Monday, March 11, 2019

Bipolar Disorder: Biopsychosocial Etiology and Treatments, and its Place on a Cognitive Spectrum


Bipolar Disorder: Biopsychosocial Etiology and Treatments, and its Place on a Cognitive Spectrum

by Brendan Bombaci

Copyright Brendan Bombaci 2014
Lulu Press
ISBN: 978-1-312-68030-2

Introduction


Although most people will subscribe to the brain disease model of schizophrenia because of its unearthly qualities, many believe that depression is caused solely by psychosocial stress (Angermeyer and Dietrich 2006:165).  To a large extent, it seems they may be right (Bracken et al. 2012:431, Kohrt et al. 2014, Lee et al. 2007), though new large-sample examinations of population genetic data on file with the popular genetic testing organization 23andMe reveal 15 genetic loci associated with increased risk (Hyde et al. 2016).  Also, cultural consonance research utilizing genetic tests for serotonin receptor polymorphisms has revealed that depression symptom expression happens most with one particular polymorphism, but majorly when cultural consonance in family life is decreased due to having had adverse childhoods as well (Dressler et al. 2016); they actually display increases in cultural consonance beyond the highest levels of those with the other polymorphisms who have experienced low childhood adversity levels, revealing a hypersensitivity and plastic reactiveness to social context (Dressler et al. 2016).  The contradiction between the genetic and sociocultural findings may make Bipolar Disorder (“manic depression”) a seemingly more confusing or unbelievable diagnosis than depression alone, given that it is marked by inconsistent bouts of contrasting depressive lows and euphoric highs.  Unless critics know firsthand the effects of illicit drugs such as cocaine or methamphetamine (Frey et al. 2006), they may only have a schematic reference to highly caffeinated states, and not actually to mania – the mind-riding high that lasts hours, days, weeks, or months at a time depending on how the afflicted person “cycles.”  So, mania may not seem like an unmanageable problem to them.  They are likely also influenced by the growing knowledge that Bipolar Disorder sufferers can be creative geniuses (Jamison 1996).  This may lead to notions that afflicted persons are merely hypersensitive eccentrics.  Indeed, there is evidence that Bipolar Disorder is more stigmatized than depression (Ellison, Mason, and Scior 2013:818). 

Now correlated with risks for and presence of Bipolar Disorder are five nuclear DNA genes (Muhleisen et al. 2014, Xu et al. 2014), as well as mitochondrial DNA mutations – possibly increasing oxidative stress leading to apparent damage to DNA and proteins seen with increased symptom severity (Siwek et al. 2013:1559,1567).  This may make the sufferer and those in their social climate less “culpable” for their own lack of wellbeing, however, Bipolar Disorder can be socially exacerbated to the point of episodic psychosis, a point worth detailed elaboration in this paper.  The millions of people worldwide that live with the neurophysiological rollercoaster of Bipolar Disorder have incredible fortitude, as they must frequently overcome what could instantaneously force them into an extremely abject livelihood.  Being subject to the fluctuating feelings of Bipolar Disorder and/or the delusional and hallucinatory intensity of “Bipolar Disorder –Severe with Psychotic Features” (APA 1994:351) requires a mostly unrecognized sort of heroism, especially as many are not “cured” so much as remediated into functionality by medication, let alone therapy (Basco et al. 2007, Miklowitz 2009).  But there is certainly a steadily increasing degree of hope for the afflicted.

Prevalence, the Addiction Connection, and Family Interaction


            Bipolar Disorder occurs in up to 1.6% of the world population (Muhleisen et al. 2014, Xu et al. 2014).  “The World Health Organization classifies BD as one of the top 10 leading causes of the global burden of disease for the age group of 15-44-year-old people,” and “the heritability estimates for BD range between 60 and 80%” (Muhleisen et al. 2014).  Some people with Bipolar Disorder also have a variant of the MAOA gene (Mueller 2007, Preisig et al. 2000), aka “Warrior Gene,” that decreases normal inhibition of neurotransmitter flooding.  This variant is not unique to them, but this factor alone can explain a lot about manic episodes, as the neurochemical action of general MAO inhibition is to over-activate endogenous and dietarily-increased serotonin, melatonin, nor/epinephrine (adrenalin), phenylethylamine, and dopamine.  Through this, amplification will occur for sensations of euphoria, reward, energy levels, excitement, physiological hypertension, aggression, and, quite possibly, hallucinatory altered states.  The latter could occur via either the un/intentional consumption of DMT or 5-MeoDMT [Rätsch 2005:815,852], or unintentionally increased endogenous levels of the former [Barker, McIllhenny, and Strassman 2012; Callaway 1988:121].  The counter to these highs will happen when the neurotransmitters run out or return to baseline.  When this rollercoaster ride is the result of food or substance intake, and given the variety of chemical composition in Western diets, the symptoms may seem unpredictable.  But some sufferers may be attuned, and thereby recognize those foods that lift them up, and make a habit of consuming those more often, as mania is enjoyable in contrast to depression; and, others may become more attracted and easily addicted to psychoactive substances such as nicotine (Villégier et al. 2003) and alcohol (Amsterdam et al. 2006), as their effects are more overwhelming to those with such genetics.  Substance abuse is a generally well-known issue with Bipolar Disorder sufferers (Cassidy, Ahearn, and Carroll 2008), and this may be a clue as to why.

            Culture seems to have a moderating effect on the expressions of Bipolar Disorder.  In a meta-analysis of 17 different countries in various continents, it was found that the maniatrophic cultures, or “cultures that shape a reward-rich environment by placing a high value on the individual pursuit of reward and providing opportunities to do so,” were “correlated with higher prevalence rates of Bipolar I Disorder,” specifically where either Hofstede’s cultural dimensions of “lower Power Distance [degree of power inequality] and higher individualism” or “lower Long Term [goal] Orientation and higher Performance Orientation” occurred (Johnson and Johnson 2014:1114-5).  If someone starts showing signs of Bipolar Disorder and is treated not with patience and carefulness, but with hyper-attentiveness and either fatalistic concern, judgmentalism, and/or fear, the patient may have a worse outcome in both the short and long runs.  When a loved one behaves as such, with what has been called high expressed emotion (EE) – fairly typical in Western countries or developing nations – showing “dramatic expressions of self-sacrifice, extreme devotion, overprotectiveness, or intrusiveness in the patient’s life” (Watters 2010:152), they embody the hallmarks of what have been generally seen as a psychotic patient’s inner demons: “demanding, critical, or disparaging voices” (Watters 2010:153).  This risks the precipitation or exacerbation of psychotic episodes via measurably increasing the neurophysiological stress levels of the patient.  Luhrmann, Padmavati, Tharoor, and Osei (2015) have given a term for their own, similar research-based conclusions, about schizophrenics with auditory hallucinations (a cross-disorder aspect of psychosis), whereby culture plays a large factor in the demeanor of such “voices” (and therefore the mood and functionality of the afflicted): social kindling.  In their sampling, South Indian and West African participants fared much better than Californians – even positively so.

Psychiatrists and academicians Lawrence Kirmayer and Norman Sartorius would likely explain the more negative effects, usually seen in afflicted Westerners, through their seven level framework of psychosomatic and sociosomatic “looping” wherein, most relatively here – and out of order, (4) “reactions of others to distress reinforce the experience and expression of distress,” (1) “attention to sensations increases their salience and intensity, leading to greater and more focused attention,” (2) “emotional arousal interferes with functioning, leading to performance decrements, negative self-appraisal, and greater emotional arousal,” and they end up “catastrophizing or [having] other types of pathologizing cognitions that undermine coping and elaborate negative expectations associated with symptoms” (Kirmayer and Sartorius 2007:836).   It has been found through a myriad of studies worldwide that relapse rates for psychotic episodes were three to seven times greater for patients in families that exhibit high EE (Watters 2010:153), and this looping could be why.  The social environment is key.  Perhaps intuitively then, Westerners who experience a condition which includes depression are more likely to be perceived as best helped by only a creatively supportive psychosocial intervention rather than antipsychotic medications (Angermeyer and Dietrich 2006:169).  The truth is that the condition is both genetic and psychosocial; so, in a world where the social environment is so uncertain and globalizing (a proxy term for Westernizing, really), both treatments in conjunction might be the best approach to keeping the sufferer in between extremes, let alone non-psychotic.

Trait Selection and the Disordered Origins of “Visionaries”


It has been pondered why Bipolar Disorder is expressed in our genes at such a high rate, when fecundity of sufferers has not been seen as high in the last century.  We must turn to biological and cultural anthropology.  There is an ongoing and contentious argument in paleoanthropology circles as to whether or not Neanderthals had symbolic thought, let alone religion.  Something that separates humans from Neanderthals is the gene NRG3, associated to schizophrenia (Gibbons 2010:684, Kao et al. 2010).   The case may be the same for Bipolar Disorder, with the NRG1 gene (Jung et al. 2010:1).  With the fairly new genetic predisposition to strange psychotic and/or bipolar states of consciousness, our ancestors may have become intrigued by the rare band or tribe member that had otherworldly ideations and/or euphoria or reclusiveness without the likely-practiced consumption of psychoactive substances amongst others in the tribes (Merlin 2003, Vitebsky 2001:85-87, Winkelman and Baker 2010:126-7).  Validation of the honesty in their experiences and states of consciousness would be made when tribe members witnessed the same phenomena happening with those rare afflicted members of other groups as well (with the aforementioned fact that 1.6% of the global population is afflicted, we can assume that more than 1 in 100 tribe members would be). 

The afflicted may have been (and in some cases still are) seen as people who are able to perceive facets of reality that others cannot.  Because of a shared belief in non-physical beings between shamanism, religion, and psychosis, and because within those beliefs “the assumption that certain people are especially likely to receive supernatural messages from gods or spirits,” it can be argued that “religious thinking resembles some forms of psychosis” and that “the near [cross-cultural] universality of specific religious thoughts imparts a potential genetic etiology upon religion” (Polimeni and Reiss 2002:246, emphasis added).  However, religion may have developed for the purposes of environmental adaptation and group cohesion (Polimeni and Reiss 2002:246) and/or thought compression for moral coding and record keeping to perpetuate transmission of culture as well (Barber and Barber 2006).  In this case, supernatural ideologies, part and parcel of the attractive development of such social institutions, may have originally gained legitimacy through frequently repeated psychotic or manic dramatization; and, bipolar sufferers may have been so peculiar to have given the reverent a reason to uphold them and to carry on their genetic material (Polimeni and Reiss 2002:247), perhaps even preferentially selecting for the disorder phenotypes, explaining why we see such disorders at a high rate today.  

Through phylogenetic trees and linguistic classification (Peoples, Duda, and Marlow 2016), we see animism – a belief that spirits are in everything – predating even shamanism; and, archaeological evidence reveals a past where shamanism, in all of its notions of “contracts” with disembodied beings and altered states of consciousness, is the foundation of religions (Winkelman and Baker 2010:135-148).  Religion may be said, in turn, to be the foundation of science, given that The Enlightenment which led to the Scientific Revolution was a philosophical retaliation both borne of and against religious dogma.  Perhaps not so ironically then, first degree relatives of Bipolar Disorder sufferers tend to find themselves in more scientifically creative occupations.  So, families of those with Bipolar Disorder might have had a better understanding of the world, or higher levels of communication proficiency and persuasiveness, and therefore better overall attractiveness and fecundity, themselves (Kyaga et al. 2011:378).  Perhaps such skills were (and can yet be again, sans stigma) useful in carefully shoring up the ethos of their disordered relative, and, concomitantly, of their entire family lineage.  It is likely the case that every human has some degree and unique permutation of the mental traits that contribute to schizophrenia and bipolar disorder both, as there are literally thousands of common alleles of very small effect that code for increased risk for their florid, or “full blown,” presentation (Purcell et al. 2009).  However, whatever the threshold is between productivity and functionality, and distraction to the point of detrimental breakdown, is currently unknown.

Those family members can be seen to thrive on the creative/”open” as well as “unusual ideas/experiences” end of a theoretical cognitive spectrum – one now corroborated with DT scans (Jung et al. 2010) and social science as well as clinical psychiatric research (Nettle 2006) – where poetry and art are sided with divergent thinking, schizophrenia, and affective disorder, but, where “creatives” don’t exhibit the anhedonia and avolition at the schizophrenic extreme (ibid).  Implications for the afflicted person are that, if they are a Bipolar Disorder sufferer experiencing psychotic mania, rather than a catatonic schizophrenic, they are in just the right position for passion-consumed and uncontrollable artistry or writing.  This may sound like a blessing, but it won’t be a productive experience for all afflicted people.  There are those who feel that beyond-threshold sufferers are wasting a gift when they get treatment: that they should instead use their affliction for pinpoint and endless focus on creative works, revolutionary philosophy, or even spiritual healing.  It must be recognized that bouts of mania, even exclusive of psychotic symptoms, can also lead to self-endangering behaviors such as running away, violent aggression, and crime (Faedda et al. 2014:319); spending the family savings and having indiscriminate sex (Boland and Keller 2005:2-3); drug abuse (Miklowitz 2009:114); and even suicide (Miller and Bauer 2014), especially when the depths of depression are reached.  The consequences of these ups and downs are a high price to pay for intense creativity.

Amongst 300,000 people in a recent study of mental illness and creativity, Bipolar Disorder sufferers do indeed tend to find more work in creative professions than sufferers of schizophrenia or unipolar depression (Kyaga et al. 2011:376), but given the fact that most people in stable professions are stable themselves, these people are likely sub-threshold or psychiatrically managed.  In regards to feelings that such sufferers should be spiritual guides, i.e., it is the case that a myriad of shamans aren’t even psychiatrically abnormal (Lewis 2003:161-165).  In fact, many of them harness public recognition of the overwhelming power of mental illness by feigning such illness themselves - not dishonestly but rather for a necessary cultural drama – and then “overcoming” the affliction/s through a show of shamanic initiation, in order to have a legitimized niche role in society (ibid:165-172, Vitebsky 2001:52-92).  If they accept the label of oddity, they are both alienated and upheld, fitting a role that most have no desire for (as even they will admit to), but one that is verily respected and has good job security.  Their altered states are likely gained from extreme exertion and/or dietary tools.  Of the latter, “in those drug-using societies where adequate data exist, one finds that it is generally recognized that the shaman is a specific individual whose nervous system and level of maturity permit him to deal most competently with the realms of unconscious activity generated by hallucinogenic plant use” (Dobkin de Rios et al. 1974:152).  And indeed, most societies are, or stem from, those who sanction some legitimate use of such substances (Rätsch 2005).  As mentioned already, it may be that mentally stable relatives of the afflicted were, and are yet (in modern tribal societies), those responsible for the enduring practices of shamanism and religion in the modern day.  A Bipolar Disorder sufferer, out of control or immobile, and a danger to the self and others, is not a particularly good candidate for the job of independent shaman.  Some of our most creative and/or calculating members of society may be just on the verge of Bipolar Disorder, or may be, without stigmatizing, autonomically modeling their thought patterns after those of the suffering.

Hope and Mindful Caretaking


Firstly, I must say that there is hope in medicine for the whole Bipolar Disorder spectrum, and, at least for Westernized people, it should be considered no matter what social intervention is taking place.  Whatever can be done should be done for those, in situations socially or physiologically debilitating, or life-threatening, who fight against medication.  If such a a sufferer, in a manic episode, has a hyper-positive sense of self, feeling “mildly high” about personal attributes such as “being more persuasive, creative, dynamic, entertaining, outgoing, and so on,” they may show less response to cognitive therapy (Lam, Wright, and Sham 2005:70), even if their mania symptom rating is not significantly different from someone who is more responsive (ibid:76).  For them, medication can certainly get them on the right path.  Bipolar tendencies towards extreme religiosity can also make them feel in depression as though they don’t deserve treatment, or, in a mixed episode as though they are going against the will of higher powers, or, in mania, as though they are a sort of god themselves who would be defiled by or impervious to treatment (Boland and Keller 2005, Polimeni and Reiss 2002).  They likely will need to be carefully reasoned with.  It can help such a sufferer in either a manic or nihilistic episode to know that a state of wellbeing is something different from what they have known and felt, something that would offer a challenge to their views about the world, and that trying it on for size with treatment doesn’t imply permanent commitment. 

Antipsychotic medications, unlike tricyclic and SSRI antidepressants (Bracken et al.: 431) for depression, have efficacy well in contrast to placebo for treating both schizophrenia (Leucht et al. 2012) and Bipolar Disorder (Cruz et al. 2010, Johnson et al. 2007, Loebel 2014).  If the patient or concerned caretaker is worried about side effects, there is good news.  The newer, “atypical” antipsychotics have less consistent, less endangering, and less occurring side effects than the older classes (Tandon 2002).  Some, such as “mood stabilizers,” which in many cases are the same class of drugs that treat convulsions, have been used safely and effectively for many decades, corroborating that there is indeed some sort of correlation between this psychologically disabling disorder and a physiologically disabling one.  Medications can have the effect of reducing creativity levels, however (Kyaga et al. 2011:373).  This may just be a matter of reduction in manic drive to, for example, focus on one creative task for days on end.  Even if they can be persuaded to take a low dose, where they may still be able to hold onto such a piece of the disorder they feel is uniquely “them,” it could still be enough to get them thinking straight, sleeping well, and able to function individually and cooperatively in society.  They may well grow to like the stability they have when medicated.  It must be remembered that, as bipolar disorder experiences are not just biomedical but rather biopsychosocial, the patient must be convinced that therapies will benefit them rather than just make it easier on the caretaker or easier for them to conform to societal norms.  They may feel manipulated otherwise.  Some sufferers of Bipolar Disorder, who experience psychotic delusions and/or hallucinations without provocation, may feel that such experience is a normal part of their disordered mentality.  For them, it may be far more difficult to reduce or disable such effects, but non-oppressive therapeutic activities have been, and are being, explored for both them and non-psychotic Bipolar Disorder patients. 

For those who do not necessarily experience psychosis as part of their disorder, nascent research shows that mindfulness meditation may be therapeutic when in remission (Williams et al. 2007) and when treated with mood stabilizers and/or atypical antipsychotics (Miklowitz, et al. 2009).  Disorder Specific Psychotherapies (DSPs) such as Cognitive Behavioral Therapy (CBT), Family-Focused Therapy (FFT), and Interpersonal and Social Rhythm Therapy (IPSRT) all have proven statistically helpful, though it is not certain which methods work best in which combinations to make a difference on “the durability of treatment effects, the relative effects of DSPs on mania versus depression, or their effects on psychosocial functioning” (Miklowitz 2009:117).  Such methods include foci on “early identification of prodromal symptoms, medication adherence, sleep/wake cycle stabilization, cognitive restructuring, and family communication styles” as well as “psychoeducation, including information about medications and side effects, [...] and community advocacy for the patient” (ibid:117-118).  That advocacy is but one social environment key to health: 1 in 5 Bipolar Disorder sufferers across Europe experience psyche-destructive self-stigma (Brohan et al. 2011), and it is likely that reductions in societal stigma, enacted through proper illness education and anti-discrimination legal defense, can reduce self-stigma prevalence.  Promising research into this has being ongoing in Europe via the Time to Change Program (Henderson and Thornicroft 2009; Henderson et al. 2016), and is crucial because there is currently no unified model of public stigma towards Bipolar Disorder to be effectively transformed (Ellison, Mason, and Scior 2013:818).

Though corroboratively concluded to be mostly effective via randomized controlled trials (Prasko et al. 2013), there are still confounders with the DSPs that may actually be sharply addressed by such social reform.  “[B]rief interventions emphasizing medication adherence or early identification and intervention with prodromal symptoms have significant effects on manic symptoms but virtually no impact on depression” (Miklowitz 2009:118), which seems to require intensive long term care with therapies used for schizophrenia or Major Depressive Disorder.  Of all methods mentioned, CBT seems more published on, and proves to be useful in many cases (Basco et al. 2007:8-11), however, when results of research where patient treatments in one study were controlled for in regards to the amount of times they had experienced prior episodes, those with >12 were much harder to treat (Basco et al. 2007:11; Miklowitz 2009:119).  CBT may be most promising, but these findings may “reflect the greater chronicity and cyclicity of BPD over time” (Basco et al. 2007:11) and may therefore “indicate that intensive [CBT] should be considered at an early point in the “illness career” of individuals with BD [Bipolar Disorder] rather than after multiple episodes” (Miklowitz 2009:119, emphases added).  This tells of how the aforementioned social campaigning is important for another reason: helping a non-stigmatizing public to recognize early onsets of Bipolar Disorder in each other, and then to give suggestive warnings.  This could make a dramatic difference in treatment requirements and outcomes.  It could be that someone who is more educated about the disorder and begins to show signs of it themselves will not even need such warnings, and will choose to self-admit.  Even further effectiveness would come from genetic testing at the doctor’s office thereafter.  No matter what is done for them, sufferers will be positively altered by treatment in one way or another – especially by a pharmacological approach – and most all people have a degree of fear or uncertainty towards major personal change, even if they are even somewhat aware that it will be for the better.  I have something to say about this. 

A Personal Note


The following are suggestions of my own, wrought from personal experience with Bipolar Disorder.  If the patient damns themselves or feels supernaturally damned for even the slightest of wrongs they have ever done, or for the slightest imperfections in their being, they can be reminded that everyone makes mistakes and nobody is perfect, and, that if humanity, as a collective, or even cosmic powers, did not offer living things the opportunity to cooperate, let alone be different (rather than "imperfect") enough to change the status quo, the very idea of beauty would be narrow, shallow, and vain.  There is also promise in the idea that treatment can help a bipolar sufferer reduce the number of risky or careless decisions they make, in both action and interaction, therefore offering a return to balance of inner self and peaceful socialization.  If the sufferer is unreasonably self-loathing beyond this, it can help to let them know that they are for the most part like everyone else in the world, but with complications that are helping everyone to know more about where the wonderful gift we call consciousness even comes from, and that their perspective is valued whether or not historically (to Westerners) it was feared - that social campaigns, spearheaded by those who empathize, are in the works to help the public understand, care for, and respect sufferers.   This may make them feel useful but not better; it is probably good to let them know that the recent and forthcoming advances in medicine and technology can help them to feel increasingly more stable and comfortable over time as they update their treatment plans.  If, in mania, they feel irrationally empowered, with seemingly no need for sleep and no limit to their capacity for either sharpened interaction or the creative process, justifying through that empowerment their continued existence as an untreated person, it might be helpful to remind them of some famous, similarly disordered people existing today who, since embracing therapy, are self-reportedly far more independent and happy, let alone socially powerful.  After all, both euphoria and augmented social agency are very enticing for people in manic episodes, and there is promise in these existing outside of an untreated state.  And, no matter what, it can't hurt to remind a sufferer that self-destructive behaviors in either mania or depression do not resonate with their existence as an "enlightened" being (i.e., depending on which extreme they are in, many bipolar sufferers, unlike MDD sufferers, will feel at least somewhat more enlightened than others).  They must remember that they are appreciated for their potential role in the world, and only a step away from the success in relationships and productivity that they both toil and despair over.

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