ABSTRACT
Deficits in social memory, cognition, and aberrant responses to stimulants are common among persons affected by schizophrenia and other conditions with a presumed developmental etiology. We previously found that expression changes in the adenosine metabolizing enzyme adenosine kinase (ADK) in the adult brain are associated with deficits in various cognitive domains. To distinguish between developmental and adult functions of ADK, we used two transgenic mouse lines with widespread disruption of ADK expression in the adult brain, but differences in the onset of ADK deletion. Specifically, we compared Nestin-Cre+/-:ADK-floxfl/fl (ADKΔBrain) mice with global loss of ADK in the whole brain, beginning in mid-gestation and persisting for life, with Gfa2-Cre+/-:ADK-floxfl/fl (ADKΔAstro) mice that have normal ADK expression throughout development, but lose astrocyte-specific ADK-expression in young adulthood. Because ADK-expression in adulthood is generally confined to astrocytes, adult ADKΔAstro mice show a similar expression profile of ADK in key areas of the brain related to neuropsychiatric behavior, compared to adult ADKΔBrain mice. We sought to determine a neurodevelopmental role of ADK on the expression of psychiatric behaviors in adult male and female mice. Adult ADKΔBrain mice showed significant deficits in social memory in males, significant contextual learning impairments in both sexes, and a hyper-responsiveness to amphetamine in males. In contrast, ADKΔAstro mice showed normal social memory and contextual learning but hypo-responsiveness to amphetamine in males. Our results demonstrate a key developmental role of ADK in mediating behaviors in adulthood related to neuropsychiatric disease and support the greater prevalence of these disorders among males.
Subject(s)
Adenosine Kinase/physiology , Central Nervous System Sensitization/genetics , Learning/physiology , Memory/physiology , Sex Characteristics , Adenosine Kinase/genetics , Age Factors , Amphetamine/pharmacology , Animals , Female , HSP40 Heat-Shock Proteins/genetics , Male , Mice , Mice, Transgenic , Nestin/geneticsABSTRACT
BACKGROUND: Possible health effects for employees of efforts to improve the psychosocial competence of managers have not been studied scientifically in the past. OBJECTIVE: To explore how efforts to improve management will change the work environment and health of the employees. METHODS: Managers of the experimental department in a large insurance corporation underwent 2-hour biweekly training sessions for 1 year-altogether, 60 hours. A control group of employees in other departments in the corporation not affected by the modification was followed with the same assessments. Morning blood samples for the assessment of serum cortisol were collected both at baseline and after 1 year in 155 participants in the experimental group and in 147 subjects in the control group. Liver enzymes and lipids were also assessed. In the questionnaire part of the 1-year follow-up study, there were 119 participants in the experimental group and 132 in the control group. RESULTS: When repeated-measures ANOVA was used, a significant interaction effect was found for the level of serum cortisol; serum cortisol levels were decreased in the intervention group and were unchanged in the control group (ANOVA two-way interaction, p =.02; after exclusion of the managers, p =.005). A significant interaction effect was also observed for decision authority, with increased decision authority in the intervention group and, conversely, a decreased level in the control group (p =.001; after exclusion of managers, p =.02). CONCLUSIONS: The study indicates that a moderately intensive psychosocial manager program lasting for 1 year can be beneficial for the employees with regard to both lowered serum cortisol and improved authority over decisions.
Subject(s)
Administrative Personnel/education , Stress, Psychological/prevention & control , Administrative Personnel/psychology , Adult , Cholesterol/blood , Decision Making , Education/methods , Female , Follow-Up Studies , Freedom , Humans , Hydrocortisone/blood , Male , Middle Aged , Organizational Culture , Stress, Psychological/blood , Stress, Psychological/etiology , Sweden , gamma-Glutamyltransferase/bloodABSTRACT
Khat is a plant whose leaves are chewed for their stimulating effect. This effect is attributed to cathinone, an alkaloid identical to dextroamphetamine. Khat chewing is widespread among eastern African and Yemenite populations and is believed to be innocuous. Our experience shows, however, that a substantial number of chronic khat chewers experience persistent hypnagogic hallucinations - a symptom that has not yet been described. Three vignettes illustrates this phenomena, which often interferes with psychiatric diagnosis. Different explanatory models are discussed, among them chronic suppression of REM sleep.
