Can Ketamine Research Offer New Insights into the Causes of Psychosis in People With Schizophrenia?

Problems abound in defining schizophrenia. Its primary symptom is psychosis; the two most common functional psychoses are schizophrenia and bipolar disorder (also known as manic-depressive illness). The distinction between the two is not easy to make and psychiatrists in different parts of the world at different times have drawn the boundaries in different ways.

The cause of the illness is equally hard to pin down. “There is no single organic defect or infectious agent which causes schizophrenia, but a variety of factors increase the risk of getting 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. “

New research reported in the European Journal of Neuroscience into how the NMDA receptor inhibitor ketamine affects the brains of rats may eventually lead to a better understanding of the causes of psychosis in people with schizophrenia.

Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a treatment for depression, a pain management tool, and—like similar substances—sometimes misused as a recreational drug. Ketamine was derived from phencyclidine in 1962, in pursuit of a safer anesthetic with fewer hallucinogenic effects.

In healthy individuals, ketamine can induce a mental state similar to psychosis. “In normal healthy subjects and rodents, complex integration processes, like sensory perception, induce transient, large-scale synchronized beta/gamma oscillations in a time window of a few hundred ms (200-700 ms) after the presentation of the object of attention (eg, sensory stimulation),” researchers wrote. “Our goal was to use an electrophysiological multisite network approach to investigate, in lightly anesthetized rats, the effects of a single psychotomimetic dose (2.5 mg/kg, subcutaneous) of ketamine on sensory stimulus-induced oscillations.”

“Researchers monitored rat responses to having their whiskers stimulated before and after ketamine administration. Microelectrodes implanted in the animals recorded electrical activity in the thalamus and the somatosensory cortex, a region of the brain responsible for processing sensory information from the thalamus,” Jolynn Tumolo explained on Psych Congress Network.

“The discovered alterations in thalamic and cortical electrical activity associated with ketamine-induced sensory information processing disorders could serve as biomarkers for testing antipsychotic drugs or predicting the course of disease in patients with psychotic spectrum disorders,” Sofya Kulikova, a member of the research team told Psych Congress Network.

Ketamine increased the power of beta and gamma oscillations in the cortex and the thalamus, even in the resting state before the stimulus occurred, the research team reported. The amplitude of beta/gamma oscillations in the 200–700 ms post-stimulus period at each cortical and thalamic site was significantly lower following ketamine administration, which appears to be associated with impaired perception.

“By inhibiting NMDA receptors, ketamine also added noise to gamma frequencies in the post-stimulation period in one thalamic nucleus and in one layer of the somatosensory cortex,” Tumolo reported the result of the analysis. “This noise increase further impaired the ability of neurons to process incoming sensory signals, researchers believe.”

The researchers believe “the present findings support the hypothesis that NMDA receptor antagonism disrupts the transfer of perceptual information in the somatosensory cortical-thalamo-cortical system.” The findings could eventually lead to new methods for the treatment of psychotic episodes in schizophrenia.

Colorado Recovery provides services for adults with serious mental illnesses that will stabilize their illness, minimize symptoms, improve functioning, and enhance each person’s social inclusion, quality of life, and sense of meaning in life.

We provide residential and outpatient treatment options for schizophrenia, bipolar, schizoaffective disorder, and other mental health conditions. Call us at 720-218-4068 to discuss treatment options for you or the person you would like to help.

New Hope For People with Social Anxiety Disorder

Social Anxiety Disorder (SAD)—also known as “social phobia”—is a longstanding and excessive fear of social situations. According to the Mental Health Foundation, “the average age of onset of SAD is between 10 to 13 years, and SAD is rarely diagnosed after the age of 25.”

“In social anxiety disorder, fear and anxiety lead to avoidance which can disrupt your life,” informs the Mayo Clinic. “Severe stress can affect your relationships, daily routines, work, school, or other activities.”

SAD can have a severe impact on a person’s quality of life. “Social anxiety disorder is a chronic mental health condition that causes sufferers to be anxious in social situations where they may be exposed to scrutiny and perceived judgment,” Scott Anderson explained on Psychology Today. “Everyday social interactions can lead to embarrassment, fear, and excessive self-consciousness.”

Now, there is new hope for patients with this condition. Researchers recently looked at a known culprit: the gut-brain axis. “Since the first mouse experiments a decade ago, the gut-brain axis has been found to be involved with anxiety, depression, autism, dementia, and schizophrenia,” wrote Anderson. A new study by Butler, Cryan, et al. from University College Cork (UCC) now adds social anxiety disorder to that list.

“The human gastrointestinal tract (GIT) harbors a vast assembly of microorganisms, predominantly bacteria but also fungi, viruses, protozoa, and archaea,” the authors wrote. “It is estimated that the number of bacteria in the human gut is slightly in excess of the total number of human cells, at approximately 380 trillion, and that the collective genome of these bacterial cells vastly exceeds the amount of human DNA present in the body. Given this enormous, modifiable reservoir of genetic potential, it is unsurprising that there is keen interest in the potential role of the gut microbiome in the etiology and treatment of many disease processes.”

This microbiome is interconnected with the host body in intricate ways. It has now been recognized to be deeply involved in bidirectional signaling between the gut and brain, with the term ‘microbiome-gut-brain’ (MGB) axis describing this communication network.

The UCC study demonstrates, “for the first time, that the gut microbiome is compositionally and functionally altered in people with social anxiety disorder (SAD) compared with healthy controls. Moreover, it increases the growing evidence linking social brain function and the microbiome.”

“If microbes play a role, that’s good news,” concluded Anderson in his Psychology Today article because “we can manipulate our gut microbes with dietary changes, and that might provide a valuable lever to lift the anxiety.”

The study discovered two species of bacteria in particular that correlated to anxiety, one positively and one negatively. “Levels of the bacteria Anaeromassilibacillus An250 were higher in the anxiety group. This tracks with a 2022 Harvard study finding that negative emotions were also associated with higher levels of Anaeromassilibacillus An250,” reported Anderson.

“On the positive side, the study noted that levels of the beneficial bacteria Parasutterella excrementihominis were higher in the control group than in the anxiety group. Microbes that are associated with better mood have been termed psychobiotics. The study found other psychobiotic microbes as well, all diminished in patients with social anxiety disorder.”

In conclusion, the authors of the UCC study wrote that “the gut microbiome of patients with SAD differs in composition and function to that of healthy controls, raising the possibility that the MGB axis may represent a biomarker reservoir and potential therapeutic target for this early-onset, chronic disorder.”

Further studies are required but there is new hope that innovative dietary approaches and new medications can in the future help find better treatment modalities for SAD and other mental health conditions.

If you are searching for treatment options for yourself or someone you care about following a diagnosis of schizophrenia, bipolar disorder, or other severe mental health conditions, call us at 720-218-4068 to discuss treatment options for you or the person you would like to help.