Graveyard of Neuropathology

[Enkidu]

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I have a book called "the neuropathology of schizophrenia" which is quite interesting and has piqued my interest in studying the neuropathology of psychiatric disease. The book also mentions that schizophrenia had been dubbed the "graveyard of neuropathologists", apparently because their careers all died after they began working on it.

I wonder if any of you think that there will be a role for neuropathology in diagnosing psychiatric disease, perhaps on autopsy, or that this will remain purely in the realm of basic science research.

edit: This isn't meant to be too serious a question... just a vague idea I got from reading the book. My guess is that it would be some ways off based on our current poor understanding of psychiatric illness.

 

[KCShaw]

IMO, neuropathology alone won't be able to identify, predict, or diagnose the breadth of psychiatric disease. Form and function only overlap so far, not entirely unlike the arguments surrounding nature vs nurture.

Not that it can't be an interesting subject, I just think that in isolation neuropathologic evaluation of psychiatric disease is likely to remain of limited value, far more likely to incite discussion than utility.

 

[SaltySqueegee]

At least for me, this topic is particulary relevant. I'm in the midst of my Psych clerkship, and for someone who is 99.9% sure I'm heading into Pathology with a research bent, I am daily asking myself if certain questions are even answerable with the scientific methods/tools that are available today.

Schizophrenia, like many other complex genetic traits is likely the makeup of many cis-acting genetic variations responding in a decompensated way to environmental cues. Studies from the distant, but still complex genetic trait, of cancer risk, suggest that specific cellular pathways are typically dysregulated or suboptimal to environmental cues. Moreover, these mutations are likely low-penetrant but accumulate their effect at the intermediate phenotype levels. Thus, along these lines there could be better development of pathway specific biomarkers, specific phosphorylation signals, that indicate the activity of entire signal transduction cascades. How to measure the inherent dysregulation in these entire trans-signal cascades is currently lacking. In other words it is presently difficult to determine the functionality of an entire pathway, not just the individual components? This question may be at the heart of the paradigm of complex genetics. Subtle changes coordinating their dysregulation within a particular pathway to create a large phenotypic deficit; i.e. risk.

Because the dysregulation is so subtle at the individual gene level, individual protein level, biomarkers based on these signals will not yield sufficient odds ratios to be clinically useful.

I guess what I'm getting at is how can we take a sub-global assessment of intermediate phenotypes which comprise the activity of pathways important for risk in development of schizophrenia? The other difficulty is that identifying causative cis-variants is a relatively easy walk in the park compared to identifying causative trans-effects.

And of course, map on top of this a structure/function component with neuropathology. Very difficult to parse out the cause and effect.

Sorry for the drawn out post. This area (complex genetic traits) is of great interest to me, and I'm interested in reading thoughts from others in this area.

 

[malchik]

The question of the role of the neuropathologist in diagnosis of schizophrenia is simple: is there a morphologic correlate to schizophrenia?
And then, Can that morphology be discerned through current pathologic methods (gross exam, light microscopy, EM)?
I think schizophrenia is probably more a functional change, with structural changes being limited to connectivity/ circuitry. These are essentially impossible to analyze through current neuropathologic approaches. If someone identifies another approach like a biomarker, this will likely not require the neuropathologist's expertise to interpret.

 

[oldfatman]

I have a book called "the neuropathology of schizophrenia" which is quite interesting and has piqued my interest in studying the neuropathology of psychiatric disease. The book also mentions that schizophrenia had been dubbed the "graveyard of neuropathologists", apparently because their careers all died after they began working on it.

Sounds like this should be more of a hobby than a serious career pursuit. If you do chase this, you might as well move to leper island.

 

[Enkidu]

Hi, thanks for the comments. I was thinking that there could be histological markers of neural function, perhaps transcription factors that are under the control of synaptic receptors or other markers that might indicate normal versus altered function of a group of neurons.

To be honest, I'm partly trying to find a clear way to bridge my research interests in neurophysiology with a career in neuropathology. It doesn't seem like a natural marriage, but perhaps there could be a link?

Sent from my Droid using Tapatalk

 

[caffeinegirl]

Neurophysiology and neuropathology do have a link in research..especially in the field of neurodegenerative diseases as well as neuromuscular disease. I suggest that you look into the basic science studies that the neuropathology faculty are currently involved in and also look into academic institutions that have strong neuroscience departments. The best advice, IMHO would be from a current neuropathology attending at such institutions that has a basic science lab.

 

[KCShaw]

By immunostain or similar techniques, I'd say there -are- markers related to function. General pathology uses those techniques as indicators quite regularly, though often limited to inferring whether or not there is tumor or to classify tumor. Of course, you don't have to be a board certified neuropathologist to engage in neuropathologic research -- PhD's do it all the time. Now, where current knowledge ends and current or future research begins, I don't know -- I think the suggestion of talking to someone active in the field is a good one in that regard.