THE ASSOCIATION BETWEEN 5-HTTLPR GENOTYPE, HARM AVOIDANCE, AND AGGRESSIVE BEHAVIOR

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1 THE ASSOCIATION BETWEEN 5-HTTLPR GENOTYPE, HARM AVOIDANCE, AND AGGRESSIVE BEHAVIOR Daniel Linford Faculty Mentors: Dr. Matthew Schmolesky, Dr. Barb Trask, Prof. Kraig Chugg.

2 Psychology Theories of Aggression There are currently five major independent modern psychological theories on aggression containing much overlap. These theories are based in concepts such as social interaction, learned behavior, and environmental pressures. A comprehensive theory is needed that uses biology as a basis with social interaction influencing expressed behavior.

3 Hypothalamic Aggression Pathways Neurological research has described two topographically and functionally separate pathways involved in aggression. Defensive Rage Aggressive posturing and vocalizations. Produced by electrical stimulation of the ventromedial hypothalamus Mostly descending neurons Not initially violent behavior, but will attack if provoked. Predatory Aggression Immediate silent attack with intent to kill. Produced by stimulation of the ventrolateral hypothalamus and corresponding sights in the Periaqueductal Grey. Descending and ascending neurons.

4 Hypothalamic Aggression Pathways Defensive Rage Predatory Aggression

5 z-scores of SLC6-A4 mrna Staining PAG and Raphe Nuclei are primary centers of serotonergic neurons within the brain. This image shows mrna concentrations for the SLC6A4 gene from postmortem sectioning and staining of the brainstem of an African American Male. Brighter areas indicate higher scores, which indicates a greater expression of the gene (Gene SLC6A4, 2014). This pattern is representative of an ethnically diverse sample of donors.

6 5-HTTLPR Polymorphic genotype Recent studies have shown a correlational relationship between the serotonin linked polymorphic region (5-HTTLPR) of the promoter region of the serotonin transporter gene and maladaptive behavior. Two functional polymorphisms of this base pair repeat have been described: the short form, which has 14 copies and is less transcriptionally efficient, and the long form that contains 16 copies.

7 5-HTTLPR Polymorphic genotype The effect of possessing the short form of the gene is the serotonin transporter protein will be produced at a slower rate, resulting in reduced reuptake of serotonin. This short form of the gene is generally considered to be the maladaptive form.

8 Our Study No current study has shown the relationship between harm avoidance, aggressive behaviors, and polymorphism of the serotonin receptor in a nonpathogenic and mixed-sex group in humans. This study will add a deeper understanding of the interactions of the serotonin system and neurotic and aggressive behaviors. This understanding could contribute to the production of therapeutic measures that would ultimately improve the quality of life for affected individuals and prevent the loss of life in the case of suicide.

9 The Buss-Perry Aggression Questionnaire (BAPQ) The Buss-Perry Aggression Questionnaire (BAPQ) returns scores on aggressive behavior in four dimensions: physical aggression, verbal aggression, anger, and hostility. Physical and verbal aggression subscales represent the instrumental or motor component of hurting or harming others. Anger represents the affective component of aggressive behavior, encompassing the physiological arousal in preparation for action. Hostility is the cognitive component of aggressive behavior. It encompasses a feeling of ill will for others, and sense of personal injustice.

10 Harm Avoidance One of the character traits of Cloninger s Temperament and Character Inventory (TCI) TCI is a series of questions/ statements evaluated on a 5-point scale. Includes subscales: Anticipatory Worry and Pessimism vs. Uninhibited Optimism (HA1) Fear and Uncertainty (HA2) Shyness with strangers (HA3) Fatigability vs. Vigor (HA4)

11 Individuals who score high in HA typically display excessive worrying, pessimism, shyness, fearful and doubtful behavior, and are easily fatigued. They are timid, careful individuals who are insecure, negativistic and pessimistic even in situations where most people would not be.

12 Correlation of Total Aggression and Total Harm Avoidance Total Harm Avoidance Total Aggression

13 Pearson s Correlation Between Buss- Perry and TCI Subscales. Variables top to bottom, Anticipatory Worry and Pessimism vs. Uninhibited Optimism (HA1), Fear and Uncertainty (HA2), Shyness with strangers (HA3), Fatigability vs. Vigor (HA4). Aggression Variables left to right Physical Aggression, Verbal Aggression, Hostility, Total Aggression.

14 HA and Aggression Relationships A physically aggressive person will be very pessimistic, and expect the worst outcomes from situations where an average person would not. A verbally aggressive person will be less pessimistic and will not be afraid of changes in routine or uncertain situations, but will be easily fatigued. A person scoring high in hostility will be pessimistic about the outcomes of many social situations and show an inordinate amount of fearfulness

15 Hostility and HA Hostility Anticipatory Worry and Pessimism vs. Uninhibited Optimism (HA1)

16 Male vs. Female t-tests Table 2. Male (n=33) vs. Female (n=76) Harm Avoidance t-test values on a scale of 1-5 the subscales. Total scores are a summation of all the subscales. Table 3. Male (n=33) vs. Female (n=76) Aggression score t-test values on a scale of 1-7 for the subscales. Total scores are a summation of all the subscales.

17 Hostility and HA1 100% 90% 80% Percent of Population 70% 60% 50% 40% 30% Females Males 20% 10% 0% Total Harm Avoidance Figure 4. Comparison of male and female total Harm Avoidance scores by population percentage.

18 Male and Female Total Aggression scores by population percentage. 100% 90% Compound Frequency (percent of Subjects) 80% 70% 60% 50% 40% 30% 20% Females Males 10% 0% Total Aggression

19 Genotyping 76 of original study and 16 of new study successfully genotyped to date. Current data shows no significant relationship with 5-HTTLPR and Harm Avoidance or Aggression. Extremely small skewed sample. Only one male Subject. Our results contradict literature showing relationship between HA and 5-HTTLPR. Genotyping to be completed in the near future will yield more substantial results.

20 Acknowledgements and Thanks Dr. Schmolesky for his mentorship and for use of his research grant funds for this capstone project. Dr. Trask for the generous use of her genetics lab and expert instruction on the genotyping process. Office of Undergraduate Research for a travel grant to present this research at NCUR 2014.

21 Looking Back Harm Avoidance Character Trait Pessimism, fearfulness, shyness with strangers. Buss-Perry Aggression Physical, Verbal, Hostility, Anger. 5-HTTLPR 2 functioning polymorphisms. Short form is less transcriptionally active.

22 Questions?