Tuesday, August 2, 2011

Adventures In Chemicals The Affect The Brain And Seasonal Birth Effects

I've abstracted a hodgepodge of interesting new research studies on the impact of chemicals and birthdays on mental health.  We a finally reaching the frontier where the actual biological mechanism behind mental health conditions long believed to have a biological basis are understood in a meaningful fashion with clinical applications.

Cortisol hormone response patterns linked to temperament in toddlers

Cortisol responses to stress in toddlers reflect their temperaments and may also have significant environmental responses. Personality traits which otherwise seem to have only suggestive oppositions to each other seem to have a biological root as different dimensions of cortisol responses to stress. In particular, anxiety and depression may be the opposite side of the coin the same trait that at the other extreme may be associated with ADHD. It wouldn't overstate the matter to infer that the Big Five personality trait conscientiousness may also be linked to this tendency that is present in very early childhood.

Is your kid a "dove" -- cautious and submissive when confronting new environments, or perhaps you have a "hawk" -- bold and assertive in unfamiliar settings? . . .

Children exposed to high levels of interparental aggression at home showed different reactions to [a staged] telephone quarrel. Doves with parents who fought violently produced elevated levels of cortisol, a hormone that is thought to increase a person's sensitivity to stress. Hawks from such stressful home environments put the breaks on cortisol production, which is regarded as a marker for diminishing experiences of danger and alarm.

Heightened cortisol levels characteristic of the doves were related to lower attention problems but also put them at risk for developing anxiety and depression over time. By contrast, the lower cortisol levels for hawks in aggressive families were associated with lower anxiety problems; however, at the same time, these children were more prone to risky behavior, including attention and hyperactivity problems.

Previous research has focused more on neurotransmitters and general stimulants in these conditions.

Dopamine flows from anticipation of reward, not the reward itself.

The treatment of psychiatric conditions like depression or schizophrenia often revolves around regulating monoamine neurotransmitters like serotonin, norepinephrine and dopamine.

Dopamine is an important neurotransmitter that functions in a lot of behaviors and reactions, such as movement, lactation, aggression, fear, etc. In diseases like Parkinson, dopamine levels lower and movement becomes uncontrolled. In other diseases like schizophrenia, either dopamine levels are high or response to dopamine is higher, and paranoia & hallucinations manifest. Treating schizophrenia involves blocking dopamine receptors. As you can imagine, a common side effect of antipsychotics is movement disorders — or Parkinsonism. . . .

Our cultural and behavioral predisopostions ultimately boil down to chemicals in our brain interacting and stimulating other areas. One of the most important functions of dopamine is in the reward system of the brain, an area called the nucleus accumbens that primes pleasurable behavior to repeat, such as sex, eating, and drugs. . . .

Robert Sapolsky of Stanford Neurology makes the distinction between how dopamine levels rise in the anticipation of pleasure and not as a response to pleasure.

From here.

Drug Addition Linked To Salt Appetite System

[T]he gene patterns activated by stimulating an instinctive behavior, salt appetite, [a]re the same groups of genes regulated by cocaine or opiate (such as heroin) addiction.

"[B]locking addiction-related pathways . . . powerfully interfere[s] with sodium appetite. . . . [The] findings . . . could lead to a new understanding of addictions and the detrimental consequences when obesity-generating foods are overloaded with sodium. . . . Though instincts like salt appetite are basically genetic neural programs, they may be substantially changed by learning and cognition . . . Once the genetic program is operating, experiences that are part of the execution of the program become embodied in the overall patterns of an individual's behavior, and some scientists have theorized that drug addiction may use nerve pathways of instinct. . . . one classic instinct, the hunger for salt, is providing neural organization that subserves addiction to opiates and cocaine."

From here.

Ketamine Has Different Roles At Different Doses

Ketamine is finding new applications in both legal and illegal applications.

The anesthetic ketamine works against depression by quickly boosting levels of a brain compound that has been linked to the condition . . . [which] may lead to highly effective and fast-acting antidepressants that provide relief within hours instead of weeks. . . . Traditional antidepressants can be effective but often take weeks or months to improve symptoms. . . . “Here is increasing evidence that you can go more directly at the target, and that’s maybe why you get more of a rapid antidepressant effect.”

Mice receiving a single injection of ketamine showed fewer signs of depression just half an hour after the shot, and they continued to show multiple signs of reduced depression for a week. . . .

At high doses, ketamine renders a person unconscious. At lower doses, the drug can induce euphoria, hallucinations and out-of-body experiences, properties that make “Special K” a popular drug of abuse. . . . the study . . . used low doses that wouldn’t induce psychotic effects.

They found that ketamine kicks off a series of biochemical changes in the brain that culminate in the production of a protein called BDNF. Low BDNF levels have been linked to depression. . . . mice genetically engineered to be unable to produce BDNF didn’t respond to ketamine.

From here.

A small trial reported in 2010 found Ketamine to be safe and effective in treating treatment-resistant bipolar patients, suggesting that it acts on a different mechanism than existing depression treatments. Unlike traditional anti-depressants, whose efficacy has been seriously questioned as being little more than placebo effect in a significant class of patients treated with them, Ketamine's effect is so rapid and pronounced that its short term effectiveness is beyond question, although its tendency to be associated with mild psychiotic side effects is a concern.

British drug enforcement authorities have seen increased abuse of ketamine:

Once seen as a drug exclusively for the rave and dance scene, its popularity is now growing among Britain's middle-class users due to its price – a gram of ketamine costs £20, half as much as the same amount of cocaine – and the fact that it is seen as a "safe" and "clean" drug. . .

a survey carried out by Professor David Nutt, the chairman of the Government's drug advisory panel, ranks the class C drug as the sixth most dangerous illegal drug available – more harmful than Ecstasy and cannabis. The mistaken belief that the substance is risk-free is encouraging more young people to try ketamine and to take it in increasingly higher doses. . . . it can cause heart or lung failure and point to the fact that it has been linked to 23 deaths between 1993 and 2006. In 2006 it was classified as a class C drug [in the U.K.] . . . the drug, which can be snorted, swallowed, injected and even smoked, . . . [had] an estimated 60,000 users [in the U.K.] between 1998 and 2000 . . . [and] about 113,000 in 2008. . . .

Originally used to treat injured soldiers in Vietnam, ketamine is most commonly used now as a horse tranquilliser. It has also been experimented with to treat depression and alcohol and heroin addiction. It was classified as an illegal drug in 2006 by the UK Government. It is usually sold in powder or liquid form for about £20 per gram. Unlike cocaine and heroin, it is not physically addictive, but, like cannabis and Ecstasy, it is psychologically addictive.

David first tried ketamine as a 20-year-old student at university in London. Now a 27-year-old marketing executive, living in Shoreditch, east London, he still takes the drug once a month. "I see it as a fun, sociable drug," he said. "I do it at house parties or if I'm having a big night out. I used to do cocaine, but I suppose I gradually replaced coke with ket. Coke is much more expensive and it generally makes everyone very loud and aggressive. Ket is different. It costs less and you use it in smaller quantities so it lasts a lot longer. The feeling you get is different too. It makes you feel anaesthetised to your worries. You forget about your normal life and everything is euphoric. Sometimes I've had bad trips, but I've never felt angry when on ketamine. I think it is a lot safer too. I've read it can have long-term effects on your health, but it doesn't seem as dangerous as cocaine. When on coke I used to feel my heart pounding and it didn't feel right. The other reason I changed is because of the classification. I've got a proper job and a career and I don't want to lose that. Ketamine is a class C drug so if I get caught I'm probably only going to get a slap on the wrist."

Hallucinating Computers

Efforts to create neural network computer models of the brain's circuits for processing language in an effort to understand schizophrenic auditory hallucinations have managed to reproduce the phenomena of coherent auditory hallucinations (i.e. hearing voices) by both of two different mechanisms suspected to be a work in this phenomena in the real world.

Hearing voices is a hallmark of schizophrenia and other psychotic disorders, occurring in 60-80% of cases. These voices are typically identified as belonging to other people and may be voicing the person’s thoughts, commenting on their actions or ideas, arguing with each other or telling the person to do something. Importantly, these auditory hallucinations are as subjectively real as any external voices. They may in many cases be critical or abusive and are often highly distressing to the sufferer.

However, many perfectly healthy people also regularly hear voices – as many as 1 in 25 according to some studies, and in most cases these experiences are perfectly benign. In fact, we all hear voices “belonging to other people” when we dream – we can converse with these voices, waiting for their responses as if they were derived from external agents. Of course, these percepts are actually generated by the activity of our own brain, but how?

The two different models that were both supported in the computerized neural network were as follows:

There are two major hypotheses that were modelled: the first is that networks in schizophrenia are “over-pruned”. This fits with a lot of observations, including neuroimaging data showing reduced connectivity in the brains of people suffering with schizophrenia. It also fits with the age of onset of the florid expression of this disorder, which is usually in the late teens to early twenties. This corresponds to a period of brain maturation characterised by an intense burst of pruning of synapses – the connections between neurons.

In schizophrenia, the network may have fewer synapses to begin with, but not so few that it doesn’t work well. This may however make it vulnerable to this process of maturation, which may reduce its functionality below a critical threshold. Alternatively, the process of synaptic pruning may be overactive in schizophrenia, damaging a previously normal network. (The evidence favours earlier disruptions).

The second model involves differences in the level of dopamine signalling in these circuits. Dopamine is a neuromodulator – it alters how neurons respond to other signals – and is a key component of active perception. It plays a particular role in signalling whether inputs match top-down expectations derived from our learned experience of the world. There is a wealth of evidence implicating dopamine signalling abnormalities in schizophrenia, particularly in active psychosis. Whether these abnormalities are (i) the primary cause of the disease, (ii) a secondary mechanism causing specific symptoms (like psychosis), or (iii) the brain attempting to compensate for other changes is not clear.

Birth Season Effects On Mental Health

A causal mechanism isn't obvious, but some mental health conditions so seasonal effects.

Anorexia nervosa is more common among people born in the spring. . . . [Researchers] found an excess of anorexia births between March and June, and a deficit from September to October. . . . A number of previous studies have found that mental illnesses such as schizophrenia, bipolar disorder and major depression are more common among those born in the spring -- so this finding in anorexia is perhaps not surprising. . . .researchers believe that environmental factors around the time of conception or when the baby is developing in the womb may be responsible. . . . Seasonal changes in temperature, sunlight exposure and vitamin D levels, maternal nutrition and exposure to infections are all possible risk factors. Identifying these risk factors is important in helping us understand and maybe even prevent illness in future.


An examination of the birth records of the more than 7 million children born in the state of California during the 1990s and early 2000s has found a clear link between the month in which a child is conceived and the risk of that child later receiving a diagnosis of autism." The risk of having a child with an autism spectrum disorder grew progressively throughout the fall and winter to early spring, with children conceived in March having a 16 percent greater risk of later autism diagnoses, when compared with July conceptions.

The researchers said the finding suggests that environmental factors, for example, exposure to seasonal viruses like influenza, might play a role in the greater risk they found of children conceived during the winter having autism.

"The study finding was pronounced even after adjusting for factors such as maternal education, race /ethnicity, and the child's year of conception." . . . Each month was compared with July, with an 8 percent higher incidence in December, increasing to 16 percent higher in March.

The study lacked the means to discern if conception or some later point in pregnancy was the source of the vulnerability.

No comments: