Trinity Student Medical Journal 2003

Poles Apart: The Highs and Lows of Bipolar Affective Disorder

An Anonymous Medical Student

INTRODUCTION

One in every hundred adults suffers from manic-depression (bipolar affective disorder). I was officially diagnosed two and a half years ago, yet have experienced fluctuations in mood for nearly seven years. I have noticed peoples’ misconceptions and stigmatisation of the illness. My aim here is therefore two-fold: to give a first-hand account of this condition and also to include relevant medical information.

Bipolar Disorder (BD) takes a cyclical course with periods of mania or hypomania (the mild form of mania) alternating with bouts of depression. The intervals between attacks usually consist of a stable mood. Becoming manic can be very exciting. I had more energy, I needed less sleep, I felt as though I could achieve anything and I had the self-confidence I always wanted. My speech became louder and more forceful; my jovial banter became threatening. Within a couple of weeks my mind started to play tricks on me. I experienced everything from being paranoid that an atom bomb would strike at any moment to feeling certain of being able to cure all disease. I even was convinced that I may be carrying the second immaculate conception! I have walked for miles thinking that I was part of a spy operation.  I would see blue and green lights on the streets and follow them.  I would occasionally lose shoes, coats and bags while manic. Only a few of my friends and relatives have seen me like this and they have told me that it can be quite frightening. My major episodes have both ended with police intervention, hospitalisation and powerful antipsychotic medication. Average manic episodes last for two months.¹  The diagnosis of bipolar disorder came after more than one episode.  Once diagnosed, I was started on lithium in conjunction with antipsychotics.        

The flip side of the coin, depression, is a much less enjoyable experience. In the last seven years, I have been depressed almost annually for several months at a time. I usually switched straight from mania to depression. During these periods I felt as though simple tasks were beyond me and that I was a worthless human being. I tended to sleep and seek relief from the scary world I perceived by staying in bed and avoiding school or college. The feelings of depression always came on suddenly and usually occurred in the winter. I found socialising a nightmare and academic work virtually impossible. My depressive episodes have usually lasted for several months before normality returned.

It has taken me a while to feel comfortable with the diagnosis. For a long time I felt that it was unfair, something to be ashamed of, and that the doctors were, quite simply, wrong. It is just not possible to "snap out" of an episode of depression or elation.  Generous and empathetic support of family and friends is invaluable in coping with this illness.

THE CLASSIFICATION OF BIPOLAR AFFECTIVE DISORDER

Emil Kraepelin, often thought of as the father of psychiatric classification, was the first to describe manic-depressive illness around the turn of the twentieth century. Schizophrenia tends to have a deteriorating course in which over the years the patient tends to become mentally weaker and also becomes increasingly incapable of functioning (though not necessarily continuous). Whereas, manic-depressive patients tend to experience a course of illness which is intermittent and patients are relatively symptom-free between the intervals of mania and depression. Though certain manic-depressive patients may sustain long-lasting or even permanent impairment, this tends to be much less frequent and severe than in schizophrenia.²  The current classification of bipolar affective disorder falls into many categories, the main ones being:  Bipolar I, which is characterised by mania with/without major depression; Bipolar II, a form in which severe depression and hypomania occur; Cyclothymia which is numerous brief episodes of hypomania and minor depression.  This classification is based on defined criteria listed in the Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV; USA) or the International Classification of Diseases (ICD 10; UK).^3,4

AETIOLOGY

The causes of manic-depression are not fully known although it is suggested that the influence is about 70% genetic and 30% environmental.⁵ The average age of onset is 21. It is equally prevalent in men and women, unlike unipolar depression which is more prevalent amongst women. First-degree relatives have a 15% risk of developing bipolar disorder and the concordance rate increases to 60-80% in monozygotic twins.¹ This suggests that genetics play a significant role.  Stress factors such as bereavement may play a role in precipitating mania or depression. In my case, none of my family has any history of mental illness. However, I personally recognise mild forms of symptoms in certain family members. At present, studies are underway to examine genetic linkage but no specific association has emerged. The biochemistry of the brain also seems to be important. It has been suggested that bipolar disorder results from a dysfunction of the G-protein/second-messenger system operating in neurones using noradrenaline and serotonin to regulate mood. Inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) act as second messengers in a-adrenergic transmission. To activate protein kinase C and mobilise intracellular Ca2+, IP3 and DAG are produced from phosphatidylinositol-4,5-bisphoshate (PIP2) and an overactivity of these PIP2-dependent pathways may cause the alterations in mood outside normal ranges. The neurotransmitters dopamine, glutamate and acetylcholine may also be involved in mood swings. A monoamine theory of depression suggests that depression may be a result of reduced monoamine (noradrenaline, dopamine and serotonin) activity in the brain and conversely mania is caused by excessive activity of these neurotransmitters.⁶ However, given that many factors come into play, it seems unlikely that pure neurobiology can fully explain the characteristics of this illness.

TREATMENT

Lithium is a widely used pharmacological treatment for manic-depression. Its properties have been utilised as far back as the second century A.D. when the Greek physician Seranus Ephisios recommended bathing in salt pools containing lithium for his manic patients. More recently John Cade, an Australian psychiatrist working in the 1940s, believed that the urine of manic patients might hold some clues. In order to inject uric acid samples into guinea pigs, Cade used a lithium urate solution. He found that the animals became lethargic and sedate.  He then injected lithium preparations into several chronically manic patients and found that their mood returned to normal, to a degree that led them to be releasd from wards and allowed return to work.^7,8

As lithium is toxic in high doses, it was not until the 1970s that it was adopted as a mainstream drug. This naturally occurring salt acts as an inhibitor; it prevents the build up of membrane inositol monophosphate and therefore PIP2, the precursor of IP3 and DAG. A patient’s mood is thereby returned to stability soon after an elevation or depression has begun. Lithium may have other modes of action and tends to have a greater ability to prevent mania than depression. Kidney and thyroid gland function can be affected, therefore both of these, along with blood lithium level (therapeutic range 0.5-1.3 mmoles/L), must be checked regularly. Side effects include nausea, diarrhoea, hand tremor, polyuria (nephrogenic diabetes insipidus), polydipsia, hypothyroidism, weight gain and drug-interactions. Skin conditions such as acne and psoriasis can be exacerbated by treatment. The therapeutic index for lithium is low and lithium toxicity can occur for a host of reasons such as overdose, kidney disease, dehydration, sodium deficiency, and interactions with various drugs. Intoxication can result in death or permanent damage of the cerebellum.^9,10   One of the most iritating side effects that I have experienced has been the influence exherted bylithim on mental acuity and memory. It is not easy to be on medication indefinitely, nor does it always seem logical to take a drug when feeling fit and well. Doctors have often played down the suggestion that lithium marred functioning but a study in which non-affected volunteers took the drug found that there was a slight but definite decline in performance in psychological tests^.7 Taking lithium while pregnant can cause malformation of the heart and great vessels with the greatest risk being in the first three months of pregnancy.¹¹ Since a woman may not know that she is pregnant initially, birth control and careful planning are recommended. Lithium cannot be taken while breast-feeding as it is passed on to the baby. Side effects are dose-related and can be a major cause of non-compliance. In the event of non-compliance there is a high risk of relapse and in a few cases lithium may lose some of its effectiveness upon return to treatment.

Other treatments are available, such as some anti-epileptic drugs like sodium valproate, carbamazapine and lamotrigine. These act as mood stabilisers in bipolar disorder for those who are refractory to lithium therapy. Electro-Convulsive Therapy (ECT) is used to alleviate chronic depression that has proved resistant to other courses of action, although it is used to a lesser extent nowadays. Anti-psychotic medications such as haloperidol and risperidone are nearly always necessary to stabilise manic patients, but have unpleasant side effects. The side effects are a vacant expression, glazed eyes, gastro-intestinal discomfort, frequent urination, confusion, lack of concentration and tiredness; the overall effect is a zomboid appearance. Anti-depressants are often used in conjunction with lithium either before or during a depressive episode. Studies have shown that taking antidepressants before the predicted onset of depression can reduce the severity and length of the attack. I have used venlafaxine, a potent inhibitor of serotonin re-uptake and weak inhibitor of noradrenaline transport, and found that it took several weeks to induce an effect. I still had to "wait out" the depressive episode. Some patients have to try several different antidepressants, which can be disappointing, ineffective and time-consuming. Some studies show that there is little difference between an antidepressant and a placebo in the long term.¹² Although lithium is not completely effective in removing mood swings altogether, it reduces their intensity, frequency and allows near-normal life to continue. Many sufferers find that psychotherapy or cognitive-behavioural therapy can help with self-management and acceptance of the illness. Despite available treatment, fifteen percent of manic-depressives die by suicide.¹³ There are several groups that act as a support network such as those run by Aware in Ireland and the Manic-Depression Fellowship and MIND in the UK.

ARE MADNESS AND BRILLIANCE LINKED?

Madness and creativity are often associated in people’s minds. In a controlled form it can be used for creativity. The writer Samuel Johnson was thought to be manic-depressive.  He used the manic phase for writing and the depressed phase for self-criticism. Socrates’ view was that "madness, provided it comes as the gift of heaven, is the channel by which we receive the greatest blessings." Vincent van Gogh, Robert Schumann, Virginia Woolf and Spike Milligan were all suspected to have suffered from manic-depressive illness. The psychiatrist Ernst Kretschmer wrote that geniuses display qualities that are "identical with the psychopathic structures in the personality" and that, "For some types of genius, this inner dissolution of the mental structure is an indispensable prelude." He concluded that if "demonic unrest" and "mental tension" were removed, only a normal, talented individual would remain.¹⁴ Adele Juda conducted a study which suggested the opposite. She studied brilliant artists and scientists from German-speaking countries since 1650 and concluded that "there is no definite relationship between highest mental capacity and mental health or illness" and that psychoses, in particular schizophrenia, "proved to be detrimental to creative ability."¹⁵ Manic-depression, on the other hand, has been largely shown to have a link with creativity, although the debate continues.

Jonathan Swift, author of Gulliver’s Travels (used as evidence of his alleged insanity), left all his money to found St. Patrick’s Hospital for Imbeciles in Dublin when he died in 1745.¹⁶ He wrote these lines for his own epitaph:

             He gave the little wealth he had,

             To build a house for fools and mad.

             And shew’d by one satiric touch,

             No nation wanted it so much.

CONCLUSION

Being manic-depressive has definitely had an impact on my life. However, I do not think I would choose to change this fact. Despite occasional low periods, I have been relatively stable for the last two years and hope that this state continues. At present I am drawn towards a career in psychiatry and feel that I would be in the fortunate position to offer my own understanding and empathy to guide others who suffer from mental illness. I sometimes worry about how I will be perceived as a doctor with bipolar disorder but I am convinced that determination, self-assurance and support will stand in my stead.

REFERENCES

1. Kumar P, Clark M, editors. Clinical medicine. 5th ed. London: W. B. Saunders; 2002.

2.Wikipedia, the online encyclopaedia:  www.wikipedia.org/wiki/Emil_Kraepelin

3. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM - IV - TR. 4th ed. Washington: American Psychiatric Association; 2000.

4. The Icd-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. Geneva: World Health Organization; 1992.

5. McKeon P. Coping with depression and elation, 3rd ed. London:  Sheldon; 1999.

6. Katzung BG, Basic and clinical pharmacology, 8th ed. Los Angeles:  Lange; 2000.

7. Schou, Mogens. Lithium treatment at 52. J Affective Disorders 2001; 67:21-32.

8. Le Fanu J. The rise and fall of modern medicine. London:  Abacus; 1999.

9.  McKeon P, O’Brien S, Fehily J. Lithium: A practical guide. Dublin: Aware; 1987.

10. Goodwin FK, Jamison KR. Manic-depressive illness. Oxford: Oxford University Press; 1990.

11. Mondimore FM. Bipolar Disorder: A guide for patients and families. Baltimore: John Hopkins  University Press; 1999.

12. Moncrieff J. The antidepressant debate. Br J Psychiatry 2002; 180:193-4.

13. Gregory RL, editor. The oxford companion to the mind. Oxford: Oxford University Press; 1987.

14. Kretschmer E. Geniale menschen. Berlin: Springer; 1958.

15. Juda A. Hochstbegabung: ihre erbverhaltnisse sowie ihre beziehungen zu psychischen anomalien. Munich: Urban & Schwartzenburg; 1953

16. Jamison KR. Touched with fire: manic-depressive illness and the artistic temperment.  New York: Free Press Paperbacks; 1992.