negative life event score significantly predicted a decrease in happiness. The results suggested that the diathesis-stress model was partially supported, and men and women were different in terms of the criterion mental-health variables that could be predicted by the interaction terms.