Thunderclap headache as the presenting symptom of myocardial infarction

Headache as the presenting symptom of myocardial ischemia has been reported in more than 20 cases. These headaches have been described as of gradual onset, associated with exertion and with EKG changes. We present herein the first case of thunderclap headache occurring at rest as the sole symptom of an acute myocardial infarction.     

Comparison of the Heritability of Schizophrenia and Endophenotypes in the COGS-1 Family Study

Background:

Twin and multiplex family studies have established significant heritability for schizophrenia (SZ), often summarized as 81%. The Consortium on the Genetics of Schizophrenia (COGS-1) family study was designed to deconstruct the genetic architecture of SZ using neurocognitive and neurophysiological endophenotypes, for which heritability estimates ranged from 18% to 50% (mean = 30%). This study assessed the heritability of SZ in these families to determine whether there is a “heritability gap” between the diagnosis and related endophenotypes.

Methods:

Nuclear families (N = 296) with a SZ proband, an unaffected sibling, and both parents (n = 1366 subjects; mean family size = 4.6) underwent comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives of interviewed subjects (N = 3304 subjects; mean family size = 11.2). Heritability estimates of psychotic disorders were computed for both nuclear and extended families.

Results:

The heritability of SZ was 31% and 44% for nuclear and extended families. The inclusion of bipolar disorder increased the heritability to 37% for the nuclear families. When major depression was added, heritability estimates dropped to 34% and 20% for nuclear and extended families, respectively.

Conclusions:

Endophenotypes and psychotic disorders exhibit comparable levels of heritability in the COGS-1 family sample. The ascertainment of families with discordant sibpairs to increase endophenotypic contrast may underestimate diagnostic heritability relative to other studies. However, population-based studies also report significantly lower heritability estimates for SZ. Collectively, these findings support the importance of endophenotype-based strategies and the dimensional view of psychosis.Key words: schizophrenia, psychosis, endophenotypes, cognition, biomarkers, heritability     

Bioenergetic medicine

Here we discuss a specific therapeutic strategy we call ‘bioenergetic medicine’. Bioenergetic medicine refers to the manipulation of bioenergetic fluxes to positively affect health. Bioenergetic medicine approaches rely heavily on the law of mass action, and impact systems that monitor and respond to the manipulated flux. Since classically defined energy metabolism pathways intersect and intertwine, targeting one flux also tends to change other fluxes, which complicates treatment design. Such indirect effects, fortunately, are to some extent predictable, and from a therapeutic perspective may also be desirable. Bioenergetic medicine-based interventions already exist for some diseases, and because bioenergetic medicine interventions are presently feasible, new approaches to treat certain conditions, including some neurodegenerative conditions and cancers, are beginning to transition from the laboratory to the clinic.

Linked Articles

This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8     

Paternal age of schizophrenia probands and endophenotypic differences from unaffected siblings

We evaluated the discrepancy of endophenotypic performance between probands with schizophrenia and unaffected siblings by paternal age at proband birth, a possible marker for de novo mutations. Pairs of schizophrenia probands and unaffected siblings (N=220 pairs) were evaluated on 11 neuropsychological or neurophysiological endophenotypes previously identified as heritable. For each endophenotype, the sibling-minus-proband differences were transformed to standardized scores. Then for each pair, the average discrepancy was calculated from its standardized scores. We tested the hypothesis that the discrepancy is associated with paternal age, controlling for the number of endophenotypes shared between proband and his or her sibling, and proband age, which were both associated with paternal age. The non-significant association between the discrepancy and paternal age was in the opposite direction from the hypothesis. Of the 11 endophenotypes only sensori-motor dexterity was significant, but in the opposite direction. Eight other endophenotypes were also in the opposite direction, but not significant. The results did not support the hypothesized association of increased differences between sibling/proband pairs with greater paternal age. A possible explanation is that the identification of heritable endophenotypes was based on samples for which schizophrenia was attributable to inherited rather than de novo/non-inherited causes.     

Cancer mortality in relatives of women with breast cancer: The OPCS study

Mortality from cancer and other causes in male and female first-degree relatives of women with breast cancer diagnosed before age 60 has been examined in a large population-based cohort study, providing estimates of familial risks free from ascertainment or recall bias. Relatives of 3,295 patients with breast cancer diagnosed in the UK between 1954 and 1981 were identified through a register of households established in 1939. The 11,678 first-degree relatives thus identified were followed up through national records until the end of 1992. Over this period 5,421 deaths (including 1,527 cancer deaths) occurred in these relatives. Mortality from breast cancer was significantly raised in first-degree relatives (SMR 187, 248 deaths), and there was also significant excess mortality from cancers of the larynx (SMR 177, 17 deaths), endometrium (SMR 166, 29 deaths) and unspecified neoplasms (SMR 153, 70 deaths). The SMR for ovarian cancer was 130, based on 58 deaths (p = 0.06). There was no marked excess for other sites or for non-neoplastic causes of death, but there was a significant deficit in mortality from cervical cancer (SMR 63, 18 deaths). The SMR for breast cancer increased significantly with decreasing age of the relative. After allowing for age, sisters of cases had a slightly (though non-significantly) higher risk than mothers (ratio of SMRs 1.22). These results, together with penetrance estimates from linked families, suggest that approximately one woman in 800 carries BRCAI, the susceptibility gene on chromosome 17q, and that this gene causes about 1% of all breast cancers. © 1996 Wiley-Liss, Inc.     

A population-based study of cancer risk in twins: Relationships to birth order and sexes of the twin pair

One thousand and sixty-three twins with cancer whose co-twin was born alive were identified among patients born since September 1939 with cancers incident in England and Wales during 1971–1984 at childhood and young adult ages. Site-specific risks of cancer were analysed in relation to birth order within the twinship and sexes of the twin pair, using adjusted national birth data to give control distributions of these variables. Risk of leukaemia was increased in first-born twins, risk of testicular cancer was increased in second-born twins with female co-twins but decreased in second-born twins with male co-twins and lung cancer risk was increased in first-born twins with same-sex co-twins. Cutaneous melanoma risk was increased in persons with opposite-sex co-twins, nervous system cancer risk was increased in females with opposite-sex co-twins and Hodgkin's disease risk was increased in persons with same-sex co-twins. For most of the findings, no previous comparable analyses are available, so interpretation of the results must be provisional until the analyses can be repeated on other data. The result for leukaemia would accord with previous suggestions that leukaemia may be of prenatal origin and may sometimes lead to intrauterine death. The Hodgkin's disease result would fit with theories of an infectious aetiology, and this view is strengthened by reanalysis of previous data on paralytic poliomyelitis in twins, which show a pattern similar to that for the Hodgkin's disease patients. Cancer risk in relation to birth order and sex of twins can give novel, objective data relating to prenatal and infectious disease aetiology of cancers. © 1996 Wiley-Liss, Inc.     

Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes

AIMS/HYPOTHESIS: Although ischaemic heart disease is the predominant cause of mortality in older people with diabetes, age-specific mortality rates have not been published for patients with Type 1 diabetes. The Diabetes UK cohort, essentially one of patients with Type 1 diabetes, now has sufficient follow-up to report all heart disease, and specifically ischaemic heart disease, mortality rates by age. METHODS: A cohort of 23,751 patients with insulin-treated diabetes, diagnosed under the age of 30 years and from throughout the United Kingdom, was identified during the period 1972 to 1993 and followed for mortality until December 2000. Age- and sex-specific heart disease mortality rates and standardised mortality ratios were calculated. RESULTS: There were 1437 deaths during the follow-up, 536 from cardiovascular disease, and of those, 369 from ischaemic heart disease. At all ages the ischaemic heart disease mortality rates in the cohort were higher than in the general population. Mortality rates within the cohort were similar for men and women under the age of 40. The standardised mortality ratios were higher in women than men at all ages, and in women were 44.8 (95%CI 20.5-85.0) at ages 20-29 and 41.6 (26.7-61.9) at ages 30-39. CONCLUSIONS/INTERPRETATION: The risk of mortality from ischaemic heart disease is exceptionally high in young adult women with Type 1 diabetes, with rates similar to those in men with Type 1 diabetes under the age of 40. These observations emphasise the need to identify and treat coronary risk factors in these young patients.