Running head: BIPOLAR DISORDER: A JIGSAW PUZZLE FOR RESEARCHERS 1 Bipolar Disorder: A Jigsaw Puzzle for Researchers Tiffany Sinclair Columbia College April 30, 2011
BIPOLAR DISORDER 2 AbstractBipolar disorder (BD) appears to be one of the ultimate jigsaw puzzles for researchers, withmany constant developments and angles of approaching this disorder without a clear picture toassemble the corners first. Is there hope for this disorder that has daunted medicine and escapeda diagnostic clarity to confident and effective treatment? This paper searches for these answersutilizing research to seek out studies and findings of the many difficulties plaguing a simpleanswer to detect, define, diagnose, and treat BD. Symptoms, possible causes, the role ofbiological elements, genetics, possible early indicators, and treatments will be examined basedon a range of findings from those that seek answers one piece of the puzzle at a time from theinside out.
BIPOLAR DISORDER 3 Bipolar Disorder: A Jigsaw Puzzle for Researchers Bipolar disorder (BD) can be a diagnostic nightmare requiring extensive time and effortlooking into multiple elements of behavioral, psychological, and physiological characteristicssignaling the disorder and co-morbid facets encompassing it. Among the research availableaddressing BD, a common word used by most authors in reference to the overall puzzle of BDwas “elusive”. Why is it still so difficult to determine with confidence a diagnosis of BD givenso many presented symptoms and associations known to reflect BD in a patient? What takes solong to come to the bipolar conclusion? The puzzle analogy is fitting as there is so much known in connection with BD, with solittle cohesion due to the overwhelming alternative diagnostic possibilities to assemble thecomplete picture for an early diagnostic certainty. Undoubtedly, the frustration shared byresearchers and doctors extents to the patients anxiously awaiting answers in desperation forpeace within themselves and their lives. Where are those corner pieces anyway? We will start atthe beginning with a patient‟s symptoms and search through the box of findings and researchpieces to begin assembling BD from the inside out. What is bipolar disorder (BD)? Unipolar depression, the most common initial diagnosis(Berk, et al., 2010), is characterized by people experiencing variations in normality and one-poledepression, where as BD causes people to alternate between two poles: depression and mania(Kalat, 2009). Some characteristics of BD are “increased daytime napping … „atypical‟depressive symptoms…pathological guilt, psychomotor slowing…abrupt onset and offset ofepisodes, postpartum onset…sub-threshold manic symptoms, and a family history of bipolardisorder” (Berk, et al., 2010).
BIPOLAR DISORDER 4 Mania can vary in intensity resulting in the categorical differentiation of bipolar I and IIdisorders. Patients with mania have shown in testing to have executive function impairments inverbal and spatial working memory and sustained attention, while BD patients also performedpoorly in the areas of verbal memory and fluency in comparison to unipolar patients tested(Palaniyappan & Cousins, 2010). Bipolar I disorder exemplifies mania extremes of “restlessactivity, excitement, laughter, self-confidence, rambling speech, and loss of inhibitions”, whilebipolar II disorder is displayed more largely as agitation and anxiety driven with hypomaniaphases (Kalat, 2009). Where does BD originate from within in a person and is early detection possible?Increasing interest and awareness of possible and likely neurological indicators, predictors, andimaging are overwhelming. To cover all of the developments, theories, and prospectiveimplications would be too large a scope for this paper, however the implication of brain networkmodels certainly warrant attention given the immense need for more substantiated evidencecorrelating directly to BD diagnosis, treatment, and prevention. Is BD a cognitive, emotional, and behaviorally based disorder detectable only by meansof observation and symptom presentation? Are neurological indicators or predictors availablewith brain imaging? There seems to be reluctance to accept neurologically based determinantsas a primary or even verifiable BD causation, despite many valid and significant findings tosuggest strong correlations (Palaniyappan & Cousins, 2010). Ultimately, validity in networkmodels and network dysfunction connected with bipolar disorder holds great promise and even apractical resolution to a causation piece of the puzzle.
BIPOLAR DISORDER 5 Perhaps the most encompassing and effective way to address the brain piece of the puzzleis to associate BD with “brain network dysfunction” when referring to neurological causation(Palaniyappan & Cousins, 2010). As BD progresses and stages of recurring episodes take place,evidence suggest neurostructural changes emerge (Berk, et al., 2010). The networks proposed bynetwork models are thought to control emotions and cognitive processes impacted negatively andeven altered structurally by BD (Palaniyappan & Cousins, 2010). Neurotransmissions of “brain chemicals such as dopamine, serotonin, GABA andglutamate” are conducted within these networks proposed and are common impact and targetsites for “mood stabilizers such as lithium, valproate (VPA), carbemezapine (CBZ), and theatypical antipsychotics” (Palaniyappan & Cousins, 2010) which are used and thought to beeffective in treatment models of BD. The use of medications targeting specific brain chemicalsor transmissions lends to the validity of the network model of BD, accepting that dysfunctionalnetworks may be improved relieving symptoms of BD by network alteration through medication. Pathological investigation and imagery have proven the occurrence of structural changesto brain areas thought to be associated with “complex thought and cognition” (Palaniyappan &Cousins, 2010). Mood regulating and behavior modulation in areas of the brain such as the“orbito-frontal cortex, medial temporal lobe structures, striatum and cerebellum” (Bradfield,2010), have shown structural abnormalities in those with BD, as well as “right ventricularenlargement” (Bradfield, 2010). Neurological data is compelling and warrants we pay attentionto the implications of pharmaceutical benefits to the neurological processes affected by BD evenin children as great progress has been shown (Bradfield, 2010).
BIPOLAR DISORDER 6 As with any studies of psychological illness, complications can arise in research andtesting due to medication use by patients, in particular medications intended to impact neuralconnectivity and functional activity being measured and assessed (Palaniyappan & Cousins,2010). This is one of the complications in developing complete and non conflicting data usingscans and other measurement devices detecting neural connection abnormalities. Withincreasing imaging technology being developed, the network model may find a vital role inapplications and more definitive approaches to BD research, indicators, and treatments not yetconsidered for diagnostic criteria. Among the vast research work on bipolar disorder, a common thread of genetic orhereditary involvement seems to be a cornerstone of common ground for many researchersseeking the epidemiology of BD. Genetic commonalities alone are not guarantees for acquiringBD, however may lead to increased risk (Kalat, 2009). The genetic links to bipolar are animportant research element in treatment and diagnostic clarity. By finding genetic correlations, treatments effective in targeting those genes andchemicals may be more effectively developed or even allow for prevention of later or aggressivestages of BD in the future. Much of successful treatment in progressed or co-morbid conditionswith BD rely on multiple medications carefully combined to target each symptom or chemicalcontributing to the overall state of BD. How do these brain chemicals interact withanticonvulsant and antipsychotic medications currently used in treatment of BD, and what are thegenetic findings in relation to BD?
BIPOLAR DISORDER 7 Haloperidol is a dopaminergic antipsychotic medication used in the treatment of acutemania (Grunze, 2010). Dopamine genes: D4, transport genes, as well as “gene encoding for theDARPP 32”, may have a genetic tie to BD (Grunze, 2010). Serotonergic transmissionmodulation, in part is addressed with antipsychotics such as lithium (Grunze, 2010). Serotoninalso may have a genetic implication due to the increased risk of developing bipolar associatedwith the “AA genotype of the tryptophan hydroxylase which limit the synthesis of serotoninenzymes” (Grunze, 2010). Anticonvulsants such as CBZ increase modulation in the GABA A receptor, and VPAwhich “increases GABA release in different areas of the brain”. GABA transmission in BDpatients is suspected to be an underlying cause of the disorder with possible genetic basis tied tothe encoding of “GABA A receptor beta 1 sunbunit, GABRB1” (Grunze, 2010). “GABRA 4,GABRB3, GARBA5, and GABRR1 also appear related to BD” (Grunze, 2010). Pathological investigation and imagery have proven the occurrence of structural changesto brain areas thought to be associated with “complex thought and cognition” (Palaniyappan &Cousins, 2010). As with any studies of psychological illness, complications can arise in researchand testing due to medication use by patients, in particular medications intended to impact neuralconnectivity and functional activity being measured and assessed (Palaniyappan & Cousins,2010). This is one complication in developing complete and non conflicting data using scansand other measurement devices detecting neural connection abnormalities. With increasingimaging technology being developed, the network model may find a vital role in applications andmore definitive approaches to BD research, indicators, and treatments not yet considered fordiagnostic criteria.
BIPOLAR DISORDER 8 Is it possible BD could be predicted or prevented? The staging model consists of layersof individual identifiable indicators with individual treatment directives, progressing andcontributing ultimately to the overall diagnosis of BD (Berk, et al., 2010). The stages begin at 0signaling risk factors without symptoms then progress to stage 1, the prodromal stage, wheresymptoms begin manifestation and identification (Berk, et al., 2010). Stage 2 is reached upon“the first episode of illness” or first episode of mania for bipolar I and hypomania for bipolar II(Berk, et al., 2010). There is evidence to suggest this stage requires the most aggressiveapproach in treatments aimed at preventing further neural damage that progression of BD causesdue to recurrence in episodes (Berk, et al., 2010). Stage 3 is marked by symptomatic “recurrence” in subdivided layers (Berk, et al., 2010).Stage 4 “resistance” is reached when symptoms are persistent and a more aggressive approachbecomes considered (Berk, et al., 2010). Early intervention through possible predictors asoutlined in the staging method may prove instrumental in combination with other findings oflongitudinal research to aid in preventing late diagnosis. The later stages of BD requiring moreintense treatments are accompanied by greater risks than may occur if earlier symptoms areaddressed and treated (Berk, et al., 2010). While the staging model does not pose absolutes indiagnostic path, it may provide as an asset to the overall scope of diagnostic indicators andpossible outcomes (Berk, et al., 2010). Longitudinal research examining the course of illness in stages beginning with“nonspecific childhood antecedents” (Duffy, 2010), may prove to be beneficial approach bydetermining treatments necessary for individual stages. Determining origin may mean redefiningwhen we assess and determine associated illnesses in relativity to a BD diagnosis based onlongitudinal research (Duffy, 2010). In order to benefit from longitudinal research, some
BIPOLAR DISORDER 9acceptance of early symptoms separate from the existing criteria for overall BD diagnosis wouldbe necessary. Further study and testing to mark early indicators as valid predictors of BD, isproviding yet another complication requiring more research to evade the puzzling nature of BD. Why is treatment so difficult? Perhaps it is because treatment occurs to late or lacks co-morbid considerations within the criterion essential for early success. BD is generally not simplya relationship between depression and mania; there are individual anxiety disorders in BDshowing higher lifetime prevalence ratings of co-morbid anxiety disorders in comparison to thegeneral public (Kauer-SantAnna, Kapczinski, & Vieta, 2009). These anxiety disorders ratedhigher were: Generalized anxiety disorder, post traumatic stress disorder, social phobias, panicdisorder, and specific phobias (Kauer-SantAnna, Kapczinski, & Vieta, 2009). Co-morbid anxiety disorders appear to be an important factor relating to the severity andoutcome of BD. Co-morbid post traumatic stress disorder shows overwhelming commonalityamong BD patients reporting child abuse, “up to 50% in some samples, and in a cross sectionalstudy up to 98% of patients with BD presented histories of traumatic experiences” (Kauer-SantAnna, Kapczinski, & Vieta, 2009). Axis I conditions commonly shown with BD, as well as anxiety and substance abusefound often in clinical settings with BD patients (Kauer-SantAnna, Kapczinski, & Vieta, 2009),all beg for a place in the criterion puzzle of diagnosis and treatment of BD. The higher theprevalence of Axis 1 conditions with BD in patients, the greater likelihood is shown that thepatient will suffer increased severity of BD subtypes and the high risks associated such as:“Mixed or dysphoric states, rather than pure mania, high rates of suicidal behavior, high rates of
BIPOLAR DISORDER 10rapid cycling, more depressive episodes and worse functioning” (Kauer-SantAnna, Kapczinski,& Vieta, 2009). The STEP-BD study examined multiple facets of BD, one of which was anxiety co-morbidity (Parikh, LeBlanc, & Ovanessian, 2010). Out of 1000 participants with BD, just over30% had co-morbid anxiety disorders (Parikh, LeBlanc, & Ovanessian, 2010). Results fromthese participants over the course of a year showed an overall lower quality of life combinedwith reduced wellness, increased risk of earlier relapse, and an increase recovery time likely fordepression contributing in poorer BD outcome (Parikh, LeBlanc, & Ovanessian, 2010). Co-morbid anxiety treatment is essential in the prevention of BD progression (Parikh, LeBlanc, &Ovanessian, 2010), adding to the need for more puzzle pieces in the findings box before thecorners will be found. Co-morbid conditions requiring targeted medication in addition to treating depression andmania associated with BD ultimately make treatment a diagnostic puzzle short of the cornerpieces for completion without co-morbid conditions considered. The current categoricalcriterion used for BD falls short of more direct applications and clarity in co-morbid associationsand specific data relating them with BD (Kauer-SantAnna, Kapczinski, & Vieta, 2009). In theinterests of improving diagnostic assessments and BD research a “dimensional approach” mayprove beneficial in determining more accurate anxiety co-morbidity rates (Kauer-SantAnna,Kapczinski, & Vieta, 2009). A study seeking clarification in the stability and change over time of defense and copingmechanisms of “clinical crisis situations in patients presenting with bipolar effective disorder”(Kramer, 2010) brought about an interesting concept of stress with BD and clinical treatment
BIPOLAR DISORDER 11effects. Although other studies have examined the relationship of defense and coping, this studyutilized observer-rater systems for coping and defense mechanisms (Kramer, 2010). Specific symptomatic measures, hierarchical linear modeling, observer-rater systems forcoping and defense mechanisms, in addition to symptom check list-90-R were also used tomeasure stability and change over time (Kramer, 2010). The study assessed 18 in-patientspresenting BD and 18 matched non-clinical control subjects in an interview and follow upmethod (Kramer, 2010). “Defensive functioning remained stable while only in-patient subjectssaw an “increase in coping function”. At discharge seemingly related to stress reduction or crisisrelief, coping improved, where the control group saw no increase (Kramer, 2010). In patients had a variety of co-morbid conditions and the control group was not randomlyselected contributing to limitations of this study; however conclusions may have some clinicalin-patient crisis intervention use value. The findings were that “opposition and delegationcoping” associated with dysphoric mood and aggression, which increases suicide risk in BDpatients, “increases in the crisis situation” (Kramer, 2010). Coping and defense concepts andstrategies for the inpatient group revealed lower scores in both categories than the control groupin the first session with coping scores increasing and almost meeting the control groups by thesecond interview (Kramer, 2010). Defense functioning fluctuates less rapidly than copingfunctioning. This suggests short term treatments such as skills training to address coping and along term rehabilitative approach for defense functioning may be most effective for in crisisinterventions for BD in-patients (Kramer, 2010). The implications that coping mechanisms and concepts are more immature in BD in-patients than the control group may be indicative of stress perceptions and processing abilities
BIPOLAR DISORDER 12being impacted by BD. “BD is the most lethal of major psychiatric disorders, with an estimated15% mortality owing to suicide alone.” (Parikh, LeBlanc, & Ovanessian, 2010). Crisisintervention which improves coping functions that when reduced increase risks for suicide inthose with BD, could provide insight into more effective primary treatment goals andmethodologies aimed at suicide prevention in these patients. Further research aimed at morecontrolled co-morbid associations and outcomes could be highly beneficial in developing moredata concerning risk differentials among co-morbid conditions. A STEP-BD study of 1556 participants analyzed “suicide attempts and completions” overa 2 year period followed by competent clinicians (Parikh, LeBlanc, & Ovanessian, 2010). Thestudy found that 56 participants of the sample attempted suicide of which 7 completed suicides,and that previous suicide attempts and days depressed were “significant predictors” (Parikh,LeBlanc, & Ovanessian, 2010). Co-morbid factors such as anxiety disorders in BD patientsknown to increase recovery time for depression may serve as important key elements of researchto suicide prevention, especially those with a previous attempt. Discussion Bipolar disorder is complicated medical puzzle with many pieces not yet on the table forconnection. The hopelessness and frustration of the lacking clarity necessary to more easilydiagnose, prevent, and treat this disorder impacts children and adults in varying stages that whenallowed to progress can result in devastating realities for those that suffer. Hospitalizations inmental facilities, failed medication methods time after time, miss-diagnosed co-morbidconditions, familial breakdowns, and suicide can be an unfortunate part of the waiting game
BIPOLAR DISORDER 13often played in the ruling out of symptomatic relationships one at a time before official diagnosiscan be offered. One common link among almost all BD research is hope. Aside from the aggravatingunknowns for researchers, much work and effort is being invested in solving this puzzle. TheBiological and brain based research being done has an enormous positive implication for successwith improved imaging resources coming to light (Palaniyappan & Cousins, 2010). Theideology that bipolar disorder originates for network dysfunction (Palaniyappan & Cousins,2010) provides opportunities for answers and possibilities that have previously not beenavailable. The possibilities longitudinal research (Duffy, 2010), and the staging model (Berk, et al.,2010), may have in early detection and prevention pose endless possibilities for treatment modelsand neuroprotection possibilities. The genetic findings and pharmaceutical advancements andadaptations being discovered and implemented are gaining ground in the search for answers toeffective treatments (Grunze, 2010). The extensive studies of STEP-BD provide a wealth ofinformative data and useful statistical baselines from a multifaceted view of BD, and provideapplications for research learned to benefit clinical care, diagnostic measures, and suicideprevention measures (Parikh, LeBlanc, & Ovanessian, 2010). The recognition and information of co-morbid impact and implications on treatment anddiagnosis as vital to BD outcome and preventative progression, will aid in better treatment andunderstanding of the complexities of BD. These conditions being assessed in accordance withBD diagnosis more accurately will result in improved treatment and therapy methods on
BIPOLAR DISORDER 14individualized levels. More research will be instrumental in ensuring co-morbid factors findtheir place among necessary criteria for successful treatment of BD. The current pitfalls of patient medication impacting participant studies with BD certainlychallenge validity, accuracy, and empirical evidence standards most researchers would like tomeet. Technology currently still holds limitations for the definitive evidence sought regardingbrain involvement. Network function in BD can be masked or altered by medicated participantsin studies, preventing the ability for long term observational studies and conclusions free ofuncontrolled variables (Palaniyappan & Cousins, 2010). Clinical care is occurring too late in BDdevelopment, requiring more aggressive approaches of treatment necessary (Berk, et al., 2010). Aside from the shortcomings of the bipolar jigsaw puzzle, one study at a time connectsanother piece needed to find the corners and finish the picture. Perhaps the whole picture willnever be complete until research pauses and action resumes beyond a strictly empirical model?If practitioners and clinicians wait until the picture of BD diagnosis is complete to make adiagnosis it often can be too late, or pose a greater risk to patient by medication mishaps fromuntreated elements of co-morbid associations not considered. Further criterion changes need to be made to put co-morbid conditions as a high priorityon the list of BD diagnostic necessities. Further research investigating longitudinal and stagemodel ideals may prove beneficial in prevention and protection approaches, especially withfamily history and genetic indicators as predispositions in children and adult patients. Diagnosticconfidence has to occur earlier in the process treatment. Suicide attempts in BD patients should signal strong indication of recurrence possibilities(Parikh, LeBlanc, & Ovanessian, 2010). Medication combinations including the use of mood
BIPOLAR DISORDER 15stabilizers, antipsychotics and anticonvulsants (Grunze, 2010), are finding success when initiatedearly and used in combination with current effective BD treatments (Berk, et al., 2010). Overall,much knowledge is left to be gained, but so much is available and yet still under-utilized.
BIPOLAR DISORDER 16 ReferencesBerk, M., Hallam, K., Malhi, G. S., Henry, L., Hasty, M., Macneil, C., et al. (2010). Evidence and implications for early intervention in bipolar disorder. Journal of Mental Health , 19 (2), 113-126.Bradfield, B. C. (2010). Bipolar Mood Disorder in children and adolescents: in search of theoretic, therapeutic and diagnostic clarity. South African Journal of Psychology , 40 (3), 241-249.Duffy, A. (2010). The early natural history of bipolar disorder: What we have learned from longitudinal high-risk research. Canadian Journal of Psychiatry , 55 (8), 477-485.Grunze, H. C. (2010). Anticonvulsants in bipolar disorder. Journal of Mental Health , 19 (2), 127-141.Kalat, J. W. (2009). Biological Psychology (10 ed.). Belmont, CA, USA: Wadsworth Cengage Learning.Kauer-SantAnna, M., Kapczinski, F., & Vieta, E. (2009). Epidemiology and management of anxiety in patients with bipolar disorder. CNS Drugs , 23 (11), 953-964.Kramer, U. (2010). Defence and coping in bipolar affective disorder: Stability and change of adaptational processes. British Journal of Clinical Psychology , 49 (3), 291-306.Palaniyappan, L., & Cousins, D. A. (2010). Brain networks: Foundations and futures in bipolar disorder. Journal of Mental Health , 19 (2), 157-167.Parikh, S. V., LeBlanc, S. R., & Ovanessian, M. M. (2010). Advancing Bipolar Disorder: Key Lessons From the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Canadian Journal of Psychiatry , 55 (3), 136-143.