Foundation-Funded Research Suggests Prenatal Beginnings of Schizophrenia, Could Aid Early Diagnosis

Fred H. Gage, Ph.D. - Brain & behavior research expert on schizophrenia
Fred H. Gage, Ph.D.

An inter-institutional team using state-of-the-art stem-cell technology has bolstered evidence that schizophrenia begins to take shape in the womb even though full-blown symptoms of the disorder usually don’t appear until adolescence or early adulthood.  

The research was supported in part by a 2013 NARSAD Distinguished Investigator Grant to Fred H. Gage, Ph.D., of the Salk Institute and was published online on April 1st in the journal Molecular Psychiatry. The study was co-designed by Dr. Gage and Kristen Brennand, Ph.D., of the Icahn School of Medicine at Mount Sinai, and 2013 NARSAD Young Investigator Grantee Kazue Hashimoto-Torii, Ph.D., of Yale University and the Children’s National Medical Center, also participated in the research.

In the study, skin cells from four patients with schizophrenia and six healthy control subjects were converted into stem cells called neural progenitor, or precursor, cells (NPCs), which are comparable to fetal brain cells destined to mature into neurons. The objective of the study was to look for the earliest changes in these cells that could affect brain development and be linked to schizophrenia. The authors explain that although postmortem studies of brains of people with schizophrenia have identified defects in neurons, “these findings represent disease end points and reveal little about disease predisposition or initiation.”

The research showed that the NPCs from the schizophrenia patients behaved differently from the NPCs from the controls in migration and cell adhesion patterns, processes important in making appropriate connections in building the brain. The patients’ NPCs also showed increased levels of oxidative stress, which can lead to cell death.  

Although the sample in the study was small, the researchers believe that their approach can be applied to expanded numbers of patients, making NPCs potentially valuable tools with which to study the developmental mechanisms that contribute to schizophrenia. Revealing that they were “surprised at how early in the developmental process that defects in neural function could be detected," Dr. Gage states that the study “hints that there may be opportunities to create diagnostic tests for schizophrenia at an early stage."

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Article comments

The creation of the 'diagnostic tests' to test 'schizophrenia at an early stage' (in the womb) can't come soon enough. This is an amazing study, and so exciting to read about. I hope there can be more funding targeting this development, as the second and third generation of the ill family members worry tremendously about the possibility of their offspring's potential to develop neural defects leading to schizophrenia.

This makes a lot of sense. As the Mother of four, I can clearly look back & see that there were definite differences in the emotional development & behaviours of my now 29 year old son, as opposed to that of his three sisters from the very beginning. He would not sleep in his own bed until the age of 12 or 13, seeming to desperately require the comfort of someone else for him to get to sleep. Then would almost immediately wake up if I crept out of the bed even after he was asleep! He was definitely more "clingy" & jumpy as a toddler & would stop dead & cling to me if a noisy truck or other similar vehicle would pass by in the street. By age ten or eleven he was diagnosed with ADHD & had a horrible time in school, barely graduating High School. Yet, in College made almost perfect grades until his first Schizophrenic break down at age 24 & has always struggled socially. Being the only son, I thought it was the difference between males & females, but always had a nagging feeling that there was something else that was not quite right. Now I know my intuition was right!!

It would be wonderful if early diagnosis and treatment were possible. Reading Ms Rignault's comments makes me hope that researchers will also be able to study early behavioral patterns of children who later develop schizophrenia. My son was also fearful and clingy. Additionally, he had numerous imaginary friends - cute at 4, not so much at 14. If parents knew early behaviors to look for, perhaps more patients could have better teen and young adult lives, which would lead potentially to more happy and productive adulthood.

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