Linking Stress and Schizophrenia: A Focus on Prepulse Inhibition

Douma, Tessa N.; Millan, Mark J.; Olivier, Berend; Groenink, Lucianne

doi:10.5772/26944

“…Chronic stress, however, can lead to serious health problems and can affect nearly every system of the human body, as suggested by physical, cognitive, affective and behavioral symptoms. Indeed, in a certain percentage of the general population, chronic stress raises the blood pressure, increases the risk of heart attack and stroke [2], suppresses the immune system [3] and increases the vulnerability to psychiatric disorders such as anxiety, depression or schizophrenia [4,5,6]. …”

Section: Introductionmentioning

confidence: 99%

Insufficient Coping Behavior under Chronic Stress and Vulnerability to Psychiatric Disorders

Möhr

¹

,

Braun

²

,

Bridler

³

et al. 2014

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Background: Epidemiological data indicate that 75% of subjects with major psychiatric disorders have their onset of illness in the age range of 17-24 years. An estimated 35-50% of college and university students drop out prematurely due to insufficient coping skills under chronic stress, while 85% of students receiving a psychiatric diagnosis withdraw from college/university prior to the completion of their education. In this study, we aimed at developing standardized means of identifying students with insufficient coping skills under chronic stress and at risk for mental health problems. Sampling and Methods: A sample of 1,217 college students from 3 different sites in the USA and Switzerland completed 2 self-report questionnaires: the Coping Strategies Inventory (COPE) and the Zurich Health Questionnaire (ZHQ), which assesses ‘regular exercises', ‘consumption behavior', ‘impaired physical health', ‘psychosomatic disturbances' and ‘impaired mental health'. The data were subjected to structure analyses by means of a neural network approach. We found 2 highly stable and reproducible COPE scales that explained the observed interindividual variation in coping behavior sufficiently well and in a socioculturally independent way. The scales reflected basic coping behavior in terms of ‘activity-passivity' and ‘defeatism-resilience', and in the sense of stable, socioculturally independent personality traits. Results: Correlation analyses carried out for external validation revealed a close relationship between high scores on the defeatism scale and impaired physical and mental health. This underlined the role of insufficient coping behavior as a risk factor for physical and mental health problems. Conclusion: The combined COPE and ZHQ instruments appear to constitute powerful screening tools for insufficient coping skills under chronic stress and for risks of mental health problems.

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“…Extensive studies have shown associations between impaired prepulse inhibition and schizophrenia in humans and animals (Braff, Geyer, & Swerdlow, 2001;Douma, Millan, Olivier, & Groenink, 2011;Le Pen, 2002;Ludewig, Geyer, & Vollenweider, 2003;Mcdowd, Filion, Harris, & Braff, 1993;Mena et al, 2016;Parwani et al, 2000). Prepulse inhibition was measured using bursts of white noise as the startle response, and lower intensity white noise as the prepulses.…”

Section: Immune Stimulation Timingmentioning

confidence: 99%

Analysis of gene expression and DNA methylation in a cognitive phenotype model of schizophrenia

Rutherford-Ymker¹

0

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<p>The underpinning hypothesis of this study is that the environmental insults implicated in schizophrenia cause epigenetic changes that trigger deleterious gene expression, resulting in deviations from normal neurodevelopment. The behavioural abnormalities in schizophrenia can be grouped into the three common classes of symptoms: positive, negative, and cognitive. Cognitive symptoms are symptoms that impair cognitive processing and have detrimental effects on individuals with schizophrenia. Maternal immune activation refers to a rat model that stimulates a maternal immune system with an infection or infectious-like stimulus resulting in adverse phenotypes. A cognitive phenotype, maternal immune activation (MIA) model of schizophrenia was employed to use epigenetic markers to discover what deleterious genes drive the cognitive deficits phenotype. Previous work has discerned many changes in gene expression that are implicated in schizophrenia. A hypothesis-driven approach was utilized to determine whether previously studied candidate genes are relevant in the cognitive symptoms of schizophrenia in this cognitive-phenotype model. It was found that prenatal treatment of lipopolysaccharide (LPS) (which is the major outer membrane component of gram-negative bacteria and mimics bacterial infection) on prenatal day 10 and 11 led to changes in mRNA levels in the prefrontal cortex of adolescent rats. Typically, an increase in the amount of transcript in the LPS condition compared to the saline condition, or a greater variability in the amount of transcript between replicates in the LPS condition than the saline condition, was observed. Statistical analysis revealed that these changes did not met statistical significance. To build towards a whole genome DNA methylation analysis, two discrete approaches were used. The first utilized bisulfite modification and investigated changes in candidate genes as a precursor to genome-wide BS-sequencing. DNA methylation was measured across CpG rich regions and an absence of DNA methylation was detected in these regions in both the LPS and saline conditions in the candidate genes. The second approach utilized a long-read sequencing platform to establish the feasibility of a bisulfite conversion-free method for whole-genome DNA methylation approach within our lab. Through the establishment of this method factors that affect the reliability, quality, and accuracy of the final sequencing product were explored. Many of which were in the downstream-from-sequencing, data analysis component of the process. Discoveries were also made regarding how much data would be needed to make direct DNA methylation detection feasible. The data presented here demonstrated that the cognitive-phenotype MIA model had altered gene expression correlating with previously measured behavioural cognitive deficits in the prefrontal cortex in genes that were known to be associated with schizophrenia. To extend this further, a whole genome approach would be needed to discover novel drivers of the phenotype. In the current study, headway was made towards the development and establishment of a whole genome DNA methylation detection method to further this continued aim.</p>

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“…Extensive studies have shown associations between impaired prepulse inhibition and schizophrenia in humans and animals (Braff, Geyer, & Swerdlow, 2001;Douma, Millan, Olivier, & Groenink, 2011;Le Pen, 2002;Ludewig, Geyer, & Vollenweider, 2003;Mcdowd, Filion, Harris, & Braff, 1993;Mena et al, 2016;Parwani et al, 2000). Prepulse inhibition was measured using bursts of white noise as the startle response, and lower intensity white noise as the prepulses.…”

Section: Immune Stimulation Timingmentioning

confidence: 99%

Analysis of gene expression and DNA methylation in a cognitive phenotype model of schizophrenia

Rutherford-Ymker¹

0

View full text Add to dashboard Cite

<p>The underpinning hypothesis of this study is that the environmental insults implicated in schizophrenia cause epigenetic changes that trigger deleterious gene expression, resulting in deviations from normal neurodevelopment. The behavioural abnormalities in schizophrenia can be grouped into the three common classes of symptoms: positive, negative, and cognitive. Cognitive symptoms are symptoms that impair cognitive processing and have detrimental effects on individuals with schizophrenia. Maternal immune activation refers to a rat model that stimulates a maternal immune system with an infection or infectious-like stimulus resulting in adverse phenotypes. A cognitive phenotype, maternal immune activation (MIA) model of schizophrenia was employed to use epigenetic markers to discover what deleterious genes drive the cognitive deficits phenotype. Previous work has discerned many changes in gene expression that are implicated in schizophrenia. A hypothesis-driven approach was utilized to determine whether previously studied candidate genes are relevant in the cognitive symptoms of schizophrenia in this cognitive-phenotype model. It was found that prenatal treatment of lipopolysaccharide (LPS) (which is the major outer membrane component of gram-negative bacteria and mimics bacterial infection) on prenatal day 10 and 11 led to changes in mRNA levels in the prefrontal cortex of adolescent rats. Typically, an increase in the amount of transcript in the LPS condition compared to the saline condition, or a greater variability in the amount of transcript between replicates in the LPS condition than the saline condition, was observed. Statistical analysis revealed that these changes did not met statistical significance. To build towards a whole genome DNA methylation analysis, two discrete approaches were used. The first utilized bisulfite modification and investigated changes in candidate genes as a precursor to genome-wide BS-sequencing. DNA methylation was measured across CpG rich regions and an absence of DNA methylation was detected in these regions in both the LPS and saline conditions in the candidate genes. The second approach utilized a long-read sequencing platform to establish the feasibility of a bisulfite conversion-free method for whole-genome DNA methylation approach within our lab. Through the establishment of this method factors that affect the reliability, quality, and accuracy of the final sequencing product were explored. Many of which were in the downstream-from-sequencing, data analysis component of the process. Discoveries were also made regarding how much data would be needed to make direct DNA methylation detection feasible. The data presented here demonstrated that the cognitive-phenotype MIA model had altered gene expression correlating with previously measured behavioural cognitive deficits in the prefrontal cortex in genes that were known to be associated with schizophrenia. To extend this further, a whole genome approach would be needed to discover novel drivers of the phenotype. In the current study, headway was made towards the development and establishment of a whole genome DNA methylation detection method to further this continued aim.</p>

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Linking Stress and Schizophrenia: A Focus on Prepulse Inhibition

Cited by 5 publications

References 124 publications

Insufficient Coping Behavior under Chronic Stress and Vulnerability to Psychiatric Disorders

Insufficient Coping Behavior under Chronic Stress and Vulnerability to Psychiatric Disorders

Analysis of gene expression and DNA methylation in a cognitive phenotype model of schizophrenia

Analysis of gene expression and DNA methylation in a cognitive phenotype model of schizophrenia

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