BIPOLAR DISORDER MANIC DEPRESSIVE ILLNESS. Bipolar disorder — sometimes classified as Bipolar Affective Disorder or Manic-Depressive illness — is a common, severe, and persistent mental illness. 


Bipolar Disorder, which in the ICD-10 is classified as Bipolar Affective Disorder, or Manic-Depressive Illness (MDI), is a common, severe, and persistent mental illness.

In the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders, (DSM-5), Bipolar Disorder constitutes a spectrum of mood disorders that includes Bipolar Disorder type I (BPI) , BiPolar Disorder type II (BPII), and Cyclothymia and are thought to be a “bridge” between Schizophrenia spectrum disorders and Depressive Disorders in terms of the symptomatology, family history, and genetics. 



Bipolar Affective Disorder is characterized by periods of deep, prolonged, and profound Depression that alternate with periods of an excessively elevated euphoric and/or irritable mood known as Mania.

Manic Episodes 

Manic Episodesare a feature of at least 1 week of profound mood disturbance, characterized by elation/euphoric, irritability, or expansiveness (referred to as gateway criteria). At least 3 of the following symptoms must also be present

  • Grandiosity
  • Diminished need for sleep
  • Excessive talking or pressured speech
  • Racing thoughts or flight of ideas
  • Clear evidence of distractibility
  • Increased level of goal-focused activity at home, at work, or sexually
  • Many projects may be started, but not completed, or disorganized. 
  • Excessive pleasurable activities, often with painful consequences

Hypomanic Episodes 

Hypomanic Episodesare characterized by an elevated, expansive, or irritable mood of at least 4 consecutive days’ duration. The diagnosis of hypomania requires at least three of the symptoms listed above. 

The Difference between Hypomania and Mania

The distinguishing feature between hypomania and mania  being that in hypomania these symptoms are not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization and are not associated with psychosis (e.g. thought disorder).

Major Depressive Episodes 

Major Depressive Episodes are characterized as, for the same 2 weeks, the person experiences 5 or more of the following symptoms, with at least 1 of the symptoms being either a depressed mood or characterized by a loss of pleasure or interest.   

  • Depressed mood
  • Markedly diminished pleasure or interest in nearly all activities (i.e. Anhedonia) 
  • Significant weight loss or gain due to significant loss of appetite or increase in appetite
  • Hyper-somnia or insomnia
  • Psychomotor retardation or psychomotor agitation
  • Loss of energy or fatigue
  • Feelings of worthlessness or excessive guilt
  • Decreased concentration ability or marked indecisiveness
  • Preoccupation with death or suicide; patient has a plan or has attempted suicide

The Highs and Lows of Mania 

The symptoms of mania include decreased sleep time accompanied by a decreased need for sleep, pressured speech, increased libido, reckless behavior without regard for consequences, poor judgment, impulsivity, high distractibility hyperactivity, starting many projects without any follow-through, grandiosity, and severe thought disturbances, which may or may not include psychosis. 

*****Between these highs and lows, many patients, if adequately medicated and in psychotherapy, usually experience periods of higher functionality and can lead a productive life. Even without pharmaceutical medication treatment, some patients function well and productively between extremes, but usually remain in psychotherapy and social support networks.

The Age of Onset of Bipolar Disorder Varies Greatly. 

The age range is from childhood to 50 years, with a mean age of approximately 21 years. Most cases of bipolar disorder commence when individuals are aged 15 to 19 years. The second most frequent age range of onset is 20 to 24 years.

BIPOLAR Disorder and GENDER 

BPI occurs equally in both sexes; however, rapid-cycling bipolar disorder (≥ 4 episodes/year) is more common in women than in men. 

The incidence of Bipolar Disorder type II (BPII) is higher in females than in males. Most studies report a nearly equal male-female ratio in the prevalence of Bipolar Disorder; however, most studies also report a higher risk in women for BPII/hypomania, rapid cycling, and mixed episodes.

Diagnostic Work up for BIPOLAR Disorder Manic Depressive Illness

Examination of patients with suspected Bipolar Affective disorder includes evaluation using the Mental Status Examination as well as assessment of the following:

  • Appearance
  • Affect/mood
  • Thought content
  • Perception
  • Suicide/self-destruction
  • Homicide/violence/aggression
  • Judgment/insight
  • Cognition
  • Physical health

Laboratory Test WorkUp for BIPOLAR Disorder Manic Depressive Illness 

Although Bipolar Disorder is diagnosed based on the patient’s history and clinical course, laboratory studies may be necessary to rule out other potential causes of the patient’s signs and symptoms as well as to have baseline results before administering certain medications.

Laboratory and Work up tests for Bipolar Manic Depressive Illness

Lab tests include the following:

  • CBC count
  • ESR levels
  • Fasting glucose levels
  • Electrolyte levels
  • Protein levels
  • Thyroid hormone levels
  • Creatinine and blood urea nitrogen levels
  • Liver and lipid panel
  • Substance and alcohol screening

Depending on the patient’s presentation, other laboratory tests may be indicated, which may include the following:

  • Urinary copper levels
  • Antinuclear antibody testing
  • HIV testing
  • VDRL testing

****Electrocardiography is important in elderly patients and before antidepressant therapy. Electroencephalography and/or MRI may be appropriate for selected patients.

MANAGEMENT of BIPOLAR Disorder Manic Depressive Illness 

The treatment of Bipolar Affective Disorder is directly related to the phase of the episode (i.e, depression or mania) and the severity of that phase, and it involves a combination of psychotherapy and medication. 

I always evaluate patients with mania, hypomania, or mixed episode, and those with bipolar depression, for suicidality, homicidality, acute or chronic psychosis, or other unstable or dangerous conditions.

Pharmacotherapy Medications for Bipolar Disorder 

Medications used to manage patients with bipolar disorder include the following:

  • Benzodiazepines – for acute agitation (e.g. lorazepam, clonazepam).  Highly addicting and should only be used acute agitation. 
  • Antimanic agents (eg, lithium)
  • Anticonvulsants (eg, carbamazepine, valproate sodium, valproic acid, divalproex sodium, lamotrigine)
  • First-generation antipsychotics (eg, inhaled loxapine, haloperidol)
  • Second-generation antipsychotics (eg, asenapine, ziprasidone, quetiapine, risperidone, aripiprazole, olanzapine, olanzapine and fluoxetine, clozapine, paliperidone, lurasidone)
  • Phenothiazine antipsychotics (eg, chlorpromazine)
  • Dopamine agonists (eg, pramipexole)

***It is important to determine whether current medications may be causing the patient’s manic, hypomanic, or mixed manic episode. In such patients, discontinue antidepressants or other mania-inducing agents. However, antidepressants known to have associated discontinuation syndromes should be tapered over several weeks. 

Pharmacological Risk Factors in Bipolar Disorder

There is the risk that antidepressant treatment may propel the patient into a Manic episode. Researchers investigated the association between antidepressant therapy and the later onset of Mania/Bipolar disorder. 

***Results suggest that in people with unipolar depression, antidepressant treatment is associated with an increased risk of subsequent mania/bipolar disorder. These findings highlight the importance of considering risk factors for mania when treating people with depression. 

I evaluate and closely monitor patients with Bipolar Depression for the risk for mood destabilization or switching to Mania and for the presence of emergent symptoms following initiation of pharmacotherapy for a depressive episode.

Nonpharmacotherapy and Psychotherapy for BIPOLAR Disorder 

Psychotherapy has been proven to help to decrease relapse rates, improve quality of life, and/or increase functioning, or more favorable symptom improvement. 

I consider psychosocial interventions (eg, psycho-education; psychotherapy strategies such as cognitive behavioral therapy [CBT], interpersonal and social rhythm therapy [IPSRT], family focused therapy; and chronic care model-based interventions. This is in align with National Institute of Mental Health recommendations.

****Electroconvulsive therapy (ECT) may be useful in selected patients with Bipolar Disorder.

Other mental disorders and general medical conditions are more prevalent in patients with Bipolar Disorders than in patients in the general population. 

Among the general comorbid conditions, cardiometabolic conditions such as cardiovascular disease, diabetes, and obesity are a common source of morbidity and mortality for persons with Bipolar Disorder.


White matter hypersensitivities are more common in individuals with Bipolar Disorder than in those without. Myelin pallor, tissue rarefaction associated with myelin and axon loss, and mild gliosis are pathological findings in regions of white matter hyperintensity

Neuroimaging studies of individuals with Bipolar Disorder or other mood disorders also suggest evidence of cell loss or atrophy in these same brain regions. 

Thus, another suggested cause of Bipolar Disorder is damage to cells in the critical brain circuitry that regulates emotion. According to this hypothesis, mood stabilizers and antidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels of neurotrophic factors to improve cellular resiliency.

Oligodendrocytes produce myelin membranes that wrap around and insulate axons to permit the efficient conduction of nerve impulses in the brain. Therefore, loss of myelin is thought to disrupt communication between neurons, leading to some of the thought disturbances observed in bipolar disorder and related illnesses. 

Brain imaging studies of persons with Bipolar Disorder also show abnormal myelination in several brain regions associated with this illness.

Interestingly, gene expression and neuroimaging studies of persons with Schizophrenia and Major Depression also demonstrate similar findings, indicating that mood disorders and Schizophrenia may share some biologic underpinnings, possibly related to psychosis. These types of data may also lead to the future revision of psychiatric diagnostic manuals based on a new understanding of the etiology of these disorders.


Bipolar Disorder, especially BPI, has a major genetic component, with the involvement of the ANK3, CACNA1C, and CLOCK genes. First-degree relatives of people with BPI are approximately 7 times more likely to develop BPI than the general population. Remarkably, offspring of a parent with Bipolar Disorder have a 50% chance of having another major psychiatric disorder.

One longitudinal study found that sub-threshold Manic or Hypomanic episodes were a diagnostic risk factor for the development of subsequent manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder. High-risk offspring, compared with offspring of parents without bipolar disorder, also had higher rates of ADHD, disruptive behavior disorders, anxiety disorders, and substance use disorders. [44]

Pathophysiology Bipolar Disorder 

The pathophysiology of Bipolar Affective Disorder, or Manic-Depressive Illness (MDI), has not been determined, and no objective biologic markers correspond definitively with the disease state. However, twin, family, and adoption studies all indicate that Bipolar Disorder has a significant genetic component. In fact, first-degree relatives of a person with bipolar disorder are approximately 7 times more likely to develop Bipolar Disorder than the rest of the population, and the heritability of Bipolar Disorder type 1 (BPI) has recently been estimated at 0.73. 

Genetics of Bipolar Disorder 

The genetic component of Bipolar Disorder appears to be complex: The condition is likely to be caused by multiple different common disease alleles, each of which contributes a relatively low degree of risk on its own. Such disease genes can be difficult to find without very large sample sizes, on the order of thousands of subjects.

When the genetics of Bipolar Disorder were first being studied, less precise tools were available, but they still yielded interesting information. Many loci are now known to be associated with the development of Bipolar Disorder. These loci are grouped as Major Affective Disorder (MAFD) loci and numbered in the order of their discovery. 

Specific expression of common genetic variants at different times during development, or in different regions of the brain, and in concert with other genetic variants could help to explain differences in disease phenotypes.,

Gene Expression Studies of Bipolar Disorder Manic Depressive Illness

Gene expression studies are one way of measuring the relative activity or inactivity of genes, and they have already been proven useful for illuminating the pathophysiology of psychiatric disorders, including Bipolar Disorder. 

For example, studies comparing specific regions of postmortem brain tissue from persons with Bipolar Disorder with tissue from control subjects have consistently shown that levels of expression of oligodendrocyte-myelin–related genes appear to be decreased in brain tissue from persons with Bipolar Disorder. 

As with genetic studies, gene expression profiling studies require very large sample sizes to produce replicable data. Furthermore, they must focus on the correct brain region(s) thought to be functioning differently in Bipolar Disorder, a point still under some debate. Therefore, research in this area is ongoing and frequently subject to update.


A number of factors contribute to Bipolar Affective disorder, or Manic-Depressive Illness (MDI), including genetic, biochemical, psychodynamic, and environmental factors.

Twin Studies of Bipolar Manic Affective Disorder 

Twin studies demonstrate a concordance of 33-90% for BPI in identical twins. As identical twins share 100% of their DNA, these studies also show that environmental factors are involved, and there is no guarantee that a person will develop Bipolar Disorder, even if they carry susceptibility genes.

Adoption studies prove that a common environment is not the only factor that makes Bipolar Disorder occur in families. Children whose biologic parents have either BPI or a major depressive disorder remain at increased risk of developing an affective disorder, even if they are reared in a home with adopted parents who are not affected. Frey and colleagues’ work supports the genetic contributions in bipolar affective disorder. [45, 46]

Gene expression studies also demonstrate that persons with Bipolar Disorder, Major Depression, and Schizophrenia share similar decreases in the expression of oligodendrocyte-myelin-related genes and abnormalities of white matter in various brain regions.

Biochemical Factors in Bipolar Disorder 

Multiple biochemical pathways likely contribute to Bipolar Disorder, which is why detecting one particular abnormality is difficult. 

Neurotransmitter Role in Bipolar Manic Affective Illness 

A number of neurotransmitters have been linked to this disorder, largely based on patients’ responses to psychoactive agents as in the following examples.

The blood pressure drug reserpine, which depletes catecholamines from nerve terminals, was noted incidentally to cause depression. This led to the catecholamine hypothesis, which holds that an increase in epinephrine and norepinephrine causes mania and a decrease in epinephrine and norepinephrine causes depression.

Drugs used to treat depression and drugs of abuse (eg, cocaine) that increase levels of monoamines, including serotonin, norepinephrine, or dopamine, can all potentially trigger mania, implicating all of these neurotransmitters in its etiology. Other agents that exacerbate mania include L-dopa, which implicates dopamine and serotonin-reuptake inhibitors, which in turn implicate serotonin.

****One study found that as many as a third of all patients with substance use-induced psychosis may go on to develop Schizophrenia or Bipolar Disorder within five years.

Evidence is mounting on the contribution of glutamate to both bipolar disorder and major depression. A postmortem study of the frontal lobes of individuals with these disorders revealed that the glutamate levels were increased. 

Calcium channel blockers have been used to treat mania, which may also result from a disruption of intracellular calcium regulation in neurons as suggested by experimental and genetic data. The proposed disruption of calcium regulation may be caused by various neurologic insults, such as excessive glutaminergic transmission or ischemia. Interestingly, valproate specifically upregulates expression of a calcium chaperone protein, GRP 78, which may be one of its chief mechanisms of cellular protection.

Hormone Imbalances and Hypothalamic-Pituitary-Adrenal Axis 

Hormonal imbalances and disruptions of the hypothalamic-pituitary-adrenal axis involved in homeostasis and the stress response may also contribute to the clinical picture of bipolar disorder.

Neurophysiologic Factors in Bipolar Disorder 

In addition to structural neuroimaging studies that look for volumetric changes in brain regions regardless of brain activity, functional neuroimaging (fMRI) studies are performed to find regions of the brain, or specific cortical networks, that are either hypoactive or hyperactive in a particular illness. 

  • Decreased activation and diminution of gray matter in a cortical-cognitive brain network, which has been associated with the regulation of emotions in patients with Bipolar Disorder. 
  • Increased activation in ventral limbic brain regions that mediate the experience of emotions and generation of emotional responses was also discovered.
  • fMRI studies provide evidence for functional and anatomic alterations in Bipolar Disorder in brain networks associated with the experience and regulation of emotions. [50]

Psychodynamic Factors in Bipolar Disorder 

Many practitioners see the dynamics of manic-depressive illness as being linked through a single common pathway. They see the depression as the manifestation of losses (ie, the loss of self-esteem and the sense of worthlessness). Therefore, the mania serves as a defense against the feelings of depression. Melanie Klein was one of the major proponents of this formulation.

A study by Barnett et al found that personality disturbances in extraversion, neuroticism, and openness are often noted in patients with Bipolar Disorder and may be enduring characteristics. 

Environmental Factors in Bipolar Disorder 

In some instances, the cycle may be directly linked to external stresses or the external pressures may serve to exacerbate some underlying genetic or biochemical predisposition. 

For example, pregnancy is a particular stress for women with a manic-depressive illness history and increases the possibility of postpartum psychosis. 

Seasons and BiPolar Disorder 

There have been a number of studies linking bipolar disorder and increased amount of sunlight during the day (e.g. spring, summer). Studies suggests that a large increase in spring and summer time solar insolation may impact the onset of bipolar disorder, particularly in those patients with a family history of mood disorders.

Futhermore, another study assessed psychiatric admission of 730 patients and found the admission rate for patients with bipolar disorder was significantly higher during May, June, and July; months with maximum sunlight exposure. These findings suggest photoperiod is a key element in bipolar disorder. c Depressive

Age-related differences in incidence of Bipolar Disorder Manic Depressive Illness

The age of onset of bipolar disorder varies greatly. For both BPI and BPII, the age range is from childhood to 50 years, with a mean age of approximately 21 years. Most cases of bipolar disorder commence when individuals are aged 15–19 years. The second most frequent age range of onset is 20–24 years.

Some patients diagnosed with Recurrent Major Depression may indeed have Bipolar Disorder and go on to develop their first manic episode when older than 50 years. 

These individuals may have a family history of Bipolar Disorder. However, for most patients, the onset of mania in people older than 50 years should lead to an investigation for medical or neurologic disorders, such as cerebrovascular disease.

Prognosis for Bipolar Disorder Manic Depressive Illness 

Bipolar affective disorder, or manic-depressive illness (MDI), has significant morbidity and mortality rates.

Patients with BPI fare worse than patients with a Major Depression. Within the first 2 years after the initial episode, 40-50% of these patients experience another manic attack. Only 50-60% of patients with BPI who are on lithium gain control of their symptoms. In 7% of these patients, symptoms do not recur, 45% of patients experience more episodes, and 40% go on to have a persistent disorder. *****

Often, the cycling between depression and mania accelerates with age.

Factors suggesting a worse prognosis include the following:

  • Poor job history
  • Substance abuse
  • Psychotic features
  • Depressive features between periods of mania and depression
  • Evidence of depression
  • Male sex
  • Pattern of depression-mania-euthymia

Factors suggesting a better prognosis include the following:

  • Length of manic phases (short duration)
  • Late age of onset
  • Few thoughts of suicide
    Few psychotic symptoms
  • Few medical problems

Patient Education Bipolar Disorder Manic Depressive Illness

Treatment of patients with Bipolar Affective Disorder, or Manic-Depressive Illness (MDI), involves initial and ongoing patient education. To this end, a strong therapeutic alliance is essential.

Educational efforts must be directed not only toward the patient but also toward their family and support system. 

Furthermore, evidence continues to mount that these educational efforts not only increase patient compliance and their knowledge of the disease, but also their quality of life. 

An explanation of the biology of the disease must be provided. This decreases feelings of guilt and promotes medication compliance. 

Information should be provided on how to monitor the illness in terms of an appreciation of the early warning signs, reemergence, and symptoms. Recognition of changes can serve as a powerful preventive step.

Education must also encompass the dangers of stressors. Helping the individual identify and work with stressors provides a critical aspect of patient and family awareness. Efforts should be made to educate the patient about relapses within the total context of the disorder.

Individual stories help patients and families. The National Institute of Mental Health (NIMH) has a story of a person with manic-depressive illness that can help the patient see the struggle and challenge from another perspective.Others have written about their family struggles and challenges.


Bipolar Disorder is characterized by periods of deep, prolonged, and profound depression that alternate with periods of an excessively elevated or irritable mood known as mania. This pattern of alternating severe depression and periods of mania is characteristic of bipolar disorder type I (BPI), although in rarer cases, persons may only experience episodes of mania. 

In practice, symptoms of mania and depression can also occur together in what is termed a mixed state as the illness evolves. By contrast, Bipolar Disorder type II (BPII) is diagnosed when episodes of severe depression are punctuated with periods of hypomania, a less severe form of mania that does not include psychosis or lead to gross impairment in functioning. 

A diagnosis of cyclothymic disorder is given to individuals with periods of both hypomanic and depressive symptoms without meeting the full criteria for mania, hypomania or major depression.

Important Resources for Patients and Families to Find Information on Dealing with Bipolar Disorder Manic-Depressive illness include the following:

Thank you for your time,  Dr. Shawna Freshwater

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Shawna Freshwater, PhD

Shawna Freshwater, PhD

Hi, I am Dr. Shawna Freshwater, a PhD licensed Clinical Psychologist, Neuropsychologist, and Holistic Practitioner. ** I provide Psychotherapy, Coaching, Healing, Diagnostic testing & Mental Health Check-ups. ** I meet the needs of my patients and clients that are confidential and convenient to their schedule. ** I offer Remote / Online secure interactive video conferencing to USA residents and International clients. ** I also provide Concierge services at your home, office, or private location of your choice if you reside in South Florida Major Cities. ***Please see my website for more information about my credentials and areas of expertise. Thank you. Dr. Freshwater

1 Comment

  1. Scott on March 14, 2019 at 3:49 pm

    Thank you Dr. Freshwater, this is the most comprehensive article I have read about Bipolar Disorder. I did quite a bit of research on my own as well as talking with other doctors, because a family member has this disorder. Your article was detailed but simple and complete about this complex disorder. Much appreciated

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