Schizophrenia is a brain disorder that progresses rapidly after onset with symptoms such as hallucinations and paranoia. It is found in around 1% of the U.S. population – roughly 3 million people. The suicide rate in schizophrenic populations is also alarmingly high, 4.9% higher than the rate of the general population. Literature suggests through improved neuroplasticity, patients suffering from schizophrenia may experience reduced symptoms. Neuroplasticity is the brain’s ability to reorganize itself and reorder its synaptic connections. Examples of neuroplasticity include changes in grey matter, synapse strengthening, and transferring functions to different parts of the brain. The connection between schizophrenia and neuroplasticity has been found that a loss of neuroplasticity results in an increase of schizophrenia symptoms. This claim has been supported experimentally by testing cognitive abilities of schizophrenics vs. non schizophrenics and comparing levels of neural plasticity between schizophrenic and non-schizophrenic patients. Recent studies have shown that drug abuse can negatively impact neuroplasticity, providing a possible relationship between drug abuse and schizophrenia onset in some patients (O’Brien 2009). Use of depressive and excitatory drugs can cause significant effects on pathway formation in the brain, caused by breakdown or creation of new neural synapses. Here we review the role of drug abuse induced changes in neuroplasticity associated with previously reported increases in schizophrenia development.
What is Schizophrenia?
Schizophrenia is a brain disorder that affects around 1% of the United States population with symptoms such as hallucinations, delusions, disorganized behavior, and paranoia. There are many genetic, environmental, and drug use factors that have been shown to contribute to schizophrenia onset. Other possible underlying causes of schizophrenia include pregnancy and birth defects that could be caused by stress inducing factors and epigenetic factors that could arise from environmental factors. Schizophrenia is a progressive disease and tends to deteriorate a patient’s health over time. It is usually diagnosed between the ages of 16-30 and affects both genders but presents in males more often at a ratio of 1:1.4. It is one of the biggest causes of disability worldwide (NIMH 2013). Schizophrenia presents with both positive and negative symptoms; positive symptoms include hallucinations, delusions, and disorganized speech, while negative symptoms include flattened affect, reduced speech, and lack of initiative. It has been found that about 80% of those who stop taking their medications after an acute episode will have a relapse within one year, whereas only 30% of those who continue their medications will experience a relapse in the same time period (Di Capite et al.). It is widely accepted that genetics play a role in schizophrenia development, but there is no single gene that has been found to be responsible for this disorder. However, some genes have acquired prominent attention in their possible contribution. Dr. Daniel Weinberger, Director of the Genes, Cognition, and Psychosis Program at the National Institute of Mental Health has highlighted the significance of the comt gene. Mutations in comt have been found to result in depletion of the critical neurotransmitter dopamine in the frontal lobe (McGrath 2005). A common byproduct of depleted dopamine is hallucinations and delusions which are symptoms of schizophrenia.
Neuroplasticity is the brain’s ability to reform and organize synaptic connections. Neuroplasticity also includes reductions in synapses resulting in a reduction of synaptic strength and pruning axons that are not in use. Events like learning, injury, or stress can help develop and strengthen preexisting neuron pathways or lead to the breakdown of pathways (McEwen et. al. 2016). Experience-dependent plasticity is when certain skills are learned and practiced, leading to a greater part of the brain being connected to the learned skill. In this process there are many neuronal-level changes, such as dendritic spine growth, synaptogenesis, and axon arborization (Diering et. al. 2014). These changes in neuroplasticity have been shown to affect schizophrenia in multiple ways.
Neurobehavior and Schizophrenia
Schizophrenia is associated with functional changes in the cortex. It has been found that neurons in some schizophrenic patients fire more frequently due to an increased sensitivity to excitatory signals, while in others, neurons are unable to appropriately return to their hyper-polarization state (Freeman 2010). This may contribute to schizophrenia patient’s seizures due to rapid over-firing of neurons. Michael Merzenich has started working on brain training software to help schizophrenics. Through the usage of plasticity assisted cognitive remediation (PACR), Merzenich has been using schizophrenic humans and analyzing their visual and auditory fields. By using monkeys, Merzenich has shown how neurons can switch where they receive sensory input from, in this case, the sensory neurons from the damaged hand of a monkey no longer process in the same hand, but process in the healthy hand (Hayden 2015). He used this to connect to his studies in humans, where the visual and auditory fields can still be functional even with damage in certain areas. This was a finding that helped support the claim that neuroplasticity plays an important role in how the brain reacts to stimuli such as an injury. (Hayden 2015). In the past, there have been many experiments conducted as an attempt to find the source of the link between schizophrenia and neuroplasticity. One experiment conducted in 2010 contained 32 stable schizophrenia patients who were placed in one of three cognitive training groups to assess the program’s impact on neurocognition after 6 months. Group one consisted of 12 patients that underwent 50 hours of auditory training. Group two included 10 patients that received an additional 50 hours of visual training and cognitive tasks beyond the 50 hours of auditory training. The third group, a control of 10 patients, underwent 50 hours of computer game tasks. These tasks were performed over a 6-month period and patients were then measured to see if there was any change in their neurocognition. Neurocognition is defined as the functions related to the output of certain parts of the brain. Neuroplasticity is measured by using neurocognition as a reference. At the end of the trial, the 22 patients in the cognitive training group with 50 hours of work experienced significant changes in their processing speed and cognition, but no significant changes were seen in their functional outcomes (Fisher et. al. 2010). However, the patients in the cognitive training group with 100 hours auditory and visual training with cognitive tasks showed significant gains in their cognitive control and memory.
Schizophrenia and Drug Abuse
The three most common drugs used by schizophrenics are nicotine, cannabis, and cocaine (Winklbaur et. al. 2006). These drugs have very detrimental effects in schizophrenics and have the potential to increase symptoms (Ebner 2008).
Nicotine affects patients with schizophrenia in a multitude of ways; the key concern is the impact nicotine has on dopamine and glutamate pathways. Almost 70% of patients that deal with chronic schizophrenia are addicted to nicotine (Winklbaur et. al 2006). Cigarette smoking was also found to have a close link to schizophrenia as well as other mental disorders. Smokers with disorders tend to be more heavily addicted to nicotine and are much less likely to quit smoking than a smoker without a disability (Quigley 2016). There are multiple proposed explanations for the connections between smoking and schizophrenia but there hasn’t been one clear-cut answer. The main ingredient of tobacco smoke is nicotine, which is responsible for the addictive properties of cigarettes. Nicotine travels quickly through the bloodstream and reaches the brain around 15 seconds after being inhaled. Nicotine binds to presynaptic receptors called “nicotinic acetylcholine receptors” located throughout the brain. When the nicotine binds to these receptors, it causes an ion channel to open and release cations through the cellular membrane. These cations – sodium, calcium, and potassium – activate calcium channels and in turn release neurotransmitters. Nicotine changes the release of multiple neurotransmitters – serotonin, GABA, dopamine, and acetylcholine, just to name a few. Elevated acetylcholine levels can result in depression and excess GABA can impair cognitive function (Volk 2018). Increased dopamine is also associated with schizophrenia as many schizophrenics have been found to have this neurotransmitter surplus causing delusions and an altered state of reality (MacCabe 2005).
Cannabis use has been found to be a stressor causing relapse in patients with schizophrenia (Hall et. al. 2008). In a study conducted over 15 years with Swedish participants, it was found that by the age of 18, individuals using cannabis were 2.4 times more likely to be diagnosed with schizophrenia than those who had not used cannabis (Hall et. al. 2008). The increase of the risk of developing schizophrenia directly correlated with an increase of frequency of cannabis usage. In longitudinal studies done by Hall et. al. it has been shown that cannabis use contributes to schizophrenia through regular use over long periods of time compared to non-users (Hall et. al.). There is also a lot of support for the belief that the connection between cannabis and psychosis, a symptom of schizophrenia, is biologically based (Manseau et. al. 2018). It has been found that in patients with schizophrenia there are elevated levels of anandamide, an endogenous cannabinoid agonist, in their cerebrospinal fluid (CSF) (Manseau et. al. 2018). This highlights a critical link between cannabis and schizophrenia associated symptoms of psychosis. Cocaine is another addictive drug that is commonly abused by schizophrenics. Schizophrenics that frequently use cocaine are at a higher risk for suicidal behavior, tend to be less consistent with their treatments, and are more often hospitalized than schizophrenics who do not use cocaine (Winklbaur 2006). Cocaine has a devastating effect on the neurobiological system, through disruption in reuptake of dopamine in presynaptic receptors (Verma 2015). This causes the dopamine to persist in the synaptic cleft leading to detrimental side effects in schizophrenics such as delirium (Kwak et. al. 2010). Drug abuse can affect neuroplasticity in the brain in multiple ways, depending on the narcotic that is used. There is a possibility that in controlled settings, drug usage may be helpful to schizophrenics as specified doses could possibly alleviate symptoms (Ebner 2008). Overall, there is no clear impact that drug abuse has on the neuroplasticity of schizophrenics, but this is continued to be researched through multiple ongoing clinical trials.
So far, a correlational connection between neuroplasticity and schizophrenia has been formed, but there is a lot of room for determining causation. It has been shown that training leading to an increase in neuroplasticity is associated with a decrease in schizophrenic-like behavior and methods such as cognitive remediation also helps decrease schizophrenic behavior (Mogami 2018). It has been shown that compared to healthy patients, patients with schizophrenia have a lot less neuroplasticity (Jahshan 2017). Factors influencing drug abuse may represent co-morbidities in schizophrenic patients, such as stress. Stress can be a contributing factor in initiation of drug abuse and is associated with many of the symptoms of schizophrenia. Genetic vulnerability also plays a role in drug abuse as many environmental and genetic factors can affect the development of drug addiction. A pressing question of the relationship between schizophrenia and drug abuse is – if schizophrenia onset is associated with drug abuse, is this the result of neuroplasticity increasing or decreasing? Schizophrenia has been hypothesized to affect the reward centers in our brains which increases vulnerability to drug addictions as well. Neurotransmitters are also significant in this process as the intake of certain drugs leads to an excess of dopamine for example, leading to euphoria and hallucinations (Kwak et. al. 2010). Ultimately, the question if drug abuse can cause direct changes to neuroplasticity and therefore schizophrenia still stands. However, there are clinical trials being run to try and elucidate the role of drug abuse manipulation in schizophrenic patients for a beneficial clinical impact (Winklbaur 2006).
Isha Nambisan, Youth Medical Journal 2020
- Administrator. “Schizophrenia – Fact Sheet.” Treatment Advocacy Center, http://www.treatmentadvocacycenter.org/evidence-and-research/learn-more-about/25-schizophre nia-fact-sheet#:~:text=Schizophrenia%20is%20a%20chronic%20and%20severe%20neurol ogical%20brain%20disorder%20estimated,untreated%20in%20any%20given%20year.
- Begley, Sharon. “Neuroplasticity May Help Schizophrenics.” Newsweek, Newsweek, 13 Mar. 2010, http://www.newsweek.com/neuroplasticity-may-help-schizophrenics-78863.
- Capite, Suzanne Di, et al. “The Relapse Rate and Predictors of Relapse in Patients with First-Episode Psychosis Following Discontinuation of Antipsychotic Medication.” Wiley Online Library, John Wiley & Sons, Ltd, 13 Oct. 2016, onlinelibrary.wiley.com/doi/abs/10.1111/eip.12385.
- “Disorders of Synaptic Plasticity and Schizophrenia.” Google Books, Google, books.google.com/books?hl=en&lr=&id=7Rau8ZjDDMwC&oi=fnd&pg=PA19&dq=schiz ophrenia%2Bneuroplasticity&ots=RCU6Z1V6xL&sig=4xPy6QEFnHu7Bf8s18GNnctvW L0#v=onepage&q&f=false.
- Fisher, Melissa, et al. “Neuroplasticity-Based Cognitive Training in Schizophrenia: an Interim Report on the Effects 6 Months Later.” Schizophrenia Bulletin, Oxford University Press, July 2010, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894606/.
- Hall, Wayne, and Louisa Degenhardt. “Cannabis Use and the Risk of Developing a Psychotic Disorder.” World Psychiatry : Official Journal of the World Psychiatric Association (WPA), Masson Italy, 2008, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2424288/.
- Howes, Oliver, et al. “Glutamate and Dopamine in Schizophrenia: an Update for the 21st Century.” Journal of Psychopharmacology (Oxford, England), U.S. National Library of Medicine, Feb. 2015, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902122/.
- Jahshan, Carol, et al. “Enhancing Neuroplasticity to Augment Cognitive Remediation in Schizophrenia.” Frontiers, Frontiers, 15 Sept. 2017, http://www.frontiersin.org/articles/10.3389/fpsyt.2017.00191/full.
- Karlsgodt, Katherine H, et al. “Structural and Functional Brain Abnormalities in Schizophrenia.” Current Directions in Psychological Science, U.S. National Library of Medicine, Aug. 2010, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235761/.
- Lodish, Harvey. “The Action Potential and Conduction of Electric Impulses.” Molecular Cell Biology. 4th Edition., U.S. National Library of Medicine, 1 Jan. 1970, http://www.ncbi.nlm.nih.gov/books/NBK21668/.
- Lyon, Edward R., et al. “A Review of the Effects of Nicotine on Schizophrenia and Antipsychotic Medications.” Psychiatric Services, 1 Oct. 1999, ps.psychiatryonline.org/doi/full/10.1176/ps.50.10.1346.
- McGrath, John J. “Variations in the Incidence of Schizophrenia: Data Versus Dogma.” OUP Academic, Oxford University Press, 31 Aug. 2005, academic.oup.com/schizophreniabulletin/article/32/1/195/2888593.
- Mogami, Tamiko. “Cognitive Remediation for Schizophrenia with Focus on NEAR.” Frontiers in Psychiatry, Frontiers Media S.A., 17 Jan. 2018, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5776134/.
- NHS Choices, NHS, http://www.nhs.uk/conditions/schizophrenia/causes/.
- O’Brien, Charles P. “Neuroplasticity in Addictive Disorders.” Dialogues in Clinical Neuroscience, Les Laboratoires Servier, 2009, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181920/.
- Quigley, Harriet, and James H MacCabe. “The Relationship between Nicotine and Psychosis.” Therapeutic Advances in Psychopharmacology, SAGE Publications, 1 July 2019, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604123/.
- “Researchers Find Way to Increase Neuroplasticity and Treat ‘Negative’ Symptoms of Schizophrenia.” Brain & Behavior Research Foundation, 15 Aug. 2019, http://www.bbrfoundation.org/content/researchers-find-way-increase-neuroplasticity-and-treat-% E2%80%9Cnegative%E2%80%9D-symptoms-schizophrenia.
- Salleh, Mohd Razali. “The Genetics of Schizophrenia.” The Malaysian Journal of Medical Sciences : MJMS, Penerbit Universiti Sains Malaysia, July 2004, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433970/.
- Schizophrenia.com – Schizophrenia Genetics and Heredity, http://www.schizophrenia.com/research/hereditygen.htm.
- “Schizophrenia.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 7 Jan. 2020, http://www.mayoclinic.org/diseases-conditions/schizophrenia/symptoms-causes/syc-20354443.
- “Schizophrenia.” National Institute of Mental Health, U.S. Department of Health and Human Services, http://www.nimh.nih.gov/health/statistics/schizophrenia.shtml.
- “Schizophrenia.” National Institute of Mental Health, U.S. Department of Health and Human Services, http://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml.
- “Treating Schizophrenia: Game On.” Nature News, Nature Publishing Group, http://www.nature.com/news/treating-schizophrenia-game-on-1.10126.
- Vaillancourt, David E, et al. “Dopamine Overdose Hypothesis: Evidence and Clinical Implications.” Movement Disorders : Official Journal of the Movement Disorder Society, U.S. National Library of Medicine, Dec. 2013, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859825/.
- Verma, Vivek. “Classic Studies on the Interaction of Cocaine and the Dopamine Transporter.” Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology, Korean College of Neuropsychopharmacology, 31 Dec. 2015, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662164/.
- Volk, David W, and David A Lewis. “GABA Targets for the Treatment of Cognitive Dysfunction in Schizophrenia.” Current Neuropharmacology, U.S. National Library of Medicine, Jan. 2005, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338098/.
- “What Is Neuroplasticity? A Psychologist Explains [+14 Exercises].” PositivePsychology.com, 28 Apr. 2020, positivepsychology.com/neuroplasticity/.
- Winklbaur, Bernadette, et al. “Substance Abuse in Patients with Schizophrenia.” Dialogues in Clinical Neuroscience, Les Laboratoires Servier, 2006, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181760/.