Cardiovascular fitness in late adolescent males and later risk of serious non-affective mental disorders: a prospective, population-based study.

BACKGROUND: Cardiovascular fitness in late adolescence is associated with future risk of depression. Relationships with other mental disorders need elucidation. This study investigated whether fitness in late adolescence is associated with future risk of serious non-affective mental disorders. Further, we examined how having an affected brother might impact the relationship. METHOD: Prospective, population-based cohort study of 1 109 786 Swedish male conscripts with no history of mental illness, who underwent conscription examinations at age 18 between 1968 and 2005. Cardiovascular fitness was objectively measured at conscription using a bicycle ergometer test. During the follow-up (3-42 years), incident cases of serious non-affective mental disorders (schizophrenia and schizophrenia-like disorders, other psychotic disorders and neurotic, stress-related and somatoform disorders) were identified through the Swedish National Hospital Discharge Register. Cox proportional hazards models were used to assess the influence of cardiovascular fitness at conscription and risk of serious non-affective mental disorders later in life. RESULTS: Low fitness was associated with increased risk for schizophrenia and schizophrenia-like disorders [hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.29-1.61], other psychotic disorders (HR 1.41, 95% CI 1.27-1.56), and neurotic or stress-related and somatoform disorders (HR 1.45, 95% CI 1.37-1.54). Relationships persisted in models that included illness in brothers. CONCLUSIONS: Lower fitness in late adolescent males is associated with increased risk of serious non-affective mental disorders in adulthood.

Cardiovascular fitness in early adulthood and future suicidal behaviour in men followed for up to 42 years.

BACKGROUND: Cardiovascular fitness influences many aspects of brain function. However, the relationship between cardiovascular fitness and suicidal behaviour is unknown. Therefore, we aimed to determine whether cardiovascular fitness at age 18 years is associated with future risk of suicide attempt/death. METHOD: We performed a population-based Swedish longitudinal cohort study of male conscripts with no previous or ongoing mental illness (n = 1,136,527). The conscription examination, which took place during 1968-2005, included the cycle ergonometric test and tests of cognitive performance. Future risk of suicide attempt/death over a 5- to 42-year follow-up period was calculated with Cox proportional hazards models controlling for several confounders including familial factors. RESULTS: At least one suicide attempt was recorded for 12,563 men. Death by suicide without a prior attempt was recorded in 4814 additional individuals. In fully adjusted models low cardiovascular fitness was associated with increased risk for future attempt/death by suicide [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.64-1.94]. The HR changed only marginally after exclusion of persons who received in-patient care for depression (HR 1.76, 95% CI 1.61-1.94). Poor performance on both the cardiovascular fitness and cognitive tests was associated with a fivefold increased risk of suicide attempt or suicide death (HR 5.46, 95% CI 4.78-6.24). CONCLUSIONS: Lower cardiovascular fitness at age 18 years was, after adjustment for a number of potential confounders, associated with an increased risk of attempt/death by suicide in adulthood. It remains to be clarified whether interventions designed to improve fitness in teens can influence the risk of suicidal behaviour later in life.

Fish consumption and school grades in Swedish adolescents: a study of the large general population.

AIM: To study the associations between fish intake and academic achievement as cognitive parameter among Swedish adolescents. METHODS: In 2000, a questionnaire including respiratory items, socioeconomic conditions and dietary information was mailed to all schoolchildren (n = 18 158), aged 15 and living in Västra Götaland region of Sweden. The questionnaire was returned by 10 837 subjects. One year later, the total school grades for each subject who had completed the questionnaire and who included their full personal identification number were obtained from the national registers. Multiple linear regression models were applied to evaluate the association between fish intake and academic grades among 9448 schoolchildren, while adjusting for potential confounders, e.g. parents' education. RESULTS: Grades were higher in subjects with fish consumption once a week compared with subjects with fish consumption of less than once a week (reference group) [increment in estimate 14.5, 95% confidence interval (CI) 11.8-17.1]. Grades were even higher in subjects with fish consumption of more than once a week compared with the reference group (increment in estimate 19.9, 95% CI 16.5-23.3). In the model stratified for parents' education, there were still higher grades among subjects with frequent fish intake in all educational strata (p < 0.01). CONCLUSION: Frequent fish intake among schoolchildren may provide benefits in terms of academic achievement.

Selective introduction of antisense oligonucleotides into single adult CNS progenitor cells using electroporation demonstrates the requirement of STAT3 activation for CNTF-induced gliogenesis.

We have developed a novel method in which antisense DNA is selectively electroporated into individual adult neural progenitor cells. By electroporation of antisense oligonucleotides against signal transducer and activator of transcription 3 (STAT3) we demonstrate that ciliary neurotrophic factor (CNTF) is an instructive signal for astroglial type 2 cell fate specifically mediated via activation of STAT3. Activation of the mitogen-activated protein kinase (MAPK) signaling pathway induced only a transient increase in glial fibrillary acidic protein (GFAP) expression, and inhibition of this signaling pathway did not block the induction by CNTF of glial differentiation in progenitor cells. In addition we show that microelectroporation is a new powerful method for introducing antisense agents into single cells in complex cellular networks.

Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus.

In several species, including humans, the dentate granule cell layer (GCL) of the hippocampus exhibits neurogenesis throughout adult life. The ability to regulate adult neurogenesis pharmacologically may be of therapeutic value as a mechanism for replacing lost neurons. Insulin-like growth factor-I (IGF-I) is a growth-promoting peptide hormone that has been shown to have neurotrophic properties. The relationship between IGF-I and adult hippocampal neurogenesis is to date unknown. The aim of this study was to investigate the effect of the peripheral administration of IGF-I on cellular proliferation in the dentate subgranular proliferative zone, which contains neuronal progenitor cells, and on the subsequent migration and differentiation of progenitor cells within the GCL. Using bromodeoxyuridine (BrdU) labeling, we found a significant increase of BrdU-immunoreactive progenitors in the GCL after 6 d of peripheral IGF-I administration. To determine the cell fate in progenitor progeny, we characterized the colocalization of BrdU-immunolabeled cells with cell-specific markers. In animals treated with IGF-I for 20 d, BrdU-positive cells increased significantly. Furthermore, the fraction of newly generated neurons in the GCL increased, as evaluated by the neuronal markers Calbindin D(28K), microtubule-associated protein-2, and NeuN. There was no difference in the fraction of newly generated astrocytes. Thus, our results show that peripheral infusion of IGF-I increases progenitor cell proliferation and selectively induces neurogenesis in the progeny of adult neural progenitor cells. This corresponds to a 78 +/- 17% (p < 0.001) increase in the number of new neurons in IGF-I-treated animals compared with controls.

Altering the biochemical state of individual cultured cells and organelles with ultramicroelectrodes.

We describe an efficient technique for the selective chemical and biological manipulation of the contents of individual cells. This technique is based on the electric-field-induced permeabilization (electroporation) in biological membranes using a low-voltage pulse generator and microelectrodes. A spatially highly focused electric field allows introduction of polar cell-impermeant solutes such as fluorescent dyes, fluorogenic reagents, and DNA into single cells. The high spatial resolution of the technique allows for design of, for example, cellular network constructions in which cells in close contact with each other can be made to possess different biochemical, biophysical, and morphological properties. Fluorescein, and fluo-3 (a calcium-sensitive fluorophore), are electroporated into the soma of cultured single progenitor cells derived from adult rat hippocampus. Fluo-3 also is introduced into individual submicrometer diameter processes of thapsigargin-treated progenitor cells, and a plasmid vector cDNA construct (pRAY 1), expressing the green fluorescent protein, is electroporated into cultured single COS 7 cells. At high electric field strengths, observations of dye-transfer into organelles are proposed.