“Manic-depressive insanity…(includes) certain slight and slightest colourings of mood, some of them periodic, some of them continuously morbid, which on the one hand are to be regarded as the rudiment of more severe disorders, on the other hand pass without sharp boundary into the domain of personal predisposition. In the course of the years I have become more and more convinced that all the above mentioned states only represent manifestations of a single morbid process.”
-Kraepelin
The diagnosis of MDI is based on several factors:
• Symptoms
• Family History of a Mood Disorder or Substance Abuse
• Course of Illness
• Response to Treatment
Many illnesses and drugs can produce symptoms of Mania, Hypomania or Depression and need to be distinguished and adequately treated. The most common causes are listed in the Differential Diagnosis Section.
It is almost always possible to find a history of Mood Disorders or Substance Abuse/Dependence among relatives of subjects with MDI. However, the extraordinary variability of symptom caused by MDI and the common failure to diagnose non-classic or milder forms of MDI can interfere with documenting a family history of Mood Disorders. For example: a parent or relative might suffer from pathological gambling or have a criminal history, common examples of poor impulse control.
These forms are very often undiagnosed and untreated, and rarely their connection with MDI is recognized.
The presence of cycling or recurrences of mood instability, the continuous or recurrent instability of mood and activity are quite distinctive of MDI. It is the constant change that appears to be the only constant in the variable course of this illness. For this reason, the observation of these symptoms, over time, might be the only way to document a recurrent course of illness. This was well known since antiquity and has been emphasized by Kraepelin in his seminal work on MDI.
The beneficial response to mood stabilizing agents confirms the diagnosis. The induction of hypomanic or manic symptoms with stimulants, antidepressants and other substances has been considered evidence of a ‘latent’ form of MDI, requiring an external precipitant to become apparent.
"Manic-depressive insanity…includes on the one hand the whole domain of the so called periodic and circular insanity, on the other hand simple mania, the greatest part of the morbid states termed melancholia"
-Kraepelin
The symptoms of MDI can be extremely variable from person to person, remaining fairly consistent over time in the same person. Some will experience both Mania and Depression. Others only or mostly Mania, Depression, or Mixed States.
MDI is an illness affecting energy level and mood. Mood and energy changes occur often but not always in the same direction. In general, Mania manifests as an increase of energy with cognitive and physical activation, while depression usually results in decreased mental and physical activity.
Mania can occur in a variety of clinical manifestations, including a classic, euphoric form, a dysphoric or irritable form, a mixed state, a mild form (hypomania), or a subsyndromal form (hyperthymia), often referred to as Temperament. A general feeling of wellness and eutonia is quite common in the euphoric forms but not in dysphoric mania.
Mania causes impaired judgment and poor impulse control. A manic patient might seek out dangerous, risk-taking behaviors, including impulsive spending, sexual promiscuity, aggressive driving and speeding, substance abuse, and violent or criminal behavior.
While most forms of mania are polysymptomatic -- many signs and symptoms occur at the same time, it is possible to observe manic phases with very few symptoms.
Manic symptoms are:
-"High," extremely happy or euphoric mood
-Irritable mood - provocative, explosive
-Self-importance - attention-seeking behavior, grandiosity
-Increased energy, restlessness or increased activity level
-Little need for sleep - up for a couple of nights straight
-Talkative, uninterrupted, vulgar or loud speech
-Need to use dramatic language/gestures - theatrical
-Lots of thoughts and ideas or projects
-Aggressive - verbally or physically violent
-Short attention span - distractibility and poor concentration
-Risky activities - speeding, gambling, substance abuse
-Poor judgement with impulsive behavior - overspending
Inability to recognize change from baseline - denial of illness
-Increased sexual drive, desire and/or activity
MANIA SIGNS SYMPTOMS
ACTIVITY HYPERACTIVE RESTLESS/RUSHED
PRESSURED SPEECH TALKATIVE/CHATTY
ANIMATED MULTIPLE ACTIVITIES
LITTLE NEED FOR SLEEP INSOMNIA
PROMISCUITY HIGH SEXUAL DRIVE
COGNITION DISTRACTIBLE RACING THOUGHTS
POOR CONCENTRATION CONFUSION
CREATIVE CREATIVE
PUNS/JOKES NEED TO SOCIALIZE
MOOD ELATED EUPHORIC
LAUGHS/SMILES A LOT LAUGHS/SMILES A LOT
GRANDIOSE SELF-CONFIDENT
The presence of a depressed or unpleasant mood during an episode of Mania produces a clinical picture called Dysphoric Mania. This term has been used to describe several different clinical conditions, including Irritable, Mixed and Anxious Mania. (McElroy, Hantouche)
In these syndromes, manic symptoms are prominent and often severe. The lack of euphoria however, confers to these forms a particularly painful quality. The patient suffering from these forms of Mania is highly irritable, hostile, and prone to angry outbursts or rage. When contradicted or confronted with the consequences of his behavior, the patient can become abusive, violent and destructive.
It has been suggested that Dysphoric Mania may represent a more severe form of Mania (progressing from Hypomania to Euphoric Mania and to Dysphoric Mania). Others consider Dysphoric Mania a separate, independent form of illness with characteristic clinical and therapeutic features.
Depressive symptoms are almost always present in people suffering from MDI. Depressive symptoms can vary in severity, type and duration, occurring in alternation with manic/hypomanic symptoms, in combination with them, or in their absence. Different forms or subtypes of MDI can be identified. Different types of depression have been described from a subtle, lingering form called Dysthymia to the short-lived depressive phases of Cyclothymia or the full-blown Major Depression in its recurrent, chronic or Atypical forms. For a review on Depression, see Preskorn.
During a depressed phase a person may:
feel "blue, sad or down" for most of the day, almost every day;
feel worthless or guilty every day, or nearly every day;
cry a lot -- often or for no apparent reason;
loose interest in or feel little pleasure during all or most daily activities, almost every day;
experience trouble sleeping and/or sleeping too much;
feel weak, tired or lack energy almost every day;
be unable to concentrate;
have trouble making decisions, nearly every day;
gain or loose weight without wanting to;
think often about death or suicide.
DEPRESSION SIGNS SYMPTOMS
ACTIVITY INACTIVE RESTLESS/RUSHED
DECREASED SPEECH QUIET
DULL APATHY
GREATER NEED FOR SLEEP LETHARGY
WITHDRAWAL LOW SEXUAL DRIVE
COGNITION LACKS INTEREST BORED
POOR CONCENTRATION CONFUSION
INDECISIVE DOUBTS
POOR SELF ESTEEM SELF BLAME
MOOD SAD DOWN
TEARFULNESS TEARFULNESS
DESPONDENT DESPONDENT
Depression is by far the most common diagnosis given to people with MDI, as it is almost always the reason for seeking treatment in those suffering from the forms of MDI without Mania. Studies of depression in the primary setting confirm this trend. (Manning)
The symptoms are usually those of an Atypical Depression. The bias of many clinicians towards diagnosing Depression and the relative ease of diagnosing Depression with DSM Criteria has allowed many patients with MDI to be diagnosed as “Unipolar”.
In a large study of patients diagnosed with DSM IV Major Depression (Hantouche), 40% were re-diagnosed as MDI on the basis of a semi-structured interview eliciting hypomanic symptoms -- information obtained by further questioning of patients and significant others or based on observed Hypomania.
Characterized by increased sleep and appetite with carbohydrate craving, Atypical Depression is the most common among patients with MDI. Decreased energy, impaired concentration and low sexual drive are prominent features. The increased emotional reactivity and the preferential response to some antidepressants (MAOI) point to MDI as the underlying cause of these symptoms.
Growing evidence about the differences between the depressive phase of MDI and other forms of depression have been collected in research studies. Parker documented the differences between forms of Depression among patients with or without MDI. The presence of psychomotor retardation, melancholic and psychotic features are consistently more common in MDI than in other forms of depression.
Loss of interest, anhedonia, guilt, hallucinations, non-reactivity, and variability of mood were all statistically differentiating traits.
Neurobiological differences include abnormalities in the Hypothalamic-Pituitary Axis both during an acute episode of depression and after its remission.
"We observe also clinical 'mixed forms'in which the phenomena of Mania and melancholia are combined with each other, so that states arise, which indeed are composed of the same morbid symptoms as these, but cannot without coercion be classified either with the one or with the other. Our customary grouping into manic and melancholic attacks does not fit the facts, if it is to reproduce nature."
Kraepelin, 1921
The co-occurrence of manic and depressive symptoms in MDI are referred to as Mixed State.
The presence of different admixtures of manic and depressive symptoms led Kraepelin to distinguish six types of mixed states.
In 1953, J.D. Campbell wrote: "Manic-depressive (psychosis) is a dynamic, constantly changing process which, at times, may manifest symptoms of both phases simultaneously. It is in the mixed forms that the observer graphically realizes the homogeneity of the entire process." (p. 146)
Mixed states occur during the transition from one phase to another, or as stable clinical manifestations of overlapping symptoms.
A recent review of the literature on Mixed States examined diagnostic criteria used reported rates of 30-40% among patients with MDI, and described clinical features and neurobiological characteristics. (McElroy)
Like all MDI manifestations, Mixed States are distributed on a continuum, from severe manic symptoms with mild depressive features (Mixed Mania and Dysphoric Mania) to severe depressive symptoms with hypomanic features (Agitated Depression and Mixed Depressive Syndromes, Kukopulos).
The relationship between these syndromes, illness subtype and premorbid temperament has been the subject of intensive study by Akiskal and colleagues.
Among the Mixed States, forms of Depression with severe agitation and excitatory symptoms of Hypomania are extremely common. These forms are often called Anxious or Agitated Depression. Their importance lies in the severity of these conditions due to:
a great risk of suicidal behavior, and in
the frequent worsening of symptoms with antidepressant agents.
We found the most common symptoms reported in these forms include:
racing, crowded thoughts;
restlessness, pacing, agitation;
increased speech with continuous complaining;
suicidal ideation with plan and often intent;
extreme mood lability;
dramatic, vivacious expression of suffering;
reversed diurnal mood variations (worsening in p.m. hours);
sleep disturbances, decreased sleep;
anxiety and panic symptoms -- nervousness, tension.
The rapid worsening of these symptoms in response to treatment with antidepressant or exposure to stimulants confirms the presence of an excitatory process underlying these presentations.
As suggested by Koukopoulos, these forms require treatment of the hypomanic symptoms with sedatives and antimanic agents, and only later, if necessary, treatment of depressive symptoms. It is not unusual to see complete remission of symptoms with antimanic agents or sedatives.
The presence of psychotic features in the course of MDI is a well-known phenomenon. Psychotic symptoms like delusions, hallucinations or catatonia/disorganized behavior can occur during episodes of Mania, Depression and Mixed States. If psychotic symptoms persist for two weeks or more after the resolution of mood symptoms, a diagnosis of Schizoaffective disorder is made.
Psychotic symptoms might be more common in those forms with an earlier age of onset.
The psychotic symptoms might be congruent with the mood state experienced (grandiose delusions in the course of euphoric mania) or non-congruent (delusions of guilt during mania).
In general, psychotic symptoms have been associated with a worse outcome in adults with MDI.
From the Greek ‘alternating mood’, the term Cyclothymia was first used in psychiatry by E. Hecker in 1877 and was used by Emil Kraepelin as a synonym for the newly defined category of Manic-Depressive Insanity. Kraepelin described as subjects with a cyclothymic temperament ”…people who constantly oscillate hither and tither between the two opposite poles of mood, sometimes ’rejoicing to the skies, sometimes sad as death.”
Diagnostic Criteria
Cyclothymic Disorder (DSM IV, US)
• For at least 2 years the presence of numerous periods with hypomanic symptoms and numerous periods with depressive symptoms not meeting the criteria for a Major Depressive Episode.
Note: In children and adolescents the duration must be at least 1 year.
• During the above 2-year period (1 year in children and adolescents), the person has not been without the symptoms in Criterion A for more than 2 months at a time.
• No Major Depressive Episode, Manic Episode or Mixed Episode has been present during the first 2 years of the disturbance.
Note: After the initial 2 years (1 year in children and adolescents) of Cyclothymic Disorder, there may be superimposed Manic or Mixed Episodes, in which case both Bipolar I Disorder and Cyclothymic Disorder may be diagnosed, or Major Depressive Episodes, in which case both Bipolar II Disorder and Cyclothymic Disorder may be diagnosed.
• The symptoms in Criterion A are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder or Psychotic Disorder not otherwise specified.
The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hyperthyroidism).
The symptoms cause clinically significant distress or impairment in social, occupational or other important areas of functioning.
Cyclothymia (ICD 10)
A persistent instability of mood, involving numerous periods of mild depression and mild elation. This instability usually develops early in adult life and pursues a chronic course, although at times the mood may be normal and stable for months at a time. The mood swings are usually perceived by the individual as being unrelated to life events. The diagnosis is difficult to establish without a prolonged period of observation or an unusually good account of the individual's past behavior. Because the mood swings are relatively mild and the periods of mood elevation may be enjoyable. Cyclothymia frequently fails to come to medical attention. In some cases this may be because the mood change, although present, is less prominent than cyclical changes in activity, self-confidence, sociability or appetite behavior. If required, age of onset may be specified as early (in late teens or the twenties) or late.
Diagnostic Guidelines
The essential feature is a persistent instability of mood involving numerous periods of mild depression and mild elation, none of which have been sufficiently severe or prolonged to fulfil the criteria for Bipolar Affective Disorder or Recurrent Depressive Disorder. This implies that individual episodes of mood swings do not fulfil the criteria for any of the categories described under Manic Episode or Depressive Episode.
Includes:
affective personality disorder
cycloid personality
cyclothymic personality
Differential Diagnosis
This disorder is common in relatives of patients with Bipolar Affective Disorder and some individuals with Cyclothymia eventually develop bipolar affective disorder themselves. It may persist throughout adult life, cease temporarily or permanently, or develop into more severe mood swings meeting the criteria for bipolar affective disorder or recurrent depressive disorder.
MDI has so many different presentations that a high rate of missed diagnosis and wrong diagnosis is not surprising. Several factors account for the high rate of misdiagnosis in MDI. These include:
Hypomania is difficult to diagnose clinically.
Patients are not reliable historians regarding manic/hypomanic symptoms.
Short-term follow-up precludes observation of manic/hypomanic phases.
Strict criteria make the diagnosis of hypomania difficult.
Clinicians’ bias towards diagnosing depression and anxiety disorders.
The stigma associated with MDI.
The routine use of research criteria has deprived a majority of people with MDI of proper diagnosis and treatment. For example, a survey conducted by the National Alliance for the Mentally Ill (NAMI) in 1992 reports that 48% of the patients with BPD received a correct diagnosis only after being evaluated by more than 3 psychiatrists over 5-10 years after symptoms’ onset. (Lish)
A new survey repeated recently using the same methodology in 2000 revealed that the average delay between symptoms’ onset and treatment is still more than 10 years, 69% were misdiagnosed, mostly (3/4) by psychiatrists, and the average number of doctors seen was 4.4.
As BPD is a subset of MDI, current statistics represent only the tip of the iceberg of the effects of MDI in the general population.
The age at onset of symptoms, the clinical presentation and the presence of comorbid conditions lead to different types of diagnostic errors.
Some diagnostic errors occur in patients of any age depending on the clinical presentation. Common misdiagnoses are:
Schizophrenia when psychotic symptoms are present.
Depression and Dysthymia when depressive symptoms dominate the clinical picture.
Anxiety Disorders when panic, obsessive-compulsive, social phobias or generalized anxiety symptoms are prominent.
Alcohol or Substance abuse when self-medicating behavior is most evident.
Borderline, Narcissistic or Dependent Personality Disorder when symptoms affect mostly interpersonal relationships.
Gambling, Shoplifting and other Impulse-dyscontrol symptoms are common in a subgroup of patients with MDI.
Other diagnostic errors are somewhat more age specific:
• Attention Deficit Disorder, Oppositional Defiant Disorder, Conduct Disorder and Separation Anxiety in children and young adolescents.
These children are over-represented in most psychiatric clinics and often receive antidepressants and stimulants without protection from the possible precipitation of manic or mixed states.
• Substance Abuse, Antisocial Personality Disorder, Borderline Personality Disorder, Eating Disorders, Intermittent Explosive Disorders in older adolescents and young adults.
Many adolescents fail school, have chaotic social, work and family life, often incur in serious debt or are the victim of impulsiveness. Many commit criminal acts either to support their substance abuse or to pay debt or due to poor judgement and impulsiveness.
C.F. Flemming first used Dysthymia (from the Greek abnormal mood) in psychiatry in 1844. In 1882 K.L Kahlbaum used the term Dysthymia to describe a predominantly depressive temperament that with Cyclothymia and Hyperthymia, belonged to subthreshold manifestation of Manic-Depressive Psychosis.
E. Kraepelin, in his conceptualization of Manic-Depressive Insanity preferred the term depressive temperament, a “…permanent gloomy emotional stress in all the experience of life.”
More recently, introduced in the DSM III (1980) as a diagnostic category for mild to moderate forms of chronic depression. Dysthymic Disorder has substituted previous categories such as Neurotic Depression and Depressive Personality Disorder. Criteria for Dysthymia can be viewed here (Link).
When a depressive syndrome is superimposed on a dysthymic disorder the term ‘Double Depression’ is used. The return to a dysthymic baseline after recovery from an episode of full-blown Depression is often referred to as ‘partial remission’.
Dysthymia affects about 3% of the population, runs in families and has an early age of onset. In spite of its mild symptoms, Dysthymia causes significant disability. It is a risk factor for the development of Depression and responds to antidepressant treatment. Its relationship with MDI remains unclear. A study by Klein and colleagues showed an increased frequency of antidepressant-induced Hypomania among patients treated for Double Depression.
It has been hypothesized that a dysthymic temperament occurs frequently among patients who suffer from Mania, and might lead to the development of mixed manic or dysphoric states.
Substance abuse:
Cocaine
Amphetamine
Hallucinogens
Caffeine
Over-the-counter diet pills (i.e. phenylpropanolamine)
Drug withdrawal states:
Alcohol
Antidepressants
Medications:
Steroids
Ritalin
Disulfiram (Antabuse)
Isoniazid
Sympathomimetic agents
Dopaminergic agents: L dopa, Bromocriptine
Infections:
Encephalitis
Neurosyphylis
AIDS
Endocrine:
Hyperthyroidism
Addison’s Disease
Cushing’s Disease
Other neurological diseases:
Complex partial seizure
Strokes, especially right frontal
Lupus cerebritis
Multiple sclerosis
Head injury
Tumors/Metastases
Huntington’s Disease
Psychiatric Disorders
Adjustment disorders
Alcohol/substance abuse/dependence
Anxiety disorders
Eating disorders
Major Depression, Dysthymia
Schizophrenia and Schizophreniform disorders
Somatoform disorders
Neurologic disorders
Extrapyramidal diseases (e.g., Parkinson's, Huntington's, Progressive Supranuclear Palsy)
Dementia (Alzheimer's, Pick’s, vascular)
Cerebral neoplasms
Cerebral trauma
Cerebrovascular disease
CNS infections (e.g., neurosyphilis, viral encephalitis, AIDS)
Seizure Disorders
Hydrocephalus
Migraine
Multiple sclerosis
Narcolepsy
Sleep Apnea
Wilson's disease
Endocrine disorders
Adrenal diseases (Cushing's, Addison's, Hyperaldosteronism)
Hypo- or hyperparathyroidism
Hypo- or hyperthyroidism
Premenstrual Dysphoric Disorder
Post-partum disorders
Inflammatory disorders
Rheumatoid arthritis
Sj�gren's syndrome
Systemic lupus erythematosus (SLE)
Temporal arteritis
Infections
AIDS
Hepatitis
Tuberculosis
Mononucleosis
Vitamin deficiencies
Folate
Niacin
Thiamine
Vitamin B12
Vitamin C
Other disorders
Cancer
Cardiopulmonary disease
Klinefelter's syndrome
Porphyria
Postoperative mood disorders
Renal insufficiency and uremia
Medications
-Cardiac and Antihypertensive drugs
Bethanidine
Clonidine
Digitalis
Guanethidine
Hydralazine
Lidocaine
Methoserpidine
Methyldopa
Oxprenolol
Prazosin
Procainamide
Propranolol
Reserpine
Veratrum
-Sedatives and hypnotics
Atypical Antipsychotics
Barbiturates
Benzodiazepines
Butyrophenones
Chloral hydrate
Ethanol
Phenothiazines
-Steroids and other hormones
Corticosteroids
Danazol
Oral contraceptives
-Stimulants and appetite suppressants
Amphetamines
Diethylpropion
Fenfluramine
Phenmetrazine
-Neurological agents
Amantadine
Baclofen
Bromocriptine
Carbamazepine
Levodopa
Methsuximide
Phenytoin
Tetrabenazine
-Analgesics and anti-inflammatory drugs
Benzydamine
Fenoprofen
Ibuprofen
Indomethacin
Opiates
Phenacetin
Phenylbutazone
Pentazocine
-Antibacterial, antiviral, and antifungal drugs
Ampicillin
Clotrimazole
Cycloserine
Dapsone
Ethionamide
Griseofulvin
Interferon
Metronidazole
Nalidixic acid
Sulfonamides
Streptomycin
Tetracycline
Trimethoprim
Zidovudine
-Antineoplastics
L-Asparaginase
Azidouridine
Bleomycin
Plicamycin
Vincristine
-Miscellaneous drugs
Acetazolamide
Anticholinesterases
Choline
Cimetidine
Cyproheptadine
Diphenoxylate
Disulfiram
Isotretinoin
Lysergide
Mebeverine
Meclizine
Methysergide
Metoclopramide
Salbutamol