How Specific Genes May Cause Schizophrenia and Other Disorders

A team of researchers has developed a new way to study how genes may cause schizophrenia and other neurodevelopmental disorders by growing tiny brain-like structures in the lab and tweaking their DNA.

These so-called “assembloids,” described in the journal Nature in September, could help researchers in the future develop targeted treatments for schizophrenia, autism spectrum disorder, intellectual disability, and epilepsy.

Combining two cutting-edge technologies, Stanford Medicine investigators and their colleagues revealed the impact of a multitude of genes that are associated with neurodevelopmental disorders but whose effects on human brain development were previously unknown.

“This really accelerates our effort to try to understand the biology of psychiatric disorders,” Dr. Pașca told NPR. The study comes after decades of work identifying hundreds of genes that are associated with particular neurodevelopmental disorders. However, “scientists still don’t know how problems with these genes alter the brain,” reported Jon Hamilton for NPR. “The challenge now is to figure out what they’re actually doing, how disruptions in these genes are actually causing disease,” Pașca said. “And that has been really difficult.”

Despite extensive research, the causes of schizophrenia are still unclear. “There is no single organic defect or infectious agent which causes schizophrenia, but a variety of factors increase the illness—among them genetics and obstetric complications,” wrote the late Colorado Recovery founder Richard Warner, MD, in his influential book The Environment of Schizophrenia

A new study published in May by the Lieber Institute for Brain Development, for example, suggested that the placenta, and not only the brain, plays a central role in the genetic risk of schizophrenia. 

“For ethical reasons, scientists can’t just edit a person’s genes to see what happens,” NPR’s Jon Hamilton explained. “They can experiment on animal brains, but lab animals like rodents don’t really develop anything that looks like autism or schizophrenia. So Pașca and a team of scientists tried a different approach, which they detailed in their new paper.”

The Stanford team conducted a series of experiments using tiny clumps of human brain cells called brain organoids. These clumps will grow for a year or more in the lab, gradually organizing their cells much the way a developing brain would. By exposing an organoid to certain growth factors, scientists can coax it into resembling tissue found in brain areas including the cortex and hippocampus.

“We can actually make different parts of the nervous system in a dish from stem cells,” Pașca explained. When these parts are put in the same dish, they will even form connections, much like an actual brain. The resulting structure is called an assembloid.

Pașca’s team hopes these assembloids can be used to study how developmental disorder genes affect special brain cells called interneurons, which are thought to play a role in several psychiatric disorders.

Brain networks rely on a delicate balance between excitatory and inhibitory neurons. Too much acceleration and the result can be an epileptic seizure. Too much slowing down and vital information may get lost or delayed. The research shows how gene variants could lead to schizophrenia or other neurodevelopmental disorders by disturbing interneurons.

The novel approach allowed the team to study the effect of more than 400 genes associated with neurodevelopmental disorders. “They found that 46 of those genes were involved in either the generation of interneurons or with their migration,” Hamilton reported. “Knock out a part of those genes and interneurons no longer arrived where they were supposed to.”

Brain scientists now hope to be able to make the sort of advances that cancer researchers were able to achieve in recent decades. Oncologists increasingly analyze the genetic makeup of carcinomas to determine which therapy is most likely to work. A similar approach could eventually help patients with autism spectrum disorder, epilepsy, and schizophrenia. 

While new diagnostic tools can obviously play significant roles in the treatment of serious mental illnesses such as schizophrenia, meaningful recovery also requires that patients experience a sense of empowerment—a belief in their ability to take charge of their lives and manage the complex demands and consequences of such illnesses.

Colorado Recovery has been utilizing the Warner method to empower adults with mental illness for many years now. Our program approaches mental healthcare based on a path of self-reliance through developed practiced skills. Recognizing the importance of empowerment for recovery, our non-institutionalized philosophy offers comprehensive levels of care supported by an expert medical and clinical team, engaging patients in increasing community participation. 

Our treatment facility provides the services needed to address schizophrenia, bipolar disorder, and other serious mental illnesses. Call us at 720-218-4068 to discuss treatment options for you or the person you would like to help.

How Stress Can Trigger a Relapse of Psychosis

“Illness relapse following a first episode of psychosis is the rule rather than the exception,” wrote psychiatry professor Brian Miller, MD, PhD, MPH a few months ago in the Psychiatric Times. “Identification of factors associated with illness exacerbation could help identify individuals at heightened risk for relapse and develop targeted interventions.” 

Stressful life events are associated with psychosis risk and with potential illness relapses. In his article, Dr. Miller presented the case of a young African-American female with a history of schizophrenia who experienced her first episode of psychosis at the age of 22. She was stabilized on antipsychotic medication and had been stable for two years. 

Then, her elderly dog had to be euthanized and a beloved uncle died unexpectedly. Following these stressful life events, she suffered a relapse and had to be treated in a psychiatric emergency department. She was actively attending to internal stimuli, endorsing persecutory beliefs, and passive suicidal ideation. 

“People with schizophrenia seem to be exquisitely sensitive to stress,” wrote the late Colorado Recovery founder Richard Warner, MD, in his influential book The Environment of Schizophrenia, “the life events occurring before episodes of schizophrenia, and possibly triggering the relapse, are milder than those before episodes of other disorders such as depression.”

A new study by Bhattacharyya, Schoeler, et al. published in June investigated the association between stressful life events and relapse of psychosis by combining multiple inferential approaches. The researcher “investigated the effects of stressful life events across a range of outcomes, tested for a dose-response relationship, and applied a fixed-effects analysis of longitudinal data,” Miller reported. “They also used a cross-lagged path analysis approach to investigate the directionality of the association.”

The study authors concluded that their “results provide converging evidence of a causal effect of stressful life events on the risk of relapse in psychosis. They suggest that there is a need to develop interventions at the individual and health-service level that could mitigate the harmful effects of stressful life events.”

In the Warner treatment model, therapeutic intervention and relapse prevention rely on “social recovery” from severe mental illness. The treatment program at Colorado Recovery aims to empower adults with mental illness, and those who support them, with an unrelenting optimism for recovery, purposeful involvement in the community, and an enhanced sense of meaning in life.

A strong support network can be an important protective factor when dealing with stressful life situations. A 2022 study found that social support mitigates stress. “The environment shapes schizophrenia,” wrote Dr. Warner. “Antipsychotic drugs seem to be particularly important in preventing relapse in schizophrenia where people with the illness are exposed to a lot of stress, but of somewhat less importance for those living in circumstances where the stress is milder.”

Since Dr. Warner’s passing in 2015, Colorado Recovery has continued to innovate its therapy modalities, delivering exceptional outcomes through its signature continuum of care and helping create lives of purpose as they practice powerful tools in the management of their mental health disorder.

Our treatment facility provides the services needed to address schizophrenia, bipolar disorder, and other serious mental illnesses that are specific to each individual. Call us at (720) 218-4068 to discuss treatment options for you or the person you would like to help.