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Risk Taking Behavior in Bipolar Disorder <br />A very rough compilation of articles and how it may be applied to animal mo...
Negative Symptoms Surrounding Bipolar Disorder (BPD)<br /><ul><li>During stages of mania in BPD, patients exhibit altered ...
Poor judgement
Hyperactivity
Recklessness
Aggressive behavior
Increased goal directed/pleasurable activities  (Shaltiel et al.) (Yechiam et al.)
Excessive pleasure seeking can often lead to increased risk taking behaviors which are categorized by the negative implica...
Attention domains
Executive processing
Declarative memory</li></ul>Poor cognitive function has also been linked with acute psychotic symptoms in patients with BP...
Impaired Cognition<br />A study conducted by Glahn, et. al, found patients with BPD had impaired<br />Speed of processing<...
Impaired Cognition cont. <br />Glahn, et. al, found 75% of BPD patients performed more than 1 standard deviation below hea...
Risk Taking<br /><ul><li>Due to the neurocognitive changes experienced by a patient with BPD, risk taking behaviors are in...
Although these behaviors are hard to define, it has been noted that manic patients have the following risky behaviors:
Increased prevalence of HIV(King et al.)
Increased vulnerability to sexually transmitted infections(King et al.)
Substance abuse (Shaltiel et al.)
General increased pleasure seeking (Shaltiel et al.)
Belief in special physical and mental powers (Leahy)
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Risk Taking Behavior In Bipolar Disorder

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  • Bpd-oscillating depression and maniaFor the purposes of risk-taking, I will focus on mania
  • Euthmic patients are defined as those not manic or depressed…..the happy medium
  • this is important because it escillates the difficulty we have in treating bpd/risk taking without impacting other systems
  • From this we can determine that they have greater difficulty with clear thinking, and thus may engage in risky behavior
  • Physical-not needing to wear a coat in winter, belief that they can fly, believing they can drive their car into ongoing traffic Mental-receiving messages from television, ability to control the minds of others
  • It should be noted that these patients have various disorders, schz, bpd, mania, ~40% had an affective disorder
  • Impaired cognition may be a way of mimicing what manic patients experience
  • Transcript of "Risk Taking Behavior In Bipolar Disorder"

    1. 1. Risk Taking Behavior in Bipolar Disorder <br />A very rough compilation of articles and how it may be applied to animal models in our lab.<br />
    2. 2. Negative Symptoms Surrounding Bipolar Disorder (BPD)<br /><ul><li>During stages of mania in BPD, patients exhibit altered processing (Roiser et al.) including behavioral symptoms of:
    3. 3. Poor judgement
    4. 4. Hyperactivity
    5. 5. Recklessness
    6. 6. Aggressive behavior
    7. 7. Increased goal directed/pleasurable activities (Shaltiel et al.) (Yechiam et al.)
    8. 8. Excessive pleasure seeking can often lead to increased risk taking behaviors which are categorized by the negative implications involved (Yechiam et al.)</li></li></ul><li>Neurocognitive Changes<br /><ul><li>Euthymic patients with BPD have been documented to show neurocognitive impairments (Glahn et al.)
    9. 9. Attention domains
    10. 10. Executive processing
    11. 11. Declarative memory</li></ul>Poor cognitive function has also been linked with acute psychotic symptoms in patients with BPD (Glahn et al.)<br />It is hypothesized that these changes may be driven by motivational changes (increased pleasure seeking)<br /> this has also been described as increased focus on potential gains rather than losses(Yechiam et al.)<br />
    12. 12. Impaired Cognition<br />A study conducted by Glahn, et. al, found patients with BPD had impaired<br />Speed of processing<br />Attention<br />Executive functioning<br />Working and declarative memory<br />These findings suggest that BPD involves and impairs multiple brain systems (Glahn et al.)<br />
    13. 13. Impaired Cognition cont. <br />Glahn, et. al, found 75% of BPD patients performed more than 1 standard deviation below healthy volunteers on various levels of cognition<br />Greatest effects were seen in the speed of processing<br />BPD patients were also found to make increasingly random and erratic choices compared to control patients (Yechiam et al.)<br />Patients with acute BPD had a low choice consistency—they made more erratic choices<br />
    14. 14. Risk Taking<br /><ul><li>Due to the neurocognitive changes experienced by a patient with BPD, risk taking behaviors are increased during episodes of mania
    15. 15. Although these behaviors are hard to define, it has been noted that manic patients have the following risky behaviors:
    16. 16. Increased prevalence of HIV(King et al.)
    17. 17. Increased vulnerability to sexually transmitted infections(King et al.)
    18. 18. Substance abuse (Shaltiel et al.)
    19. 19. General increased pleasure seeking (Shaltiel et al.)
    20. 20. Belief in special physical and mental powers (Leahy)
    21. 21. Excessive spending or gambling (Leahy)</li></li></ul><li>Quantifying Increased Risk Taking<br /><ul><li>In a study examining sexual risk behaviors and increased pleasure seeking in an outpatient psychiatry clinic, several significant relationships were found among affective disorders versus control population (King et al.)
    22. 22. Females were found to have a high prevalence of trichomoniasis
    23. 23. Paitents noted having snorted/smoked cocaine and/or heroin within the past 6 months
    24. 24. Patients reported having had an STI within the past 6 months</li></li></ul><li>Quantifying Cont.<br />Statistically significant relationships<br />How does this impact risk-taking behavior?<br /><ul><li>Those with a substance abuse problem (affective disorder patients), were more likely to report having exchanged sex for drugs
    25. 25. Increased number of sexual partners
    26. 26. Little STI protection was used – more than half reported no use of condoms during their last 5 sexual acts (King)</li></ul>BPD patients, in some cases, have been found to express hypersexuality, which may augment their risk taking behavior (King)<br />The addition of drug use to hypersexuality further exploits a BPD patient’s risk-taking behavior<br />
    27. 27. Sleep Deprivation (Killgore et al.)<br /><ul><li>As previously mentioned, BPD patients experience hyperactivity during episodes of mania
    28. 28. Sleep deprivation has been found to decrease the global brain activity and slow cognitive processes,
    29. 29. One research article found that cognitive processes become
    30. 30. Slowed
    31. 31. Effortful
    32. 32. Inconsistent
    33. 33. Impaired Cognition
    34. 34. Creative thinking
    35. 35. Verbal fluency
    36. 36. Decision making
    37. 37. Moral reasoning
    38. 38. Divergent thinking</li></li></ul><li>Whats the Point?<br />“Judgement and decision making processes associated with risk taking may be impaired by sleep deprivation, along with motivation to act upon these judgments” (Killgore et al.)<br />In a manic patient, the sleep deprivation would not lead to decreased motivation or energy to act<br />Therefore, sleep deprivation augments a patient with mania to engage in risky behaviors<br />
    39. 39. Gambling and Spending<br /><ul><li>During episodes of mania, patients demonstrate “poor probabilistic reward learning due to oversensitivity to occasional rewards when choosing stimuli primarily associated with punishment” (Roiser et al.)
    40. 40. It was noted in one article, “patients in a manic state often believe they have unlimited financial resources” (Leahy)
    41. 41. Thus, patients with BPD are oversensitive to rewards of gambling/spending without financial means to recover from losses
    42. 42. This demonstrates the multi-faceted nature of risk-taking behavior in BPD</li></li></ul><li>Animal models of Risk taking behavior---what does this stuff mean for our lab<br />Many of the methods used in the discussed experiments can be modified to fit animal models<br />These experiments include<br />Sleep Deprivation<br />Quantifying Risk<br />Diet<br />Lithium Therapy<br />Valproate Therapy<br />Other medications<br />
    43. 43. Sleep Deprivation<br /><ul><li>As previously mentioned, sleep deprivation augments a manic’s ability and desire to engage in risk taking behavior
    44. 44. Sleep deprivation causes a decrease in cognitive processing-much like mania, but this may not be enough for an accurate model of mania because of the decreased energy expenditures (Killgore et al.)</li></ul> However, it was found that administration of dextroamphetamine most closely mimicked the high energy level, racing thoughts, increased propensity to seek out risky activities associated with mania. (Killgore et al.)<br /><ul><li>Thus, sleep deprivation with amphetamine administration will increase activity with little changes to the impaired cognition which provides a model for mania
    45. 45. This may help us quantify risk taking behaviors and provide us with ways to test medications for the attenuation of mania</li></li></ul><li>Quantifying Risk in the Lab Setting<br />The elevated plus maze (EPM) is a way to measure anxiety or risk taking behavior in mice (Shaltiel et al.).<br />By placing mice in the EPM, we can assess how “risky” they are being based on the amount of time in the open fields and how many times they enter the open fields. <br />Thus, including EPM in future experiments, we can quantify risk-taking behavior<br />
    46. 46. Diet<br /><ul><li>It was found that reduction in dietary tryptophan reduced the synthesis of CNS serotonin
    47. 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. 48. In animals, ingestion of tryptophan free amino acid mixtures rapidly reduced plasma tryptophan levels without directly affecting other neurotransmitters (Applebaum et al.)
    49. 49. This study found that depressive symptoms were not exacerbated by serotonin but also tryptophan free amino acid mixtures administered with valproic acid had a strong, rapid antimanic effect (Applebaum et al.)</li></li></ul><li>Medication Therapy<br /><ul><li>Many medications have been found to have antimanic effects
    50. 50. Of these, several have been validated in animal models
    51. 51. Lithium
    52. 52. Valproate
    53. 53. Common BPD treatments in humans include
    54. 54. Lithium
    55. 55. Valproate
    56. 56. Ondansetron
    57. 57. Atypical antipsychotics-rispiridone
    58. 58. Carbamazepine
    59. 59. Clozapine</li></ul>**These may all have value in animal models as their use in humans is becoming increasingly more common**<br />
    60. 60. Lithium<br /><ul><li>Lithium has been commonly used as a mood stabilizer in BPD patients. (Willson)
    61. 61. Lithium has well established efficacy for the prevention of mania and, to some extent, depression.(Alda et al.)
    62. 62. In rats and mice, lithium administration has been shown to attenuate amphetamine induced hyperactivity. (Willson)
    63. 63. Because lithium is the standard treatment for manic patients, it serves as a cornerstone for experiments testing mania and risk taking behavior.</li></li></ul><li>Valproate<br /><ul><li>Valproate is widely used as a mood stabilizer for BPD in humans.(Willson)
    64. 64. Valproate is less validated for preventing manic symptoms than lithium.(Alda et al.)
    65. 65. In rats and mice, Valproate has been shown to as an effective pre-treatment for attenuation of hyperactivity (Willson).
    66. 66. In humans, valproate has been shown to significantly attenuate amphetamine induced energy, happiness, and alertness (Willson)
    67. 67. This evidence suggests that valproate may be an effective treatment for mania induced risk-taking behavior.</li></li></ul><li>Atypical Antipsychotics and Other measures<br /><ul><li>One study suggests that olanzapine, aripiprazole, and quetiapine have mood stablilizing properties and may serve as long-term therapy options (Alda et al.)
    68. 68. Antipsychotics have had mixed results in terms of attenuation of amphetamine-induced mania, but should not be discounted from future studies
    69. 69. Because of the link between serotonin and mania, administering a tryptophan free diet may provide an alternate way to attenuate manic-like symptoms
    70. 70. In addition to depriving the body of serotonin precursors, serotonin receptor antagonist (such as ondansetron 5-HT3 antagonist) may also be effective for the attenuation of mania (Willson)</li></li></ul><li>Works Cited<br />Alda, Martin, Hajek, Tomas, Calkin, Cynthia and O'Donovan, Claire(2009)'Treatment of bipolar disorder: New perspectives',Annals of Medicine,41:3,186 — 196<br />Applebaum, Julia, Yuly Bersudsky, and Ehud Klein. “Rapid tryptophan depletion as a treatment for acute mania: a double-blind, pilot controlled study.” Bipolar Disorders 9 (2007): 884-887. Web. 1 Aug. 2009.<br />Glahn, David C., Carrie E. Bearden, Marcela Baraguil, Jennifer Barrett, Abraham Reichenberg, Charles L. Bowden, Jair C. Soares, and Dawn I. Velligan. “The Neurocognitive Signature of Psychotic Bipolar Disorder.” Society of Biological Psychiatry 62 (2007): 910-916. Web. 1 Aug. 2009. <http://www.sobp.org/journal>.<br />Killgore, William D.S., Nancy L. Grugle, Desiree B. Killgore, Briam P. Leavitt, George I Watlington, Shanelle McNair, and Thomas J. Balkin. “Restoration of Risk-Propensity During Sleep Deprivation: Caffeine, Dextroamphetamine, and Modafinil.” Aviation, Space, and Environmental Medicine 79.9(2008): 867-874. Web. 1 Aug. 2009<br />King, Cynthia, Jacqueline Feldman, Yvonne Waithaka, Inmaaculada Aban, Jianfang Hu, Sijian Zhang, Edward Hook, and Laura H. Bachmann. "Sexual Risk Behaviors and Sexually Transmitted Infection Prevalence in an Outpatient Psychiatry Clinic." American Sexually Transmitted Diseases Association 35.10 (2008): 877-82. Web.<br />Leahy, Robert. L. “Clinical Implications in the Treatment of Mania: Reducing Risk Behavior in Manic Patients.” Cognitive and Behavioral Practice 12 (2005):89-98. Association for Advancement of Behavior Therapy. Web. 1 Aug. 2009.<br />Rosier, J., A. Farmer, D. Lam, A. Burke, N. O’Neill, S. Keating, G. Powell Smith, B. Sahakian, and P. McGuffin. “The effect of positive mood induction on emotional processing in euthymic individuals with bipolar disorder and controls.” Psychological Medicine 39 (2009):785-791. Cambridge University Press 2008.<br />Shaltiel, G., S. Maeng, O. Malkesman, B. Pearson, R. J. Schloesser, T. Tragon, M. Rogawski, M. Gasior, D. Luckenbaugh, G. Chen, and H. K. Manji. "Evidence for the involvement of the kainate receptor subunit GluR6 (GRIK2) in mediating behavioral displays related to behavioral symptoms of mania." Molecular Psychiatry. Nature Publishing Group, 2008. Web. 1 Aug. 2009. <http://www.nature.com/mp>.<br />Willson, Morgan C., Emily C. Bell, Sanjay Dave, Sheila J. Asghar, Brent M. McGrath, and Peter H. Silverstone. "Valproate attenuates dextroamphetamine-induced subjective changes more than lithium." European Neuropsycopharmacology 15 (2005): 633-39. Elsevier. Web. 1 Aug. 2009. <http://www.elsevier.com/locate/euroneuro>.<br />Yechiam, Eldad, Elizabeth P. Hayden, Misty Bodkins, Brian F. O’Donnell, William P. Hetrick. “Decision making in bipolar disorder: A cognitive modeling approach.” Psychiatry Research 161 (2008). Elsevier. Web. 1 Aug. 2009. <http://www.sciencedirect.com><br />
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