Глюкокортикостероиды и риск суицида

Glucocorticoid medications given in primary care settings are associated with suicidal behaviors and severe neuropsychiatric disorders, new research suggests.

In a large, population-based study of adult patients in the United Kingdom (UK), those receiving glucocorticoids were almost 7 times more likely to commit or attempt suicide, more than 5 times more likely to develop delirium, more than 4 times more likely to develop mania, and almost twice as likely to develop depression than those with the same underlying conditions who did not receive the medications.

In addition, patients younger than 30 years were at particular risk for suicide attempts, women were more at risk for depression, and men were at especially increased risk for mania and delirium/confusion/disorientation. Higher dosages of the medications were also linked to an overall greater risk for adverse outcomes.

 Glucocorticoids Linked to Suicide, Neuropsychiatric Disorders

Лекарственные средства вызывающие депрессию

Interferons are powerful antivirals but they have the dubious honor of being one of the few medical drugs clearly implicated in causing depression. Others include reserpine, an anti-hypertensive and rimonabant, a weight-loss drug (it got banned for this reason).

The anti-malarial mefloquine can cause a range of neuropsychiatric symptoms including depression but also hallucinations and nightmares, as can the HIV drug efavirenz which I covered recently.

Most people who take each of these drugs don't experience problems but in a non-trivial minority it happens. It obviously poses a serious problem for doctors, but it's also very interesting for people researching mood and depression. Work out why these drugs cause depression, and it might help work out why people get "normal" clinical depression.

For example, just recently it was shown that mefloquine has a unique and unusual effect on cells in the dopamine system of the brain, responsible for motivation and pleasure. Whether this explains the side-effects is an open question but without mefloquine we wouldn't even be able to ask it.

As for interferons, which are actually not drugs as such but rather molecules produced by the immune system during infections, it's given rise to the inflammation theory of depression. There's always a risk, though, that by focussing too much on just one class of depressing drug, you'll end up with a narrow theory that can't account for the others.

Antivirals and Suicide

Сезонное аффективное расстройство в рамках БАР и рекуррентной депрессии

Many see seasonal affective disorder (SAD) as synonymous with winter depression. However, depression is only half of the problem; spring and summer mania tend to be ignored. Beginning with winter depression, core symptoms resemble hibernation. People sleep more, eat more, and are less interested in usual activities. They are not sad in mood, typically, and may be unaware that their slowed down, uninterested behavior reflects a kind of depression.

Moreover, light itself is not the only cause of depression. Light interacts with a person's own sensitivity to depression. Some people, especially those with bipolar disorder or recurrent unipolar depression, are sensitive to changes in light, and will develop winter depression even in areas with reasonable light levels, such as Georgia or Italy. Others are insensitive to light, and will not develop SAD even in areas with low light levels, such as New England or Scandinavia.

This leads to another misconception about SAD. It is a diagnosis of exclusion, and should not be diagnosed in persons with bipolar disorder or recurrent unipolar depression. SAD means someone has only depression in the winter, and almost never has depression any other time of year.

Light entrains our circadian rhythms; it is what keeps us on regular sleep-wake cycles. When sleep is impaired and reduced, an antidepressant effect occurs, and, in sensitive persons, mania materializes. This is what takes place in the spring and summer when light greatly increases. Longer duration of sleep leads to depression in sensitive persons. Circadian cycles appear to be biologically abnormal in people with bipolar disorder and recurrent depression, hence their sensitivity to light. One of the effects of lithium, for instance, is to lengthen circadian cycles, which appear to be abnormally shortened in animal models of mania.

I've developed my own recommendations for both winter depression and summer mania, which one could call "light precautions." They are as follows, briefly.

In winter. Increase your exposure to light as much as possible. Go out for a walk at noon for up to an hour without any sunglasses on; sleep with all the blinds up.

In summer. Reduce your exposure to light as much as possible: Always wear sunglasses; get room-darkening shades; and sleep in as much darkness as possible. (It is key to adjust one's exposure to natural morning sunlight. It is amazing how many people who oversleep never think of pulling up their window shades, and how many people who don't sleep enough don't think about getting room-darkening window shades.)
Light Box Treatment

Light box treatment essentially replaces the sunlight that is missing in wintertime. Most light boxes provide about 10,000 lux of light, and are meant to be used in the mornings, which is when the sun would normally have risen earlier than it does in the depths of winter. Patients should read or eat breakfast while exposed to indirect light from the box at about arm's length for about 30 minutes daily. Just as one does not directly look at the sun, patients should not directly look at light boxes; this causes ocular damage.

The Truth About Seasonal Affective Disorder

изотретионин, депрессии, суицид, акне

"Isotretinoin (13-cis-retinoic acid) has been used since the 1980s to treat severe recalcitrant nodular acne with good effect, but case reports and spontaneous reporting of adverse drug reactions have suggested an association between isotretinoin, depression, and suicidal behaviour," write Anders Sundström, from the Karolinska Institute in Stockholm, Sweden, and colleagues. "Observational studies have had conflicting results, however."

Severe acne is associated with the risk for suicide attempt even before treatment with isotretinoin was started, although the risk is increased during treatment and up to 6 months afterward, according to the results of a retrospective Swedish cohort study reported online first November 12 in the BMJ.

Severe Acne Linked to Suicide Risk Even Before Treatment Is Started

Противосудорожные препараты и риск суицида

Suicide, Epilepsy-Drug Link Becomes a Little Clearer

Suicide Intent Scale

Objective Circumstances Related to Suicide Attempt
1. Isolation
1. Somebody present
2. Somebody nearby, or in visual or vocal contact
3. No one nearby or in visual or vocal contact

2. Timing
1. Intervention is probable
2. Intervention is not likely
3. Intervention is highly unlikely

3. Precautions against discovery/intervention
1. No precautions
2. Passive precautions (as avoiding other but doing nothing to prevent their intervention; alone in room with unlocked door)
3. Active precautions (as locked door)

4. Acting to get help during/after attempt
1. Notified potential helper regarding attempt
2. Contacted but did not specifically notify potential helper regarding attempt
3. Did not contact or notify potential helper

5. Final acts in anticipation of death (will, gifts, insurance)
1. None
2. Thought about or made some arrangements
3. Made definite plans or completed arrangements

6. Active preparation for attempt
1. None
2. Minimal to moderate
3. Extensive

7. Suicide Note
1. Absence of note
2. Note written, but torn up; note thought about
3. Presence of note

8. Overt communication of intent before the attempt
1. None
2. Equivocal communication
3. Unequivocal communication

Self Report
9. Alleged purpose of attempt
1. To manipulate environment, get attention, get revenge
2. Components of above and below
3. To escape, surcease, solve problems

10. Expectations of fatality
1. Thought that death was unlikely
2. Thought that death was possible but not probable
3. Thought that death was probable or certain

11. Conception of method's lethality
1. Did less to self than s/he thought would be lethal
2. Wasn't sure if what s/he did would be lethal
3. Equaled or exceeded what s/he thought would be lethal

12. Seriousness of attempt
1. Did no seriously attempt to end life
2. Uncertain about seriousness to end life
3. Seriously attempted to end life

13. Attitude toward living/dying
1. Did not want to die
2. Components of above and below
3. Wanted to die

14. Conception of medical rescuability
1. Thought that death would be unlikely if he received medical attention
2. Was uncertain whether death could be averted by medical attention
3. Was certain of death even if he received medical attention

15. Degree of premeditation
1. None; impulsive
2. Suicide contemplated for three hours of less prior to attempt
3. Suicide contemplated for more than three hours prior to attempt

Other Aspects (Not included in total score)
16. Reaction to attempt
1. Sorry it was made; feels foolish; ashamed
2. Accepts both attempt and failure
3. Regrets failure of attempt

17. Visualization of death
1. Life after death, reunion with descendants
2. Never-ending sleep, darkness, end of things
3. No conceptions of or thoughts about death

18. Number of previous attempts
1. None
2. One or two
3. Three or more

19. Relationship between alcohol intake and attempt
1. Some alcohol intake prior to but not related to attempt; reportedly not enough to impair judgment, reality testing
2. Enough alcohol intake to impair judgment; reality testing and diminish responsibility
3. Intentional intake of alcohol in order to facilitate implementation of attempt

20. Relationship between drug intake and attempt
1. Some drug intake prior to but not related to attempt; reportedly not enough to impair judgment, reality testing
2. Enough drug intake to impair judgment; reality testing and diminish responsibility
3. Intentional intake of drug in order to facilitate implementation of attempt


15-19 Low Intent
20-28 Medium Intent
29+ High Intent
There is also a greater risk of repeated attempts the higher the intent rating.

The Question of Intent in Suicide Attempts

Астма, загрязнение воздуха и суицид

The sensitivity analysis demonstrated only a small potential confounding effect on the association between asthma and suicide. But Ferri said it is possible that depression may play a mediating role in suicide—individuals who developed depression after baseline might, for instance, have been more likely to interpret respiratory symptoms as a serious medical disorder, especially when symptoms were persistent and severe. (The sensitivity analysis is posted online at AJP in Advance as a data supplement to the article.)

Asthma, Air Pollution Linked to Increased Suicide Risk

Токсоплазмоз, шизофрения, суицидальное поведение

Studies of mice and rats infected by T. gondii have shown risky behavior changes, including an attraction to the smell of cat urine that makes them vulnerable to attacks. These findings may have parallels in behavioral changes in people, from schizophrenia to depression and reflex impairment.

Glenn McConkey, a researcher at the University of Leeds in England, reported last year that two genes in T. gondii's DNA contain instructions for the production of an enzyme that makes a brain chemical called dopamine.

"That's somewhat unusual, because other parasites don't have that [dopamine]," said Sarven Sabunciyan, Yolken's colleague at Hopkins. After all, microbes have no brains.

But in higher animals with nervous systems, dopamine is a neurotransmitter with important roles in regulating behavior. Some anti-psychotic drugs used to treat schizophrenia work by blocking dopamine action in the brain.

In May, Hopkins researcher David J. Schretien published a study suggesting that some brain changes and cognitive symptoms in schizophrenics may be caused or worsened by exposure to a herpes simplex virus. A 2005 Czech study found evidence of personality changes in humans infected by another herpes virus called cytomegalovirus. And numerous studies have suggested that flu infections during pregnancy may increase a child's risk of schizophrenia and autism.

Evidence that T. gondii infections may be a cause of schizophrenia, while not yet conclusive, is growing, Yolken said. A review of past studies, published last year by Yolken and Torrey, collected a variety of intriguing correlations. For example: People with schizophrenia have a higher prevalence of T. gondii antibodies in their blood. There are unusually low rates of schizophrenia and toxoplasmosis in countries where cats are rare, and unusually high rates in places where eating uncooked meat is customary. And some adults with toxoplasmosis show psychotic symptoms similar to schizophrenia.

Studies have linked a history of toxoplasmosis with increased rates of other mental changes, too, including bipolar disorders and depression. A 2002 study in the Czech Republic noted slowed reflexes in Toxoplasma-positive people and found links between the infection and increased rates of auto accidents.

Still, the links between schizophrenia and toxoplasmosis are not simple. For example, most people infected with T. gondii never become schizophrenic. And not all schizophrenics have been exposed to toxoplasma.

Yolken believes additional factors, such as an unlucky combination of genes, are probably needed to produce schizophrenia among Toxoplasma-infected people. The parasite's DNA may also be important, since some strains are known to cause more disease.

Studies have also suggested that the timing of the infection — early in life when the brain is developing — and the place in the brain where the cysts settle, may be important, he said.

Yolken said that while T. gondii cysts are invisible to the immune system, they are not totally passive. Inside the cysts, the microbes are alive, sensing their environment, periodically trying to break out, multiply and form more dopamine-making cysts. The flare-ups probably occur when the host's immune system is weakened by illness or stress.

Sabunciyan has reported promising results with a class of anti-malarial drugs, called artemisinins, which appear to be effective at killing T. gondii in tissue cultures. "The next step is to do that in animals," Yolken said.

Yolken, a cat owner who says he has tested positive for Toxoplasma antibodies, said the potential link between Toxoplasma infections and mental illness is no reason for cat owners to panic — they just need to keep some basic hygienic precautions in mind.

Researchers explore link between schizophrenia, cat parasite

Низкий уровень холестерина как фактор риска аффективных расстройств

In the early 1990s several studies suggested a link between low cholesterol (< 160 mg/dL) and unnatural deaths, including suicide.2-4 Follow-up studies confirmed associations between low cholesterol and suicide attempts, especially violent ones.5 These associations are compelling given the neurobiologic effects of cholesterol, such as a net reduction of serotonergic function (Box 1). Low cholesterol may predispose an individual to aggression, impulsivity, and violence (Table 1).6 Many studies have found that patients with mood disorders have lower cholesterol levels;7 however, other research suggests they are at increased risk of hyperlipidemia, typically hypertriglyceridemia rather than hypercholesterolemia.

The neurobiologic effects of low cholesterol—particularly those related to serotonergic hypofunction—are thought to be mediate impulsive, aggressive, and violent behaviors that may predispose an individual to suicide.a,b The CNS contains one-fourth of the body’s free cholesterol,c which is synthesized primarily in situ.

Cholesterol improves membrane stability, reduces permeability, and may influence serotonergic function. Cholesterol depletion may impair function of 5-HT1A and 5-HT7 receptorsd,e and serotonin transporter activity.f Reduced cholesterol after treatment with simvastatin—an HMG-CoA reductase inhibitor that readily crosses the blood-brain barrier—resulted in acute (1-month) increases in serotonin transporter activity followed by subacute (>2 months) decreases.g Lower cholesterol levels may further decrease expression of serotonin receptors and cause a net reduction in serotonergic activity.

In addition, cholesterol is necessary for synapse formation and myelin production. Cholesterol depletion may have more diffuse effects on neurotransmission, such as gamma-aminobutyric acid receptors,hN-methyl-D-aspartate receptors,i opioid signaling,j and excitatory amino acids transport.k

Impulsivity associated with low serotonergic function and low total cholesterol has been suggested as a potential pathway for suicide.l Low cholesterol is associated with self-report measures of impulsivity;m however, increased impulsivity associated with lipid-lowering therapy may be temporary,n which is similar to the time-limited changes in serotonin transporter activity.g Human and animal data have suggested that low cholesterol may be linked to violent behaviors, including suicide.o

Multiple randomized controlled trials have not shown increased depression and suicide with use of lipid-lowering agents in healthy populations

Closely monitor individuals with mood disorders for changes in behavior or mental status after starting a lipid-lowering agent

Cholesterol, mood, and vascular health: Untangling the relationship

Simple Test Identifies Suicide Risk from Antidepressants

Aimee Hunter, an assistant research psychologist in the UCLA Department of Psychiatry, and colleagues report that by using quantitative electroencephalographic (QEEG), a noninvasive measurement of electrical activity in the brain, they were able to observe a sharp reduction of activity in a specific brain region in individuals who proved susceptible to thoughts of suicide. The reduction was noticeable within 48 hours of the start of treatment.

Simple Test Identifies Suicide Risk from Antidepressants

Ketamine Leaves BDNF Unchanged

Suicidal Ideation Abates After Ketamine Infusion

генетические предикторы усиления суицидальной идеации

Genetic Predictors of Increase in Suicidal Ideation During Antidepressant Treatment in the GENDEP Project