scholarly journals Social defeat: Risk factor for schizophrenia?

2005 ◽  
Vol 187 (2) ◽  
pp. 101-102 ◽  
Author(s):  
Jean-Paul Selten ◽  
Elizabeth Cantor-Graae
Keyword(s):  
Risk Factor ◽  
Social Defeat ◽  
Dopamine System ◽  
Mesolimbic Dopamine System ◽  
Baseline Activity ◽  
Increased Risk ◽  
The Social ◽  
System Data ◽  
Long Term Experience

SummaryThe hypothesis that chronic and long-term experience of ‘social defeat’ may increase the risk for schizophrenia is proposed. This increased risk may result from sensitisation of the mesolimbic dopamine system and/or increased baseline activity of this system. Data supporting the social defeat hypothesis are presented.

scholarly journals Stress vulnerability promotes an alcohol prone phenotype in a preclinical model of sustained depression

2018 ◽  
Author(s):  
Danai Riga ◽  
Leanne JM Schmitz ◽  
Yvar van Mourik ◽  
Witte JG Hoogendijk ◽  
Taco J De Vries ◽  
...  
Keyword(s):  
Social Defeat ◽  
Preclinical Model ◽  
Self Administration ◽  
Depression Vulnerability ◽  
Stress Vulnerability ◽  
The Social ◽  
Depression Proneness ◽  
Male Wistar Rats ◽  
Alcohol Seeking

AbstractMajor depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat-induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (5 episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction and cue-induced reinstatement of alcohol-seeking were examined in the two subpopulations. SDPS-prone animals showed increased alcohol SA, excessive motivation to acquire alcohol, persistent alcohol-seeking despite alcohol unavailability, extinction resistance and increased cue-induced relapse; the latter could be blocked by the α2 adrenoreceptor agonist guanfacine. In SDPS-resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol-seeking and -taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD-like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long-term.

Abstract 15934: Higher Midlife Serum Levels of Kidney-injury Molecule-1 (KIM-1) are Associated With Incident Fatal CHD Over Very Long-term Follow-up Among Men

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Rachel H Mackey ◽  
Greg G Grandits ◽  
Lewis H Kuller ◽  
Joel Estis ◽  
John A Todd ◽  
...  
Keyword(s):  
Risk Factor ◽  
Limit Of Detection ◽  
Kidney Injury ◽  
Multiple Risk Factor ◽  
Serum Samples ◽  
Increased Risk ◽  
Long Term Follow Up ◽  
Kidney Injury Molecule 1

Introduction: Higher levels of kidney-injury molecule-1 (KIM-1) measured in urine are associated with presence and progression of acute renal disease. A recent study reported similar results for KIM-1 measured in blood. Hypothesis: We hypothesized that KIM-1 measured in stored serum from middle-aged men who participated in the Multiple Risk Factor Intervention Trial (MRFIT) would differentiate very long-term risk of fatal CHD vs. survival to a mean age of 80 over approximately 30 year follow-up. Methods: We conducted a nested case-control study within MRFIT, which in 1973-76 randomized 12,866 high risk but CVD free men ages 35-57 to risk factor intervention vs. usual care. Serum samples were collected at baseline and stored for future use. The trial concluded in 1982 but long-term mortality follow-up was ascertained through 2005 using the National Death Index. From MRFIT participants with stored serum from baseline, we sampled 100 men who died of CHD (mean age 47.3 at baseline and 73.9 at death), and 100 men who survived to 2005 (mean age =48.4 at baseline and 80.1 in 2005.) KIM-1 was assayed from stored serum samples using high sensitivity single-molecule counting technology (Erenna ® Immunoassay System, Singulex), with limit of detection (LoD)=0.5 pg/ml, and lower limit of quantification (LLoQ)=2.0 pg/ml. Results were compared between cases and controls using Wilcoxon rank tests and logistic regression. Results: Inter-assay %CVs were 8%. Median KIM-1 was higher for smokers vs. non-smokers and for men with vs. without hypertension, but was not associated with high cholesterol. KIM-1 was significantly higher in cases (183 pg/ml (IQR: 137-239) versus controls, (161 pg/ml (IQR:109-212), p=0.03; OR (95%CI)for Q4 versus Q1 was 2.26 (1.02 - 5.02) Adjusted for age and smoking the OR(95%CI) of fatal CHD for Q4 vs. Q1 was 2.34 (1.02- 5.37), and further adjusted for diastolic BP and serum cholesterol at baseline, was 2.0 (95% CI: 0.8-4.7). Conclusions: Higher serum KIM-1 levels at midlife were associated with a ∼2-fold increased risk of fatal CHD vs. survival over ∼30 years of follow-up. This is the first report of a longitudinal association of circulating KIM-1 levels with fatal CHD in long-term follow-up.

Air Pollution as Risk Factor for Mental Disorders: In Search for a Possible Link with Alzheimer’s Disease and Schizophrenia

2021 ◽  
Author(s):  
Luigi Attademo ◽  
Francesco Bernardini
Keyword(s):  
Mental Health ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Risk Factor ◽  
Air Pollutants ◽  
Epidemiological Studies ◽  
Increased Risk ◽  
The Central Nervous System

As a global problem that has increasingly been causing worldwide concern, air pollution poses a significant and serious environmental risk to health. Risks of cardiovascular and respiratory diseases, as well as various types of cancer, have been consistently associated with the exposure to air pollutants. More recently, various studies have also shown that the central nervous system is also attacked by air pollution. Air pollution appears to be strongly associated with a higher risk of cognitive defects, neurodevelopmental (e.g., schizophrenia) and neurodegenerative (e.g., Alzheimer’s disease) disorders. Subjects with schizophrenia, as well as subjects with Alzheimer’s disease, experience a variety of neuropsychological deficits and cognitive impairments. This determines an adverse effect on social and professional functioning, and it contributes to the long-term disease burden. However, no final conclusions have been drawn on the matter of the direct relationship between schizophrenia and Alzheimer’s disease. In recent years, the topic of urbanicity and mental health has become increasingly important. Urban exposure to environmental toxins and pollution is currently described as a reliable risk factor for schizophrenia and other psychoses, and it has been demonstrated more and more how exposure to air pollutants is associated with increased risk of dementia. Pathways by which air pollution can target and damage the brain, leading to an increased risk for developing schizophrenia and Alzheimer’s disease, are multiple and complex. Results from epidemiological studies suggest potential associations, but are still insufficient to confirm causality. Further studies are needed in order to verify this hypothesis. And if confirmed, the clinical implications could be of substantial relevance for both public and mental health.

scholarly journals Endocrine and Metabolic Diseases Among Colorectal Cancer Survivors in a Population-Based Cohort

2019 ◽  
Vol 112 (1) ◽  
pp. 78-86
Author(s):  
Makenzie L Hawkins ◽  
Brenna E Blackburn ◽  
Kerry Rowe ◽  
John Snyder ◽  
Vikrant G Deshmukh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factor ◽  
General Population ◽  
Metabolic Diseases ◽  
The United States ◽  
Population Cohort ◽  
Increased Risk ◽  
General Population Cohort ◽  
Time Periods

Abstract Background There are an estimated 1.4 million colorectal cancer (CRC) survivors in the United States. Research on endocrine and metabolic diseases over the long term in CRC survivors is limited. Obesity is a risk factor for CRC; thus it is of interest to investigate diseases that may share this risk factor, such as diabetes, for long-term health outcomes among CRC survivors. Methods A total of 7114 CRC patients were identified from the Utah Population Database and matched to a general population cohort of 25 979 individuals on birth year, sex, and birth state. Disease diagnoses (assessed over three time periods of 1–5 years, 5–10 years, and >10 years) were identified using electronic medical records and statewide ambulatory and inpatient discharge data. Cox proportional hazard models were used to estimate the risk of endocrine and metabolic disease. Results Across all three time periods, risks for endocrine and metabolic diseases were statistically significantly greater for CRC survivors compared with the general population cohort. At 1–5 years postdiagnosis, CRC survivors’ risk for diabetes mellitus with complications was statistically significantly elevated (hazard ratio [HR] = 1.36, 99% confidence interval [CI] = 1.09 to 1.70). CRC survivors also experienced a 40% increased risk of obesity at 1–5 years postcancer diagnosis (HR= 1.40, 99% CI= 1.66 to 2.18) and a 50% increased risk at 5–10 years postdiagnosis (HR = 1.50, 99% CI= 1.16 to 1.95). Conclusions Endocrine and metabolic diseases were statistically significantly higher in CRC survivors throughout the follow-up periods of 1–5 years, 5–10 years, and more than 10 years postdiagnosis. As the number of CRC survivors increases, understanding the long-term trajectory is critical for improved survivorship care.

scholarly journals Synaptic plasticity in the mesolimbic dopamine system

2003 ◽  
Vol 358 (1432) ◽  
pp. 815-819 ◽  
Author(s):  
Mark J. Thomas ◽  
Robert C. Malenka
Keyword(s):  
Synaptic Plasticity ◽  
Drugs Of Abuse ◽  
Neural Circuit ◽  
Long Term Potentiation ◽  
Brain Regions ◽  
Mesolimbic Dopamine ◽  
Dopamine System ◽  
Mesolimbic Dopamine System

Long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical mechanisms that contribute to the neural circuit modifications that mediate all forms of experience-dependent plasticity. It has, however, been difficult to demonstrate directly that experience causes long-lasting changes in synaptic strength and that these mediate changes in behaviour. To address these potential functional roles of LTP and LTD, we have taken advantage of the powerful in vivo effects of drugs of abuse that exert their behavioural effects in large part by acting in the nucleus accumbens (NAc) and ventral tegmental area (VTA); the two major components of the mesolimbic dopamine system. Our studies suggest that in vivo drugs of abuse such as cocaine cause long-lasting changes at excitatory synapses in the NAc and VTA owing to activation of the mechanisms that underlie LTP and LTD in these structures. Thus, administration of drugs of abuse provides a distinctive model for further investigating the mechanisms and functions of synaptic plasticity in brain regions that play important roles in the control of motivated behaviour, and one with considerable practical implications.

scholarly journals DETERMINATION OF PERSONAL SIGNIFICANCE AND CONTENT OF VALUES

2020 ◽  
Vol 8 (4) ◽  
pp. 445-455
Author(s):  
A.M. Lesin ◽  
Keyword(s):  
Semantic Content ◽  
Test Methods ◽  
Self Reflection ◽  
Personal Significance ◽  
Scientific Schools ◽  
The Social ◽  
Psychological Structure ◽  
Long Term Experience

This article poses a problem associated with the difficulties of studying and identifying the motivational potential of the value sphere, as well as the discrepancy between the content of the same values in different people or in the same, but at different times. The article describes the results of a theoretical search associated with different approaches to understanding and studying values in different sciences and scientific schools. Also, the main variants of classifications of values and the ways of their formation in the direction of the personality in the process of ontogenesis are determined. The difficulties associated with the study of values with the help of tests, taking into account the social desirability and expectation of answers or the lack of self-reflection ability of the respondents, are described. The modern non-test methods and approaches to the study of the value sphere are analyzed, which make it possible to identify personally significant values and the level of their motivational potential. A method is proposed for determining the personal significance of values , as opposed to their reflec tive representation, using the magnitude of the conflict between the significance and the implementation of values. The long-term experience of using this method among various respondents is described. Variants of the destructive level of personal significance of some values are demonstrated. The possibilities and examples of the study of values in relation to the psychological structure of initiative are shown. The possibilities of content analysis in determining the content are illustrated, examples of different semantic content of the same values are given. It is concluded that, in addition to classical test methods, it is necessary to apply such methods as well, which will help to distinguish between value ideas and personal values proper, as well as to determine their content.

Rheumatoid Arthritis is a Risk Factor for Refracture in Patients with Fragility Fractures

2021 ◽  
Author(s):  
Hotaka Ishizu ◽  
Hirokazu Shimizu ◽  
Tomohiro Shimizu ◽  
Taku Ebata ◽  
Yuki Ogawa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factor ◽  
Propensity Score ◽  
Primary Outcome ◽  
Fragility Fractures ◽  
Increased Risk ◽  
Substantial Risk ◽  
Multivariable Analyses

Abstract Objectives To determine whether patients with rheumatoid arthritis (RA) who have had fragility fractures are at an increased risk of refractures. Methods Patients with fragility fractures who were treated surgically at ten hospitals from 2008 to 2017 and who underwent follow-up for more than 24 months were either categorized into a group comprising patients with RA or a group comprising patients without RA (controls). The groups were matched 1:1 by propensity score matching. Accordingly, 240 matched participants were included in this study. The primary outcome was the refracture rate in patients with RA as compared to in the controls. Multivariable analyses were also conducted on patients with RA to evaluate the odds ratios (ORs) for the refracture rates. Results Patients with RA were significantly associated with increased rates of refractures during the first 24 months (OR: 2.714, 95% confidence interval [95% CI]: 1.015–7.255; P = 0.040). Multivariable analyses revealed a significant association between increased refracture rates and long-term RA (OR: 6.308, 95% CI: 1.195–33.292; P=0.030). Conclusions Patients with RA who have experienced fragility fractures are at an increased risk of refractures. Long-term RA is a substantial risk factor for refractures.

scholarly journals Gender-Specific Roles for the Melanocortin-3 Receptor in the Regulation of the Mesolimbic Dopamine System in Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (5) ◽  
pp. 1718-1727 ◽  
Author(s):  
Rachel N. Lippert ◽  
Kate L.J. Ellacott ◽  
Roger D. Cone
Keyword(s):  
Dopaminergic Neurons ◽  
Energy Homeostasis ◽  
Fluorescent Protein ◽  
Sexually Dimorphic ◽  
Mesolimbic Dopamine ◽  
Dopamine System ◽  
Mesolimbic Dopamine System ◽  
System Data ◽  
Green Fluorescent ◽  
Gender Specific

The melanocortin-3 receptor (MC3R) and MC4R are known to play critical roles in energy homeostasis. However, the physiological functions of the MC3R remain poorly understood. Earlier reports indicated that the ventral tegmental area (VTA) is one of the highest sites of MC3R expression, and we sought to determine the function of the receptor in this brain region. A MC3R-green-fluorescent protein transgenic mouse and a MC3R knockout mouse strain were used to characterize the neurochemical identity of the MC3R neurons in the VTA and to determine the effects of global MC3R deletion on VTA dopamine (DA) homeostasis. We demonstrate that the MC3R, but not MC4R, is expressed in up to a third of dopaminergic neurons of the VTA. Global deletion of the MC3R increases total dopamine by 42% in the VTA and decreases sucrose intake and preference in female but not male mice. Ovariectomy restores dopamine levels to normal, but aberrant decreased VTA dopamine levels are also observed in prepubertal female mice. Because arcuate Agouti-related peptide/neuropeptide Y neurons are known to innervate and regulate VTA signaling, the MC3R in dopaminergic neurons provides a specific input for communication of nutritional state within the mesolimbic dopamine system. Data provided here suggest that this input may be highly sexually dimorphic, functioning as a specific circuit regulating effects of estrogen on VTA dopamine levels and on sucrose preference. Overall, this data support a sexually dimorphic function of MC3R in regulation of the mesolimbic dopaminergic system and reward.

scholarly journals Hypothesis: social defeat is a risk factor for schizophrenia?

2007 ◽  
Vol 191 (S51) ◽  
pp. s9-s12 ◽  
Author(s):  
Jean-Paul Selten ◽  
Elizabeth Cantor-Graae
Keyword(s):  
Social Factors ◽  
Social Defeat ◽  
Hearing Impairments ◽  
Middle Income ◽  
Mesolimbic Dopamine System ◽  
Middle Income Countries ◽  
Baseline Activity ◽  
History Of ◽  
Low Iq ◽  
Neuroreceptor Imaging

SummaryThe increased schizophrenia risks for residents of cities with high levels of competition and for members of disadvantaged groups (for example migrants from low- and middle-income countries, people with low IQ, hearing impairments or a history of abuse) suggest that social factors are important for aetiology. Dopaminergic dysfunctioning is a key mechanism in pathogenesis. This editorial is a selective literature review to delineate a mechanism whereby social factors can disturb dopamine function in the brain. Experiments with rodents have shown that social defeat leads to dopaminergic hyperactivity and to behavioural sensitisation, whereby the animal displays an enhanced behavioural and dopamine response to dopamine agonists. Neuroreceptor imaging studies have demonstrated the same phenomena in patients with schizophrenia who had never received antipsychotics. In humans, the chronic experience of social defeat may lead to sensitisation (and/or increased baseline activity) of the mesolimbic dopamine system and thereby increase the risk for schizophrenia

Abstract 11875: Risk of Malignant Cancer Among Women With New-onset Atrial Fibrillation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
David Conen ◽  
Jorge A Wong ◽  
Roopinder K Sandhu ◽  
Nancy R Cook ◽  
I-Min Lee ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Risk Factor ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Health Study ◽  
Incident Cancer ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
New Onset

Introduction: A substantial proportion of patients with atrial fibrillation (AF) die of non-cardiovascular causes, and recent studies suggest a link between AF and cancer. However, this association has not been evaluated in long-term prospective studies. Methods: A total of 34691 women ≥45 years and free of AF, cardiovascular disease and cancer at baseline were prospectively followed for incident AF and malignant cancer within the Women’s Health Study. All incident AF and cancer events were validated by medical record review. Cox proportional-hazards models using time-updated covariates were constructed to assess the relationship of new-onset AF with incident cancer and to adjust for potential confounders. We then assessed the risk of incident AF among women with cancer using a similar modelling approach. Results: Mean age at baseline was 55±7 years. During 19.1 years of follow-up, we observed 1467 (4.2%) AF and 5130 (14.8%) cancer events. AF was a significant risk factor for incident cancer in age-adjusted (hazard ratio (HR) 1.58, 95% confidence interval (CI), 1.34, 1.87, p<0.0001) and multivariable adjusted (HR 1.49, 95% CI, 1.26, 1.77, p<0.0001) models, and was increased among women with paroxysmal (HR 1.35, 95% CI 1.09, 1.67, p=0.005) and non-paroxysmal AF (HR 1.61, 95% CI 1.23, 2.09, p=0.0004). The risk of cancer was highest in the first 3 months after new-onset AF (HR 3.53, 95% CI 2.05, 6.08, p<0.0001) but remained significant beyond 1 year (adjusted HR 1.44, 95% CI 1.19, 1.73, p=0.0001). New-onset AF was also associated with an increased risk of cancer mortality (adjusted HR 1.37, 95% CI 1.01, 1.85, p=0.04). In contrast, women with new-onset cancer had an increased risk of incident AF within 3 months (HR 4.61, 95% CI 2.81, 7.54, p<0.0001) but not beyond 1 year (HR 1.17, 95% CI 0.97, 1.41, p=0.11). Conclusions: In this large cohort of initially healthy women, new-onset AF was a significant risk factor for the short and long term diagnosis of incident cancer. In contrast, cancer was not associated with an increased AF risk over the long term. Our results may suggest that AF could be an early sign of occult cancer or an underlying systemic process conferring an increased cancer risk.

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