As seen in Psychology Today.

Schizophrenia affects between an estimated 0.25 percent and 0.64 percent of Americans, which translates into roughly 800,000 to 2 million people. On account of its prevalence, schizophrenia can also be a burdensome illness. A study published in the Lancet recently claimed that it is one of the top 15 causes of disability worldwide. Other studies have found that it can significantly reduce one’s lifespan (by an estimated 28.5 years in the United States); increase the probability of developing other serious medical conditions such as heart disease, liver disease, and diabetes; and have a deleterious effect on one’s finances, largely due to high healthcare costs and lowered productivity, among other factors. DSM-5 claims that, “Approximately 5%-6% of individuals with schizophrenia die by suicide, about 20% attempt suicide on one or more occasions, and many more have significant suicidal ideation.”

While treatments have come a long way in recent decades and are constantly improving, schizophrenia is a very serious condition and it can be difficult to have a productive life while grappling with the illness. New research indicates that it may also disrupt one’s circadian rhythms, and that this may be another key to better understanding the disease.

What Is Schizophrenia?

“Schizophrenia” comes from a combination of the prefix “schizo-” and the suffix “-phrenia,” both of which are borrowed from Ancient Greek. “Schizo-” (σχίζω) means ‘to split’ and is related to word “schism.” “-Phrenia” (ϕρην) refers to the soul or the mind. The term was coined by the Swiss psychiatrist Eugen Bleuler in 1908. Prior to this, the illness was often called dementia precox, which translates into “precocious madness,” which was initially an umbrella term to describe severe mental illnesses in young patients.

Bleuler argued that patients with schizophrenia experienced, “A splitting of the psychological functions: as the disease becomes distinct, the personality loses its unity.” This language may seem to describe dissociative identity disorder (formerly known as multiple personality disorder). However, this is not what the term “schizophrenia” refers to. Instead, it refers to the fragmented thinking that is common among those with the illness.

In recent years, a more systematic definition of schizophrenia has emerged. According to DSM-5, schizophrenia is a chronic brain disorder that tends to emerge between the time a patient enters their late teens and their mid-30s. The manual notes that first onset has been observed in patients over the age of 40 in rare cases. The specifics of the disorder vary, as schizophrenia is a heterogeneous clinical syndrome, though its core components include at least one of the following:

· Delusions

· Hallucinations

· Disorganized speech

Additional symptoms include:

· Disorganized or catatonic behavior

· Negative symptoms, which may include a diminished emotional expression, interest in social activities, motivation, or speech output.

Additional diagnostic criteria may include the duration of symptoms (including prodromal or residual symptoms); the patient’s level of functionality; and the patient’s history, including family history, psychiatric history, and history with substance abuse. At this time, there are no radiological, laboratory, or psychometric tests that can detect the disorder, though researchers hope to one day discove

r more objective means of distinguishing schizophrenia from other serious and persistent mental illnesses.

What Are the Causes of Schizophrenia?

Researchers are still trying to determine the exact causes of schizophrenia, which have remained elusive even after more than a century of robust scientific inquiry. There appears to be a large genetic component to the illness. If an individual has been diagnosed with schizophrenia, there is a 7 percent to 9 percent chance that a sibling will be diagnosed with the illness. If a parent has schizophrenia, there is a 10 percent to 15 percent chance that their child will develop the illness. If both parents have it, those chances increase to nearly 40 percent.

However, genetics are clearly not the sole determining factor. There have been numerous cases in which only one identical twin develops schizophrenia. Though the two share nearly 100 percent of the same genes, the probability of getting schizophrenia if an identical twin has it is only around 50 percent. This indicates that there must be another factor involved in the development of the illness.

While researchers have struggled to find all the components that influence the development of schizophrenia, they have become more confident in their understanding of how schizophrenia alters the brain. Furthermore, researchers are stressing that schizophrenia should be understood as a brain disease similar to Parkinson’s or Alzheimer’s diseases.

There are neurological and neurochemical distinctions between key regions of the brain that are different in individuals with schizophrenia than in individuals who do not have the condition. Similarly, differences in cellular architecture, white matter connectivity, and gray matter volume in areas like the prefrontal and temporal cortices have also been observed. At least one study authored by Zhang XY et al has found that abnormal glucose metabolism in the brain may be another indication of schizophrenia.

Schizophrenia and Circadian Rhythms

One’s circadian rhythm is, at its most basic level, the body’s biological clock. While other factors affect the sleep/wake cycle on a 24-hour (diurnal) basis, such as the color and intensity of natural light that we observe during the course of a normal day, one’s circadian rhythm is primarily responsible for regulating the hormones that cause us to feel alternately alert or sleepy depending on what time of day it is. In patients with schizophrenia, this cycle gets disrupted, which can lead to difficulties sleeping, suboptimal sleep consolidation, and abnormal sleep architecture.

What may be surprising to learn is that this kind of daily cycle is not limited to one’s conscious mind. Gene expressions also abide by a diurnal cycle and can have a wide range of effects—many of which a patient may not even be cognizant. In a study recently published in the journal Nature Communications, lead author Dr. Colleen McClung, a professor of psychiatry at the University of Pittsburgh, examined rhythmic gene expression in schizophrenic subjects and controls and found disparities that affected cell mitochondria and other genes responsible for responding to inflammation. She and her team found that “subjects with schizophrenia have a very different set of diurnally rhythmic genes and a different rhythmic pattern in the dlPFC (the dorsolateral prefrontal cortex) compared to control subjects.” In other words, some gene expressions had developed diurnal rhythms that were absent in controls, such as those that affect mitochondria, while other gene expressions, like those related to immune function, lost rhythmicity.

Dr. McClung used the following analogy to better explain the findings: “In a normal house—like a healthy brain—let’s say the lights are turned on at night, but the refrigerator needs to be on all the time. What we saw was that in a schizophrenia-affected brain, the lights are on all day and the refrigerator shuts down at night.”

Rather than focusing on means of mitigating symptoms, the study describes some potential mechanisms that may explain how schizophrenia develops on a molecular level. More research needs to be conducted to further explore this line of inquiry, but the discovery that the cycle of certain diurnal or arrhythmic gene expressions can be affected by schizophrenia reveals that the disease is far more comprehensive than previously thought. It also demonstrates the importance of taking a more holistic approach with patients, not only when recommending potential remedies, but when searching for the underlying causes of disease.

Dr. Ahmad reports no conflict of interest. He is not a speaker, advisor, or consultant and has no financial or commercial relationship with any biopharmaceutical entity whose product/device may have been mentioned in this article.

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