Mania & Bipolar Disorder.

More About Mania and Bipolar Disorder.

On the level of psychopathology, seen in clinical presentation, bipolar disorder involves two syndromes that most often alternate between each other referred to as (hypo)mania and depression. In mania, there is excitation of psychomotricity (motor activity) and affectivity (positively or negatively grandiose or irritable mood), and inhibition of thought. On the other hand, in depression, there is inhibition of psychomotricity and affectivity, and excitation of thought.

This psychopathology is largely due to network balancing alterations, with an overall pattern of disrupted cortico-striatal-limbic circuits (according to the cortico-limbic hypothesis). In mania, there is increased sensorimotor and salience network (SMN and SN, respectively) activity and decreased default mode network (DMN) activity. In depression, there is decreased SMN and SN activity and increased DMN activity. The salience network corresponds with affectivity. The sensorimotor network corresponds with psychomotricity. The default mode network corresponds with thought.

These networking abnormalities are largely related to underlying subcortical-cortical coupling abnormalities, which refer to the way that upper and lower brain regions communicate with each other. This is reflected in underlying neurotransmitter (brain chemical messenger) signaling changes, which are related to structural changes and dysconnectivity along with over-activity in the limbic network (which includes the brainstem nuclei that synthesize and store neurotransmitters). This is evident in corresponding white matter microstructure abnormalities, which are especially evident in the limbic or subcortical regions of the brain.

Signs and Symptoms.

The syndrome of depression is well-captured by the acronym (SIGECAPS):

• S: Sleep disturbances

• I: Interest decreased, referred to as anhedonia

• G: Guilt and/or feelings of worthlessness

• E: Energy decreased

• C: Concentration problems

• A: Appetite and weight changes

• P: Psychomotor agitation or sluggishness, changes in activity/movement

• S: Suicidal ideation or death preoccupation

The syndrome of mania is well-captured by the acronym (DIGFAST):

• D: Distractible

• I – Insomnia (decreased need for sleep)

• G – Grandiose (positive or negative)

• F – Flight of ideas/racing thoughts

• A – Agitation (psychomotor) or increased goal-directed activity

• S – Speech (increased pressure, hyperverbal)

• T – Thoughtlessness (impulsivity, unrestrained buying, sexual indiscretions, etc.)

Mania and hypomania differ in episode length: Mania lasts one week or more, and hypomania lasts four days or less.

Causes.

The leading theoretical cause of bipolar disorder that sets all of these changes in motion is immune dysregulation. It has been extensively shown in multiple studies that there is widespread immune activation with a predominant pro-inflammatory profile. However, bipolar disorder is a complex illness that likely includes a combination of biological, lifestyle/environmental, and psychological factors. These factors contribute to the aforementioned networking abnormalities and include the following:

Biological Factors:

• Impaired genetic abnormalities (e.g., MTHFR or COMT abnormalities). Bipolar disorder is one of the most heritable conditions with a 75-80% heritability rate. Having a first-generation relative (i.e., mother or father) with bipolar disorder greatly increases the risk of developing this condition.

• Impaired immunity (i.e., inflammatory hypothesis)

• Altered endocrine function (e.g., hypothyroid, hyperthyroid, hypercortisolemic/adrenal, and glycemic dysregulation)

• Post-partum and peri-menopausal changes

• Dysregulated chemical signaling (serotonin, norepinephrine, and dopamine)

• An imbalance of brain growth and development hormone (e.g., neurotrophins such as brain-derived neurotrophic factor).

• Imbalanced cofactors, methylation, and nutritional factors (e.g., vitamins and minerals)

• Impaired receptor responsiveness (i.e., reception and response to brain chemicals)

• Impaired gut health (i.e., gut dysbiosis)

• Substance-induced dysregulation (e.g., cannabis, alcohol, benzodiazepines, opioids, cocaine, methamphetamine, hallucinogens). Cannabis use greatly increases one’s risk for activated bipolar disorder.

• Medication-induced (certain medications can contribute to mood dysregulation in bipolar disorder such as steroids, contraceptives, and beta blockers; also serotonergic drugs like SSRIs/SNRIs and Tricyclic antidepressants may activate a manic-like syndrome)

Lifestyle/Environmental Factors: traumatic experiences (single incident, multiple incidents, developmental, or transgenerational), adverse childhood experiences, stressful events (accumulation of small stressors and/or large stressors), socioeconomic strain, impaired or dysfunctional relationships, separation or loss, sedentary lifestyle or impaired ability to exercise, nutritional imbalances and food intolerances/sensitivities, inadequate or impaired sleep, substance use at al. addictions, seasonal changes and nature deficit.

Psychological Factors: coping skills and resources, stress responsivity, perception of self (including a mismatch between ability and performance), sensitivity to rejection, interpretation bias, rumination, negative emotionality, attachment style, and personality structure (including personality disorder).

Screening.

The most widespread tool for screening for depression is the Mood Disorder Questionnaire (MDQ). This is a brief tool used to rule out bipolar disorder. A more recent and well-validated screening tool is the Rapid Mood Screener (RMS). The 6-item RMS was developed to reduce the potential for false positive screening and has slightly better psychometric properties compared with the MDQ. Answering “yes” to 4 or more items is a positive screen with 88% sensitivity and 80% specificity (McIntyre et al., 2020). Answering “yes” to 3 or more items suggests a higher likelihood of bipolar disorder than major depressive disorder with an estimated 97% sensitivity and 59% specificity (McIntyre et al., 2020). Sensitivity refers to the ability of a test to “rule out” a diagnosis. The higher the sensitivity, the more accurate the test is at ruling out the diagnosis if the test is negative. Specificity on the other hand refers to the ability of a test to “rule in” a diagnosis. The higher the specificity, the more accurate the test is at ruling in the diagnosis if the test is positive. In both cases, the specificity remains significantly high, but the specificity remains low. This is where clinical and diagnostic expertise comes in to ensure that your symptoms are not more consistent with another condition.

Diagnosis.

To meet criteria from a Conventional Psychiatry perspective using the standardized DSM-5, bipolar disorder requires a current or historical episode of 3 or more symptoms of mania and a current or historical episode of 5 or more depressive symptoms (one of which must be low mood or loss of interest). Bipolar 1 disorder is defined as an experience of manic episode(s) that last 1 week or more. In Bipolar 2 disorder the individual experiences hypomanic episodes lasting 4 days or less. In Bipolar 2 disorder, depressive episodes are typically worse and there is a higher suicide rate compared with Bipolar 1 disorder. Another variant is Cyclothymic disorder, which is an oscillation between subsyndromal mania and depression. Oftentimes, bipolar disorder starts with depression (especially early onset) and evolves into what’s referred to as a Mixed State prior to experiencing (hypo)manic episodes, these states involve what is commonly referred to as the 4 A’s (Agitation - physical restlessness, Anger/irritability, Anxiety, Attention disturbance). This can precede (hypo)manic episodes or be the predominant cycling mood state in bipolar disorder.

It seems however that more emergent research and clinical findings suggest that bipolar and related disorders lie on a multidimensional spectrum. One spectrum speaks to the mood elements (i.e., depression and mania) and another spectrum speaks to the psychotic elements of bipolar and related disorders. Bipolar disorder shares some genetic commonalities with schizophrenia and is being considered as potentially on the same spectrum. That being said, there seems to be more variants of bipolar spectrum than just 1, 2, and cyclothymic. Some researchers have identified as many as 12 variants along the mood disorder spectrum. These phenotypes tend to respond differently to treatments and it may benefit clinicians and those experiencing bipolar symptoms to consider these.

In the specialty of integrative psychiatry, we expand these syndromic labels to identify particular morphologies (subtypes) that are indicative of particular root causes. Then the focus becomes exploring the root causes of mood and affective disorders so that a more individualized plan of care can be developed for you.

Treatment.

Mania and Bipolar disorder often necessitate a combination of treatments, which is much more likely to yield positive results, and this combination depends on the individual’s experience.

Medications.

Common medications used in the treatment of bipolar disorder include second-generation antipsychotics (SGAs) and mood stabilizers. Sometimes monotherapy is effective, but more often than not, combination treatment is required to achieve mood stability. Standard antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs) are not recommended alone in the treatment of bipolar depression. These options are often, at best, ineffective but, in many instances, contribute to activation where the individual experiences manic symptoms in the context of standard antidepressants.

Nutraceutical.

Nutraceutical treatments may not be a first-line for bipolar disorder, especially moderate-to-severe bipolar disorder. However, nutraceutical options can certainly treat some of the underlying causes and contributing factors that lead to mood dysregulation in bipolar disorder. In some cases, a fully naturopathic approach to bipolar disorder is appropriate. Some treatments may be considered as add-on options such as vitamin and mineral replacement and supplementation (depending on bloodwork), anti-inflammatory nutraceuticals such as curcumin and N-acetylcysteine, and other adjunctive treatments such as L-methylfolate and Inositol.

Bodily-based Evaluation.

An evaluation of body systems is crucial in the context of mania and bipolar disorder. A baseline evaluation of critical body systems should be conducted to rule out any causes or contributing factors. Many of these areas are addressed above in the “causes” section. Of particular importance is evaluating factors that drive inflammation and autoimmunity, which are at the core of bipolar pathophysiology and should be examined and stabilized. Your integrative psychiatry professional will be able to help you navigate these considerations based on your experiences.

Lifestyle.

Several lifestyle modifications can help improve bipolar disorder symptoms:

• Habits: Reducing and eliminating substance use and other addictions. Although easier said than done, this often involves multimodal treatment and exploration of root causes.

• Sleep: Stabilization of sleep routines and patterns (e.g., reducing blue light exposure from screens 4 hours before bed, avoiding stimulating activity before bed, etc.) with a goal of 6-7 hours per night (sometimes medication or nutraceutical options are helpful here).

• Exercise: Moderate intensity exercise (e.g., walking) with a goal of 3-4 times per week has the best evidence basis for improving upon depression as well as mania, though any activity is better than none. It’s recommended to start with something you enjoy and build upon a routine and habit from there. Excessive strenuous exercise tends to contribute to more inflammation and can contribute to mood instability.

• Nutrition: Dietary adjustments such as sugar reduction (<10% added sugar in products) and a goal of a Mediterranean diet with healthy fats and high fiber have been shown to improve depressive and manic symptoms. Having nutrient-dense snacks while experiencing mania is helpful, too, to prevent nutritional deficits that can worsen bipolar symptoms.

Therapy.

Therapy aims to re-establish top-down control and typically involves a bi-modal approach: interventions to help with cortical strengthening (e.g., cognitive restructuring, behavioral activation, goal-oriented activity, navigating through problems and stressful encounters et al.) and subcortical strengthening (e.g., emotion regulation, stress reduction, et al.). There may be an incorporation of other tools, such as trauma-related work and existential therapy, to alter the impact of trauma.

Common therapy modalities used in the treatment of depression include cognitive-behavioral therapy (CBT), dialectical behavioral therapy (DBT), psychodynamic psychotherapy (PDT), positive psychotherapy (PPT), and solution-focused or problem-solving therapy (SFT/PST), among others.

If I were to recommend one thing, I would encourage monitoring activities in some way, tracking the mood associated with activities. This gives a tremendous insight into how your daily activities impact your mood and where you could make changes to improve your mood. Try this free downloadable Activity Monitoring Template. Feel free to use or adjust the instructions based on your needs. This can be used broadly to monitor most activities, or you could focus on specific activities and track how they impact your mood.

Additional Treatments.

Targeting biological derangements with treatments such as thyroid supplementation, B12/folate supplementation, iron, and vitamin D can reduce symptoms of depression and mania. Transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) have also been used in bipolar disorder. Ketamine therapy is being used more commonly to treat bipolar disorder as well and has been effective in several cases, especially those with refractory depressive symptoms.