Diseases and Disorders

Schizophrenia and the Loss of Brain Matter

Olakunsi Peters


Abstract

Once someone is diagnosed with schizophrenia, it can be difficult for that person to navigate back into the life they had before being diagnosed. Schizophrenia can be different for everyone. Some may experience delusions and hallucinations, while others may experience various voices in their head. This is why researchers are working tirelessly to find a cure that can cater to many schizophrenics. From consistent symptoms to novel clinical trials, this paper will explore an overview of what goes on in the brain of a schizophrenic.

 

Symptoms

Schizophrenia is a disabling mental disorder characterized by delusions, disturbed perceptions, and inappropriate behaviors. People with schizophrenia may seem like “they have lost touch with reality.” For males, symptoms usually start in their early 20s, whilst for females, symptoms usually start in the late 20s. Schizophrenics suffer from both ‘negative’ and ‘positive’ symptoms – with the psychotic behaviors that are not seen in ‘healthy’ people considered as positive. Hallucinations, delusions, thought and movement disorders are all positive symptoms [2]. Negative symptoms include  “inexpressive faces, blank looks, monotone and monosyllabic speech, few gestures, seeming lack of interest in the world and other people, [and] inability to feel pleasure or act spontaneously” [3]. Schizophrenics may not even find pleasure in their daily hobbies. Some patients may experience severe or subtle cognitive symptoms. Sometimes, their working memory may be impaired. At other times, they may be inattentive [2].

Positive symptoms usually indicate whether or not someone has schizophrenia; acute treatments pinpoint these symptoms. Even though negative symptoms may occur early in this  illness, they can be seen in the later stages. Those who have both types of symptoms respond positively to acute and aggressive treatments [2]. 

 

Decreases in White and Grey Matter

MRI’s and CT’s allow physicians to see the “structural and functional changes in the cortex” of schizophrenia patients.  Functional imaging techniques also showcase abnormal activity during decision making and even short-term memory in schizophrenics [4].

MRI studies of schizophrenia display a decrease in grey matter in the superior and medial temporal lobe and the prefrontal lobe. All of these regions of the brain specialize in episodic memory, short-term memory, auditory processing, and decision making. The loss of grey matter indicates a reduction of synapses and dendrites [4]. A study conducted by the Johns Hopkins School of Medicine shows that grey matter loss happens early in the life of an adolescent who has schizophrenia (Figure 2). Deficits begin in the parietal region. Over the course of five years, the damage moved to the temporal lobes (specifically, the sensorimotor, dorsolateral prefrontal cortices, and frontal eye fields) [5]. These are the reasons why schizophrenics have psychotic symptoms [4].

 This mental illness also causes disrupted neural connectivity [4]. White matter is made out of axons. Each neuron in the brain has a long axon that comes off of the cell body. Electrical signals from the cell body travel along the axon to other neurons [6]. Neuroimaging techniques have allowed scientists to see white matter reduction in both the first episode and chronic patients. The myelin sheath covers neural fibers and ensures that connections between the brain and body are efficient. From late adolescence to early adulthood, more myelin surrounds the neural fibers (myelination). This is also when psychosis starts to occur in schizophrenics. Scientists have theorized that a decrease in white matter in schizophrenics is related to a disruption in the myelin sheath [4].

MRIs have made it possible to see a reduction in grey matter in schizophrenia patients, but it is difficult to see what happens with the white matter. As a result, there are not many studies that have tried to find white matter differences between people with and without schizophrenia. Wible and coworkers (authors of “Prefrontal cortex and schizophrenia: a quantitative magnetic resonance imaging study”) [7] found associations between white matter and the temporal lobe (specifically, the superior temporal gyrus and amygdala-hippocampal complex). Also, Breier and coworkers (authors of “Brain morphology and schizophrenia: a magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures”)[8] saw a reduction of white matter in the amygdala and hippocampal complex [9].

 

Cognitive-Behavioral Therapy

Those with schizophrenia usually have lifelong treatment because there isn’t a cure. Chronic cases usually require hospitalization [10]. Cognitive-behavioral therapy (CBT) usually lasts an hour for 12 to 16 weeks. This therapy helps a schizophrenic think about their positive and negative symptoms differently. A therapist must find various ways to change any “negative thoughts” or delusions schizophrenics may have about themselves or the world around them [11].

According to Ann K. Morrison, MD in psychiatry, non-pharmacological therapy should be taken alongside medication, even though some schizophrenic symptoms resist pharmacological treatments [12]. An example of CBT is cognitive restructuring. In cognitive restructuring, the patient has to figure out various ways to show how some of their beliefs are unreal. As a result of having cognitive restructuring, many schizophrenics realize that they tend to have delusions from time to time. Over time, more positive thoughts will overcome negative thoughts. CBT can also improve a patient’s conversational skills so that they can work on previous relationships and form new ones [13].

 

Yoga Therapy

People with schizophrenia can also use yoga therapy with their medication to reduce symptoms. Yoga tends to help positive symptoms,  negative symptoms, and weight gain. In contrast, weight gain, “endocrinological and menstrual dysfunction,” can be a result of antipsychotics [13].

A study conducted by N Gangadhar Bangalore and Shivarama Varambally [14] shows how effective yoga therapy is on patients. In this study, there were two groups of patients who were given antipsychotics. For one month (“12 sessions”), one group did yoga exercises while another group did physical exercises. In the end, the researchers saw a significant improvement in the yoga group as they had ”better negative symptom scores than the physical exercise group.” It is reasonable to infer that yoga therapy worked because of oxytocin [14]. In another study done by David Feifel, patients who took oxytocin had less severe negative and positive symptoms [13].

 

Antipsychotics

First-generation antipsychotics (FGAs) or typical antipsychotics were created in the 1950s and second-generation antipsychotics (SGAs) or atypical antipsychotics were created in the 1980s. FGAs are serotonin-dopamine antagonists (a drug that blocks dopamine from binding to the receptor), while SGAs are dopamine partial agonists (a drug that activates the dopamine biological response) [13].FGAs such as chlorpromazine usually bring along “metabolic adverse effects.” FGAs are best in decreasing many of the positive symptoms like hallucinations and hostility. SGAs such as Clozapine usually have “extrapyramidal side effects'' (EPS). Clozapine is used after a patient does not show improvement with FGAs. This antipsychotic can also cause cardiac complications [14].

A trial was done by Afaque H Khan and Samina Zaidi, which showed improvements in negative symptoms. So far, Clozapine has been proven to be the best antipsychotics for schizophrenics who have persistent negative symptoms. Two of the patients showed  improvements in “psychotic and negative symptoms including insight and judgement improvement in disorganization.” Two other patients “demonstrated robust response with significant improvement in negative symptoms including insight, judgment, affect, avolition, and disorganization and also an improvement in psychotic symptoms” [15].

 

Conclusion and Novel Treatments

Scientists have not yet found a cure for schizophrenia. It is unfortunate that in this year alone, there were 1.5 million around the world who were diagnosed with schizophrenia. Many children and teenagers will not know that they could potentially develop schizophrenic symptoms. Currently, researchers do not know how schizophrenia starts. However, they do know that schizophrenics produce too much dopamine, which leads to hallucinations and delusions.  FGAs and SGAs do not help “cognitive impairments, lack of motivation, dulled emotion, and social withdrawal” [16].

Sunovion Pharmaceutical Inc. created a new drug to treat symptoms of schizophrenia, such as psychosis. After completing a clinical trial with 245 people, researchers found that SEP-363856 targets more symptoms and does not have as many adverse side effects. SEP-363856 affects receptors that allow for “dopamine signaling” [17]. These researchers created drug screenings with PsychoGenics Inc. Using artificial intelligence, they were able to see what would happen to mice as they came into contact with SEP-363856. Once the researchers found a drug that mimicked the effects produced by D2-targeting drugs, they were able to continue with testing. Interestingly enough, the researchers saw that SEP-363856 targeted TAAR1 and 5-HT1A instead of D2 receptors. Sunovion Pharmaceutical Inc. is still in the process of finalizing mechanisms, but SEP-363856 has opened new doors of possibilities [15].


References


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  4. Karlsgodt, Katherine et al. (19/08/2010). Structural and Functional Abnormalities in Schizophrenia. US National Library of Medicine National Institutes of Health. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235761/. Retrieved: 22/07/2020.

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  6. Axons: the cable transmission of neurons.  Queensland Brain Institute. https://qbi.uq.edu.au/brain/brain-anatomy/axons-cable-transmission-neurons. Retrieved: 24/07/2020.

  7. C. G Wible and coworkers. Prefrontal cortex and schizophrenia. A quantitative magnetic resonance imaging study. National Library of Medicine. https://pubmed.ncbi.nlm.nih.gov/7702444/. Retrieved: 05/08/2020.

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  9. Shenton, Martha  and coworkers. (27/10/2009). Evidence for white matter abnormalities in schizophrenia. US National Library of Medicine National Institutes of Health. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768599/. Retrieved: 24/07/2020.

  10. “Cognitive Behavioral Therapy for Schizophrenia.” NYU Langone Health. https://nyulangone.org/conditions/schizophrenia/treatments/cognitive-behavioral-therapy-for-schizophrenia#:~:text=Cognitive%20behavioral%20therapy%20is%20a,of%2012%20to%2016%20weeks.Retrieved: 26/07/2020.

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  12. Morrison, Ann. (12/2020). Cognitive Behavior Therapy for People with Schizophrenia. US National Library of Medicine National Institutes of Health. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811142/. Retrieved: 05/08/2020.

  13. Krishna R. Patel and coworkers. (09/2020).  Schizophrenia: Overview and Treatment Options. US National Library of Medicine National Institutes of Health. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159061/. Retrieved: 05/08/2020.

  14. Yoga Therapy for Schizophrenia. US National Library of Medicine National Institutes of Health. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410202/#:~:text=Yoga%20as%20a%20therapy%20in%20psychosis%2C%20specifically%20schizophrenia%2C%20has%20been,asanas%20and%20pranayama%2C%20avoiding%20meditation. Retrieved: 27/07/2020.

  15. Introduction: First-Generation Versus Second-Generation Antipsychotics in Adults: Comparative Effectiveness. US National Library of Medicine National Institutes of Health. https://www.ncbi.nlm.nih.gov/books/NBK107237/. Retrieved: 29/07/2020.

  16. Maroney, Megan. An Update on Current Treatment Strategies and Emerging Agents for the Management of Schizophrenia. AJMC. https://www.ajmc.com/journals/supplement/2020/unmet-medical-needs-new-treatments-and-health-economics-associated-with-schizophrenia-supplement/an-update-on-current-treatment-strategies-and-emerging-agents-for-the-management-of-schizophrenia. Retrieved: 30/07/2020.

  17. Servick, Kelly. Experimental schizophrenia drug could reduce long-neglected symptoms. Science. https://www.sciencemag.org/news/2020/04/experimental-schizophrenia-drug-could-reduce-long-neglected-symptoms. Retrieved: 30/07/2020.

Olakunsi Peters

Olakunsi Peters


My name is Olakunsi Peters. I am currently in the 11th grade. I love learning about different neurological disorders (such as Multiple Sclerosis and Parkinson's disease). After participating in the Brain Bee at my local hospital, I have gained more interest in various neuroscience topics. I hope to connect with other students who have similar interests as me on this platform.