This May Lead to 40-Fold Increased Risk of Schizophrenia: Study

Scientists reveal the absence of a gene associated with schizophrenia may alter brain function

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The deletion of a single gene and the crippling effects this has on mitochondria may be responsible for a 40-fold increased risk of developing a devastating mental illness, a new study finds.

For decades, researchers have theorized that several genetic underpinnings play a critical role in the development of schizophrenia. But an investigation led by scientists at Emory University and Rutgers published in Science Advances reveals that a missing gene 3q29 could cause the psychiatric disorder due to the significant adverse impact its absence has on mitochondrial function.

The 3q29 gene is a micro portion of chromosome 3. The consequences of a lack of this small piece of DNA in each cell vary widely, with some individuals ending up with no problems at all. In contrast, others may suffer from more severe things like delayed development, intellectual disabilities, and behavioral and mental health issues. About 1 in 30,000 people are born with 3q29 deletion syndrome.

To get to the bottom of the association between 3q29, mitochondria, and schizophrenia, researchers used two experimental models to examine the impact such a loss has on isogenic cortical organoids, commonly referred to as human “mini brains” grown in a lab and perinatal mice. They used sophisticated RNA sequencing techniques to track changes in brain cells over time and how the changes affect overall neurodevelopment.

Mitochondria are considered the powerhouse of a cell and the foundation for energy production in the form of ATP. In the experiment, cells were supposed to mature to produce energy more efficiently. However, with 3q29 removed, the mitochondria functioned poorly instead of becoming more efficient, resulting in reduced energy production, which is detrimental to nearly all bodily processes, including neurodevelopment.

“Bridging the gap between genetic risk and biological mechanisms is a major challenge for psychiatry. In this study, we sought to use systematic methods to identify the most salient, conserved transcriptomic effects of the [schizophrenia] associated 3q29Del in disease-relevant tissues as an important step toward determining cellular and molecular phenotypes of this important variant. These findings should motivate further work to determine the mechanisms of these 3q29Del sequelae and their relevance to various clinical phenotypes,” the authors wrote.

How Common Is Schizophrenia?

Data from the World Health Organization (WHO) show while schizophrenia may be one of the least common mental disorders, it still affects an estimated 24 million people, or 1 in 300 people worldwide. An estimated 1 in 40,000 children under 13 years old are diagnosed annually in the United States.

Early Signs and Symptoms

There are several early signs and symptoms of schizophrenia in children and teenagers. Symptoms may include the following problems with thinking, behavior, and emotions that may worsen with age:

• Problems with thinking and reasoning.
• Bizarre ideas or speech.
• Confusing dreams or television with reality.
• Withdrawal from friends and family.
• Sleep disruptions.
• Lack of motivation.
• Strange behavior.
• Violent or aggressive behavior or agitation.
• Recreational drug or nicotine use.
• Irritability or depressed mood.
• Lack of emotion or emotions inappropriate for the situation.
• Strange anxieties and fears.
• Excessive suspicion of others.

Later Signs and Symptoms

As children with schizophrenia age, more typical signs and symptoms of the disorder begin to appear and may include:

• Delusions involving being harmed, harassed, or that a major catastrophe is going to happen.
• Hallucinations, such as seeing things or hearing voices.
• Disorganized thinking that impacts clear communication, resulting in incoherent answers.
• Extremely abnormal behavior like unpredictable anger, resistance to instructions, or a complete lack of response.
• Neglecting personal hygiene like bathing or dressing.
• Appearing emotionless by avoiding eye contact, changing facial expressions to fit situations, and speaking in a monotone.

Diagnosis and Treatment

Early diagnosis and treatment are critical in reducing psychotic episodes and keeping children with schizophrenia under control before serious complications arise. Medications, electroconvulsive therapy, and individual and family talk therapy can improve a child’s chances of success as they move into adulthood.

Complications

Without treatment, schizophrenia can result in serious complications both in childhood and adulthood. A 2021 study found people with schizophrenia have a 4.5-fold increased risk of dying by suicide. Studies also show 65 percent of patients with schizophrenia present with anxiety symptoms to the degree that they are diagnosed with conditions like obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD).

Substance abuse is also common. An estimated 47 percent of patients with schizophrenia have serious problems with drugs or alcohol compared to 16 percent of the general population. Schizophrenia also comes with a host of other medical problems like diabetes, heart disease, obesity, and an increased risk of death.

Relapse Rates

Schizophrenic relapse rates are high and attributable to several factors, including medication nonadherence, family criticism or hostility toward the patient, and stressful life events. A previous review found medication nonadherence was associated with a fourfold increased risk of relapse. Those who persistently abused substances had a threefold increased risk of relapse, and those who experienced critical comments from caregivers had more than double the risk.