We Might Be Treating Schizophrenia All Wrong (2023)

We Might Be Treating Schizophrenia All Wrong (1)

For more than 70 years, doctors treated the symptoms of schizophrenia—delusions, hallucinations, cognitive impairments—with antipsychotic medications. Prevailing theories suggest that elevated dopamine signaling in the brain leads to schizophrenia, so these antipsychotics provide relief by tempering dopamine activity. Yet, it has never been entirely clear how these drugs quiet dopamine activity. And due to their nature, these drugs impact other parts of the body and foster unwanted side effects including weight gain, constipation, and drowsiness. On top of that, more than nearly a third of patients don’t even respond to two or more common antipsychotic treatments.

What if there was a better way to treat the more than 24 million people around the world with schizophrenia? A new study run by researchers in Japan and published earlier this year in Cell Reports Medicine suggests that for at least a significant portion of patients, the immune system is mistakenly attacking a protein in the brain—which may be the real mechanism giving rise to schizophrenic symptoms in the first place.

This study is the tip of the iceberg too.

“We don’t know what causes schizophrenia,” Roger McIntyre, psychiatrist and professor of psychiatry and pharmacology at the University of Toronto (who was unaffiliated with this work), told The Daily Beast. “Rigorous scientific studies that have been conducted and they have concluded that for some people, some of the symptoms of schizophrenia may be a consequence of a disturbance in the immune inflammatory system.”

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This in turn, may open the door to an entirely new way of treating schizophrenia—one that’s unencumbered by the challenges holding back current antipsychotics.

The team behind the new study analyzed blood from about 200 patients with schizophrenia and compared it to blood samples from more than 200 healthy individuals. In about 6 percent of schizophrenia patients, the researchers found elevated levels of an antibody that targeted NCAM1, a protein crucial for cell communication in the brain. None of the healthy individuals enrolled in the study produced this antibody.

We Might Be Treating Schizophrenia All Wrong (2)

That’s a surprising finding, but was this antibody actually responsible for the symptoms themselves? Or just another marker of the condition?

The researchers isolated the antibodies and injected them into mice. In addition to causing cognitive impairments and other behaviors characteristic of schizophrenia, the NCAM1 autoantibodies also reduced the number of connections in the brain.

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“Even though the mice only had these autoantibodies in their brains for a short time, they had changes in their behavior and synapses that were similar to what is seen in humans with schizophrenia,” Hidehiko Takahashi, a professor of psychiatry and schizophrenia researcher at Tokyo Medical and Dental University and co-author of the new study, said in a press release.

McIntyre added that there’s other connections between schizophrenia and the immune system, including a subset of patients who have antibodies against other proteins in the brain, like the NMDA receptor or other signs of immune dysregulation. “People who live with schizophrenia or bipolar disorder or depression are at higher risk of contracting COVID-19, ending up in hospital and dying,” he said, citing an earlier study his research group published in JAMA Psychiatry.

A 2018 study found that people with an existing autoimmune disorder are more than 70 percent more likely to develop schizophrenia. This is not too surprising given that prominent genetic risk factors for the disease occur as mutations on a gene locus called the major histocompatibility complex. This complex is important for teaching the immune system the difference between the body’s own proteins and invading pathogens.

And the immune system-schizophrenia evidence goes beyond genetics. The brain’s resident immune cells, the microglia, have also been implicated in the development and pathology of the disease.

Microglia are the avid plant-enthusiasts and gardeners of the brain. As neurons sprout and grow early in life, the microglia take care to cut off any unused or unneeded connections. Then they provide continued support by dealing with pathogens and infection, clearing any debris, and getting rid of dysfunctional cells. Like the handiwork of a terrible gardener, microglia can leave behind a trail of mayhem.

Maternal infection during pregnancy is known to increase the risk of developing schizophrenia—animal models implicate microglia as the mediators of this effect. In post-mortem studies, researchers found elevated levels of activated microglia “attacking” other cells in the brain.

And that’s not all—they also release and respond to many signaling proteins called cytokines which may also play a role in schizophrenia. In 2011, researchers discovered that the levels of several cytokines are either higher or lower than the levels found in healthy individuals. Some cytokines, including interleukin-1β and interleukin-6 were elevated after a first psychotic episode as well as in patients experiencing a relapse of symptoms. Antipsychotic treatments also lowered the levels of these proteins, bolstering the idea that these cytokines are targets for new treatments.

All of that research has led to a very important question: Could existing medications that reduce inflammation or target specific cytokines boost the response to antipsychotic medication?

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Results in 2014 showed that a broad approach to treat overall inflammation in patients with schizophrenia found that taking aspirin, estrogen, or an antioxidant called N-acetylcysteine in addition to antipsychotic medication had a small but meaningful impact on symptom severity. Zeroing in on microglia, other researchers discovered in 2017 that taking antipsychotics along with minocycline—a drug that prevents microglia from activating—also improved overall symptoms.

According to McIntyre, minocycline is often prescribed as an off-label treatment. “You're not going to see minocycline as a recommended treatment because this is very much outside the usual practice,” he said. “But clinicians spend a lot of their time treating patients who are not benefiting from the usual practice.”

Since individuals with schizophrenia can experience a wide range of symptoms and pathologies, scientists are working toward developing more specific, personalized treatments. “We really think that schizophrenia is a group of disorders there’s different biological causative pathways,” McIntrye said, adding that many people who don’t benefit from current antipsychotic medications display symptoms strongly associated with immune dysregulation.

These treatments could have more powerful effects for people hospitalized with schizophrenia, as well as those who don’t respond to current treatments.

Can Adderall Abuse Trigger Temporary Schizophrenia?

“What’s most debilitating is the cognitive symptoms: that is the ability to focus, concentrate, your memory, your processing speed, and also what’s called negative symptoms,” McIntyre said. “In other words, people who have schizophrenia often have this lack of motivation.”

In 2014, two treatment-resistant patients received an antibody against the protein interferon gamma-1b—responsible for amplifying the body’s immune response. Both patients showed improvements in symptoms over seven weeks.

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Two years later, researchers ran an eight-week clinical trial, finding that tocilizumab, a type of antibody-based drug that reduces inflammation approved for treating arthritis, improved cognitive symptoms in schizophrenia patients. The antibody-based drug works by blocking the activity of the interleukin-6 receptor, preventing the activation of the body’s inflammatory response. But a 2018 study involving 36 patients didn’t find any improvement from tocilizumab.

Still, more trials are underway, recruiting more patients to test existing immune-modulating drugs against schizophrenia. One antibody-based drug targeting interleukin-6 and may augment the effects of antipsychotic treatments. Another targets activated microglia, is also being tested in early trials. McIntyre expects that new treatments may be approved by the FDA in the next five or 10 years.

With all that we know so far, it is still difficult to develop better treatments. The immune system is complex and there are many different ways that it can go haywire. The NCAM1 autoantibodies were only present in around 6 percent of people with schizophrenia within the study. Personalized approaches to treating schizophrenia could target the specific aspects of the immune system that aren’t functioning, whether it is autoantibodies, microglia or specific cytokines.

“There are certain forms of breast cancer, you can genotype somebody, and based on the genotype, you can determine whether they are especially going to respond to certain drugs, for example, breast cancer,” McIntyre said. “We’re not there yet in psychiatry, but that’s exactly the direction people want to go.”

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FAQs

Why is treatment difficult in schizophrenia? ›

Because medications for schizophrenia can cause serious side effects, people with schizophrenia may be reluctant to take them. Willingness to cooperate with treatment may affect drug choice. For example, someone who is resistant to taking medication consistently may need to be given injections instead of taking a pill.

What is the success rate for treating schizophrenia? ›

50% of people with schizophrenia recover or improve to the point they can work and live on their own. 25% are better but need help from a strong support network to get by. 15% are not better. Most of these are in the hospital.

Can schizophrenia get better without medication? ›

New study challenges our understanding of schizophrenia as a chronic disease that requires lifelong treatment. A new study shows that 30 per cent of patients with schizophrenia manage without antipsychotic medicine after ten years of the disease, without falling back into a psychosis.

Why do schizophrenics stop taking medication? ›

The single most significant reason why individuals with schizophrenia and bipolar disorder fail to take their medication is because of their lack of awareness of their illness (anosognosia). Other important reasons are concurrent alcohol or drug abuse; costs; and a poor relationship between psychiatrist and patient.

Do schizophrenics know they are ill? ›

Early Warning Signs of Schizophrenia

One is that people with the disorder often don't realize they're ill, so they're unlikely to go to a doctor for help. Another issue is that many of the changes leading up to schizophrenia, called the prodrome, can mirror other normal life changes.

Can you be happy with schizophrenia? ›

Responses suggest that about 37 percent of schizophrenia patients were happy most or all of the time, compared with about 83 percent for those in the comparison group. Approximately 15 percent of schizophrenia patients reported being never or rarely happy.

What happens when schizophrenia is not treated? ›

Left untreated, schizophrenia can result in severe problems that affect every area of life. Complications that schizophrenia may cause or be associated with include: Suicide, suicide attempts and thoughts of suicide. Anxiety disorders and obsessive-compulsive disorder (OCD)

Can you make a full recovery from schizophrenia? ›

Most people with schizophrenia make a recovery, although many will experience the occasional return of symptoms (relapses). Support and treatment can help you to manage your condition and the impact it has on your life.

How long is remission for schizophrenia? ›

Remission has been defined as a level of symptomology that does not interfere with an individual's behaviour, and is also below that required for a diagnosis of schizophrenia. Symptom improvements should last for a minimum of six months in order for remission to be reached. Recovery is less precisely defined.

Will I be on antipsychotics forever? ›

Some people need to keep taking it long term. If you have only had one psychotic episode and you have recovered well, you would normally need to continue treatment for 1–2 years after recovery. If you have another psychotic episode, you may need to take antipsychotic medication for longer, up to 5 years.

Does sugar affect schizophrenia? ›

Adolescents consuming an excessive amount of sugar could risk developing schizophrenia or other mental disorders by causing inflammation in neurons in the brain, according to experiments conducted on mice.

Can you ever get off antipsychotics? ›

Some people may be able to stop taking antipsychotics without problems, but others can find it very difficult. If you have been taking them for some time, it can be more difficult to come off them. This is especially if you have been taking them for one year or longer.

Do schizophrenics get worse with age? ›

Schizophrenia is a chronic disorder that may wax and wane in severity, but it does not typically worsen with age. 1 For some people, the symptoms of schizophrenia will improve over time while for others the symptoms will stay the same or get worse.

When is schizophrenia hospitalized? ›

You may have to go to the hospital if: You're having a psychotic episode. This means that you can't tell the difference between what is real and what isn't real. You talk about suicide or hurting yourself or others.

Can you force a schizophrenic to take medication? ›

It can be both emotionally and legally difficult to force a person with a mental disorder to get treated, but if a loved one becomes dangerous, friends and family members may need to call the police to take the person to the hospital, according to NAMI.

Is a schizophrenic a psychopath? ›

Psychopathy and schizophrenia are both frequently represented in popular culture—in thrillers and on TV shows—and they are both significantly more common among men than women, with the result that they are often confused and conflated. However, psychopathy and schizophrenia are two very different conditions.

Does caffeine affect schizophrenia? ›

High doses of caffeine are particularly concerning for individuals with schizophrenia; caffeine alters dopaminergic activity at post-synaptic neurons through its actions at adenosine A2A receptors, which may exacerbate positive symptoms, such as delusions and hallucination.

Can a person with schizophrenia act normal? ›

With the right treatment and self-help, many people with schizophrenia are able to regain normal functioning and even become symptom-free.

Are schizophrenics self centered? ›

Schizophrenia may blur the boundary between internal and external realities by over-activating a brain system that is involved in self-reflection, and thus causing an exaggerated focus on self, a new MIT and Harvard brain imaging study has found.

What it feels like to have schizophrenia? ›

Schizophrenia is a complicated disorder. This makes it hard to say what it feels like. Generally, it all boils down to a person's unique symptoms. This can include disorganized thinking, paranoia, delusions, hallucinations, agitation, or a loss of interest in activities.

Can you live on your own with schizophrenia? ›

Living a normal life with schizophrenia doesn't necessarily mean never having symptoms again—it means being able to manage this chronic illness in order to live independently, or mostly independently, and do all the things other adults do, such as work and have families.

Does untreated schizophrenia cause brain damage? ›

Schizophrenia has been described as the “worst disease” to afflict mankind. It causes psychosis, which is an abnormal state of mind marked by hyperarousal, overactivation of brain circuits, and emotional distress. An untreated episode of psychosis can result in structural brain damage due to neurotoxicity.

How long does someone with schizophrenia live? ›

According to the World Health Organization (WHO), the decline in life expectancy among people with more severe mental illness ranges from 10–25 years . Most studies of schizophrenia show a life expectancy reduction of 10–20 years.

Is untreated schizophrenia violent? ›

Untreated schizophrenia People with untreated schizophrenia had a significantly increased risk of violence compared to those with continuous or discontinuous treatment for schizophrenia (OR=3.33, 95% CI 1.03 to 10.75), or people with no history of psychosis (OR=3.43, 95% CI 1.10 to 10.72).

Does schizophrenia show on a brain scan? ›

In patients with schizophrenia, MR imaging shows a smaller total brain volume and enlarged ventricles. Specific subcortical regions are affected, with reduced hippocampal and thalamic volumes, and an increase in the volume of the globus pallidus.

What percentage of schizophrenics recover completely? ›

People recover from schizophrenia

Over the course of months or years, about 20 to 25 percent of people with schizophrenia recover completely from the illness – all their psychotic symptoms disappear and they return to their previous level of functioning.

How do you comfort a schizophrenic? ›

Here are some tips:
  1. Educate yourself. ...
  2. Listen. ...
  3. Use empathy, not arguments. ...
  4. Don't take it personally. ...
  5. Take care of yourself, too. ...
  6. Maintain your social network. ...
  7. Encourage your loved one to keep up with their treatment and recovery plan. ...
  8. Take action if you think you or your loved one is in danger.

Can schizophrenia regress? ›

Sometimes, though, symptoms can suddenly worsen or become more frequent despite medications and consistently following lifestyle recommendations. A doctor may consider schizophrenia regression as a possible cause when this happens.

Do antipsychotics reduce IQ? ›

Patients on non-standard antipsychotic medication demonstrated poorer performance than those on standard medication on visual memory, delayed recall, performance IQ, and executive function.

Does your brain go back to normal after antipsychotics? ›

For neurological, neuropsychological, neurophysiological, and metabolic abnormalities of cerebral function, in fact, there is evidence suggesting that antipsychotic medications decrease the abnormalities and return the brain to more normal function.

Can you live a long life on antipsychotics? ›

Previous studies found that the death rate among people with schizophrenia on antipsychotic medications was 30%-50% lower than among those who took a placebo. But most of the studies were shorter than six months, which does not reflect the fact that antipsychotic treatment is often lifelong, the study authors noted.

What foods should schizophrenics avoid? ›

Also, schizophrenia patients had poor dietary patterns with more saturated fats, sugar and alcohol as well as less intakes of fish, vegetables, and fruits, which may be related to impaired cognitive function [12,13].

What vitamin is good for schizophrenia? ›

B vitamins.

A large review of over 800 patients found that people who took high-dose B-vitamins like B6, B8, and B12 in addition to their medications significantly reduced symptoms of schizophrenia, compared with those who took medicines alone.

What food is good for schizophrenia? ›

People with schizophrenia tend to eat diets higher in fat and lower in fiber. Make sure your diet includes plenty of fruits, vegetables, and whole grains. Eating a healthy diet can also help you avoid the weight gain that antipsychotic medicines may cause.

Can psychosis go away naturally? ›

Can Psychosis Go Away on Its Own? If the psychosis is a one-time event, such as with brief psychotic disorder, or substance-induced psychotic break, it may go away on its own. However, if the psychosis is a result of an underlying mental health disorder, it is unlikely the psychosis will go away naturally.

What can happens if you take antipsychotics and don't need them? ›

If you stop antipsychotics suddenly it can cause 'rebound psychosis'. This means that the symptoms of your illness return suddenly, and you may become unwell again.

What happens when a normal person takes antipsychotics? ›

Side-effects of typical antipsychotics vary depending on the drug and may include drowsiness, agitation, dry mouth, constipation, blurred vision, emotional blunting, dizziness, stuffy nose, weight gain, breast tenderness, liquid discharge from breasts, missed periods, muscle stiffness or spasms.

Can schizophrenia turn into dementia? ›

Researchers found a significant increase in the risk of developing dementia when a person also had schizophrenia. Another 2018 study found a close correlation between very late onset schizophrenia and developing dementia. People with very late onset schizophrenia had a threefold increase in dementia rates.

What can trigger schizophrenia? ›

Some people may be prone to schizophrenia, and a stressful or emotional life event might trigger a psychotic episode.
...
The main psychological triggers of schizophrenia are stressful life events, such as:
  • bereavement.
  • losing your job or home.
  • divorce.
  • the end of a relationship.
  • physical, sexual or emotional abuse.

What is the injection for schizophrenia? ›

INVEGA TRINZA® (paliperidone palmitate) a 3-month injection, is an atypical antipsychotic indicated for the treatment of schizophrenia in patients after they have been adequately treated with INVEGA SUSTENNA® (1-month paliperidone palmitate) for at least four months.

How many schizophrenics are violent? ›

Only about 10% of people with schizophrenia will engage in violence during their lifetime (2, 3); however, they are three to four times more likely to act violently compared with the general population, after adjustment for socioeconomic factors (4).

Where do they put schizophrenic people? ›

Hospitals can be the best place for people with schizophrenia to learn to live with their illness. A hospital can help you get the full picture of your symptoms and learn how to treat them. You may need to go to one if you have hallucinations or if you want to harm yourself.

What is the new drug for schizophrenia? ›

The field of treating schizophrenia with drugs has been stuck in a long drought but, this month, a late-stage clinical trial found a new drug called KarXT could treat a range of symptoms. Schizophrenia is a debilitating mental health condition that affects around 24 million people worldwide.

Can you live with schizophrenia without medication? ›

New study challenges our understanding of schizophrenia as a chronic disease that requires lifelong treatment. A new study shows that 30 per cent of patients with schizophrenia manage without antipsychotic medicine after ten years of the disease, without falling back into a psychosis.

Why do people with schizophrenia not take their meds? ›

The single most significant reason why individuals with schizophrenia and bipolar disorder fail to take their medication is because of their lack of awareness of their illness (anosognosia). Other important reasons are concurrent alcohol or drug abuse; costs; and a poor relationship between psychiatrist and patient.

Why is there no cure for schizophrenia? ›

The complex heterogeneity of schizophrenia means that a single cure may not be found. New strategies to stratify etiologically complex patients, diagnosing high-risk individuals prior to psychosis onset, makes possible a future whereby we prevent, rather than treat, schizophrenia.

Why are schizophrenic patients difficult? ›

People with schizophrenia often also experience persistent difficulties with their cognitive or thinking skills, such as memory, attention, and problem-solving. At least one third of people with schizophrenia experiences complete remission of symptoms (1).

What are some of the challenges in treating individuals diagnosed with schizophrenia? ›

Multiple risk factors have been identified, ranging from previous suicide attempts, substance abuse, hopelessness, depression, and male sex2 to lack of social support, lack of problem-solving skills, and stress.

What are the challenges of schizophrenia? ›

Thus, many people with schizophrenia continue to live with the following challenges:
  • untreated negative symptoms.
  • medication side effects.
  • weight management.
  • suicidal thoughts.
  • substance use.
  • job challenges.
17 Nov 2021

What is a risk inherent in using medications in the treatment of schizophrenia? ›

Uncontrollable movements, such as tics, tremors, or muscle spasms (this risk is higher with first-generation antipsychotics) Weight gain (this risk is higher with second-generation antipsychotics) and other metabolic effects like development of diabetes and high cholesterol. Drowsiness. Restlessness.

What movie is based on schizophrenia? ›

A Beautiful Mind (2001)

Perhaps the best-known movie about schizophrenia, “A Beautiful Mind” is a powerful account of the life of mathematician and Nobel Prize winner John Nash (Russell Crowe).

What drug is most used for schizophrenia? ›

Haloperidol, fluphenazine, and chlorpromazine are known as conventional, or typical, antipsychotics and have been used to treat schizophrenia for years. However, they sometimes have movement-related side effects, such as tremors and dystonia, a condition that causes involuntary muscle contractions.

Does schizophrenia worsen with age? ›

Schizophrenia is a chronic disorder that may wax and wane in severity, but it does not typically worsen with age. 1 For some people, the symptoms of schizophrenia will improve over time while for others the symptoms will stay the same or get worse.

Can you live a good life with schizophrenia? ›

Schizophrenia treatment includes medication, therapy, social and family support, and the use of social services. Treatment must be ongoing, as this is a chronic illness without a cure. When schizophrenia is treated and managed over the long-term, most people can live normal, productive, and fulfilling lives.

Can you live with a schizophrenic person? ›

Living with family can be a good option for someone with schizophrenia if their family members understand the illness well, have a strong support system of their own, and are able to provide whatever assistance is needed.

Are schizophrenics self centered? ›

Schizophrenia may blur the boundary between internal and external realities by over-activating a brain system that is involved in self-reflection, and thus causing an exaggerated focus on self, a new MIT and Harvard brain imaging study has found.

How do schizophrenics think? ›

Schizophrenia involves a range of problems with thinking (cognition), behavior and emotions. Signs and symptoms may vary, but usually involve delusions, hallucinations or disorganized speech, and reflect an impaired ability to function. Symptoms may include: Delusions.

How does a person with schizophrenia feel? ›

Drastic changes in behaviour may occur, and the person can become upset, anxious, confused, angry or suspicious of those around them. They may not think they need help, and it can be hard to persuade them to visit a doctor. Read more about understanding psychotic experiences.

What living with schizophrenia is like? ›

Individuals will show a lack of interest and pleasure in everyday life. There may be a lack of ability to maintain planned activities, and a person will often not speak when spoken to. A person who shows negative symptoms often needs help with everyday activities, such as personal hygiene.

What can happens if you take antipsychotics and don't need them? ›

If you stop antipsychotics suddenly it can cause 'rebound psychosis'. This means that the symptoms of your illness return suddenly, and you may become unwell again.

What is the new treatment for schizophrenia? ›

Currently available drugs can control only a portion of these symptoms but, on August 8th, Karuna Therapeutics announced its completion of a phase 3 clinical trial that found a new drug called KarXT could treat both positive and negative symptoms of schizophrenia.

What happens when a normal person takes antipsychotics? ›

Side-effects of typical antipsychotics vary depending on the drug and may include drowsiness, agitation, dry mouth, constipation, blurred vision, emotional blunting, dizziness, stuffy nose, weight gain, breast tenderness, liquid discharge from breasts, missed periods, muscle stiffness or spasms.

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