Donna Cohen

Transcriptional activation and repression by Fos are independent functions: the C terminus represses immediate-early gene expression via CArG elements.

The Fos-Jun complex has been shown to activate transcription through the regulatory element known as the AP-1 binding site. We show that Fos down regulates several immediate-early genes (c-fos, Egr-1, and Egr-2) after mitogenic stimulation. Specifically, we demonstrate that the target for this repression is a sequence of the form CC(A/T)6GG, also known as a CArG box. Whereas Fos bound to the AP-1 site through a domain rich in basic amino acids and associated with Jun via a leucine zipper interaction, mutant Fos proteins lacking these structures were still capable of causing repression. Furthermore, Jun neither enhanced nor inhibited down regulation by Fos. Critical residues required for repression are located within the C-terminal 27 amino acids of c-Fos, since v-Fos and C-terminal truncations of c-Fos did not down regulate. In addition, transfer of 180 c-Fos C-terminal amino acids to Jun conferred upon it the ability to repress. Finally, Fra-1, a Fos-related protein which has striking similarity to Fos in its C-terminal 40 amino acids, also down regulated Egr-1 expression. Thus, Fos is a transcriptional regulator that can activate or repress gene expression by way of two separate functional domains that act on distinct regulatory elements.

Depression in family members caring for a relative with Alzheimer's disease.

The reformulated learned helplessness model of depression was tested in a study of families caring for relatives with Alzheimers disease who did not participate in family support groups or have access to respite care. Family members who identified themselves as major caregivers, ie, those providing daily assistance to the patient, received a clinical psychiatric interview, the Beck Self‐Report Depression Scale, and a modified Hammen and deMayo Attributional Style Questionnaire. The results showed that 55% of major caregivers, primarily spouses, living with an older relative with dementia experienced clinical depression. Depressed caregivers were more likely to perceive a lack of control over their situation than those who were not depressed. Contrary to the reformulated learned helplessness hypothesis, they did not perceive their situation to be the result of internal, stable, and global attributions. The results suggest the need to study depression in ecologically stressful natural settings and to develop effective clinical intervention strategies.

A newspaper surveillance study of homicide-suicide in the United States.

The objective of this study was to identify the number and subtypes of homicide-suicides in the United States by age group and state over a 3-year period from 1997 through 1999. A total of 673 homicide-suicides, including 674 perpetrators and 779 victims, were identified from Internet searches of 191 national newspapers, and they were classified according to a modified Hanzlick-Koponen typology. One quarter of the homicide-suicides were perpetrated by persons 55 years or older, and 77% were spousal/consortial, higher than the 57% observed in the younger age group; 11% of the older homicide-suicides were familial, compared with 16% in the younger age group. Whereas only 3% of older homicide-suicides were infanticide/pedicide, 16% of the younger homicide-suicides involved parents killing their children. Forty-five states, including the District of Columbia, reported a homicide-suicide during the 3-year period, and they occurred most frequently in Florida (163), California (98), Texas (36), and New York (35). Newspaper surveillance is useful to identify where homicide-suicides are occurring most frequently, but they are underestimates of the true prevalence. However, the number of incidents detected is large enough that the cases detected may be a fairly representative sample.

A statewide case-control study of spousal homicide-suicide in older persons

OBJECTIVE Homicide-suicides are rare relative to suicides and homicides, but these lethal events are an emerging public health concern. They have a mortality count similar to meningitis, pulmonary tuberculosis, influenza, and viral hepatitis, and the rate may be increasing in the United States, especially among older persons. The goal of this case-control study was to identify factors that differentiate older married men who commit homicide-suicide from those who commit suicide only. METHODS A total of 20 spousal homicide-suicides involving persons age 55 years and older were ascertained in Florida between January 1, 1998 and December 31, 1999 from medical examiner records. Two suicide controls were matched to each homicide-suicide perpetrator by age, race, marital status, method of death, and medical examiner district. Perpetrator groups were compared on sociodemographic characteristics, medical variables, and autopsy findings. RESULTS Homicide-suicide perpetrators displayed significantly more domestic violence or were caregivers for their wives, in contrast to suicide perpetrators, who had health problems and were receiving care from their spouses. Both groups of perpetrators had reported depressed mood, and there were no differences in sociodemographic factors. CONCLUSIONS Depression plays a significant role in both homicide-suicide and suicide, but the associated factors are different: we see caregiving strain in perpetrators of homicide-suicide, and living with physical health disorders as a care-recipient in men who commit suicide. Marital conflict is a significant factor in some spousal homicide-suicides.

Drug Use Patterns of Persons with Alzheimer's Disease and Related Disorders Living in the Community

Objective: To describe drug use patterns by persons with Alzheimers disease, multi‐infarct dementia, and mixed Alzheimers disease and multi‐infarct dementia.

A comparison of antecedents of homicide-suicide and suicide in older married men.

The authors compared characteristics of 27 older men who perpetrated a spousal homicide-suicide and 36 age-matched married men who committed suicide in west central Florida between 1988 and 1994. Data were collected as part of an ongoing retrospective study of homicide and suicide among older adults in Florida. Men who committed suicide had significantly more disease conditions than homicide-suicide perpetrators (P<0.0001). Half of the latter were in caregiving roles, vs. 17% of the suicides (chi(2)=5.40; P=0.027). Depression was a prominent premorbid feature of both groups, but none of the perpetrators tested positive for antidepressants postmortem.

Sex differences in the psychiatric manifestations of Alzheimer's disease.

Objective: To test the null hypothesis, ie, that there are no gender differences in psychiatric problems manifest in patients with Alzheimers disease.

Alzheimer's Disease and Maternal Age

Findings from several studies suggest a relationship between Alzheimers disease and0020Downs syndrome. It has long been known that advanced maternal age is a risk factor for Downs syndrome, and that mothers who give birth to a child with this syndrome have characteristics consistent with accelerated aging. Little is known about risk factors for Alzheimers disease, other than age. In this study, documentation is supplied for a hypothesis concerning a relationship between Alzheimers disease and advanced maternal age.

Epidemiologic Aspects of Alzheimer's Disease: Facts and Fragments

To date, the classical approach of epidemiology has been neither exhaustive nor particularly helpful in developing insights into the nature of Alzheimers disease. The inability both to diagnose the disease and predict its clinical course hampers our ability to conduct adequate research on cause, prevention, clinical trials, and other treatment modalities as well as to select those key patients for whom greater efforts toward securing autopsies must be made. We are engaged in establishing an Alzheimers Disease Patient Registry, to determine the data needed to embark on major etiologic and epidemiologic studies. Our studies of Alzheimers disease in families and in forms of social and financial milieu are designed to develop humanitarian and potentially cost-effective approaches.

Psychotropic drug use in relation to psychiatric symptoms in community-living persons with Alzheimer's disease.

We attempted to determine the relationship between psychiatric symptoms and psychotropic drug use in persons with Alzheimers disease based on a multicenter patient registry of 671 community‐living persons diagnosed with the disease by published criteria. Logistic regression was performed to determine which symptoms were associated psychotropic use after controlling for age, sex, and Mini‐Mental Status Examination (MMSE) score. At least one psychotropic drug was reported by 31% of patients, and 66% had at least one psychiatric symptom. Antipsychotics were associated with a lower MMSE score (odds ratio=0.92, 95% confidence interval 0.88‐0.97), emotional lability (OR=4.52, 95% CI 1.69‐11.94), and hallucinations (OR=6.54, 95% CI 2.99‐14.26). Antidepressants were associated with depressive symptoms (OR=5.8, 95% CI 2.61‐13.46), and benzodiazepines with a lower MMSE score (OR=0.93, 95% CI 0.90‐0.97). Community‐living persons with Alzheimers disease are frequently prescribed psychotropic drugs; however, more than 50% of patients with a psychiatric symptom did not report taking one of these agents. This suggests that alternative therapies and no treatment are also prevalent.