Genetic and immunological factors interact in a mouse model of CNS antiphospholipid syndrome.

The antiphospholipid syndrome (APS) includes systemic and central nervous system (CNS) pathology associated with antibodies to a complex of phospholipids and beta(2)-glycoprotein I (beta(2)-GPI). We have recently reported the induction of APS associated with behavioral and cognitive deficits in BALB/c female mice that developed 4-5 months after immunization with beta(2)-GPI. In the present study, we examined the influence of genetic factors on the ability to induce experimental APS with CNS involvement by testing several mouse strains immunized with beta(2)-GPI. Female mice from five strains were immunized once with beta(2)-GPI in complete Freund's adjuvant (CFA) or with CFA alone (controls). Autoantibody levels were examined at 1 and 5 months after immunization. Neurological assessment in a staircase test was performed 4-5 months following the immunization. Induction of APS resulted in elevated levels of antibodies against negatively charged phospholipids and beta(2)-GPI in all five mouse strains. Autoantibody levels were significantly higher in Balb/c, ICR, and C57BL/6 mouse strains compared to AKR and C3H. aPL levels dropped significantly more in the C57BL/6 compared to Balb/c mice over a period of 4 months. Hyperactivity reflected by higher number of stairs climbed in 3 min, was induced by APS in the Balb/c and ICR, mouse strains. Exploratory behavior reflected by more frequent rears, was seen in the APS-Balb/c and AKR mice. Hypoactivity and less exploration were seen in the APS-C57BL/6 and C3H mice. The study supports a link between high levels of aPL and behavioral changes in a mouse APS model. Qualitative differences in behavioral patterns may be due to nervous system as well as immune genetic factors. The minimal effect of APS in C57BL/6 mice may provide a suitable background for the study of transgenes in these mice.

Mental pain: a multidimensional operationalization and definition.

An operationalization of mental pain is presented in three studies. The first study describes the operationalization of mental pain and the factor structure of the items produced by a content analysis of self-reports yielding a scale with nine factors: the experience of irreversibility, loss of control, narcissistic wounds, emotional flooding, freezing, estrangement, confusion, social distancing, and emptiness. Study 2 tested the relationship between mental pain and depression and anxiety in a normal population. Study 3 focused on the relationship between mental pain and coping. Mental pain is conceptualized as a perception of negative changes in the self and its functions that are accompanied by negative feelings. It is suggested that it can be meaningfully applied to the study of different mental states, life conditions, and transitions in life.

Mental pain and its relationship to suicidality and life meaning.

Shneidman (1996) proposed that intense mental pain is related to suicide. Relatedly, Frankl (1963) argued that the loss of life's meaning is related to intense mental pain. The first goal of this research was to test Shneidman's proposition by comparing the mental pain of suicidal and nonsuicidal individuals. Meaning in life and optimism are the polar opposites of suicidality and hopelessness, and the examination of these variables in relation to mental pain was undertaken to provide a test of Frankl's proposition. In two studies, a relationship between a newly developed measure of mental pain--the Orbach & Mikulincer Mental Pain Scale, 2002 (OMMP; see also Orbach, Mikulincer, Sirota & Gilboa-Schechtman, 2002)--and suicidal behavior and life meaning were examined. Results confirmed both propositions. Implications for the study of mental pain and suicide are discussed.