The Highs and Lows of Bipolar Disorder

Kanye West, Jimi Hendrix, Carrie Fisher, Frank Sinatra, and Vincent Van Gogh-what comes to mind when you hear these names? Many would say creative, gifted, accomplished, and brilliant due to the incredible art and talent they have shared with the world. However, what many do not realize is that all of these individuals have suffered from bipolar disorder (BD) [1]. BD is a psychiatric illness characterized by extreme mood swings, which include emotional highs known as mania and hypomania, and lows, otherwise known as depression [2]. Mania is described as a period when one experiences increased energy and activity, high irritability, and racing thoughts [3]. Hypomania exhibits similar symptoms as mania, however the main difference is the duration and intensity [3]. Some individuals suggest that people with BD are unstable, and prone to violence, but when treated appropriately by medical and psychology professionals, many of the symptoms of BD are manageable such that patients can have relatively normal lives [4]. Globally, the prevalence of BD is around 1%, with an equal distribution of the disorder between men and women [5]. In those with BD, around one out of three individuals attempt to commit suicide, and about 15-20% of those attempts are successful [5].  Based on these statistics, it is important to shed light on the symptoms and causes of BD, neurological changes in those diagnosed, as well as current treatments available, in order to reduce misinformation and destigmatize the disorder. 

Types of Bipolar Disorders and Symptoms: 

Medical professionals categorize BD into two subtypes called BD Type 1 and BD Type 2. In order to be diagnosed for BD type 2, one must experience at least one depressive and hypomanic episode in their lifetime, but have never experienced a manic episode [2]. BD type 1 involves one or more manic episodes or mixed (manic and depressive) episodes and may include a major depressive episode, however a depressive episode is not required for a diagnosis [6]. Each type exhibits similar symptoms, yet the intensity of these symptoms depend on the type of disorder a person has. The main difference between these disorders is the occurrence of a manic episode, as in BD type 1, versus a hypomanic episode, as in BD type 2, with either occurring at least once in their lifetime [6]. Individuals in a manic episode may exhibit impulsive decision making, often leading them to use drugs and alcohol, feelings of high self-confidence, and the inability to sleep [3]. If the episode is severe enough, individuals may also experience psychosis, which is when one experiences disruptions to their perception and thoughts, making it very difficult for them to know what is real and what is not [2]. Symptoms of psychosis can include delusions, visual and auditory hallucinations, confusion, and paranoia [7].

Although BD type 1 and BD type 2 differ with respect to mania, both subtypes exhibit similar symptoms in terms of depression [5]. Symptoms include hopelessness, guilt, sleep disturbances, suicidal ideation, and anhedonia (the inability to feel joy during pleasurable activities) [5]. The length of a depressive episode typically differs among patients with BD Type 1 versus Type 2. Depression in BD type 2 tends to last longer, with the average duration of the episode lasting around 5-6 months. In BD type 1, episodes can be as short as 2 weeks, if depressive episodes occur [8]

Etiology of Bipolar Disorder: 

Despite decades of research, scientists do not have a complete picture of how BD works neurologically and the main factors that contribute to its development [9]. Nonetheless, it is theorized that interactions between several genes, neurochemical imbalances, and environmental factors are involved in the etiology, or cause of the disorder [9]. Research evidence supports that complications with several genes, such as the dopamine transporter (DAT1) gene and serotonin transporter (5-HTT, SERT) gene play a role in the manic and depressive symptoms of BD [9]. Dopamine is a neurotransmitter, or a chemical messenger that is associated with feelings of reward and reinforcement, motor control, and motivation [10]. Within the brain, DAT is responsible for the reuptake of dopamine back into the neuron synapse [11]. In comparison, serotonin is a neurotransmitter involved in various functions, such as mood, sleep, appetite, and digestion [10]. For serotonin, SERT is responsible for its reuptake back into the neuron [12]. In BD, it is hypothesized that manic symptoms are caused by excess dopamine within the brain, whereas the depressive symptoms are caused by a lack of serotonin [12]. Though gene complications and neurochemical imbalances play a large role in BD, these are not the only factors that contribute to its development. An individual’s environment and life stressors also have a significant impact on the expression of symptoms related to BD [13]. Life stressors including trauma or PTSD, head injuries such as a concussion, and lack of social or familial support are a few of the environmental factors that can contribute to BD development [13]. Although genetics and chemical imbalances, as well as environmental stressors may influence the development of BD, there are a number of potential causes that researchers are attempting to better understand. 

Neurological Changes in Bipolar Brains:

Neurological changes within the brains of those with BD have been examined in various brain imaging studies comparing healthy individuals to bipolar individuals. It has consistently been found that those with the disorder have a reduced amount of grey matter in various areas of the brain, as well as neuronal death [14]. Grey matter is mostly composed of the cell bodies of neurons, which are known as soma, and serves to process information within the brain. It also sends new information to the white matter, which contains the neuron axons that send electrical signals throughout the brain [15]. In a meta-analysis study examining 50 MRI experiments involving over 1,800 BD participants and 2,200 controls, or healthy participants, it was found that those with the disorder had a significant reduction of grey matter in the frontal lobe of the brain, more specifically in the anterior cingulate gyrus (ACC) and prefrontal cortex (PFC) [16]. The frontal lobe is extremely vital for executive functions such as attention, problem-solving, emotional regulation and judgment, with the ACC and PFC further aiding in these functions [17]. Specifically, the ACC has shown to help with decision-making, socially-driven interactions, and responses related to empathy [18]. The PFC plays a vital role in the frontal lobe of the brain and integrates information from various areas in the outer layer of the cerebrum [19]. The PFC is involved in higher processing of complex behaviors, such as working memory, sensory processing, emotion, and is heavily involved in the development of personality [19]. Grey matter loss and neuronal death in these brain areas have been linked to manic episodes, with each episode causing more damage, making it important to seek treatment as soon as someone experiences an episode [14]. Furthermore, research shows that decreases in brain-derived neurotrophic factor (BDNF) also plays a role in the disorder [12]. BDNF is a chemical molecule with diverse roles in the brain. It is most commonly involved in neuronal plasticity, which is the brain’s ability to adapt and change based on one’s experiences, and the growth and survival of neurons.  In the case of BD, various post-mortem studies indicate a significant decrease in BDNF levels in bipolar brains, ultimately suggesting its involvement in various aspects of BD [20].

Treatments for Bipolar Disorder: 

Pharmacological treatments for mania in BD include mood stabilizing medications such as lithium, anticonvulsants, and second generation antipsychotics (SGAs) [21]. Since the 1960’s, lithium has been the standard pharmacological drug used to treat manic and depressive symptoms in both BD type 1 and 2, and has been found to decrease the amount of mood episode recurrences [21]. Neurologically, lithium works by reducing the excitatory neurotransmitters dopamine and glutamate, which are abundant in the brain during mania, as well as increasing the inhibitory neurotransmitter Gamma Aminobutyric Acid (GABA), ultimately helping to slow down neuronal firing [22]. During a manic episode, neurons are rapidly firing and sending signals quickly throughout the brain, and in order to combat this, medications like lithium are prescribed to slow down excitatory neurotransmitter release and increase inhibitory neurotransmitter release in order to stop rapid neuronal firing [22]. When excitatory neurotransmitters like dopamine and glutamate are released, it makes it more likely for neurons to fire and send signals throughout the brain. Inhibitory neurotransmitters, on the other hand, make it less likely for neurons to fire when they are released [22]. SGAs are also used to treat manic BD symptoms and work similarly to lithium by reducing excitatory neurotransmitter release by blocking dopamine sites and increasing inhibitory neurotransmitter release [21]. SGAs are typically prescribed if an individual is experiencing symptoms of psychosis during a manic episode, but can also be prescribed to treat mania without psychosis symptoms, as well as depressive symptoms [23]. If a SGA by itself does not help treat depressive symptoms, a doctor may also prescribe another mood-stabilizing medication like lithium, or an antidepressant to take alongside the antipsychotic [23]. However, individuals with BD should never take an antidepressant alone, as it can induce a manic episode and cause rapid cycling, meaning one would experience four or more episodes of either mania, hypomania, or depression in a one year period [24]. Therefore, antidepressants should always be taken with a mood stabilizer [25]. Lastly, anticonvulsants can also be used as mood stabilizers, despite their primary use being for seizures caused by epilepsy [26]. Neurologically, they work in a similar way as lithium and SGAs and are known for their effective antimanic properties [26]. Like lithium, anticonvulsants can be used to treat depression, but their impact in treating mania is more successful [26]. Additionally, lithium, anticonvulsants, such as valproate, and antidepressants have been shown to increase BDNF levels in rodents within the brain areas associated with memory (hippocampus) and executive functioning (PFC). This suggests that medications like lithium, valproate and antidepressants have the ability to impact human emotion and could have mood stabilizing effects [20]. Although taking medication to treat BD is extremely important and necessary to combat severe symptoms and recurring episodes, doctors recommend that individuals with the disorder attend therapy in order to gain specific coping mechanisms geared towards living with BD [23]. By taking medication and going to therapy, those struggling with BD can live a healthy life that is not disrupted and controlled by the highs and lows of the disorder. 

The last few decades of bipolar research has been extremely useful in understanding how the disorder works in the brain, which brain areas and systems are impacted, and which medications are the most effective in treating symptoms in both types of the disorder. Despite the new knowledge scientists have gained through research, substantial information remains unknown about the neurological changes that cause and maintain BD [9]. Additionally, there is a tremendous amount of work that needs to be done in reducing misinformation and stigma surrounding the disorder. One of the key factors in reducing stigma is proper education about the disorder and its symptoms [27]. When discussing the disorder, it is important to use the appropriate terminology and to correct others who are using incorrect wording and spreading misinformation. Small actions such as being educated about BD, being conscious about using correct terminology when discussing the disorder, and increasing discussion about the disorder, can create a big change in how ourselves and others view BD, which ultimately helps to reduce the stigma surrounding the disorder. 

References:

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