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How Does Bipolar Disorder Impact the Brain, and Are There Remedies?

Dr. Khalid is a health researcher and science writer with a Ph.D. in clinical research.

Bipolar disorder affects multiple areas of the brain, leading to changes in cognition, mood, and behavior.

Bipolar disorder affects multiple areas of the brain, leading to changes in cognition, mood, and behavior.

What Is Bipolar Disorder?

Bipolar disorder (BD) or bipolar affective disorder (BPAD) is a multicomponent condition associated with physiological changes, immunological alterations, neuropsychological deficits, and severe mood disturbances (Rowland & Marwaha, 2018). It is associated with an elevated rate of premature mortality based on co-morbidities and suicide. It is a serious, disabling condition based on severe mood swings that lead to the development of displeasure, loss of interest, sadness, and hopelessness.

Hypomanic or manic depression in bipolar disorder not only irritates the affected patients but often makes them unexpectedly euphoric while deteriorating their rational thinking abilities, behavior, judgment, activities, energy, and sleep pattern (Mayo-Clinic, 2020). BD patients tend to deviate from the recommended pharmacotherapeutic interventions (Hilty, Leamon, Lim, Kelly, & Hales, 2008).

What Are the Symptoms of Bipolar Disorder?

Bipolar disorder leads to the development of the following symptoms as defined by the DSM–5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) criteria (Culpepper, 2014).

Manic Episodes

  1. Irritable, expansive, and elevated mood (reported throughout the day, and for the 1-week duration)
  2. Elevated goal-directed activities (reported throughout the day, and for the 1-week duration)
  3. Elevated energy level (reported throughout the day, and for the 1-week duration)
  4. Elevated activity level (reported throughout the day, and for the 1-week duration)
  5. Elevated engagement in irrational activities, including inappropriate business investments, injudicious venereal inclination, and sprees
  6. Psychomotor agitation and goal-directed interventions
  7. Distractibility
  8. Racing thoughts (subjective experience) and fight of ideas
  9. Excessive talking
  10. Reduced sleep requirement
  11. Grandiosity/self-esteem inflation
  12. Occupational and social impairments based on mood disturbance/psychotic conduct warranting hospitalization to minimize the risk of harmful behaviors
  13. Psychotic episodes unrelated to substance/medication/drug abuse

Hypomanic Episodes

  1. Persistently elevated energy level/goal-directed activity (reported throughout the day and for 4-consecutive days)
  2. Persistently irritable/expansive/elevated mood (reported throughout the day and for 4-consecutive days)
  3. Grandiosity/self-esteem inflation
  4. Reduced sleep requirement
  5. Excessive talking pressure
  6. Racing thoughts (subjective experience) and fight of ideas
  7. Distractibility based on external stimuli
  8. Psychomotor agitation and elevated goal-directed activity at personal, professional, and social fronts
  9. Elevated engagement in irrational activities, including inappropriate business investments, injudicious venereal inclination, and sprees
  10. Unique changes in personality and functioning
  11. Noticeable functional change and mood disturbances
  12. A noticeable manic episode or an episode devoid of psychotic symptoms without any marked impact on occupational and social functioning
  13. The symptoms do not correlate with the consumption (use or misuse) of medications and/or drugs

Note: Bipolar–I disorder is based on the occurrence of a manic episode (at least once in a lifetime) and does not necessarily require the reporting of hypomanic episodes (Culpepper, 2014). However, the diagnosis of bipolar–II disorder warrants the affirmation of both major depressive and hypomanic episodes (with current or past status).

Is There a Difference Between Bipolar Disorder and Major Depressive Disorder?

Psychiatrists and physicians experience challenges in differentiating bipolar disorder from major depressive disorder (MDD). Patients affected with bipolar disorder experience depressive episodes for a prolonged tenure (Culpepper, 2014). The following interventions effectively help distinguish bipolar disorder while ruling out the occurrence of MDD.

  1. Assessment of the family history of depressed patients is necessary to rule out MDD. This is because a family history of mood disorders potentially increases the risk of bipolar disorder and its manifestations.
  2. Assessment of treatment history helps to identify the onset of bipolar disorder in depressed patients. This is because antidepressant mono-therapy elevates the risk of manic episodes in BD patients. Furthermore, the absence of therapeutic response to antidepressant therapy in depressed patients also elevates the risk of bipolar disorder.
  3. Illness pattern assessment is a robust measure to identify the occurrence of bipolar disorder in patients suspected for MDD. This is because bipolar disorder is associated with recurrent episodes of depression based on psychosis and melancholia.
  4. Assessment of atypical depression features is necessary to affirm the onset of bipolar disorder in suspected patients. The atypical depression attributes of bipolar disorder include pathological guilt, psychomotor retardation, psychotic symptoms, mood lability, rejection sensitivity, hyperphagia, and hypersomnia.
  5. Age evaluation of depressed individuals is necessary to identify the risk of bipolar disorder. This is because bipolar disorder patients exhibit preliminary symptoms during their adolescent tenure (i.e., the age range of 13–18 years). Contrarily, MDD patients report their preliminary symptoms after acquiring the age of 20 years.

Note: The occurrence of hypomania or mania is a prerequisite for diagnosing bipolar disorder. The occurrence of mania in depressed patients is indicative of bipolar-I disorder. However, the onset of hypomania in MDD suspects indicates bipolar-II disorder. This is why MDD suspects require a thorough evaluation of their manic and/or hypomanic episodes. Psychiatrists must utilize clinical interviews and bipolar screening tools to affirm/rule out the occurrence of bipolar disorder in MDD suspects.

What Are the Risk Factors of Bipolar Disorder?

Genetic Predisposition/Vulnerability

Children of patients with a clinical history of bipolar disorder (BD) experience a high risk of inheriting mania and depression (Miklowitz & Johnson, 2006). The BD genes potentially induce dopamine dysregulation that gradually facilitates the development of psychotic episodes. Numerous genes interact with the environmental factors in a manner to cause neurological changes conducive to the development of bipolar disorder. However, prospective research studies are required to evaluate the interactive patterns and BD-causing potential of these deleterious genes.

Dysregulation of Neurotransmitters

Evidence-based clinical literature claims the association of manic episodes with dopamine/ norepinephrine elevation (Miklowitz & Johnson, 2006). Researchers also correlate manic episodes and mood fluctuations with dysregulated serotonin/dopamine systems and their interaction with Substance-P and GABA (i.e., neurotransmitter systems). Sleep deprivation and consumption of dopaminergic drugs adversely impact dopamine receptors in a manner that induces the development of manic episodes.

Various research studies have discovered interactions between dopamine receptors in various brain centers (i.e., striatum, ventral tegmentum, and nucleus accumbens) that potentially trigger the reward motivation processes. This eventually leads to psychomotor stimulation and behavioral sensitization of the affected individuals. Furthermore, the elevated secretion of dopamine triggers the behavioral dysregulation processes that result in the onset of preliminary BD symptoms.

Dysregulation of Brain Regions

Various research studies reveal functional abnormalities in the below-mentioned regions of the human brain that elevate the risk of bipolar disorder and associated clinical manifestations (Miklowitz & Johnson, 2006).

  1. Prefrontal cortex (volume/activity reduction)
  2. Basal ganglia (volume reduction, leading to elevated reward motivation)
  3. Hippocampus (volume reduction)
  4. Anterior cingulate (volume reduction)
  5. Amygdala (volume/activity elevation, leading to emotional sensitivity)
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Emotional dysregulation in BD patients potentially reduces their emotional sensitivity to negative stimuli during the manic episode. They eventually exhibit limited neural responsiveness to acts of intimidation and instead become hyperactive under the impact of elevated reward motivation.

Psychological Attributes

Bipolar disorder relapses through the active contribution of the following psychological predictors (Miklowitz & Johnson, 2006).

  1. Stress score of greater than 4.5
  2. The exposure of bipolar–I disorder patients to family attitudes based on guilt-induction, emotional over-involvement, hostility, and criticism
  3. Interaction with expressed-emotion conduct or affective negativity
  4. Negative threats
  5. Sleep deprivation due to stressful life events, including childbearing and trans-meridian flights
  6. Goal engagement/attainment elevation
  7. Defensive responses
  8. Social stresses or social stimulation
  9. Stressful job based on rotational shifts
  10. Disruption of the sleep-wake cycle or circadian rhythm

Can You Prevent Bipolar Disorder?

No standard preventive measure has been developed so far to challenge the onset of bipolar disorder in predisposed individuals. However, some of the below-mentioned steps can assist in identifying and controlling the preliminary symptoms of BD to some extent (McNamara, Nandagopal, Strakowski, & DelBello, 2010; Health Link BC, 2019).

  1. Identification and treatment of prodromal mood symptoms
  2. The proactive administration of mood stabilizers and psycho-stimulant/antidepressant drugs following the onset of a manic episode
  3. Administration of neuro-protective/neurotrophic omega-3 fatty acids
  4. Family-focussed therapy following the appearance of psychotic symptoms and depression
  5. Regular exercise
  6. Maintenance of healthy sleep pattern
  7. Consumption of a balanced diet
  8. Maintenance of discipline in daily routine
  9. Stress management
  10. Regular monitoring of mood swings
  11. Enhancement of self-efficacy
  12. Proactive configuration of an action plan to counter the occurrence of manic episodes
  13. Avoidance of illicit drugs, alcohol, and similar substances
  14. Reduced intake of caffeine

It is best to consult a physician or psychiatrist if someone exhibits early signs of bipolar disorder before attempting prevention or treatment regimens.

What Are the Possible Treatment Options for Bipolar Disorder?

Pharmacological Management

Mood stabilizers can help control serious mood fluctuations in BD patients (Shah, Grover, & Rao, 2017). The commonly utilized mood stabilizers for treating bipolar disorder include:

  1. Lithium
  2. Valproate/Divalproex
  3. Oxcarbazepine/carbamazepine
  4. Lamotrigine
  5. Topiramate
  6. Gabapentin

Lithium helps control BD relapse episodes and also reduces the risk of suicide among psychotic patients. However, lithium therapy is also associated with the risk of ataxia, dysarthria, tremor, gastrointestinal complications, polydipsia, and polyuria.

Physicians need to consistently monitor serum lithium levels of BD patients, particularly in scenarios where they concomitantly receive diuretics for treating their kidney problems. Biannual repeat investigations to record serum calcium, eGFR, thyroid function, serum creatinine, serum urea, urinary proteins, and urine volume are highly necessary to reduce the risk of adverse effects during lithium therapy.

Valproic acid and valproate, or Divalproex, assist in controlling mixed BD episodes and acute mania. Careful administration of Divalproex is required while treating the BD patients affected with bleeding problems, hematological complications, and hepatic manifestations. Most importantly, serum valproate must not exceed its therapeutic range of 50-100 mcg/ml.

Lamotrigine helps control the relapse of depressive episodes in BD patients. The adverse effects of lamotrigine include toxic epidermal necrolysis, Stevens-Johnson syndrome, and skin rash.

Carbamazepine helps in controlling the relapse of acute bipolar mania. However, the thorough monitoring of hepatic dysfunction and blood dyscrasias during carbamazepine therapy is highly needed to reduce the risk of clinical complications. The side effects of carbamazepine therapy include skin reactions, hematological dysfunction, and hepatic impairment. Physicians need to ensure that serum carbamazepine must not exceed its therapeutic level of 4-12 mcg/ml following the administration of carbamazepine therapy.

Antidepressant therapy for BD patients is based on the administration of drugs including mirtazapine, bupropion, norepinephrine/selective serotonin reuptake inhibitors, serotonin, and other tricyclics (Shah, Grover, & Rao, 2017).

Antipsychotic pharmacotherapy is the treatment of choice for bipolar mania and bipolar depression. First/second-generation antipsychotic medications include long-acting preparations and depot/parenteral/oral drugs (Shah, Grover, & Rao, 2017).

Somatic treatments for BD include t-DCS (transcranial direct current stimulation), r-TMS (trans-cranial magnetic stimulation), and ECT (electroconvulsive therapy). These treatments help in controlling bipolar depression, mixed episodes, and acute mania (Shah, Grover, & Rao, 2017).

Adjunctive pharmacotherapy for BD treatment is based on lithium carbonate, anticonvulsants, hypnotic-sedatives, benzodiazepines, anti-depressants, and anticholinergics (Shah, Grover, & Rao, 2017).

Non-Pharmacological Management

IPSRT (Interpersonal and social rhythm therapy) helps enhance BD patients’ interpersonal relationships and social rhythms. IPSRT also assists in improving the social routines of BD patients to enhance their satisfaction levels (Shah, Grover, & Rao, 2017). This therapy increases the patients’ awareness of stressful events and medication non-compliance issues that potentially elevate the risk of manic episodes. The regular administration of IPSRT to BD patients reduces their risk of mood swings and circadian rhythm disruption. IPSRT improves the overall coping skills of BD patients for the systematic management of their mental health complications.

CBT (Cognitive Behavior Therapy) requires co-administration with the maintenance treatment (of bipolar disorder) to reduce the intensity and frequency of manic depression (Shah, Grover, & Rao, 2017). CBT helps BD patients improve their treatment compliance and problem-solving skills. CBT also assists BD patients in improving their coping skills related to the management of psychosocial stressors and depressive episodes.

FFT (Family-focused therapy) is based on psycho-education (of BD patients and their family members) related to treatment adherence, etiology, early recognition, and symptoms (Shah, Grover, & Rao, 2017). This therapy also enhances the stress-coping potential of BD patients while improving their communication skills and overall personality.

Dietary and lifestyle modifications are paramount to reducing manic and/or hypomanic episodes in BD patients. Some of these lifestyle approaches include smoking/alcohol abstinence, dietary modifications, and physical exercises (Shah, Grover, & Rao, 2017).

FIMM (Facilitated integrated mood management) sessions assist in reducing the recurrence of BD symptoms through the provision of comprehensive mood management strategies (Miklowitzs et al., 2012). This potentially helps in improving the daily routines of BD patients. FIMM also modifies the sleeping pattern of BD patients while reducing their risk of substance abuse.


Culpepper, L. (2014). The Diagnosis and Treatment of Bipolar Disorder: Decision-Making in Primary Care. The Primary Care Companion for CNS Disorders, 16(3). doi:10.4088/PCC.13r01609

Health Link BC. (2019). Bipolar Disorder: Preventing Manic Episodes. Retrieved from

Hilty, D. M., Leamon, M. H., Lim, R. F., Kelly, R. H., & Hales, R. E. (2008). A Review of Bipolar Disorder in Adults. Psychiatry, 3(9), 43-55. Retrieved from

Mayo Clinic. (2020). Bipolar disorder.

McNamara, R. K., Nandagopal, J. J., Strakowski, S. M., & DelBello, M. P. (2010). Preventative Strategies for Early-Onset Bipolar Disorder: Towards a Clinical Staging Model. CNS Drugs, 24(12), 983-996. doi:10.2165/11539700-000000000-00000

Miklowitz , D. J., & Johnson, S. L. (2006). The Psychopathology and Treatment of Bipolar Disorder. Annual Review of Clinical Psychology. doi:10.1146/annurev.clinpsy.2.022305.095332

Miklowitz , D. J., Price , J., Holmes, E. A., Rendell, J., Bell, S., Budge, K., . . . Geddes, J. R. (2012). Facilitated Integrated Mood Management for Adults With Bipolar Disorder. Bipolar Disorders, 14(2), 185-197. doi:10.1111/j.1399-5618.2012.00998.x

Rowland , T. A., & Marwaha, S. (2018). Epidemiology and risk factors for bipolar disorder. Therapeutic Advances in Psychopharmacology, 251-269. doi:10.1177/2045125318769235

Shah, N., Grover, S., & Rao, G. P. (2017). Clinical Practice Guidelines for Management of Bipolar Disorder. Indian Journal of Psychiatry, 59(1), S51-S66. doi:10.4103/0019-5545.196974

This content is for informational purposes only and does not substitute for formal and individualized diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed medical professional. Do not stop or alter your current course of treatment. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2020 Dr Khalid Rahman


Dr Khalid Rahman (author) from India on February 20, 2020:

Thanks for your valuable inputs and feedback :-)

Lorna Lamon on February 19, 2020:

An excellent and well structured article Khalid. I treat clients who have this condition and find it to be one of the most challenging to treat. Thank you for sharing.

sarahkhalid on February 18, 2020:

Very good i liked it a lot and i gained a lot of knowledge.!!!thank you dr khalid.

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