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The Genetic Connection between Schizophrenia, Bipolar Disorder and Major Depression

It may seem as though schizophrenia, bipolar disorder, and major depression have vastly different presenting characteristics. However, as researchers progress in investigating these conditions, they are uncovering more commonalities than you might initially anticipate.

Schizophrenia is a mental disorder that is characterized by a broad range of unusual behaviors which cause profound disruption in the lives of people suffering from the condition, as well as in the lives of the people around them. The behaviors include hallucinations (auditory, visual, olfactory, or tactile) and delusions.

Bipolar disorder is characterized by mood swings between high energy and activity (known as mania or hypomania) and feelings of sadness or depression, lasting for days, weeks or months at a time.

Major depression, or major depressive disorder, is characterized by an overwhelming depressed mood for more than two weeks. The depressed mood affects all facets of the person’s life, including work, home life, relationships and friendships. A person with this kind of depression often finds it difficult to do much of anything or get motivated, so even going to seek treatment for this condition can be challenging.

Per the National Institute of Mental Health, approximately 1 percent of adults develop schizophrenia, about 2.5 percent have bipolar disorder and almost 7 percent of people develop major depression over their lifetimes.

All three aforementioned mental disorders run the gamut of severity owing that cognition runs along a spectrum. There are also different types of sub-conditions within each diagnosis which further complicates things. For example, schizoaffective disorder encompasses a combination of symptoms of both schizophrenic and mood disorders.

For many psychiatric disorders, genetic factors explain more than half the risk. Many of the genetic variants associated with one illness, such as schizophrenia, alter risk for other common psychiatric disorders, including mood and anxiety disorders. Scientists at Johns Hopkins have found common groups of genes disturbed among people with schizophrenia, bipolar disorder and major depression. The commonly affected gene sets, identified with RNA sequencing methods, engage in making proteins, controlling brain cell communications and mounting an immune system response.

Sarven Sabunciyan, Ph.D., a researcher in the Stanley Division of Developmental Neurovirology at the Johns Hopkins University School of Medicine said that, even though there are subtle differences in individual genes which are involved in different processes in the brain of people with a variety of severe mental disorders, they could identify “the broad functional overlaps, knowing there is a lot of variability among individuals with mental disorders.”

For the study, the researchers collected 100 tissue samples from donor brains from the Stanley Medical Research Institute (SMRI) Array Collection. All the donor samples were from the hippocampus which is responsible for memory and spatial navigation. Thirty-five brains were from people with schizophrenia, 33 were from people with bipolar disorder and 32 were controls without a mental disorder. They also used 57 samples from a region of the brain’s outer cortex near the eye, the orbitofrontal cortex: thirteen of those brain samples were from people with schizophrenia, 14 with bipolar disorder, 15 with major depression and 15 from controls.

Results indicated that out of a total of 1,070 gene sets, 13 of these gene groups changed in common ways among all three mental disorders.

In another similar study, specific genetic alterations modulated by stress have been identified in children marked as being at “high risk for bipolar disorder,” with high risk being the genetic predisposition to develop it later on in adulthood.

Gabriel R. Fries, Ph.D. of the Department of Psychiatry and Behavioral Sciences at McGovern Medical School at UTHealth said that “by analyzing the blood of children of controls and comparing it to children of bipolar patients, we identified several genes or markers that can explain the increased risk.”

For this experiment, they examined the surrounding blood mononuclear cells from a total of 18 children and adolescents in three matched groups: the bipolar patients, unaffected offspring of bipolar parents and children of parents with no history of psychiatric disorders at all.

Results for the study showed that bipolar patients and the children of bipolar parents had genetic changes that can influence the response to stress.

Both studies are remarkable, as they demonstrate the malleability of genetics and the role that it plays in psychiatric illness.

Additionally, the reason the results of each study and the connections drawn from them are so significant is because common genetic deficiencies could indicate similar treatment strategies for researchers in the near future, and that is a very promising concept indeed.

References

Duff, Barbara J. et al.  Human brain imaging studies of DISC1 in schizophrenia, bipolar disorder and depression: A systematic review.  Schizophrenia Research , Volume 147 , Issue 1 , 1 – 13.  (Cross-referenced) Accessed 18 May 2017.

Life Sciences, News-Medical. Net.  Scientists identify commonly affected genes sets among people with three mental disorders.  (Original Source Johns Hopkins Hospital).  26 October, 2016.  Accessed 18 May 2017.
Scientists identify commonly affected genes sets among people with three mental disorders

Medical Xpress, Researchers identify genes in children linked to stress, bipolar disorder.  8, May, 2017.  Accessed 18 May 2017.  https://medicalxpress.com/news/2017-05-genes-children-linked-stress-bipolar.html

National Institute of Mental Health, U.S. Department of Health and Human Services.  Accessed 18 May 2017.  http://www.nimh.nih.gov/index.shtml

National Institutes of Health (US); Biological Sciences Curriculum Study. NIH Curriculum Supplement Series. Bethesda (MD): National Institutes of Health (US); 2007. Information about Mental Illness and the Brain. https://www.ncbi.nlm.nih.gov/books/NBK20369/

Sawamura N, Sawa A.Ann.  Disrupted-in-schizophrenia-1 (DISC1): a key susceptibility factor for major mental illnesses.  PubMed.   2006 Nov; 1086:126-33.  (Cross-referenced) Accessed 18 May 2017.

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