The Dopamine Hypothesis of Schizophrenia

From the appearance, symptoms and evidence in the form of a rambling letter that makes little sense, the appropriate diagnosis for Jonas Sterling’s condition is schizophrenia with the dopamine hypothesis (DH) as its focus. The patient appears to be stressed by things in his environment such as the television, which gives him ideas and words on which to place his fears such as Obamacare and the NCIC. Because he has a paternal uncle who has been diagnosed with schizophrenia, it seems he has a genetic susceptibility to the disease also which is a factor in the DH.. Schizophrenia, using the DH, can be caused by environmental stress interaction with the genetic susceptibility and can lead to dopamine dysregulation. In one type of dopamine pathway, mesolimbic, an increase in dopamine levels can lead to psychosis and other positive symptoms of schizophrenia. In another pathway, mesocortical, dopamine levels are decreased, which can also lead to negative and cognitive symptoms of schizophrenia through abnormal focus on the environmental stimuli. Mr. Sterling’s schizophrenia appears to be of the latter type, so Quetiapine (Seroquel) is the medication that should be prescribed for him. Quetiapine is known to be effective with mesocortical dopamine pathway dysfunction and hopefully, it will help Mr. Sterling.

Neurobiological Theory Relevant to Patient Diagnosis

The pathophysiology of schizophrenia involves the four dopamine pathways in the brain. These can also be affected by illicit or pharmaceutical drugs. That is why it is important to consider these pathways when determining the best treatment for schizophrenia. Jagdale and Dhikale (2017) of the World Journal of Pharmaceutical Research explain that activity in each pathway has a unique set of physical, cognitive and psychological effects. This results in different methods of treatment being best for disturbances of each separate pathway (Jagdale & Dhikale, 2017, p. 258). The four pathways include the Nigrostriatal dopamine pathway, the Mesolimbic dopamine pathway, the Mesocortial dopamine pathway and the Tuberoinfundibular dopamine pathway.

The Nigrostriatal dopamine pathway is part of the extrapyramidal nervous system and controls movements. When this pathway degenerates, Parkinson’s disease is the result. The degeneration is in the form of a blockade which can be induced with drugs and result in movement disorders, extrapyramidal symptoms (EPS), and tardive dyskinesia (Jagdale & Dhikale, 2017, p. 258). This is not the dopamine pathway that should be considered in Mr. Sterling’s disorder.

The tuberoinfundibular dopamine pathway is also not one that is relevant to Mr. Sterling’s disorder. The tuberoinfundibular pathway inhibits prolactin release. In women who have just delivered a baby, the activity in this pathway decreases allowing for lactation. Blocking dopamine to this pathway can cause several problems including hyperprolactinemia with side effects such as galactorrhea, amenorrhea, and sexual dysfunction (Jagdale & Dhikale, 2017, p. 259). The relevant dopamine pathways to consider for Mr. Sterling’s case are the mesolimbic and mesocortical pathways.

The mesolimbic dopamine pathway is believed to be the pathway that causes psychosis and the positive symptoms of schizophrenia such as delusions and hallucinations. This pathway is also involved in emotions and pleasure. Addiction is often associated with malfunctions or overstimulation of this dopamine pathway. Drugs that are stimulants such as cocaine can increase dopamine activity in the mesolimbic pathway. The symptoms of psychosis and schizophrenia can be alleviated or reduced by blocking the excessive activity in this pathway (Jagdale & Dhikale, 2017, p. 258). However, it may not be the only pathway involved in schizophrenia.

The mesocortical dopamine pathway is believed to control cognitive function, and it may be responsible for both negative and cognitive symptoms of schizophrenia. This pathway is associated with reasoning, working memory, and decision making. Because the symptoms of schizophrenia linked to this pathway are thought to be caused by a dopamine deficiency, blocking dopamine, as therapy aimed at the mesolimbic pathway would do, would increase the symptoms rather than decrease them. To successfully treat the positive symptoms of the mesolimbic pathway and the negative and cognitive symptoms of the mesocortical pathway, it would require decreasing dopamine in the mesolimbic and increasing it in the mesocortical pathways (Jagdale & Dhikale, 2017, pp. 258-259). Taking amphetamines, for example, may increase the dopamine activity in this portion of the brain, but lead to addiction in the mesolimbic pathway.

The DH says that schizophrenia can be caused by environmental stress or can be drug induced. This complicates things as Hengartner and Moncrieff (2018) of the journal, Psychiatry, explain. These researchers disagree that striatal dopamine levels cause psychosis or even cause a person to be prone to psychosis (Hengartner & Moncrieff, 2018, p. 2). They believe that the relationship between stress, substance abuse and dopmaine levels may be separate and independent process just as they believe substance abuse, stress and psychosis are independent processes also. “Unless we account for the various neurobiological effects of substance abuse and environmental stress, we cannot know whether striatal dopamine concentration is directly and causally involved in psychosis or merely a spurious correlate” (Hengartner & Moncrieff, 2018, p. 2). However, Mr. Sterling denies substance abuse and seems to reflect the stress of news and information he gathers from his environment, namely the television pervasive home in which he lives. This is solid evidence that environmental stressors and his genetic propensity are the initiators of his current episode. He is displaying symptoms of schizophrenia that may well be treated by either blocking or increasing the levels of dopamine in his brain.

Pharmacological Intervention

The choice of treatment recommended for Mr. Sterling is Quetiapine (Seroquel). Adults less than 65 years old with psychosis can be started at 50 mg twice daily for a total of 100 mg per day on the first day. On day 4, the dosage should be increased by 100 mg per day to equal 400 mg per day. Then increases in the dosage in increments of 200 mg per day should occur until the maximum approved daily dose of 800 mg daily is reached on day 6. According to the National Alliance on Mental Illness (NAMI) (2016), quetiapine has been approved by the FDA for acute treatment of manic and depressive episodes of bipolar disorder, long-term treatment of bipolar disorder, and adjunctive treatment with an antidepressant of major depressive disorders (NAMI, 2016). However, it is commonly known as a treatment for schizophrenia too.

Quetiapine is known as a second generation antipsychotic (SGA) or an atypical antipsychotic. It works to rebalance the dopamine and serotonin levels in the brain so that thinking, mood and behavior are improved. Quetiapine is especially effective for certain symptoms of schizophrenia including hallucinations, delusions, disorganized thinking, lack of desire to be around other people, trouble with speaking clearly and lack of motivation. Common side effects of quetiapine include low blood pressure, dizziness or an increased heart rate especially upon standing, fatigue, sedation, dry mouth, agitation, increased appetite and constipation. SGAs also carry with them the risk for weight gain, high blood sugar and high cholesterol also known as metabolic syndrome. All antipsychotic drugs have been associated with a risk of sudden cardiac death due to arrhythmia (NAMI, 2016). Despite the risks, quetiapine appears to be the best choice for Mr. Sterling.

The reason for choosing Quetiapine over other medications to treat schizophrenia is that it works on the mesocortical dopamine pathway. Hashimoto, et al. (2015) of the Annals of General Psychiatry explain, “Quetiapine demonstrates a relatively high affinity for the 5HT2A receptor and relatively low affinity for the D2 receptor” (Hashimoto, et al., 2015, p. 2). These receptors are associated with serotonin and dopamine respectively. When they are malfunctioning together, the negative and cognitive symptoms associated with schizophrenia are often the result. “The high 5HT2A/D2 ratio leads to an overall increase in dopaminergic activity in the prefrontal cortex, and enhanced prefrontal activity is shown to be associated with the alleviation of negative symptoms and the improvement of cognitive function. It is also important because the cognitive and negative symptoms are often refractory to antipsychotic treatment and become the cause of inadequate response” (Hashimoto, et al., 2015, p. 2). If the dopamine pathways in Mr. Sterling’s brain can be straightened out using quetiapine, then the symptoms that are troubling him may ease.

Patient Teaching Points

Mr. Sterling should be counseled about the side effects of quetiapine and the necessity of not missing a dose or of stopping taking it because he is feeling better. Serious likelihood of relapse can occur if either of these things happen. He should be told that he may gain weight and feel sleepy. In his present state, however, he may interpret the side effects in light of his paranoia. A follow up appointment should be scheduled for 2 to 4 weeks in the future where Mr. Sterling can be assesses using the Brief Psychotic Rating Scale, Positive and Negative Syndrome Scale and the Minnesota Multiphasic Personality Inventory, which will assess his condition and are the basis of his treatment goals.

Treatment Goals

The first treatment goal for Mr. Sterling is to score below 3 on the Brief Psychotic Rating Scale (BPRS). The BPRS assesses 18 symptoms of schizophrenia including hostility, suspiciousness, and hallucinations. The clinician will interview Mr. Sterling at his next visit after having taken quetiapine for at least 2 weeks. During the interview, the clinician should fill out he BPRS questionnaire that rates Mr. Sterling’s symptoms on a scale from 1 to 7, with 7 being the most severe. Mr. Sterling’s parents should also fill out the BPRS questionnaire. The BPRS can be administered consecutively or concurrently with the Positive and Negative Syndrome Scale (PANSS).

The goal for Mr. Sterling is to score below a 3 on the PANSS also. The PANSS has several features that are quite complex according to Opler, Yavorsky, and Daniel (2017) of Innovations in Clinical Neuroscience, but is a thorough approach to rating the symptoms of schizophrenia. The PANSS evaluates an array of positive, negative, cognitive, neuromotor and depressive symptoms. It also involves using data from patient reports, caregiver reports, and clinical observations (Opler, Yavorsky, & Daniel, 2017, p. 77). To assess a patient correctly with the PANSS, it takes time and someone well trained and experienced in using it. The items assessed include “observations made during the interview, the patient verbal report, and/or corroborative information obtained from caregivers about symptoms and behaviors during the reference period prior to the assessment; and 3) Each item includes a set of carefully written anchors for each level of severity, from 1 (absent) to 7 (extreme)” (Opler, Yavorsky, & Daniel, 2017, p. 77). These two tests are conducted by the clinician, but the third treatment goal for Mr. Sterling would be for him to fill out the Minnesota Multiphasic Personality Inventory (MMPI) himself.

The treatment goal for the MMPI would be for Mr. Sterling to score somewhere near 65. MMPI can only be administered by a trained clinician, but the patient fills out the questionnaire usually on a computer. The clinician then interprets it. It is usually preceded by a clinical interview, which may include the BPRS and the PANSS. The clinician reviews the patient’s responses to the questions on the MMPI and interprets it in the context of the patient’s history and current issues. Framingham (2018) of Psych Central explains that the newest version of the MMPI, the MMPI-2, has “10 clinical scales which assess 10 major categories of abnormal human behavior, and four validity scales, which assess the person’s general test-taking attitude and whether they answered the items on the test in a truthful and accurate manner” (Framingham, 2018). The largest section of the MMPI-2 is the schizophrenia section. Scores on the MMPI-2 range from 30 to 120. The “normal” range is from 50 to 65. Anything above 65 or below 50 is open to interpretation by the clinician (Framingham, 2018). People with symptoms of schizophrenia would normally score above 65 on the MMPI-2.


If the quetiapine works to block the mesocortical dopamine pathway that appears to be the main cause of Mr. Sterling’s symptoms, then the symptoms should improve within the 2 to 4 weeks recommended for follow up. If Mr. Sterling’s symptoms improve, he may be able to help with the diagnosis and treatment plan at follow up. Mr. Sterling’s case is also a good test of the DH.


Framingham, J. (2018, October 13). Minnesota Multiphasic Personality Inventory (MMPI). Retrieved from Psych Central:

Hashimoto, N., Toyomaki, A., Honda, M., Miyano, S., Nitta, N., Sawayama, H., & Kusumi, I. (2015). Long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic herapeutic response—a prospective open-label study. Annals of General Psychiatry,, 14(1), 1-8. Retrieved from https://annals-general-psychia...

Hengartner, M. P., & Moncrieff, J. (2018). Inconclusive Evidence in Support of the Dopamine Hypothesis of Psychosis: Why Neurobiological Research Must Consider Medication Use, Adjust for Important Confounders, Choose Stringent Comparators, and Use Larger Samples. Psychiatry, 1-4. Retrieved from

Jagdale, A. S., & Dhikale, G. K. (2017). Dopamine in Schizophrenia its Treatment with Newer Atypical Antipsychotics: An Overview. World Journal of Pharmaceutical Research, 6(16), 250-272. doi:10.20959/wjpr201716-10203

NAMI. (2016, June). Quetiapine (Seroquel). Retrieved from National Alliance on Mental Illness:

Opler, M., Yavorsky, C., & Daniel, D. G. (2017). Positive and Negative Syndrome Scale (PANSS) Training: Challenges, Solutions, and Future Directions. Innovations in Clinical Neuroscience, 14(11/12), 77-81. Retrieved from