Modeling Schizophrenia: An In Vitro Model of a Tough DiseaseOctober 7th 2011
This column has always been about the world of molecular mental health research. I revisit the technology in this column, now aimed at one of molecular neuropsychiatry’s most intractable, frustrating lines of research: the molecular/cellular basis of schizophrenia.
Overly sensitive, aversive reactions to stress seem to run in families. The literature abounds with reports of relatives in these populations predisposed to depression, anxiety, and even suicide. Some family members present with glucocorticoid levels notched abnormally high, and in curiously deregulated concentrations. Behaviorally, they seem to exist at a permanent state of high alert.
Crime, the Hippocampus-and the Lingering EyeFebruary 5th 2010
Let’s say you’re in a crowded bar when somebody suddenly shoots at a patron. You clearly see a man carrying a firearm, but all hell breaks loose as you and everybody else scramble for the exits. In the terrifying seconds following the crime, you lose track of who discharged the firearm: it could have been 1 of 3 suspects. Afterward, the police interview you, but it is hopeless. Even bringing in the suspects for a lineup isn’t going to help you recall. There will be no “Perry Mason” moments, when the perpetrator breaks down under the weight of guilt and confesses to the crime. How can the authorities make an arrest?
The Cellular and Molecular Substrates of Anorexia Nervosa, Part 2December 7th 2009
I think I am going to talk about the neurobiology of happiness in my next column. The reason has to do with the nature of our 2-month journey into the biology of eating disorders-a subject that, considering the dearth of explanatory data, is tough to write about. It’s also a bit depressing, considering how difficult it can be to treat. This is the second installment in a 2-part series that focuses on the neurobiology of restricting-type anorexia nervosa (AN).
The Cellular and Molecular Substrates of Anorexia Nervosa, Part 1November 1st 2009
Appetite regulation is made up of complex interlocking, incentive-driven motivational hormonal and neuronal circuitries . . . that can be pulled in many directions, especially where food is cheap and readily available.
Functional MRI, Round 3: Six Items to Keep in MindOctober 2nd 2009
This is the third and final installment in a series on biophysical mechanisms of functional magnetic resonance imaging (fMRI) technologies. My overarching goal has been to explain why great care must be exercised when interpreting data derived from these magnets. The inspiration for the series came as I was reading a magazine article while waiting for a plane to take off-my reaction to what I read may have resulted in a bit of trauma to the seat pocket in front of me.
In our last installment, we discussed a familiar finding from the National Comorbidity Survey Replication (NCS-R): the peak age of onset for any mental health disorder is about 14 years. In an attempt to explain these data, we are exploring some of the known developmental changes in the teenaged brain at the level of gene, cell, and behavior.
This statistic is as familiar as it is startling. According to the National Comorbidity Survey-Replication (NCS-R), the peak age of onset for any disease involving mental health is 14 years. True for bipolar disorder. True for anxiety. True for schizophrenia and substance abuse and eating disorders. The data suggest that most mental health challenges emerge during adolescence. If true, this brings to mind an important developmental question:
Functional Magnetic Resonance Imaging: Round 2July 1st 2009
This is the second installment in a 3-part series that discusses some of the mechanisms behind functional magnetic resonance imaging (fMRI) technology. As you may recall, the genesis for this series was reactive…I got mad while sitting on an airplane reading a magazine article about how fMRIs can predict everything from product preferences to political inclination. The article hinted at something I have been noticing with increasing alarm-the confusion about what fMRI can and cannot reveal about information processing in the brain. I decided to write this series hoping that knowledge of the basic science behind fMRI technology could contribute to making more nuanced conclusions about the data it reveals.
I almost destroyed the backseat pocket of an airline seat this summer. The vandalism was inadvertent, assuredly, though the anger that fueled it was not. While waiting for my plane to take off, I had read a magazine article claiming to show that fMRI (functional magnetic resonance imaging) studies were “uncovering” the voting preferences of test subjects. An adjacent article announced that researchers could now predict the buying preferences of other test subjects using the same imaging technologies.
Fishing for Genetic Links in AutismMarch 11th 2009
In my January column (“Fishing Expeditions and Autism: A Big Catch for Genetic Research?” Psychiatric Times, January 2009, page 12), I described the great difficulties researchers face characterizing the genetic basis of the disease. Complexities range from trying to establish a stable diagnostic profile to making sense of the few isolated mutations that show clear associations (either with disease or syndrome variants).
Fishing Expeditions and Autism: A Big Catch for Genetic Research?January 2nd 2009
I am a fan of the television show Deadliest Catch-a documentary series that follows the travails of deep-sea fishermen in the Bering Sea. (Actually, it is mostly about deep crab fishing.) Living in Seattle, I have actually seen some of the boats filmed on the show.
Painting Neural Circuitry With a Viral Brush: Are the Neighbors Green?November 1st 2008
In last month’s column (“Painting Neural Circuitry With a Viral Brush,” Psychiatric Times, October 2008, page 16), I used Michelangelo’s famous fresco, “Hand of God Giving Life to Adam” on the ceiling of the Sistine Chapel as a metaphor to introduce a series of technologies that have allowed researchers to map the complex interactions of neural connections in continuously functioning neural tissues.
Blood Tests for Bipolar I Disorder: Quite a Future IndeedSeptember 1st 2008
In this column, I will discuss new progress on this Internet-boosted line of inquiry. I will begin with a few basics about differential gene expression and microarrays and will then move on to something that researchers are calling “convergent functional genomics.” As you shall see, the clever use of online databases both confirmed and extended the work done at the bench.
Trust can be a scary proposition. Among other characteristics, trusting someone involves the ability to measurably predict a behavior on the basis of nothing more than a memory, an impression, or a whim. For creatures like us, who spend a ridiculous amount of time with unpredictable strangers, brokering trust is an oddly important survival strategy.
Of Stress and Alcoholism, Of Mice and MenJuly 2nd 2008
This month I will examine the relationship between alcohol use disorder, stress, and a neuropeptide called substance P (SP). The data that led directly to research with human subjects came from the mouse-based genetic manipulation of a gene called neurokinin-1 receptor (NK1R), the receptor for SP. To understand this research thread, I will need to review some basic biology behind a class of biochemicals called tachykinins, of which SP is its most famous member. I begin, however, with an attempt to understand the relationship between the experience of stress, relapse rates in alcohol-dependent populations, and how mouse research ended up helping a cohort of stressed-out patients.
While many of the claims at improving cognition are dubious (eg, the "Mozart effect"), there is now ample reason to suspect that parental involvement in children's brain development occurs much earlier than the first 3 years. Data now suggests that maternal cues are critical to proper brain development long before birth.
Chronic Fatigue Syndrome--A Lesson in Big ScienceApril 1st 2007
I recently read issues of 2 research journals that collectively must hold some kind of scientific publishing record. The first journal, Pharmacogenomics, printed 14 papers back-to-back, all devoted to a single, large-scale study: discovering the genetics of chronic fatigue syndrome (CFS). By contrast, the journal Nature was more typical, printing single articles that described mostly research from single studies, and 1 that listed more than 100 authors. These authors are part of the Allen Brain Project, which consists of dozens of scientists who are mapping gene expression profiles of the mouse brain. By the time I finished reading about these monumental efforts, my head ached.