Tianeptine: The Rebel Antidepressant

Tianeptine (brand names: Stablon, Coaxil) is a novel anti-depressant that acts as a Selective Serotonin Reuptake Enhancer, or SSRE.  Unlike SSRIs, it reduces the amount of serotonin in the synaptic cleft, making it essentially the polar opposite of drugs like Prozac and Celexa.

But shouldn’t that make depression worse?

Actually, no.  The idea that depression is caused by low serotonin is nothing more than a marketing ploy created by the proponents of SSRIs; an oversimplified theory in a sea of possibilities.  We all remember this cute Zoloft commercial stating that “depression is caused by a chemical imbalance between nerve cells in the brain”:

In truth, depression is a broad term describing a variety of sometimes contradictory symptoms, such as insomnia/hypersomnia, or reduced appetite/overeating.  Depression comes in many forms, including major, atypical, seasonal, cyclothymic, bipolar and more.  Thus, the causes are as unique as the individual and are not always as simple as a “chemical imbalance”.

By reducing available serotonin in the brain, tianeptine single-handedly disproves the “low-serotonin-causes-depression” theory, which may be part of the reason it’s not being aggressively studied in the U.S.  Just as Xanax treats acute anxiety instantly, tianeptine fights depression symptoms immediately and has promising long-term effects such as improved neuroplasticity and cognition.  By contrast, SSRIs can take up to a month to produce any effect at all.  Tianeptine is generally well-tolerated and can even be used by elderly patients with heart problems, unlike tricyclic antidepressants.  It lacks the sexual side effects of SSRIs and has been available by prescription in Europe and Asia for decades.  It’s currently being studied as a potential treatment for asthma, IBS, fibromyalgia, ADHD and post-traumatic stress disorder (PTSD).

By no means is tianeptine a panacea for depression.  But it raises the question of whether our currently approved meds are monopolizing the depression market and keeping potentially effective drugs out.  If you’ve tried a few SSRIs, you’ve tried them all.  No one is arguing that the current drugs should be phased out–quite the opposite.  More variety simply means more options for patients in desperate need of something that works.

(For everything you ever wanted to know about tianeptine and more, see here).

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Louis Wain’s Cat Obsession

To say Louis Wain was obsessed with cats might be the understatement of the century.  The eccentric artist made a career out of painting nothing but cats for over 30 years.  While most people believe he suffered from schizophrenia, there’s a possibility he may have had Asperger’s syndrome also/instead.  (There’s even been speculation about infection with toxoplasmosis causing his descent into madness).

His style of painting offers a look at the progression of mental illness from the inside.  Here is a series of Wain’s paintings in chronological order (click to embiggen):

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Pedophilia Caused by Brain Tumor

Strange as it sounds, there are a couple cases on record of pedophilia directly caused by a brain tumor.

The subject of pedophilia is one of the most emotionally charged issues in society, and for good reason.  The idea that something so vile can be caused by a physical disease–in this case, a tumor–blurs the line between morality and biology.

This story involves a previously healthy schoolteacher who suddenly developed a number of compulsive tendencies, one being sexual desire for children.  He also began soliciting prostitutes and having fantasies of raping his landlady.  He was kicked out of a 12-step Sexaholics Anonymous program after propositioning a female patient for sex.

Despite knowing intellectually that his behaviors were wrong, he claims that the desire over-rode his morality.  After developing paralyzing headaches and balance problems, he underwent an MRI.  Lo and behold, an egg-sized tumor was found in the orbitofrontal cortex of his brain–the area that controls judgment and impulse control.  The tumor was successfully removed and he was discharged, apparently free of his dark impulses.

And here’s where things get strange.

Seven months later the inappropriate urges returned, along with the headaches.  The tumor had regrown and was removed once more, taking the pedophilic impulses away with it.

Personality changes are a common side effect of brain tumors, but this is an extreme case.  Whether the urges are caused by hormonal changes or disturbances within the orbitofrontal cortex is not entirely clear.  Unlocking these mysteries could give researchers insight into pedophilia and other impulse-driven deviant behaviors.

Here is another case similar to the one above.

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Crazy Cat Lady Syndrome

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Crazy cat lady: there’s one in every town.

You’ve all seen her:  The “crazy cat lady” with her disheveled hair, hoarder-style home, dumpster diving and–of course–the telltale parade of cats following behind her like the pied piper.

But why cats and not some other animal?  Cat hoarding, while not listed in the DSM, is associated with mental illness.  Cats carry a parasite known as Toxoplasma gondii, or T. gondii for short.  It can only reproduce in the bodies of cats but often passes to humans and other animals.

So is cat hoarding an evolutionary trick that allows T. gondii to thrive?  We’ll return to that in a minute.

Toxoplasma has a natural affinity for the brain and can have fatal consequences in the offspring of pregnant women.  Cerebral palsy, seizures and mental retardation are a few possible outcomes of maternal exposure.  This is why pregnant women are advised against changing litter boxes.

In the human brain, T. gondii creates an enzyme that interferes with dopamine function.  Schizophrenia–viewed in psychiatry as one of the most serious disorders–is highly associated with abnormal dopamine function.  A number of studies have shown a direct statistical link between schizophrenia incidence and toxoplasmosis.

But all you sane cat lovers out there needn’t worry.  A large percentage of the population is infected with T. gondii and does not have mental illness.  How you respond to the infection depends on a number of factors, including your genetic makeup, immune function and the timing of infection.  In the early days of AIDS, toxoplasmosis was a major killer in immune compromised patients.  It often caused “AIDS-related dementia” or blindness in its hosts shortly before killing them.

So how is T. gondii transmitted?  It can be acquired by touching cat feces, eating raw/undercooked meat or even handling soil while gardening.

But back to the evolutionary function of cat hoarding.  A strange phenomenon can be seen in rats infected with T. gondii:  instead of running from the scent of cats as they normally do, it causes them to lose their natural fear and even seek them out.  In this sense, T. gondii has hijacked the rat’s brain for its own purposes.  (Remember: toxoplasma can live in many animals but only reproduces in cats).  Cat then eats rat, re-infecting itself with the parasite and completing the circle of life.  [Cue Lion King music].  There’s a good chance the same thing is happening inside the brains of cat hoarders.

That’s one smart parasite.

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Sickness Behavior & Depression

Think back to the last time you were sick.  Did you feel like doing the Riverdance or retreating to a dark room to hibernate for hours?

When the body is sick, the brain responds with “sickness behavior,” a collection of symptoms that make you feel terrible but serve an important biological function.  Fatigue, low mood, reclusiveness, pain and appetite loss are a few symptoms that go hand-in-hand with fever–a primary indicator of immune activation.

While most people attribute these symptoms to the infection, the immune system is actually to blame.  When pathogens invade the body, immune cells send out substances called cytokines that tell the brain to react in this way.  Mental symptoms like fatigue and reclusiveness conserve energy to help the body fight illness and prevent spreading it to others.

They also look a lot like clinical depression.

If the immune system can trigger mental symptoms during infection, could it also play a role in mental illnesses like depression?  Many scientists think so.

Depression–both unipolar and bipolar–is common in patients with autoimmune disease (conditions in which the immune system attacks the body’s own tissues).  What’s more, mental symptoms often wax and wane in the same pattern as flare-ups/remissions of the autoimmune disease itself.

But mental symptoms are not limited to autoimmune conditions.  Any illness that causes chronic inflammation can activate these nasty mental symptoms.  This includes allergies, chronic bacterial or viral infection, heart disease and many others.  Interferon–a cytokine-producing drug used to treat hepatitis–causes serious depression in up to 40% of users.   Other common side effects include mania, fatigue, cognitive dysfunction and anxiety.

If inflammation is truly linked to mental illness, you’d expect symptoms to improve when taking anti-inflammatory drugs.  And in many cases, they do.  Patients most likely to respond to anti-inflammatory drugs are those with severe, treatment-resistant depression.

While more research is needed, one thing is certain:  the brain/immune connection is strong.  No amount of psychoanalysis or Prozac is going to change that.

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The Behavioral Effects of Allergies

This 1992 episode of the Phil Donahue Show explores the role of allergens in childhood behavioral problems.  Contains startling footage of misdiagnosed Tourette’s syndrome, temper tantrums and other mental disorders caused by common foods and chemicals.

Further evidence that “mental” conditions often have a “physical” cause.

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Altered States of America

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(Click to embiggen)

This graph says it all…

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