Archive for April, 2008

Alcohol and Epigenetics

A recent article in the Journal of Neuroscience provides insight as to why alcoholics may experience withdrawl anxiety. Neuroscientifically Challenged explains:

Previous research has pointed to the importance of a neuropeptide transmitter called neuropeptide Y (NPY) in managing anxiety, and in modulating alcohol consumption. Low levels of NPY, specifically in the amygdala, have been found in animals that have a preference for alcohol. Additionally, knockout mice who are engineered to lack NPY receptors exhibit an increased proclivity for alcohol.

The aforementioned study explores how those changes occur via epigenetic mechanisms. Epigenetics, literally “on top of” or “in addition to” genetics, studies how genetic packaging affects gene (and subsequently protein) expression.

There are two general avenues of investigation. The first is chromatin remodeling and the second individual gene promoter methylation. These investigators focused on the former.

The complex of DNA and associated nuclear proteins is called chromatin. Chromatin can be densely packed to minimize gene expression or loosely packed to maximize it. Histones, the proteins the DNA wraps around, are methylated when “closed” and acetylated when “open”.

Histone deacetylase inhibitors (HDACs) remove acetyl groups from the histones and lead to a general downregulation in gene expression. The investigators found that alcohol inhibits HDACs and subsequently upregulates NPY gene expression in areas where it has an anxiolytic capacity. Withdrawl, then, upregulated HDACs, downregulated NPY, and caused stress. Administration of a HDAC inhibitor before and during the withdrawl eliminated observable stress.

There are claims that they may have found a novel treatment for alcoholism. I, however, remain skeptical. The anxiolytic effect of the HDAC inhibitor probably has to do with an upregulation of GABA (the primary inhibitory neurotransmitters in the brain) since it is widely reported that HDAC inhibitors have an effect on GABAergic transmission. HDACs are are just too unspecific and, in many ways, carpet bomb gene expression at large. NPY, while certainly a significant part of the picture, may be overshadowed by the HDAC inhibitor induced GABA upregulation.

Nonetheless, it’s a noteworthy article.


Free Will?

Libet’s readiness potential experiments are old hat. In them, Libet measured a spike of characteristic neuronal activity up to 300ms before the decision to push a button. Even though Libet himself thought that free will acts as a veto faculty sometime after the rediness potential his data were (and are still at times) heralded by biological determinists and materialist polemicists as a denunciation of free will.

Regardless of the controversy surrounding Libet’s contribution to the free will debate, his experiment’s notoriety alone begs additional investigation. Nature Neuroscience published an interesting article by a group at the Max Planck Institute for Human Cognitive and Brain Sciences in Germany that elaborates on his studies using fMRI.

There has been a long controversy as to whether subjectively ‘free’ decisions are determined by brain activity ahead of time. We found that the outcome of a decision can be encoded in brain activity of prefrontal and parietal cortex up to 10 s before it enters awareness. This delay presumably reflects the operation of a network of high-level control areas that begin to prepare an upcoming decision long before it enters awareness.

Siong Soon et al’s findings contrast Libet’s in that they pinpoint a different and higher level control area that dictates the occurrence of the readiness potential.

These findings are a good indicator of the existence of unconscious processes that influence decision making; however, they are not a significant addition to the materialist’s bag of tricks. They do not denounce free will. They simply suggest that, as we would’ve anticipated, decision making processes have something to do with cortical neuronal activity.

Libet passed away in late 2007.

Cookie Monster

I laughed really hard when I read this introspection by the Cookie Monster probing what makes him a monster. It makes you wonder what it means to be “abnormal” in the clinical psychology sense.


(via Mind Hacks)

Natalie Portman

While perusing through MindHacks’ archives I happily stumbled on  an amazing piece of investigative reporting. Turns out Natalie Portman ( <3 ) did some neuroscience research while she was at Harvard.

Click here to see the paper she helped publish.

Happy Friday =).

Video Game Addiction

An editorial in this month’s American Journal of Psychiatry makes an argument for why Internet Addiction should be included in the new DSM.

MindHacks is critical:

Apart from the fact that these and most other supposed criteria make no distinction between using the internet and what the person is using the internet for, it’s easy to see that they don’t describe anything unique to the net.

Rather curiously, the editorial mentions the figure that 86% of people with ‘internet addiction’ have another mental illness. What this suggests is that heavy use of the internet is not the major problem that brings people into treatment.

Firstly, the author posits a diagnosis involving an explicit distinction about what people are using the computer for (not just the internet):

Conceptually, the diagnosis is a compulsive-impulsive spectrum disorder that involves online and/or offline computer usage (1, 2) and consists of at least three subtypes: excessive gaming, sexual preoccupations, and e-mail/text messaging (3).

He’s more concerned about the sheer magnitude of time young people spend on their computers and the negative ramifications thereof.

The average South Korean high school student spends about 23 hours each week gaming (8), another 1.2 million are believed to be at risk for addiction and to require basic counseling.

Furthermore, it’s not like the DSM shouldn’t have any overlap. Comorbidty is rather common. Spending 23 hours a week is obviously abnormal. If the individual feels like they’re addicted and they’re distressed by it I don’t see why we wouldn’t treat it. If they are willing to spend their time and money working out their issues and a mental health professional is willing to improve their quality of life… why not?

Not all disorders are as concrete as schizophrenia or bipolar.  I, for one, think Video Game Addiction is a worthwhile inclusion.


I was interested to learn that:

The Pentagon is working on a series of computers that monitor and adapt to a person’s brain:

Augmented Cognition relies on the idea that people have more than one kind of working memory, and more than one kind of attention; there are separate slots in the mind for things written, things heard and things seen. By monitoring how taxed those areas of the brain are, it should be possible to change a computer’s display to compensate. If people are getting too much visual information, send them a text alert. If they are reading too much at once, present some of the data visually — in a chart or map.

They are also working on technology to “tap the firings of the subconscious mind to sort through satellite pictures quickly. Early tests have shown as much as a six-fold increase in the analysts’ efficiency, when the computer and the brain work together.”

(via Clusterflock)

Genetic Model for Schizophrenia

Schizophrenia is one of the most illusive psychiatric disorders. Over the years NIH has doled out millions to research groups pursuing various mechanistic models. The dopaminergic model is the most popular and is the target of most (if not all) antipsychotic medications. Less popularized but still empirically validated models include the GABAergic model (the subject of my personal research) and a prenatal infection model.

Findings that schizophrenia is alarmingly heritable are widely reproduced; for example a recent twin study found 20/49 monozygotic twins both developed schizophrenia versus 3/57 dizigotic twins. However, despite expansive genomic screening for aberration only a few were implicated and even they only show up in an average of 10% of schizophrenia patients (SZP).

A recent study published in Science and reported on by Scientific American proposed a new genetic model for schizophrenia involving copy number variations:

In this study, researchers combed the genomes of 150 schizophrenia sufferers and 268 healthy individuals for never-before-seen copy number variations (CNVs)—mutations that result in large swaths of DNA encompassing multiple genes either being deleted or duplicated. Some such mutations have been found to be benign, but others have been implicated in ailments such as autism and cancer. The team of scientists, from research facilities across the U.S., found novel gene alterations in 5 percent of the healthy volunteers and 15 percent of the schizophrenia patients; new CNVs showed up in 20 percent of those subjects who developed symptoms at or before the age of 18.

Furthermore these SNPs were “overwhelmingly linked to changes in pathways responsible for communication between and within nerve cells” including some genes that have long been suspect in the pathophisiology of schizophrenia (SciAm, 2008).

While doubtful that SNPs will explain every instance of schizophrenia it may very well account for the previously mysterious genetic component.

King says the next step is to screen the 20 suspect genes to pinpoint specific defects common among large groups of schizophrenia patients.

Sebat acknowledges that the data presented is merely consistent with the rare mutation gene model and not direct proof of it. “It’s premature to say that these findings have diagnostic value [right now],” he says. “But, that’s exactly where we’re headed.”

I’m rather excited. Walsh et al. are onto something and I’ll anxiously anticipate their future findings. Schizophrenia research is rarely so concrete.


On a side note: Jeffrey Schaler, a psychologist and professor of law, was quoted in my last post as saying “Schizophrenia and depression refer to behavior, not to cellular abnormalities.” These findings highlight how silly that statement is.