The Relationship Between Advanced Paternal Age and Clinical Indicators Among Individuals at Clinical High Risk for Psychosis Open Access

Ryan, Arthur Thomas (2016)

Permanent URL: https://etd.library.emory.edu/concern/etds/t148fh17x?locale=en%255D
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Abstract

Since the middle of the twentieth century, researchers have demonstrated that children born to fathers of advanced age are at increased risk for a variety of health conditions, including psychotic disorders such as schizophrenia. Modern research has shown that this effect may be due to accumulating de novo mutations in the germ line sperm cells of older men. During the last twenty years, researchers have begun to investigate the pre-morbid period before the development of psychotic illnesses. Much of this research has focused on individuals determined to be at increased risk of developing a psychotic illness on the basis of clinical signs and symptoms, i.e., at clinical high risk (CHR) for psychosis. This dissertation seeks to combine these two lines of research. The relationship between paternal and maternal age with attenuated positive symptoms, negative symptoms, social functioning, and family history of psychotic illness was examined within a sample of CHR individuals. No significant relationship between paternal age and these variables was found. Maternal age was shown to have a mixed relationship with positive symptoms, in that increased maternal age predicted the presence of attenuated positive symptoms, but was inversely correlated with their severity. The null results for paternal age are interpreted in the context of the established findings linking paternal age and offspring risk for schizophrenia. Ideas for future studies to further elucidate the relationship between parental ages and psychotic illnesses are discussed.

Table of Contents

Background Literature Review 1

The Clinical High Risk Syndrome for Psychotic Illness 1

Advanced Paternal Age and Offspring Outcomes 4

Underpinnings of Link Between Father's Age and Offspring Outcomes 9

Background Summary and Hypotheses 22

Method 23

Participants 23

Symptom and Functioning Measures. 23

Familial Measures. 25

Procedures 27

Analyses and Results 28

Hypothesis One Analysis Plan 28

Hypothesis One Results 34

Hypothesis One Summary and Conclusions 39

Hypothesis Two Analysis Plan 41

Hypothesis Two Results 45

Hypothesis Two Summary and Conclusions 46

Hypothesis Three Analysis Plan 46

Hypothesis Three Results 47

Hypothesis Three Summary and Conclusions 48

Hypothesis Four Analysis Plan 48

Hypothesis Four Results 51

Hypothesis Four Summary and Conclusions 53

Further Supplemental Analyses 53

Discussion 58

Findings Related to Participant's Age and Mother's Age 59

Findings Related to Father's Age 63

Limitations and Future Directions 67

Conclusion 69

References 70

Table 1 Key Psychosis Related Terms 85

Table 2 Parent's Education Rating Values 87

Table 3 Characteristics of CHR Individuals by Positive Symptom Score 88

Table 4 Hypothesis One Summary of Correlation Coefficients Between Independent Variables / Covariates and Positive Symptom Score 89

Table 5 Hypothesis One Pair-wise Vuong Closeness Tests Comparing Regression Models 90

Table 6 Hypothesis One Zero Inflated Poisson Regression Predictors of Positive Symptom Score 91

Table 7 Hypothesis One Results of Hierarchical Analysis, Zero-Inflated Poisson Regression, Significance of Adding Father's Age 92

Table 8 Hypothesis One Results of Hierarchical Analysis, Zero-Inflated Poisson Regression, Significance of Adding Mother's Age 93

Table 9 Hypothesis One Ordinary Least Squares Regression Predicting Positive Symptom Scores 94

Table 10 Hypothesis Two Zero-Order Correlations Between Predictors / Potential Covariates and Negative Symptom Scores 95

Table 11 Hypothesis Two Ordinary Least Squares Regression Predicting Negative Symptom Score 96

Table 12 Hypothesis Two Follow-up Ordinary Least Squares Regression Predicting Negative Symptom Score with Hypothesis One Covariates 97

Table 13 Hypothesis Two Follow-up Negative Binomial Regression Predicting Negative Symptom Score 98

Table 14 Hypothesis Three Zero-Order Correlations Between Predictors / Potential Covariates and Social Functioning Scores 99

Table 15 Hypothesis Three Ordinary Least Squares Regression Predicting Social Functioning Score 100

Table 16 Hypothesis Three Follow-up Ordinary Least Squares Regression Predicting Social Functioning Scores with Hypothesis One Covariates 101

Table 17 Hypothesis Four Family History of Psychosis Group Differences on Potential Covariates 102

Table 18 Hypothesis Four ANCOVA Comparing Father's Age between Family History of Psychosis Groups 103

Table 19 Hypothesis Four T-Test Comparing Father's Age between Family History of Psychosis Groups 104

Table 20 Supplemental Analysis- Cross Tab Analysis of Family History of Psychosis and Zero vs. Non-Zero Symptom Score 105

Table 21 Supplemental Analysis- Zero Inflated Poisson Regression for Positive Symptom Score with Family History x Parent's Age Interaction Terms 106

Figure 1. Bar plot of distribution of positive symptom scores among CHR participants 107

Figure 2. Subject exclusion flow chart 108

Figure 3. Bar plot of distribution of sum of negative symptom scores among CHR participants 109

Figure 4. Histogram of current social functioning scores among CHR participants 110

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