Genetics and Mental Illness

Before beginning a discussion of genetics and mental illness, I think it is important to point out that mental illness is itself a human construct.  That is not to say it is not real; it is in fact too real.  But how we conceptualize it affects our attitudes and how it is treated.  Richard Barnett does a brief outline of some of the history behind our conceptions in an article just published in The Lancet (https://www.thelancet.com/action/showPdf?pii=S0140-6736(19)31151-10) in which among other things he points out that “depression” was not considered a distinct illness until 1980 and that the use of the word “emotion” first appeared in the 19th century.

In fact scientists are coming to view an illness like schizophrenia as actually falling on a spectrum.  How the illness manifests itself in one individual is not exactly the same as in another.  The same holds true of depression.  Here is perhaps where the issue of genetics comes in.

There is no one gene associated with any mental illness.  Not surprisingly there seems to be a complex interaction between any number of small changes in genes and the environment.  The issue of heredity has been most studied in schizophrenia.  Having a parent or sibling with the illness increases your chances of manifesting it 10%.  If both parents suffer from schizophrenia the odds increase to 40%.  For identical twins the odds rise to 48%.  But heredity is obviously not destiny as the figures for identical twins show.

There are actual physical changes in the brain of individuals with schizophrenia as compared to those who are not schizophrenic.   The former have larger spaces in the brain (ventricles), their medial temporal lobes, which involve memory and are smaller, they have fewer connections between brain cells and they tend to have differences in the chemistry of their neurotransmitters.  But when researchers looked at the brain tissue of deceased schizophrenics, they found that their brain structure often differed from that at birth. As schizophrenia usually develops in late adolescence and early adulthood, the dramatic changes occurring in the brain in this period may affect those at risk, both genetically and environmentally.

The environmental factors that are associated with increased risk include extensive exposure to marijuana among teenagers, stress and a number of prenatal conditions, including exposure to influenza, rubella, and respiratory infections, maternal deprivation in war and famine zones, low socio-economic status, urban birth and birth in late winter/early spring. (See  https://www.psychiatrictimes.com/schizophrenia/role-genetic-and-environmental-factors-development-schizophrenia/page/0/2)

The genetic component of depression has been less studied.  But just recently published research looking for ways in which treatment-resistant patients with depression, which in fact accounts for about one-third of those suffering from depression, differ from those who respond to current drug therapies is offering some very promising results.  Researchers again are not looking at any single gene but an array of small genetic variants.  They have found two arrays that seem linked to depression.  One controls the signals which regulate brain cell survival.  Previous research has linked cell death to depression.  The other controls the expression of genes, meaning ultimately protein production, which affects communication among neurons.  For a depressed individual to recover there needs to be a change in the way neurons communicate and this may be impaired in some individuals with treatment-resistant depression.  Such findings may lead the way to new approaches in developing drugs to target depression. (https://blog.journals.cambridge.org/2019/05/09/genetics-could-provide-a-pathway-to-understanding-treatment-resistant-depression)

Of course we need more research to determine under what environmental conditions such genetic pathways are activated.  Are they different for treatment-resistant depression than for those whose depression is not treatment-resistant?  Would be good to know.

 

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