This document discusses risk-taking behavior in bipolar disorder. During manic episodes, patients exhibit poor judgment, hyperactivity, recklessness, and increased goal-directed behavior which can lead to risky behaviors. Neurocognitive impairments are also present in bipolar patients including problems with attention, executive function, and memory. Sleep deprivation and impaired cognition further exacerbate risk-taking behaviors by slowing cognitive processes. Common risky behaviors for manic patients include substance abuse, gambling, excessive spending, and unsafe sexual practices. Animal models can help quantify and study risk-taking behavior and the effects of treatments like lithium, valproate, and antipsychotics.

1. Risk Taking Behavior in Bipolar Disorder A very rough compilation of articles and how it may be applied to animal models in our lab.

3. Poor judgement

4. Hyperactivity

5. Recklessness

6. Aggressive behavior

7. Increased goal directed/pleasurable activities (Shaltiel et al.) (Yechiam et al.)

9. Attention domains

10. Executive processing

11. Declarative memoryPoor cognitive function has also been linked with acute psychotic symptoms in patients with BPD (Glahn et al.) It is hypothesized that these changes may be driven by motivational changes (increased pleasure seeking) this has also been described as increased focus on potential gains rather than losses(Yechiam et al.)

12. Impaired Cognition A study conducted by Glahn, et. al, found patients with BPD had impaired Speed of processing Attention Executive functioning Working and declarative memory These findings suggest that BPD involves and impairs multiple brain systems (Glahn et al.)

13. Impaired Cognition cont. Glahn, et. al, found 75% of BPD patients performed more than 1 standard deviation below healthy volunteers on various levels of cognition Greatest effects were seen in the speed of processing BPD patients were also found to make increasingly random and erratic choices compared to control patients (Yechiam et al.) Patients with acute BPD had a low choice consistency—they made more erratic choices

15. Although these behaviors are hard to define, it has been noted that manic patients have the following risky behaviors:

16. Increased prevalence of HIV(King et al.)

17. Increased vulnerability to sexually transmitted infections(King et al.)

18. Substance abuse (Shaltiel et al.)

19. General increased pleasure seeking (Shaltiel et al.)

20. Belief in special physical and mental powers (Leahy)

22. Females were found to have a high prevalence of trichomoniasis

23. Paitents noted having snorted/smoked cocaine and/or heroin within the past 6 months

25. Increased number of sexual partners

26. Little STI protection was used – more than half reported no use of condoms during their last 5 sexual acts (King)BPD patients, in some cases, have been found to express hypersexuality, which may augment their risk taking behavior (King) The addition of drug use to hypersexuality further exploits a BPD patient’s risk-taking behavior

28. Sleep deprivation has been found to decrease the global brain activity and slow cognitive processes,

29. One research article found that cognitive processes become

30. Slowed

31. Effortful

32. Inconsistent

33. Impaired Cognition

34. Creative thinking

35. Verbal fluency

36. Decision making

37. Moral reasoning

40. It was noted in one article, “patients in a manic state often believe they have unlimited financial resources” (Leahy)

41. Thus, patients with BPD are oversensitive to rewards of gambling/spending without financial means to recover from losses

47. Serotonin plays a large role in mood regulation. It was suggested that hyperactivity of serotonin may play a role in mania and hypoactivity may play a role in depression. (Applebaum et al.)

48. In animals, ingestion of tryptophan free amino acid mixtures rapidly reduced plasma tryptophan levels without directly affecting other neurotransmitters (Applebaum et al.)

50. Of these, several have been validated in animal models

51. Lithium

52. Valproate

53. Common BPD treatments in humans include

54. Lithium

55. Valproate

56. Ondansetron

57. Atypical antipsychotics-rispiridone

58. Carbamazepine

59. Clozapine**These may all have value in animal models as their use in humans is becoming increasingly more common**

61. Lithium has well established efficacy for the prevention of mania and, to some extent, depression.(Alda et al.)

62. In rats and mice, lithium administration has been shown to attenuate amphetamine induced hyperactivity. (Willson)

64. Valproate is less validated for preventing manic symptoms than lithium.(Alda et al.)

65. In rats and mice, Valproate has been shown to as an effective pre-treatment for attenuation of hyperactivity (Willson).

66. In humans, valproate has been shown to significantly attenuate amphetamine induced energy, happiness, and alertness (Willson)

68. Antipsychotics have had mixed results in terms of attenuation of amphetamine-induced mania, but should not be discounted from future studies

69. Because of the link between serotonin and mania, administering a tryptophan free diet may provide an alternate way to attenuate manic-like symptoms