Since the discovery of chlorpromazine to treat schizophrenia, studies have been focusing on dopamine dysfunction, particularly in the mesolimbic dopamine pathway, which increases dopamine synthesis and release capacity, and can lead to psychosis [ 1, 2 ]. Many studies have indicated that schizophrenia is a disorder of the dopamine signal system.
Full Answer
Does dopamine play a role in schizophrenia?
But several discoveries are challenging the theory that elevated dopamine synthesis capacity is responsible for symptoms in all patients with schizophrenia. First, antipsychotics do not impact negative symptoms, which suggests the involvement of other neurotransmitters beside dopamine (Remington et al., 2016).
What is the locus of the dopamine deficit in schizophrenia?
The locus of the largest dopaminergic abnormality in schizophrenia is presynaptic-affecting dopamine synthesis capacity, baseline synaptic dopamine levels and dopamine release. Current drug treatments - which primarily act at D2/3 receptors - fail to target these abnormalities.
Why is the pathophysiology of schizophrenia important for treatment development?
Understanding the pathophysiology of the disorder is thus likely to be critical to the rational development of new treatments for schizophrenia. Objective: To investigate the nature of the dopaminergic dysfunction in schizophrenia using meta-analysis of in vivo studies.
Is D2/3 receptor density associated with schizophrenia?
It received support from studies of post-mortem brain tissue that found increased striatal D2/3 receptor density and dopamine levels in schizophrenia and from studies of CSF dopamine and its metabolites (see 4-6and reviews7, 8).
How does dopamine treat schizophrenia?
As the National Alliance on Mental Illness reports, dopamine may play a key role in schizophrenia. The hypothesis that dopamine was involved in schizophrenia first came about in the early 1950s , when a drug called phenothiazine, which was known to block dopamine receptors, led to a reduction in psychotic symptoms.
What are the effects of dopamine mean on schizophrenia patients?
How Does Dopamine Cause Schizophrenia Symptoms? There are two types of schizophrenia symptoms that an excess of dopamine may cause: positive and negative. Positive symptoms include delusions and hallucinations. Negative symptoms include a decrease in social activity, emotional range, and cognitive function.
Why would blocking dopamine in a patient with schizophrenia help their condition?
Because of their ability to block dopamine receptors without causing the opening of ion channels and setting off an action potential, neuroleptics can be administered to schizophrenic patients to help reduce excess levels of dopamine, and to thus help alleviate the positive symptoms of the disorder.
What is dopaminergic dysfunction?
Dopamine dysregulation syndrome (DDS) is a dysfunction of the reward system observed in some individuals taking dopaminergic medications for an extended length of time. It typically occurs in people with Parkinson's disease (PD) who have taken dopamine agonist medications for an extended period of time.
What causes schizophrenia dopamine?
Research suggests schizophrenia may be caused by a change in the level of 2 neurotransmitters: dopamine and serotonin. Some studies indicate an imbalance between the 2 may be the basis of the problem. Others have found a change in the body's sensitivity to the neurotransmitters is part of the cause of schizophrenia.
Is dopamine increased or decreased in schizophrenia?
Dopamine is an inhibitory neurotransmitter involved in the pathology of schizophrenia. The revised dopamine hypothesis states that dopamine abnormalities in the mesolimbic and prefrontal brain regions exist in schizophrenia.
What happens when dopamine is blocked?
Dopamine receptor blocking agents are known to induce parkinsonism, dystonia, tics, tremor, oculogyric movements, orolingual and other dyskinesias, and akathisia from infancy through the teenage years. Symptoms may occur at any time after treatment onset.
Why do antipsychotics block dopamine receptors?
Dopamine is a neurotransmitter, which means that it passes messages around your brain. Most antipsychotic drugs are known to block some of the dopamine receptors in the brain. This reduces the flow of these messages, which can help to reduce your psychotic symptoms. Affecting other brain chemicals.
Why is the dopamine hypothesis insufficient in the explanation of schizophrenia?
Research on dopamine concentrations in postmortem brain tissue, on homovanillic acid concentrations, and on dopamine receptors has been negative or inconclusive. Therefore, the idea that the symptoms of psychosis or schizophrenia are caused by the overactivity of dopamine is not supported by current evidence.
How is dopamine deficiency treated?
Getting enough sleep, exercising, listening to music, meditating, and spending time in the sun can all boost dopamine levels. Overall, a balanced diet and lifestyle can go a long way in increasing your body's natural production of dopamine and helping your brain function at its best.
What causes dopamine deficiency?
A dopamine deficiency may be related to certain medical conditions, including depression and Parkinson's disease. A dopamine deficiency can be due to a drop in the amount of dopamine made by the body or a problem with the receptors in the brain.
What are the symptoms of dopamine deficiency?
What are the symptoms of dopamine deficiency?You lack motivation, “the drive.”You're tired.You can't concentrate.You're moody or anxious.You don't feel pleasure from previously enjoyable experiences.You're depressed; you feel hopeless.You have a low sex drive.You have trouble sleeping or have disturbed sleep.
What is the locus of the largest dopaminergic abnormality in schizophrenia?
The locus of the largest dopaminergic abnormality in schizophrenia is presynaptic-affecting dopamine synthesis capacity, baseline synaptic dopamine levels and dopamine release. Current drug treatments - which primarily act at D2/3 receptors - fail to target these abnormalities. Future drug development should focus on the control of presynaptic dopamine synthesis and release capacity.
What is the main outcome measure of schizophrenia?
The main outcome measure was the difference in the dopaminergic imaging parameter between healthy controls and patients with schizophrenia.
What is the purpose of PET and SPECT imaging in schizophrenia?
PET and SPECT imaging has been used to investigate dopaminergic parameters in schizophrenia, beginning with studies of D2/3 receptors14, 15and later covering presynaptic function, including dopamine synthesis capacity and dopamine release, and transporters16-19(see supplementary materialsfor further background on these approaches). To our knowledge there has not been a previous meta-analysis of the presynaptic or dopamine transporter findings in schizophrenia, and, since the previous D2/3 meta-analysis in drug free/naive patients20, there have been a large number of new studies which approximately doubles the sample size.
Is schizophrenia a global disease?
Schizophrenia remains one of the leading causes of global disease burden in adults despite over fifty years of drug development .1Understanding its neurobiology is critical for future rational drug discovery.2, 3The dopamine hypothesis of schizophrenia was first proposed over thirty years ago on the basis of indirect evidence.
Is there a significant difference between schizophrenia and control?
There was no evidence of a significant difference between patients with schizophrenia and controls (figure 3, d=−0.34, 95%-CI: −0.75 to +0.07, z=−1.64, p=0.10).
Does schizophrenia have a large effect size?
There was a highly significant elevation (p<0.0001) in presynaptic dopaminergic function in schizophrenia with a large effect size (Cohen’s d=0.79). There was no evidence of alterations in dopamine transporter availability. There was a small elevation in D2/3 receptor availability (Cohen’s d=0.26), but this was not evident in drug-naïve patients and was influenced by the imaging approach used.
What are the functions of dopamine neurons?
Midbrain dopamine neurons have crucial functions in motor and emotional control and their degenera tion leads to several neurological dysfunctions such as Parkinson's disease, addiction, depression, schizophrenia, and others. Despite advances in the understanding of specific altered proteins and coding genes, little is known about cumulative changes in the transcriptional landscape of noncoding genes in midbrain dopamine neurons. Noncoding RNAs-specifically microRNAs and long noncoding RNAs-are emerging as crucial post-transcriptional regulators of gene expression in the brain. The identification of noncoding RNA networks underlying all stages of dopamine neuron development and plasticity is an essential step to deeply understand their physiological role and also their involvement in the etiology of dopaminergic diseases. Here, we provide an update about noncoding RNAs involved in dopaminergic development and metabolism, and the related evidence of these biomolecules for applications in potential treatments for dopaminergic neurodegeneration.
How do antipsychotics help with schizophrenia?
Introduction: Antipsychotic drugs are central to the treatment of schizophrenia, but their limitations necessitate improved treatment strategies . Multiple lines of research have implicated glutamatergic dysfunction in the hippocampus as an early source of pathophysiology in schizophrenia. Novel compounds have been designed to treat glutamatergic dysfunction, but they have produced inconsistent results in clinical trials. Areas covered: This review discusses how the hippocampus is thought to drive psychotic symptoms through its influence on the dopamine system. It offers the reader an evaluation of proposed treatment strategies including direct modulation of GABA or glutamate neurotransmission or reducing the deleterious impact of stress on circuit development. Finally, we offer a perspective on aspects of future research that will advance our knowledge and may create new therapeutic opportunities. PubMed was searched for relevant literature between 2010 and 2020 and related studies. Expert opinion: Targeting aberrant excitatory-inhibitory neurotransmission in the hippocampus and its related circuits has the potential to alleviate symptoms and reduce the risk of transition to psychosis if implemented as an early intervention. Longitudinal multimodal brain imaging combined with mechanistic theories generated from animal models can be used to better understand the progression of hippocampal-dopamine circuit dysfunction and heterogeneity in treatment response.
What is glutathione in schizophrenia?
Glutathione (GSH), a dominant antioxidant, is known to be involved in glutamatergic neurotransmission. To date, no study has examined GSH levels in patients with treatment-resistant schizophrenia. The aim of this study was to examine GSH levels in the dorsal anterior cingulate cortex (dACC) of patients with treatment-resistant schizophrenia. Patients with schizophrenia were categorized into three groups with respect to their antipsychotic response: (1) clozapine (CLZ) non-responders, (2) CLZ responders, and (3) first-line responders (FLR). GSH and glutamine+glutamate (Glx) levels were measured using 3T proton magnetic resonance spectroscopy. Firstly, dACC GSH levels were compared among the patient groups and healthy controls (HCs). Further, relationships between GSH and Glx levels were compared between the groups and GSH levels were explored stratifying the patient groups based on the glutamate-cysteine ligase catalytic (GCLC) subunit polymorphism. There was no difference in GSH levels between the groups. FLR showed a more negative relationship between GSH and Glx levels in the dACC compared to HCs. There were no effects of GCLC genotype on the GSH levels. However, CLZ responders had a higher ratio of high-risk GCLC genotype compared to CLZ non-responders. This study demonstrated different relationships between GSH and Glx in the dACC between groups. In addition, the results suggest a potential link between CLZ response and GCLC genotype. However, it still remains unclear how these differences are related to the underlying pathophysiology of schizophrenia subtypes or the mechanisms of action of CLZ.
What is the first episode of psychosis?
First episode psychosis (FEP), and subsequent diagnosis of schizophrenia or schizoaffective disorder, predominantly occurs during late adolescence, is accompanied by a significant decline in function and represents a traumatic experience for patients and families alike. Prior to first episode psychosis, most patients experience a prodromal period of 1-2 years, during which symptoms first appear and then progress. During that time period, subjects are referred to as being at Clinical High Risk (CHR), as a prodromal period can only be designated in hindsight in those who convert. The clinical high-risk period represents a critical window during which interventions may be targeted to slow or prevent conversion to psychosis. However, only one third of subjects at clinical high risk will convert to psychosis and receive a formal diagnosis of a primary psychotic disorder. Therefore, in order for targeted interventions to be developed and applied, predicting who among this population will convert is of critical importance. To date, a variety of neuroimaging modalities have identified numerous differences between CHR subjects and healthy controls. However, complicating attempts at predicting conversion are increasingly recognized co-morbidities, such as major depressive disorder, in a significant number of CHR subjects. The result of this is that phenotypes discovered between CHR subjects and healthy controls are likely non-specific to psychosis and generalized for major mental illness. In this paper, we selectively review evidence for neuroimaging phenotypes in CHR subjects who later converted to psychosis. We then evaluate the recent landscape of machine learning as it relates to neuroimaging phenotypes in predicting conversion to psychosis.
What are the factors that contribute to schizophrenia?
Preclinical studies have shown that neurodevelopmental, genetic, and environmental factors contribute to glutamatergic dysfunction and schizophrenia-related phenotypes. Clinical research has suggested that altered brain glutamate levels may be present before the onset of psychosis and relate to outcome in those at clinical high risk. After psychosis onset, glutamate dysfunction may also relate to the degree of antipsychotic response and clinical outcome. These findings support ongoing efforts to develop pharmacological interventions that target the glutamate system and could suggest that glutamatergic compounds may be more effective in specific patient subgroups or illness stages. In this review, we consider the updated glutamate hypothesis of schizophrenia, from a neurodevelopmental perspective, by reviewing recent preclinical and clinical evidence, and discuss the potential implications for novel therapeutics.
How to treat schizophrenia long term?
The long-term treatment of patients with schizophrenia often involves the management of relapses for most patients and the development of treatment resistance in some patients. To stabilize the clinical course and allow as many patients as possible to recover, clinicians need to recognize dopamine supersensitivity, which can be provoked by administration of high dosages of antipsychotics, and deal with it properly. However, no treatment guidelines have addressed this issue. The present review summarized the characteristics of long-acting injectable antipsychotics, dopamine partial agonists, and clozapine in relation to dopamine supersensitivity from the viewpoints of receptor profiles and pharmacokinetics. The potential merits and limitations of these medicines are discussed, as well as the risks of treating patients with established dopamine supersensitivity with these classes of drugs. Finally, the review discussed the biological influence of antipsychotic treatment on the human brain based on findings regarding the relationship between the hippocampus and antipsychotics.
What are the mitochondrial functions of schizophrenia?
Among the many brain abnormalities in schizophrenia are those related to mitochondrial functions such as oxidative stress, energy metabolism and synaptic efficacy. The aim of this paper is to provide a brief review of mitochondrial structure and function and then to present abnormalities in mitochondria in postmortem brain in schizophrenia with a focus on anatomy. Deficits in expression of various mitochondrial genes have been found in multiple schizophrenia cohorts. Decreased activity of complexes I and IV are prominent as well as abnormal levels of individual subunits that comprise the complexes of the electron transport chain. Ultrastructural studies have shown layer, input and cell specific decreases in mitochondria. In cortex, there are fewer mitochondria in axon terminals, neuronal somata of pyramidal neurons and oligodendrocytes in both grey and white matter. In the caudate and putamen mitochondrial number is linked with symptoms and symptom severity. While there is a decrease in the number of mitochondria in astrocytes, mitochondria are smaller in oligodendrocytes. In the nucleus accumbens and substantia nigra, mitochondria are similar in density, size and structural integrity in schizophrenia compared to controls. Mitochondrial production of ATP and calcium buffering are essential in maintaining synaptic strength and abnormalities in these processes could lead to decreased metabolism and defective synaptic activity. Abnormalities in mitochondria in oligodendrocytes might contribute to myelin pathology and underlie dysconnectivity in the brain. In schizophrenia, mitochondria are affected differentially depending on the brain region, cell type in which they reside, subcellular location, treatment status, treatment response and predominant symptoms.
Abstract
Context: Current drug treatments for schizophrenia are inadequate for many patients, and despite 5 decades of drug discovery, all of the treatments rely on the same mechanism: dopamine D2 receptor blockade.
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What are the roles of dopaminergic and serotonin in schizophrenia?
Background: Dopaminergic and serotonergic systems play crucial roles in the pathophysiology of schizophrenia and modulate response to antipsychotic treatment. However, previous studies of dopaminergic and serotonergic genes expression are sparse, and their results have been inconsistent. In this longitudinal study, we aim to investigate the expressions of Catechol-O-methyltransferase (COMT), serotonin 2A receptor (5-HTR2A), and serotonin transporter gene (SLC6A4) mRNA in first-episode antipsychotic-naïve schizophrenia and to test if these mRNA expressions are associated with cognitive deficits and treatment outcomes or not. Method: We measured COMT, 5-HTR2A, and SLC6A4 mRNA expressions in 45 drug-naive first-episode schizophrenia patients and 38 health controls at baseline, and repeated mRNA measurements in all patients at the 8-week follow up. Furthermore, we also assessed antipsychotic response and cognitive improvement after 8 weeks of risperidone monotherapy. Results: Patients were divided into responders (N = 20) and non-responders groups (N = 25) according to the Remission criteria of the Schizophrenia Working Group. Both patient groups have significantly higher COMT mRNA expression and lower SLC6A4 mRNA expression when compared with healthy controls. Interestingly, responder patients have significantly higher levels of COMT and 5-HTR2A mRNA expressions than non-responder patients at baseline. However, antipsychotic treatment has no significant effect on the expressions of COMT, 5-HTR2A, and SLC6A4 mRNA over 8-week follow up. Conclusion: Our findings suggest that dysregulated COMT and SLC6A4 mRNA expressions may implicate in the pathophysiology of schizophrenia, and that COMT and 5-HTR2A mRNA may be potential biomarkers to predict antipsychotic response.
Why is schizophrenia important?
This report provides an overview of the clinical characteristics, epidemiology, genetics, neuroscience, and psychopharmacology of schizophrenia to provide a basis to understand the disorder and its treatment. This educational review is integrated with a clinical case to highlight how recent research findings can inform clinical understanding. Observations The first theme considered is the role of early-life environmental and genetic risk factors in altering neurodevelopmental trajectories to predispose an individual to the disorder and leading to the development of prodromal symptoms. The second theme is the role of cortical excitatory-inhibitory imbalance in the development of the cognitive and negative symptoms of the disorder. The third theme considers the role of psychosocial stressors, psychological factors, and subcortical dopamine dysfunction in the onset of the positive symptoms of the disorder. The final theme considers the mechanisms underlying treatment for schizophrenia and common adverse effects of treatment. Conclusions and Relevance Schizophrenia has a complex presentation with a multifactorial cause. Nevertheless, advances in neuroscience have identified roles for key circuits, particularly involving frontal, temporal, and mesostriatal brain regions, in the development of positive, negative, and cognitive symptoms. Current pharmacological treatments operate using the same mechanism, blockade of dopamine D2 receptor, which contribute to their adverse effects. However, the circuit mechanisms discussed herein identify novel potential treatment targets that may be of particular benefit in symptom domains not well served by existing medications.
What is the contribution of delusion to philosophy?
This chapter addresses the contribution that the delusion literature has made to the philosophy of belief. Three conclusions will be drawn: (1) a belief does not need to be epistemically rational to be used in the interpretation of behaviour; (2) a belief does not need to be epistemically rational to have significant psychological or epistemic benefits; (3) beliefs exhibiting the features of epistemic irrationality exemplified by delusions are not infrequent, and they are not an exception in a largely rational belief system. What we learn from the delusion literature is that there are complex relationships between rationality and interpretation, rationality and success, and rationality and knowledge.
Why is obesity important for schizophrenia?
Obesity, a key risk factor for the development of cardiometabolic alterations , is more prevalent in individuals with schizophrenia. Although obesity is linked to the altered reward processing of food cues, no studies have investigated this link in schizophrenia without the confounds of antipsychotics and illness chronicity. Objective To investigate neural responsivity to food cues in first-episode psychosis without the confounds of antipsychotic medication or illness chronicity. Design, Setting, and Participants A case-control study was conducted from January 31, 2015, to September 30, 2018, in London, United Kingdom, of 29 patients with first-episode psychosis who were not taking antipsychotic medication and 28 matched controls. Main Outcomes and Measures Participants completed a food cue paradigm while undergoing a functional magnetic resonance imaging scan. Neural activation was indexed using the blood oxygen level–dependent hemodynamic response. The Dietary Instrument for Nutrition Education was used to measure diet, and the International Physical Activity Questionnaire was used to measure exercise. Results There were no significant differences in age, sex, or body mass index between the 29 patients (25 men and 4 women; mean [SD] age, 26.1 [4.8] years) and 28 controls (22 men and 6 women; mean [SD] age, 26.4 [5.5] years). Relative to controls, patients consumed more saturated fat (t46 = –3.046; P = .004) and undertook less high-intensity (U = 304.0; P = .01) and low-intensity (U = 299.5; P = .005) weekly exercise. There were no group differences in neural responses to food vs nonfood cues in whole-brain or region-of-interest analyses of the nucleus accumbens, insula, or hypothalamus. Body mass index was inversely correlated with the mean blood oxygen level–dependent signal in the nucleus accumbens in response to food vs nonfood cues in controls (R = –0.499; P = .01) but not patients (R = 0.082; P = .70). Conclusions and Relevance Relative to controls, patients with first-episode psychosis who were not taking antipsychotic medication consumed more saturated fat and showed an altered association between body mass index and neural response to food cues in the absence of differences in neural responses to food cues. These findings highlight how maladaptive eating patterns and alterations in the association between body mass index and neural responses to food cues are established early in the course of schizophrenia.
How does dopamine affect learning?
A large body of work has linked dopaminergic signaling to learning and reward processing. It stresses the role of dopamine in reward prediction error signaling, a key neural signal that allows us to learn from past experiences, and that facilitates optimal choice behavior. Latterly, it has become clear that dopamine does not merely code prediction error size but also signals the difference between the expected value of rewards, and the value of rewards actually received, which is obtained through the integration of reward attributes such as the type, amount, probability and delay. More recent work has posited a role of dopamine in learning beyond rewards. These theories suggest that dopamine codes absolute or unsigned prediction errors, playing a key role in how the brain models associative regularities within its environment, while incorporating critical information about the reliability of those regularities. Work is emerging supporting this perspective and, it has inspired theoretical models of how certain forms of mental pathology may emerge in relation to dopamine function. Such pathology is frequently related to disturbed inferences leading to altered internal models of the environment. Thus, it is critical to understand the role of dopamine in error-related learning and inference.
What is GDNF in neurology?
In addition, GDNF is a potent neurotrophic factor for midbrain dopamine neurons in culture 12 and promotes dopamine synthesis and dopaminergic neuron fibre outgrowth if applied ectopically into the brain 13 . Increased dopamine signalling is associated with different neuropsychiatric diseases, including schizophrenia, where increased levels of presynaptic dopamine in the striatum are commonly observed [14] [15] [16] . Therefore, we were particularly interested in the outcome of brain-specific elevation of endogenous GDNF levels on brain dopamine system function, and the potential relevance of altered dopamine signalling in the context of schizophrenia. ...
Does SPD have dopamine?
RationalePrevious research has suggested that schizotypal personality disorder (SPD), a condition that shares clinical and cognitive features with schizophrenia, may be associated with elevated striatal dopamine functioning; however, there are no published studies of dopamine release within subregions of the striatum in SPD.Objectives To characterize dopamine release capacity in striatal subregions and its relation to clinical and cognitive features in SPD.Methods We used positron emission tomography with [11C]raclopride and an amphetamine challenge to measure dopamine D2-receptor availability (binding potential, BPND), and its percent change post-amphetamine (∆BPND) to index amphetamine-induced dopamine release, in subregions of the striatum in 16 SPD and 16 healthy control participants. SPD participants were evaluated with measures of schizotypal symptom severity and working memory.ResultsThere were no significant group differences in BPND or ∆BPND in any striatal subregion or whole striatum. Among SPD participants, cognitive-perceptual symptoms were associated at trend level with ∆BPND in the ventral striatum, and disorganized symptoms were significantly negatively related to ∆BPND in several striatal subregions.Conclusions In contrast to previous findings, SPD was not associated with elevated striatal dopamine release. However, in SPD, there was a moderate positive association between ventral striatal dopamine release and severity of cognitive-perceptual symptoms, and negative associations between striatal dopamine release and severity of disorganized symptoms. Future larger scale investigations that allow for the separate examination of subgroups of participants based on clinical presentation will be valuable in further elucidating striatal DA functioning in SPD.
What is the main cause of schizophrenia?
Dysfunctions in the dopamine pathways have long been thought to be the main factor of symptoms in schizophrenia (Meltzer & Stahl, 1976). The so-called dopamine hypothesis posits that an increase in dopaminergic neurotransmission in the mesolimbic pathway causes atypical levels of dopamine in the striatum and the nucleus accumbens, causing the positive symptoms of schizophrenia, while dysfunctions in the mesocortical pathway may be responsible for the negative symptoms (Da Silva et al., 2008; Brisch et al., 2014).
Do glutamatergic and dopaminergic systems interact?
But even this theory may be incomplete, for the dopaminergic, glutamatergic and GABAergic systems interact and regulate each other in complex ways. Some researchers are instead considering these interconnected systems as a whole, hypothesizing a final common pathway where multiple neuronal, receptors and neurotransmitter pathways converge to trigger the dopamine hyperactivity found in many schizophrenic subjects (Howes & Kapur, 2009; Schwartz et al., 2012).
Does chlorpromazine work for schizophrenia?
To corroborate this hypothesis, it was additionally uncovered that antipsychotic drugs such as chlorpromazine work by binding to dopamine D2 receptors , acting as effective antagonists reducing neurotransmitter binding of dopamine in the mesolimbic pathway, thus reducing symptoms of schizophrenia (Ban, 2007).
Is schizophrenia a neurodegenerative disorder?
Schizophrenia is a mental disorder causing a range of psychological symptoms such as delusions, hallucinations, disordered thinking, and abnormal motor behaviour, and which is considered by many as a neurodevelopmental disorder (Murray & Lewis, 1987; Weinberger, 2003). It affects 0.5–1% of the worldwide population, with a common onset in late adolescence to early adulthood (Perälä et al., 2007). The symptoms can be divided between positive symptoms, which are superimposed on the normal mental functions of the individual; negative symptoms, which are characterised by deficits in normal functions, such as alogia and avolition (Andreasen & Olsen, 1982); as well as cognitive deficits, such as poor executive functioning (Lesh et al., 2011). It is an heterogeneous disorder which makes it difficult to define (Tsuang et al., 1990).
Do schizophrenia patients have dopamine?
More importantly, not all patients with schizophrenia feature an increase in dopamine synthesis capacity. In fact, in contrast to dopaminergic antipsychotic treatment responders, treatment-resistant patients do not show any increase in dopamine in the striatum; instead, they show elevated levels of glutamate in the frontal cortex (Mouchlianitis, et al., 2015). This would suggest that treatment-resistant schizophrenic patients do not respond to antipsychotic drugs because their symptoms are not primarily caused by elevated dopamine synthesis capacity, and that there is at least two subtypes of schizophrenia (Howes & Kapur, 2014).
