As merry as the day is long? Shakespeare on seasonal mood ...

Easy to over-interpret, however when Beatrice says in Much Ado about

Winter - North of Scotland

Nothing she is " ... As merry as the day is long", interesting to consider: was this a throw-away line, a mask for her true mood, or the mirror of "... As sad as the day is short"?  We also have young prince Mamillius saying "... a sad tale's best for winter." [Winter's Tale. II.i.25]

Hippocratic writings [On Airs, Waters, and Places: ~400 BCE] recognize the potential for seasonal variation to influence patterns of disease in general. And not a new idea that people are lower in spirits in winter months: the Roman writer Jordanes refers to winter depression in his history of the Goths [Getica: 551 AD]. Describing depression as 'the blues' dates from 1741 and 'winter blues' [la dépression hivernale] describes what many people may experience. 

However SAD syndrome (Seasonal Affective Disorder) was only formally reported as such and named in 1984 by Rosenthal and colleages at the National Institute of Mental Health in the USA. Rosenthal was initially motivated by wishing to discover the cause of his own experience of depression during the dark northern US winter. His key contribution was to suggest that reduced exposure to light is a major factor causing SAD and that exposure to more light during the day may reverse features of SAD. 
 

Of note, Much Ado (as Love's Labour's Won) is currently paired by the RSC in Stratford with the bleaker Love's Labour's Lost with its unfulfilled ending, and the poem "Winter", "When icicles hang by the wall". The only "merry note" appears to be from an owl. Chilled Dick the shepherd is "blowing his nail", greasy Joan, has "... nose, red and raw...", and the "Parson (is) drowned out by coughing flock".

Shakespeare often used winter as a metaphor for hard times and troubled characters, from the direct contrast from the opening of King Richard III

"Now is the winter of our discontent, made glorious summer ..."

to Sonnet 5

"For never-resting time leads summer on
To hideous winter and confounds him there;
Sap cheque'd with frost and lusty leaves quite gone,
Beauty o'ersnow'd and bareness every where."

There is inevitable speculation about the extent to which Shakespeare was revealing on stage aspects of his own depression, or reflecting human experience, and the influence of uncertainties of life at his time.

For the present day, there are now also biochemical hypotheses for the cause of SAD - infections are common in winter and the inflammatory chemicals (cytokines) released by the body's defence cells to fight infection may have the unwanted effect of depressing mood, through toxic actions on brain cells. This may both provide new causes for depression as well as opportunities for treatment, through blocking these harmful chemicals.

Folk wisdom and health

Shakespeare and the history of heartbreak  The Lancet
 

Sadness and the four humours in Shakespeare

Shakespeare and depression

Cancer risk, premature death and sleeping tablets?

@HealthMed A team of researchers from Scripps Institute and the Jackson Hole Center for Preventive Medicine in Jackson, Wyoming, in the United States has reported in a publication in the British Medical Open Journal that use of sleeping tablets is associated with increased risk of cancer (lymphoma or cancer of the lung, colon or prostate), and  premature death. Results were obtained by interrogating electronic case records within a large US health care service: the Geisinger Health System (GHS), the largest rural integrated health system in the USA. GHS serves a 41 county area of Pennsylvania with approximately 2.5 million people.
This report has been disseminated widely in the international media, including for example in the Los Angeles Times.
The 2 major questions raised by this work are whether findings are explained by effects caused by the sleeping tablets -  or are the kind of people who are prescribed hypnotics just more likely to develop cancer or premature death, as a result, for example, of genetic factors, lifestyle reasons or associated disease causing the sleep disturbance.
Obvious more specific questions include are whether this relationship is:
- caused by the sleeping tablets (hypnotics);
- a feature of 'reverse causation - ie resulting from the initial sleep disturbance having been caused by symptoms of at that stage undiagnosed cancer, or sleep disturbance caused by cancer risk factors such as smoking, excess alcohol or obesity - ie some cancer-related factor leading to patients seeking a prescription for hyponotics
- coincidental
- or spurious - the result of some bias in subject selection.
The short, ~2.5 year average treatment duration makes this possible early cancer effect important to exclude as an explanation.
The authors say they have made reasonable efforts to exclude other causes of increased cancer risk. A wide range of hypnotics were included in the study, making it unlikely that a direct chemical action of the tablets is responsible for the cancer risk.
An intriguing possibility is that the association is a marker of chemical changes in the brain arising from sleep disturbance: it is well recognized that disordered brain function leads to production by the brain of inflammatory mediators (cytokines). One consequence is the thought to be the increased risk of heart disease reported in patients who have depression. That has lead to interest in using new biological agents to inhibit the action of these cytokines as a new approach to treatment depression and other serious neurological disorders. Taking sleeping tablets, although prolonging sleep duration, may not be sufficient to induce a normal sleep pattern.
In the context of the Scripps study, this raises the question whether  inflammatory mediators
could modulate tumour formation or accelerate the growth of early stage cancers. This concept was discussed by Reiche and colleagues in a Lancet Oncology review in 2004. As an example, the chemical - tumour necrosis factor alpha - is a potent cytokine implicated in depression and - as the name indicates - with a role in tumour biology, for example in modulating tumour blood supply.
Although in the Scripps study the reported relative risk of cancer increased from 3.5 to 5-fold with the numbers of sleeping tablets used, there needs to be a clear description of absolute events rates. And the increase in premature death was from a very wide range for causes, from accidents to asthma, flu and diabetes.
Of note, this was an observational study controlled by the authors by aiming to find well-matched subjects not on sleeping tablets (cases: 10 529 patients who received hypnotic prescriptions;  23 676 matched controls). A randomised controlled trial aimed at assessing these particular outcomes would have been needed to test these findings with more confidence of lack of bias. 
If the relationship is confirmed as having a causative link, the study would illustrate yet again the importance of balancing benefit and risk when prescribing tablets, and ensuring that any prescription is  continued for the minimum clinically indicated time.

Taboo tablets - beta-blockers and professional string players

The following blog arose from contributing to an article in The Strad by Catherine Nelson on drugs and occupational stress amongst professional musicians.

As clinical pharmacologist and amateur violinist gives me two perspectives on performance or audition anxiety: this is due to the triggering of an extra release of
 adrenaline – and other fight-or-flight response hormones – which in turn can cause
 string players to feel anxious and suffer a shaking bowing arm. Beta-blockers can stop 
unwanted reactions to these hormones, such as an increased heart 
rate, and thus lessen detrimental effects of stress on the musician’s performance.


I had heard of a violinist who was so anxious and stiff during an audition that the bow simply flew out of his hands. Many professional musicians are worried by the stress of performance, and beta-blockers may help some players control the debilitating physical symptoms of this stress.
It is of course extremely important that musicians, for whom medical treatment of occupational stress may be indicated, work
 with a medical practitioner to ensure, if a beta-blocker appears worth a trial, that they take the right dose, provided it has been checked that this would be medically safe to do so. I am particularly concerned about anecdotal evidence of players sharing medicines - which may not be the right medicine, or a possible cause of severe and rapid onset harmful effects. People are increasingly turning to the internet to
 obtain drugs. At best these pills may be out of date – at worse 
they may be contaminated. Taking them without getting advice from a
 doctor can be very dangerous.
Beta-blockers slow the heart, helping to make people feel calmer, but they also make your heartbeat less forceful than it should be,
 so that even fit people may feel tired and short of breath, and some people may be tipped into heart failure. Players with certain pre-existing medical conditions may suffer worse adverse reactions. These
 drugs also make the airways less open, so are dangerous in asthma.
 Other side effects include sleep disturbance, weight gain and stomach upset, including increased stool frequency and urgency. There 
are also reports of people suffering depression while taking
 beta-blockers, though it may be that people with heightened anxiety are 
more prone to suffering depression. It is therefore better to avoid medicines if possible.
The message for beta-blockers should be that if they are worth a trial on medical grounds, to try a low
 dose under the advice of a medical practitioner; the dose may then be carefully increased if needed. If medically indicated, it is also very important always to 
try beta-blockers first under rehearsal conditions, as being made too relaxed or having unwanted effects could be harmful when performance really matters.

The implications of the broader issue of anecdotal widespread use of beta-blockers raise important occupational health and ethical concerns which deserve to be discussed nationally and internationally, both by the music profession and relevant medical organisations.

See The Strad for more on the article.