Bipolar disorder (BD): a psychiatric definition and treatment
Bipolar disorder (BD) is a chronic, disabling and life-threatening illness1. Patients with a diagnosis of BD have a
suicide mortality rate of more than 10 times that of the general population2-4. BD has a lifetime prevalence of 4.5%
in the adult US population, equally affecting females and males5. Currently, BD etiology is still unknown. Recent
studies hypothesize BD to be driven by the interaction between genetic and environmental factors, although no
genes have been unequivocally linked to BD, yet6.
The most updated edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) classifies BD
as a mood disorder. The DSM-IV defines BD as a “cyclic” or “periodic illness”, in which a subject experiences
mood swings from positive symptoms (mania, period of elevated mood) to negative episodes (depression), most
often transitioning through a euthymic phase (normal non-depressed and positive mood)7.
Specific symptoms characterizing the two poles of the disease are:
– Mania: on the basis of the severity of the symptoms mania can be sub-classified into hypomania, acute mania, and
delirious mania. Hypomania is a state in which the patient has a heightened mood, high self-esteem and selfconfidence;
because of that, he/she may engage themselves in other people’s lives or even in dangerous situations.
Patients are distractible, present with hypersexuality, have flights of ideas and lack the need of sleep7. During acute
mania phases, the symptoms of hypomania are exacerbated; in addition, hallucinations and delusion symptoms
appear, together with increased strength and decreased pain threshold7. The most severe form of mania is delirious
mania, in which, in addition to the exacerbation of acute mania symptoms, the patient may experience confusion,
clouded consciousness, dysphoric mood, loss of self-control, and catatonia7.
– Depression: patients experiencing depression report loss of energy and psychomotor retardation with agitation,
despair, low and irritable mood and no attraction to life, eventually leading to suicidal thoughts or attempts.
Depression presents with hallucinations, delusions of guilt and belief in deserved punishment, hyperphagia, leading
to weight gain, hyper-somnolence due to a feeling of being always exhausted, insomnia, sluggish thoughts, impaired
concentration, memory and decision making7.
BD is further classified as BD-I and BD-II, on the basis of the severity of symptoms BD-I subjects experience acute
and delirious mania symptoms, while BD-II subjects experience only hypomania.
Normally, in BD, the two phases of the disease are separated by a period of euthymia. However, sometimes a patient
shows a mixture of manic or depressive symptoms, such as “weeping uncontrollably” while saying “they never felt
so well in their lives”, or manic and depressive phases occur in direct succession.; these episodes are called mixedmanic
episodes7. In general, women tend more toward depressive episodes, while men toward manic episodes,
although the cycling, duration of each episode and the “polarity” are very subjective7.
The current treatment of BD is characterized by empirical trials and many side effects; often, the treatments include
a combination of several kinds of medications8 and psychotherapy. The main pharmacological classes of
medications prescribed to BD patients are mood stabilizers and antiepileptic drugs9, such as lithium chloride and
valproic acid. Lithium is effective in reducing mania episodes, although its mechanism of action is still unclear.
Often, mood stabilizers and antiepileptic treatments are not enough to prevent manic or depressive episodes9; when
the depressive phase of BD occurs, antidepressants, such as selective reuptake serotonin inhibitors or tricyclic drugs,
are often administered along with mood stabilizers. In general, antidepressant treatments are used for a limited time,
as it was observed that antidepressant drugs may trigger manic episodes or cause cycles to be more rapid. When
manic episodes occur, antipsychotic medications, such as haloperidol, are prescribed10. All drugs used to treat BD
have strong side effects, and can be toxic; moreover, the efficacy and dosage of these treatments are unpredictable
and subjective.
In addition to medications, psychotherapy11 and other therapies, such as electroconvulsive therapy12 for manic and
depressive episodes, vagus or vagal nerve stimulation, transcranial magnetic stimulation13 and light therapy for
depressive episodes14, are important for the treatment of BD.
Ayurveda and BD
Originating in India, Ayurveda is the most ancient health discipline. The roots of the word Ayurveda come from the
Sanskrit Ayur (life) and veda (knowledge); Ayurveda is thus the science of life. In its ancient texts (“veda”)
Ayurveda comprises etiology, pathology and pharmacology of diseases.
Ayurveda acknowledges that the constitution and illnesses of every individual are caused by three bodily humors, or
doshas: vata, pitta and kapha. According to the compendium Charaka Samhita, one of the fundamental classic texts
of Ayurveda, written in the early centuries of the Common Era, the doshas are defined as “the three body energetics,
made of qualities, which support right body function in right amount, and destroy right body function in excess or
deficiency”15.
Every dosha is built from different elements (ether, air, fire, water, earth), and thus possesses unique qualities. Vata
(air and ether) is the lighter of the doshas. In the Charaka Samhita, Charaka describes vata qualities as “nonunctuous,
cold, light, subtle, mobile, non-slimy and rough”16. Pitta (fire and water) is the only warm dosha., Its
qualities are “slightly unctuous, hot, sharp, liquid, sour, mobile and pungent” according to the Charaka Samhita17.
Kapha (water and earth) is the heavier and most still of the dosha, and it is described as “heavy, cold, soft,
unctuousness, sweet, immobile, slimy”17.
According to Ayurveda, when a person is conceived, the unique relative ratios of the doshas form the constitution, or
prakruti. Any imbalance of this relative ratio leads to a disease. The imbalanced dosha would reside in the weakest
system or organ, that can be physical (such as the digestive tract) or not physical (e.g. the mind)18.
In the same way as the body presents attributes that are driven by the doshas, Charaka Samhita describes also the
attributes of the mind (gunas): tamas (“inertia, dullness, sleep, darkness”), rajas (“momentum, desire, action”) and
sattva (“peaceful, clear, balanced, steady”)16.
The state of mind of bipolar patients is seldom sattvic; it can be said that persons experiencing milder forms of the
disease (BD-II) have a rajasic state of mind, while during severe episodes of depression or mania (BD-I) they have a
tamasic state of mind.
According to Ayurveda, there are three energies that are essential for the vitality, that are subtle counterparts of the
doshas: prana (“subtle energy of air as the master force behind all mind-body functions”)19, tejas (“subtle energy of
fire through which we digest impressions and thoughts”)20 and ojas (“subtle energy of water as our vital energy
reserve, essence of digested food, impressions and thoughts”)20. Prana is the force that allows the mind to “move
and respond to challenges”, tejas allows good judgment, and ojas is the mind’s endurance, providing psychological
stability20.
In BD patients the level of ojas is low, and this is reflected by the mental instability that characterizes the pathology.
In acute phases, prana is high during mania, where there is an excess of movement of thoughts, and low during
depression, where, opposite to manic phases, thoughts become sluggish. Tejas is high in manic phases, where
patients lack clarity and determination, and can be either high or low during depression19,20.
Although a perfect overlap between BD and ancient Ayurveda pathology definition is not found, Charaka and
Sushruta (a second fundamental classic Ayurveda author) describe symptoms of psychiatric diseases and classify
them as “unmada”. Unmada comprises all psychiatric disorders and can be translated as “psychosis”21,22. In the
Sushruta Samhita, unmada is subsequently divided in 6 subcategories: three due to the vitiation of a single dosha,
one involving the vitiation of multiple doshas, one due to anxiety and mental stress and one caused by poison. The
different types of unmada carry etiological, pharmacological and prognostic importance. Specific symptoms of BD
can then be driven by specific doshas vitiating the mind (manovaha srota). Vataja unmada is characterized by vataspecific
behaviors, such as “patients laugh without a reason, shout, and wander about”. Anger and hostility become
predominant features for patients experiencing pittaja unmada. Kaphaja unmada is accompanied by loss of appetite,
lethargic actions and voice, and increased sleeping time. From this brief overview, vataja and pittaja unmada can be
associated with the western definition of mania, while kaphaja unmada would correspond closely to depressive
phase. However, due to the volatile nature of the disease, BD can be considered more associated with vata
imbalance; indeed “vata’s excess of air causes instability and agitation in the mind”, thus being the principle
responsible for creating the space that would be eventually filled by other doshas23,24.
Between the 5 different expressions of vata (prana vayu, samana vayu, vyana vayu, udana vayu and apana vayu),
samana vayu, “mental digestion and homeostasis”, results as particularly compromised in BD. Vitiation of samana
vayu leads to an altered homeostasis of the mind, that subsequently affects vyana vayu, increasing the circulation of
thoughts, and prana vayu, altering the intake of sensory impressions in the mind20.
Ayurveda recognizes that all pathologies start in the digestive system, as the accumulation and aggravation of the
vitiated doshas. Prodromal symptoms of BD would be typical of vata vitiation (apana vayu) in the digestive system
(purishavaha srota), affecting the moisturizing of the mucous membranes of the colon, leading to constipation. Vata
would overflow from the digestive system to the mucous membranes of all the body (rasavaha srota) and the
circulatory system (raktavaha srota), producing generalized dryness and fatigue. Vyana is the vayu that becomes
vitiated at this level. The pathology manifests when vata relocates in the manovaha srota, the channel of the mind,
and modifies and diversifies, leading to the symptoms typical of BD, caused by the vitiation of samana (restlessness,
mood swings, tremors), prana and vyana vayu (vata-driven and circulated emotions and thoughts).
From this perspective, it become clear that, as BD is mainly driven by vata (that may lead to the vitiation of other
doshas in the mind) all actions taken to pacify vata would improve the symptomatology of BD. Vata’s principal
characteristic is being mobile, thus constant routines would improve vata-driven pathology such as BD; vata is also
associated with movement, that would then be reduced by “sitting or walking quietly and peacefully by” nature,
listening to “calming music”, gentle massage using sesame or almond oil, calming colors (in particular gold), “rich
and nourishing food abounding in sweet, salty and sour tastes”, “sweet, warm and calming” fragrances (“jasmine,
rose, sandalwood, eucalyptus”). Calming activities such as gentle practice of Hatha Yoga, Tai Chi, and swimming
will also have a positive effect on BD; these activities will help the mind to build peace and contentment, essential
for a good prognosis of the disease. Chanting vata-pacifying mantra, such as “Ram, Hrim, Shrim” is another way to
ameliorate BD symptoms20.
Ayurvedic pharmacopeia utilizes herbs to assist and sustain the lifestyle changes required to decrease vata in the
manovaha srota. To pacify vata in the manovaha srota, nervine tonics and sedatives should be administered.
Examples of these herbs, considered beneficial in the management of BD, are ashwagandha, shatavari, shank
pupshi, brahmi, taken with a dipanas to help digestion. The ideal anupanas for the formulation would be ghee, since
it is particularly beneficial for increasing ojas, which should be the primary goal of treatment, in order to give
stability to the system25.
Chronobiology: a new branch of western medicine
A relatively new branch of western medicine is chronobiology, that considers the timing of periodic phenomena of
essential importance. The most important periodic phenomenon is circadian rhythm.
Circadian rhythms are all the reactions and substances that occur in the body with a period of roughly 24 hours.
Circadian rhythms are very well conserved through evolution, controlling the physiology and behavior of almost all
living beings. In complex beings like mammals, the circadian rhythm is organized in a hierarchic fashion: the master
clock, the suprachiasmatic nucleus (SCN) of the hypothalamus, that possesses an endogenous rhythm, contains an
input pathway that links the external light-dark stimuli to the internal cycle and synchronizes peripheral oscillators
through a variety of stimuli; thus, light is the main entrainment cue for humans. Peripheral oscillators, virtually all
the cells of the body, possess the same molecular clock machinery as the SCN. The basis of the molecular
machinery that constitutes the circadian rhythm is a negative feedback loop. The same clock genes that are activated
and repressed in a circadian (about 24 hours) fashion are present in every cell of the body26,27.
Increasing evidence highlights the link between health and proper circadian rhythm function. It is demonstrated that
many pathologies lead to impairments of circadian rhythms (“sundown syndrome” in Alzheimer’s disease patients,
for example) and that abnormal circadian rhythms (eating at the wrong time) can cause disorders (metabolic
syndromes).
Much evidence provides support for an association between circadian rhythm dysfunction and BD. Alteration of
hormonal circadian rhythms (e.g. cortisol and growth hormone levels) and core body temperature in BD have been
reported in early studies, suggesting an involvement of the circadian system in the pathophysiology of the disease28-
35. People suffering from BD show an abnormal sleep-wake cycle, in particular a reduced need of sleep and
abnormal sleep architecture36; moreover, sleep disturbances are often prodromal to BD relapse37, and sleep length
was found to be prodromal to mania or hypomania phases38, and is one of the main symptoms considered by the
DSM-IV of both mania and depression. In addition to this evidence, many genetic studies imply that mutations in a
number of clock genes are associated with BD39.
Quite unsurprisingly, the treatment of BD with antipsychotic drugs stabilizes the circadian rhythms seen in the
amplitude of temperature rhythms, plasma melatonin, cortisol secretion levels40, although an enhanced salivary
cortisol response to waking is still present in euthymic individuals41.
Due to the strong impact of circadian rhythm dysfunction on mood disorders, many protocols are being developed to
treat psychiatric disorders, and in particular BD, with chronotherapies, treatments specifically designed to regulate
the circadian rhythms of a person, including re-establishing a good synchronization between the external light-dark
cycle and internal rhythms.
The main therapeutic resource of chronotherapies is the regulation of sleep and light exposure. Sleep deprivation has
been widely demonstrated to have a quick, but temporary, antidepressant effect, that can manifest even after 24
hours or one night of complete sleep deprivation14,42. In depressed subjects, this treatment would “reset” the clock,
ameliorating ,symptomatology. In BD subjects, however, sleep deprivation could ameliorate depressive symptoms,
but could trigger mania as well43. In a recent paper, the use of sleep deprivation was administered in conjunction
with other chronotherapies, such as bright light therapy, and sleep advance phase. Bright light therapy was
administered the day after the sleep deprivation night for three consecutive days, while following a sleep deprivation
night subjects were exposed to sleep phase advance, to reset the sleep time around 10 PM. The combination of these
therapies was shown by the authors of the paper to have a fast and long-lasting anti-depressive effect without
triggering mania44.
Morning bright light therapy was attempted in depressive phases of BD, but in the vast majority of cases it would
trigger mania; however, a higher dose of midday bright light was found beneficial45.
Similarities between Ayurveda knowledge and new western traditional medicine approaches to BD
The first striking feature that surprises us when comparing the Ayurvedic description of unmada and the more recent diagnosis and classification of BD symptoms is the similarity between these two disciplines, developed in times so far from each other. Typical vata symptoms that have been described in ancient texts and have a counterpart in modern psychiatric diagnosis methods (e.g. DSM-IV) include, for example, continuous irregular speech, excessive talking or “pressure of speech” (satatamaniyanam ca gira and bahubhasita), hyperactivity and inappropriate behaviors such as excessive smiling, laughing, or dancing (abhiksnasmitahasitanrtyagitavadi), abusive and
dangerous behavior (vikrosa). Similarly, pittaja unmada symptoms such as impatience (amarsa), anger (krodha), violence (samrambhaschasthane), raised temper (rosa), sleeplessness (vinidra) are also present in the description of BD in the DSM-IV. Both vata and pitta symptoms are translated as manic manifestations of the disease. Also when considering kaphaja unmada symptoms it is possible to find similarities to the DSM-IV diagnosis criteria for BD, such as psychomotor retardation (stillness and sluggishness) (alpacankramana and sthanamekadese), lacking of energy (alpamati), hypersomnolence (swapnanityata)46.
The main goal of chronobiology is to re-establish a physiological and personal routine in sleep and eating behaviors. This is of particular importance for a disorder as highly variable as BD in which, depending on the phase of the disease, a patient may sleep less than 3 hours per night and forget to eat, or oversleep and overeat. The same principles are considered fundamental in the management of vata-driven pathologies when samana vayu is vitiated, focusing the treatment by also improving a constant routine around sleep and eating habits20.
In addition, in BD, Ayurvedic principles can offer a mechanism behind the validity and failure of certain chronotherapies. Sleep deprivation therapies used to treat depression were demonstrated to be a non-effective treatment for BD, triggering mania in a high percentage of volunteers, despite the finding that in major depression the treatment did not have side effects. Effective vata-reducing practices improve rest and sleep time, therefore sleep deprivation would exacerbate vata vitiation and symptoms. On the other hand, BD symptoms were ameliorated when patients were treated with 14 hours of bedtime in the night in total darkness, that can be considered a vatapacifying
technique, since people with vata vitiation are extremely sensible to stimuli (“loud music or noise”20). A similar example is the bright-light therapy used in treating BD patients that was found to be effective to treat depression without triggering mania if administered during mid-day, a moment of high pitta, important for properly digesting the light.
Conclusions
All reported evidence points out that the proper management of the life-threatening disease BD is still a challenge for modern psychiatry; however, the new concept of chronobiology is helping physicians with novel therapies, such as dark and light therapy, sleep deprivation and sleep phase advance therapy. Similar concepts of ad-hoc life-style changes were already suggested from early in the Common Era by Ayurvedic practitioners for the treatment of specific disorders. The ancient, yet current, Ayurvedic knowledge can be extremely important for the proper application of chronotherapies, resulting in a more personalized and affordable treatment to counterbalance subjective imbalances in BD. Taken together, chronotherapies and Ayurveda could be a new keystone in the
treatment of BD.
References:
1 J. Angst & M. Preisig, “Outcome of a clinical cohort of unipolar, bipolar and schizoaffective patients.
Results of a prospective study from 1959 to 1985,” Schweiz Arch Neurol Psychiatr 146 1995): 17-23.
2 E. H. Hoyer, P. B. Mortensen & A. V. Olesen, “Mortality and causes of death in a total national sample of
patients with affective disorders admitted for the first time between 1973 and 1993,” Br J Psychiatry 176
(January 2000): 76-82.
3 R. Sharma & H. R. Markar, “Mortality in affective disorder,” J Affect Disord 31 (June 1994): 91-96.
4 U. Osby, L. Brandt, N. Correia, A. Ekbom & P. Sparen, “Excess mortality in bipolar and unipolar disorder
in Sweden,” Arch Gen Psychiatry 58 (September 2001): 844-850.
5 K. R. Merikangas, H. S. Akiskal, J. Angst, P. E. Greenberg, R. M. Hirschfeld, M. Petukhova & R. C.
Kessler, “Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity
Survey replication,” Arch Gen Psychiatry 64 (May 2007): 543-552.
6 C. E. Bearden & N. B. Freimer, “Endophenotypes for psychiatric disorders: ready for primetime?,” Trends
Genet 22 (June 2006): 306-313.
7 J. Cooper, “Diagnostic and Statistical Manual of Mental Disorders (DsM-IV-TR),” British Journal of
Psychiatry 179 (July 2001): 85-85.
8 J. Hirschowitz, A. Kolevzon & A. Garakani, “The pharmacological treatment of bipolar disorder: the
question of modern advances,” Harv Rev Psychiatry 18 (September-October 2010): 266-278.
9 A. Musenga, M. A. Saracino, G. Sani & M. A. Raggi, “Antipsychotic and antiepileptic drugs in bipolar
disorder: the importance of therapeutic drug monitoring,” Curr Med Chem 16 2009): 1463-1481.
10 M. Tohen & E. Vieta, “Antipsychotic agents in the treatment of bipolar mania,” Bipolar Disord 11 Suppl 2
(June 2009): 45-54.
11 E. Vieta, I. Pacchiarotti, M. Valenti, L. Berk, J. Scott & F. Colom, “A critical update on psychological
interventions for bipolar disorders,” Curr Psychiatry Rep 11 (December 2009): 494-502.
12 P. Sienaert, “What we have learned about electroconvulsive therapy and its relevance for the practising
psychiatrist,” Can J Psychiatry 56 (January 2011): 5-12.
13 C. Loo, N. Katalinic, P. B. Mitchell & B. Greenberg, “Physical treatments for bipolar disorder: a review of
electroconvulsive therapy, stereotactic surgery and other brain stimulation techniques,” J Affect Disord
132 (July 2011): 1-13.
14 F. Benedetti, B. Barbini, C. Colombo & E. Smeraldi, “Chronotherapeutics in a psychiatric ward,” Sleep
Med Rev 11 (December 2007): 509-522.
15 Gabriel Van Loon, Charaka Samhita Handbook on Ayurveda (Sharma andChaukhambha Orientalia, 2002)
Car 1#57, p.36.
16 Gabriel Van Loon, Charaka Samhita Handbook on Ayurveda (Sharma andChaukhambha Orientalia, 2002)
Car 1 1#58, p.38.
17 Gabriel Van Loon, Charaka Samhita Handbook on Ayurveda (Sharma andChaukhambha Orientalia, 2002)
Car 1 1#60, p.38.
18 Gabriel Van Loon, Charaka Samhita Handbook on Ayurveda (Sharma andChaukhambha Orientalia, 2002)
Car 3 8#101, p.137.
19 David Frawley, Ayurveda and the mind : the healing of consciousness (Lotus Press, 1997) p.23.
20 David Frawley, Ayurveda and the mind : the healing of consciousness (Lotus Press, 1997) p.24.
21 Panday Gs, Caraka Samhita: Hindi Commentary (Choukamba Publications, 1997) Car 6 6#7-7.
22 Shastry Ka, Sushruta Samhita: Hindi vyakhya (Choukamba Publications, 2002) Su 6 62#4.
23 Panday Gs, Caraka Samhita: Hindi Commentary (Choukamba Publications, 1997) Car 6 9#10.
24 Shastry Ka, Sushruta Samhita: Hindi vyakhya (Choukamba Publications, 2002) Su 6 62#5.
25 Vasant Lad David Frawley, The Yoga of Herbs: An Ayurvedic guide to herbal medicine (1986).
26 D. K. Welsh, J. S. Takahashi & S. A. Kay, “Suprachiasmatic nucleus: cell autonomy and network
properties,” Annu Rev Physiol 72 2010): 551-577.
27 D. K. Welsh, S. H. Yoo, A. C. Liu, J. S. Takahashi & S. A. Kay, “Bioluminescence imaging of individual
fibroblasts reveals persistent, independently phased circadian rhythms of clock gene expression,” Curr Biol
14 (December 2004): 2289-2295.
28 D. J. Kupfer, F. G. Foster, P. Coble, R. J. Mcpartland & R. F. Ulrich, “The application of EEG sleep for the
differential diagnosis of affective disorders,” Am J Psychiatry 135 (January 1978): 69-74.
29 P. Linkowski, M. Kerkhofs, A. Van Onderbergen, P. Hubain, G. Copinschi, M. L’hermite-Baleriaux, R.
Leclercq, M. Brasseur, J. Mendlewicz & E. Van Cauter, “The 24-hour profiles of cortisol, prolactin, and
growth hormone secretion in mania,” Arch Gen Psychiatry 51 (August 1994): 616-624.
30 Carroll, G. C. Curtis & J. Mendels, “Neuroendocrine regulation in depression. I. Limbic systemadrenocortical
dysfunction,” Arch Gen Psychiatry 33 (September 1976): 1039-1044.
31 P. Linkowski, E. Van Cauter, R. Leclercq, D. Desmedt, M. Brasseur, J. Golstein, G. Copinschi & J.
Mendlewicz, “ACTH, cortisol and growth hormone 24-hour profiles in major depressive illness,” Acta
Psychiatr Belg 85 (September-October 1985): 615-623.
32 J. D. Amsterdam, A. Winokur, E. Abelman, I. Lucki & K. Rickels, “Cosyntropin (ACTH alpha 1-24)
stimulation test in depressed patients and healthy subjects,” Am J Psychiatry 140 (July 1983): 907-909.
33 T. Tsujimoto, N. Yamada, K. Shimoda, K. Hanada & S. Takahashi, “Circadian rhythms in depression. Part
II: Circadian rhythms in inpatients with various mental disorders,” J Affect Disord 18 (March 1990): 199-
210.
34 E. Souetre, E. Salvati, T. A. Wehr, D. A. Sack, B. Krebs & G. Darcourt, “Twenty-four-hour profiles of
body temperature and plasma TSH in bipolar patients during depression and during remission and in
normal control subjects,” Am J Psychiatry 145 (September 1988): 1133-1137.
35 J. Mendlewicz, P. Linkowski, M. Kerkhofs, D. Desmedt, J. Golstein, G. Copinschi & E. Van Cauter,
“Diurnal hypersecretion of growth hormone in depression,” J Clin Endocrinol Metab 60 (March 1985):
505-512.
36 A. G. Harvey, L. S. Talbot & A. Gershon, “Sleep Disturbance in Bipolar Disorder Across the Lifespan,”
Clin Psychol (New York) 16 (Jun 2009): 256-277.
37 A. Jackson, J. Cavanagh & J. Scott, “A systematic review of manic and depressive prodromes,” J Affect
Disord 74 (May 2003): 209-217.
38 E. Leibenluft, P. S. Albert, N. E. Rosenthal & T. A. Wehr, “Relationship between sleep and mood in
patients with rapid-cycling bipolar disorder,” Psychiatry Res 63 (July 1996): 161-168.
39 E. W. Lamont, D. L. Coutu, N. Cermakian & D. B. Boivin, “Circadian rhythms and clock genes in
psychotic disorders,” Isr J Psychiatry Relat Sci 47 2010): 27-35.
40 E. Souetre, E. Salvati, J. L. Belugou, D. Pringuey, M. Candito, B. Krebs, J. L. Ardisson & G. Darcourt,
“Circadian rhythms in depression and recovery: evidence for blunted amplitude as the main
chronobiological abnormality,” Psychiatry Res 28 (June 1989): 263-278.
41 D. Deshauer, A. Duffy, M. Alda, E. Grof, J. Albuquerque & P. Grof, “The cortisol awakening response in
bipolar illness: a pilot study,” Can J Psychiatry 48 (August 2003): 462-466.
42 J. C. Wu & W. E. Bunney, “The biological basis of an antidepressant response to sleep deprivation and
relapse: review and hypothesis,” Am J Psychiatry 147 (Jan 1990): 14-21.
43 T. A. Wehr, D. A. Sack & N. E. Rosenthal, “Sleep reduction as a final common pathway in the genesis of
mania,” Am J Psychiatry 144 (February 1987): 201-204.
44 J. C. Wu, J. R. Kelsoe, C. Schachat, B. G. Bunney, A. Demodena, S. Golshan, J. C. Gillin, S. G. Potkin &
W. E. Bunney, “Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in
bipolar disorder,” Biol Psychiatry 66 (August 2009): 298-301.
45 D. Sit, K. L. Wisner, B. H. Hanusa, S. Stull & M. Terman, “Light therapy for bipolar disorder: a case series
in women,” Bipolar Disord 9 (December 2007): 918-927.
46 S. P. Suchitra, H. S. Devika, B. N. Gangadhar, R. Nagarathna, H. R. Nagendra & R. Kulkarni, “Measuring
the tridosha symptoms of unmada (psychosis): a preliminary study,” J Altern Complement Med 16 (April
2010): 457-462.