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In Bipolar Disorder

Bipolar Disorder and the Nature vs. Nurture Debate

Bipolar Disorder and the Nature vs. Nurture Debate
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An age-old question remains in understanding the root cause of bipolar disorder: To what extent does genetics or life experience play a role in the development of bipolar disorder?

Bipolar disorder is a mental illness where patients experience recurrent episodes of mania or hypomania and depression. Approximately 2% of Australians will experience bipolar disorder in their lifetime.

On The Nature Side Of The Debate, There Is Strong Evidence For Genetics Playing A Major Role In Bipolar Disorder

The origin of the idea for the genetic basis of bipolar disorder dates back to the French psychiatrist Jean Pierre Falret, who in the late 19th century observed the illness (which he characterised as a cycling mood disorder) clustered in families.

More recent twin studies have shown that bipolar disorder is one of the most heritable of medical disorders, with bipolar I and bipolar II disorder being at least partly genetically distinct. Identical twins, who are genetically identical, are much more likely to have the illness if the other twin has it compared to fraternal twins, who are not genetically identical.

Studies from the 1960s have shown the risk for bipolar disorder in first-degree relatives of those with bipolar disorder is approximately 9%, approximately ten times that of the general population.

Genetic Studies Shedding More Light

 In genetic association studies, scientists use genetic markers to directly observe a relationship between the prevalence of the illness in the population under study and the prevalence of risk-associated genetic markers in that same population. The results of modern genome-wide association studies support the idea that bipolar disorder involves a handful of candidate risk genes, but these genes are usually not specific to bipolar disorder but have instead been associated with a wide range of other disorders, including schizophrenia.

Recent evidence from genome-wide association studies has identified a risk locus for bipolar disorder containing the SYNE1 gene, a gene known to code for many proteins. Most notably, this gene codes for a brain-specific protein located at excitatory postsynaptic sites, where it regulates glutamate (the primary excitatory neurotransmitter in the brain) receptor internalisation. This particular protein, named CPG2, has been found to be significantly decreased in the postmortem brains of those with bipolar disorder. This genetic variation found may have important implications in understanding the mechanism behind synaptic dysfunction in bipolar patients, paving the way for further understanding and new effective treatments targeting brain circuitry.

Based on a meta-analysis of the current data, scientists estimate that 60-85% of the individual risk for bipolar disorder is genetically determined.

As of late 2018, The international Genetics of Bipolar Disorder Study is looking to recruit 5,000 Australians that have been treated for bipolar disorder in an internationally collaborative genome study. This high sample size study will greatly aid in the identification of genes that predispose individuals to bipolar disorder, potentially informing both prevention and future treatment options.

On the nurture side, many lifestyles and environmental risk factors may also contribute to the development of bipolar disorder.

This includes alcohol and drug dependence, physical and sexual abuse, and early childhood adversity. Other associated risk factors for bipolar disorder include social nonconformity, withdrawal and social isolation, bullying, bereavement of a close relative, and other addictive drug abuse.

It has been shown that childhood trauma triggers the onset and especially clinical course. Bipolar patients with a trauma history are more likely to show a rapid cycling course, psychotic features, high number of lifetime mood episodes. Trauma is also associated with greater risk for suicide ideation and attempts and substance misuse. Stress is also a major predictor of bipolar disorder in people who are predisposed. Stressful life events like childbirth, bereavement and job loss may trigger a mood episode.

From one meta-analysis based on bipolar patient data between 1980-2014, patients with bipolar disorder were found to be over twice as likely to have suffered from childhood adversity as those who did not. The largest factor noted was emotional abuse, such that bipolar adults were four times more likely to have suffered early emotional abuse. This fact has important implications for informing treatment options, especially for bipolar patients involved in a therapeutic relationship where these early adversities can be addressed and understood in a safe manner.

Closing Thoughts

In resolving the nature vs nurture debate, the current evidence points towards the fact that the truth is likely somewhere in the middle. It has been shown through studies from the aspiring field of epigenetics that certain emotional and physical traumas can actually affect which genes are turned on and off, making the relationship between nature and nurture more complex and cross-wired than traditionally thought.

Similarly, strong genetic predisposition does not necessarily predict disease onset or outcome, especially if positive lifestyle and environmental factors are providing stable and resilient buffers to the development of the disorder.


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