Materiały źródłowe

• #1 Psychosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK546579/

  Psychosis is a loose description of an amalgamation of psychological symptoms resulting in a loss of contact with reality. […] Psychosis is a common feature of many psychiatric, neuropsychiatric, neurologic, neurodevelopmental, and medical conditions. […] Psychosis may result from a primary psychiatric illness, substance use, or another neurologic or medical condition. Brain abnormalities have correlated with first-episode psychotic disorders, including reduced prefrontal, superior, and medial temporal grey matter. […] There is significant evidence for genetic risk factors in the pathogenesis of psychotic disorders. […] Most strongly linked to the pathophysiology of psychotic disorders is the neurotransmitter dopamine. The positive symptoms of psychotic disorders are believed to be caused by excess dopamine in the mesolimbic tract.

• #2 What is Psychosis? | Vanderbilt Early Psychosis Program

  https://www.vumc.org/early-psychosis-program/what-psychosis

  Psychosis includes experiences such as hallucinations, unusual beliefs and disorganized thoughts and behavior. […] The mechanism of psychosis remains obscure. […] Recently, several risk genes have been identified, but they do not determine the illness. […] The complex and often changing abnormalities of behavior have been associated with abnormal brain function, but they are not a consistent finding and do not define psychosis.

• #3 Psychosis of Epilepsy: An Update on Clinical Classification and Mechanism

  https://www.mdpi.com/2218-273X/15/1/56

  Psychosis is a prevalent comorbidity among patients with epilepsy, significantly diminishing their quality of life. […] The pathogenic mechanism of POE has not been conclusively established, but a number of studies have investigated its neuroimaging, neurobiology, and genetic mechanisms. […] The alterations in brain structure and function, neurotransmitters, neuroinflammatory mediators, and genetic factors discussed in this review may offer insights into the onset and progression of psychotic symptoms in epilepsy patients and are anticipated to inform the identification of novel therapeutic targets in the future. […] This review will center around the clinical classification and possible pathophysiological mechanisms of POE, with a focus on the mechanisms, and will elaborate on the possible relevant mechanisms from the perspectives of neuroimaging, neurobiology, and genetics.

• #4 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11200831/

  The most prevalent theory pertaining to the neurobiology of psychosis is that of a chemical imbalance in the brain, marked by dysregulation of the mesolimbic pathway as a result of dopaminergic hyperactivity. […] Our current understanding of psychosis does not account for many of the emerging mechanisms or describe multiple interactions. […] Exploring the underlying neurobiological mechanisms that contribute to psychosis is of utmost interest and importance. Particular attention will be paid in the current review paper to several areas of interest, including neurotransmitter dysregulation, neuroinflammation, the hypothalamic-pituitary-adrenal (HPA) axis, the gut-brain axis (GBA), oxidative stress, and mitochondrial dysfunction. […] Although many hypotheses have tried to explain the neurobiological mechanisms underlying the onset of psychosis, the dopamine hypothesis remains a widely cited explanation.

• #5 Psychosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK546579/

  Psychosis is a loose description of an amalgamation of psychological symptoms resulting in a loss of contact with reality. […] Psychosis is a common feature of many psychiatric, neuropsychiatric, neurologic, neurodevelopmental, and medical conditions. […] Psychosis may result from a primary psychiatric illness, substance use, or another neurologic or medical condition. Brain abnormalities have correlated with first-episode psychotic disorders, including reduced prefrontal, superior, and medial temporal grey matter. […] There is significant evidence for genetic risk factors in the pathogenesis of psychotic disorders. […] Most strongly linked to the pathophysiology of psychotic disorders is the neurotransmitter dopamine. The positive symptoms of psychotic disorders are believed to be caused by excess dopamine in the mesolimbic tract.

• #6 Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience | Translational Psychiatry

  https://www.nature.com/articles/s41398-017-0071-9

  Clinical studies have confirmed that dopamine abnormalities are also present prior to the onset of psychosis in schizophrenia and thus are not a consequence of psychotic episodes or antipsychotic exposure. […] We propose a network model whereby dysfunction in a central circuit, including the associative striatum, prefrontal cortex and thalamus, is critical for the expression of psychotic symptoms in schizophrenia. […] Overall, these findings in UHR subjects are congruent with those observed in schizophrenia and provide evidence indicating that presynaptic dopaminergic abnormalities are present prior to the onset of psychosis. […] Central to the networks involved in psychosis and schizophrenia, the thalamus acts as a relay for most information going to the cortex. […] This raises important questions as to how antipsychotic drugs exert their effects. In most individuals with schizophrenia, antipsychotic treatment is effective in reducing positive symptoms; therefore, excessive D2 signalling in the associative striatum appears to be critical.

• #7 Psychosis – Wikipedia

  https://en.wikipedia.org/wiki/Psychosis

  The aberrant salience model suggests that delusions are a result of people assigning excessive importance to irrelevant stimuli. […] Psychosis has been traditionally linked to the overactivity of the neurotransmitter dopamine. […] However, there is substantial evidence that dopaminergic overactivity does not fully explain psychosis, and that neurodegenerative pathophysiology plays a significant role. […] NMDA receptor dysfunction has been proposed as a mechanism in psychosis. […] The connection between dopamine and psychosis is generally believed to be complex.

• #8 Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience | Translational Psychiatry

  https://www.nature.com/articles/s41398-017-0071-9

  The stagnation in drug development for schizophrenia highlights the need for better translation between basic and clinical research. Understanding the neurobiology of schizophrenia presents substantial challenges but a key feature continues to be the involvement of subcortical dopaminergic dysfunction in those with psychotic symptoms. […] The onset of psychotic symptoms, which is strongly associated with alterations in dopamine function, is a key feature underpinning a clinical diagnosis. […] Currently there is a disparity between the tests for positive symptoms in animal models and recent clinical evidence for dopaminergic abnormalities in schizophrenia. Therefore, it is critical that this contemporary clinical knowledge actively influences the agenda in applied basic neuroscience. […] The clinical efficacy of antipsychotic drugs is heavily correlated with their ability to block subcortical dopamine D2 receptors, suggesting dopamine signalling is important. In spite of this, no consistent relationship between D2 receptors and the pathophysiology of schizophrenia has emerged. In contrast, the clinical evidence points towards presynaptic dopamine dysfunction as a mediator of psychosis in schizophrenia.

• #9 Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience | Translational Psychiatry

  https://www.nature.com/articles/s41398-017-0071-9

  The stagnation in drug development for schizophrenia highlights the need for better translation between basic and clinical research. Understanding the neurobiology of schizophrenia presents substantial challenges but a key feature continues to be the involvement of subcortical dopaminergic dysfunction in those with psychotic symptoms. […] The onset of psychotic symptoms, which is strongly associated with alterations in dopamine function, is a key feature underpinning a clinical diagnosis. […] Currently there is a disparity between the tests for positive symptoms in animal models and recent clinical evidence for dopaminergic abnormalities in schizophrenia. Therefore, it is critical that this contemporary clinical knowledge actively influences the agenda in applied basic neuroscience. […] The clinical efficacy of antipsychotic drugs is heavily correlated with their ability to block subcortical dopamine D2 receptors, suggesting dopamine signalling is important. In spite of this, no consistent relationship between D2 receptors and the pathophysiology of schizophrenia has emerged. In contrast, the clinical evidence points towards presynaptic dopamine dysfunction as a mediator of psychosis in schizophrenia.

• #10 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11200831/

  Psychosis, defined as a set of symptoms that results in a distorted sense of reality, is observed in several psychiatric disorders in addition to schizophrenia. […] The dopamine hypothesis has been a major influence in the study of the neurochemistry of psychosis and in development of antipsychotic drugs. However, it became clear early on that other factors must be involved in the dysfunction involved in psychosis. In the current review, it is reported how several of these factors, namely dysregulation of neurotransmitters [dopamine, serotonin, glutamate, and -aminobutyric acid (GABA)], neuroinflammation, glia (microglia, astrocytes, and oligodendrocytes), the hypothalamic-pituitary-adrenal axis, the gut microbiome, oxidative stress, and mitochondrial dysfunction contribute to psychosis and interact with one another.

• #11 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://www.mdpi.com/2076-3921/13/6/709

  The glutamate hypothesis proposes that symptoms of schizophrenia and cognitive impairments are the result of the hypofunction of N-methyl-D-aspartate receptors (NMDARs) on γ-aminobutyric acid (GABA) interneurons in the cerebral cortex, resulting in overactivation of downstream glutamate signaling to the VTA and, possibly, consequent dopamine release in the mesolimbic system. […] The serotonin hypothesis implicates excessive activation of 5-HT2A receptors, particularly those on glutamate neurons in the anterior cingulate cortex and dorsolateral frontal lobe in psychosis. […] Psychosis may also involve interactions with other physiological mechanisms such as neuroinflammation, oxidative stress, and mitochondrial dysfunction, which are linked to the inhibition of neurogenesis and the onset of cell death, so exploring these facets in the context of psychosis has also been an active area of research.

• #12 Video: Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders

  https://www.jove.com/science-education/15193/psychosis-pathophysiology-schizophrenia-other-psychotic

  The 'Glutamate Hypothesis’ is another critical component of understanding schizophrenia. This hypothesis links dysfunction in glutamate neurotransmission, particularly NMDA receptor hypofunction, with the manifestations of schizophrenia. […] Understanding the mechanisms of these hypotheses underscores the importance of ongoing research into the neurochemical underpinnings of this disorder, as this research holds the promise of refining therapeutic strategies and improving patient outcomes.

• #13 Psychosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK546579/

  Glutamate, an excitatory neurotransmitter, is also implicated. Multiple studies have found a decreased function of the N-methyl-D-aspartate (NMDA) glutamate receptor. […] Studies have also pointed to gamma-amino-butyric acid (GABA), an important inhibitory neurotransmitter. […] Lastly, implications point to an imbalance in acetylcholine. […] Antipsychotic medications are the gold-standard treatment for psychotic episodes and disorders, and the choice, dosing, and administration of the medication will largely depend on the scenario. […] Antipsychotics have been shown to be more efficacious in treating positive symptoms. […] There is potential for positive outcomes in patients with psychotic disorders. […] Early intervention is essential for good long-term outcomes.

• #14 Stress and GABA in the pathogenesis of psychosis

  https://wellcome.org/research-funding/funding-portfolio/funded-grants/stress-and-gaba-pathogenesis-psychosis

  Psychosis is the fourth leading cause of disability in the world. […] Current treatments do not work for about 50 per cent of patients, and have little impact on prevention. […] Psychosis is associated with producing too much of the brain chemical dopamine, but little is known about what causes this. […] Research in experimental animals shows that problems in regulating the response to stress lead to deficits in another brain chemical called GABA. […] This produces an excess of dopamine in the brain. […] When adolescent rats are given a drug that improves GABA function, the response to stress is reduced. […] This prevents an excess of dopamine. […] These studies will help us to use the stress response to identify people who are most at risk of psychosis, and new ways of preventing psychosis by reducing the response to stress.

• #15 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://www.mdpi.com/2076-3921/13/6/709

  The glutamate hypothesis proposes that symptoms of schizophrenia and cognitive impairments are the result of the hypofunction of N-methyl-D-aspartate receptors (NMDARs) on γ-aminobutyric acid (GABA) interneurons in the cerebral cortex, resulting in overactivation of downstream glutamate signaling to the VTA and, possibly, consequent dopamine release in the mesolimbic system. […] The serotonin hypothesis implicates excessive activation of 5-HT2A receptors, particularly those on glutamate neurons in the anterior cingulate cortex and dorsolateral frontal lobe in psychosis. […] Psychosis may also involve interactions with other physiological mechanisms such as neuroinflammation, oxidative stress, and mitochondrial dysfunction, which are linked to the inhibition of neurogenesis and the onset of cell death, so exploring these facets in the context of psychosis has also been an active area of research.

• #16 Drug Abuse and Psychosis: New Insights into Drug-induced Psychosis

  https://www.en-journal.org/journal/view.html?uid=330

  Scopolamine is a non-selective antagonist of muscarinic acetylcholine receptors and binds to a group of muscarinic receptors (M1-M5) which directly modulates the release of acetylcholine or indirectly of dopamine. These receptors are classified into M1-like muscarinic receptors (M1, M3, M5) and M2-like receptors, (M2, M4) which activate and inhibit second messenger transduction via G-proteins, respectively. […] The molecular function of PCP/ketamine that affects psychotic behaviors has also been examined by antipsychotic drugs. Hyper-locomotion induced by acute ketamine administration was reversed by haloperidol, clozapine, and risperidone. […] LSD is a drug of weak addictive properties and at the same time is the most potent hallucinogen. In addition, LSD modulates the serotonergic, dopaminergic neurotransmission systems which are major targets of typical and atypical antipsychotics. Although this may indicate that the LIP model is most suitable for studying psychosis as it does not induce drug effects such as dependence of amphetamine and antidepressant effect of ketamine/scopolamine, LSD enhances cognitive function. This means that LIP is, unfortunately, not adequate for schizophrenia research like the other four DIP models. Meanwhile, it also indicates that LIP is isolated set of symptoms that can be differentiated from schizophrenia.

• #17 Psychosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK546579/

  Glutamate, an excitatory neurotransmitter, is also implicated. Multiple studies have found a decreased function of the N-methyl-D-aspartate (NMDA) glutamate receptor. […] Studies have also pointed to gamma-amino-butyric acid (GABA), an important inhibitory neurotransmitter. […] Lastly, implications point to an imbalance in acetylcholine. […] Antipsychotic medications are the gold-standard treatment for psychotic episodes and disorders, and the choice, dosing, and administration of the medication will largely depend on the scenario. […] Antipsychotics have been shown to be more efficacious in treating positive symptoms. […] There is potential for positive outcomes in patients with psychotic disorders. […] Early intervention is essential for good long-term outcomes.

• #18 The role of neurotransmitter receptors in antipsychotic medication efficacy for Alzheimer’s-related psychosis | The Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Full Text

  https://ejnpn.springeropen.com/articles/10.1186/s41983-024-00848-2

  Among Alzheimers disease individual experiencing psychosis, there is a rise in dopamine 3 receptors (D3R) density in the nucleus accumbens. […] Psychotic AD has been linked to changes in the expression of the striatal D3R, whereas a therapeutic window for treatment response is determined by the presence of antipsychotics in the striatal D2R modifications. […] Psychosis in AD patients has also been linked to changes in the serotonergic system. […] The pathogenesis of AD-related psychosis is likely to include serotonin receptors, particularly 5-HT2A. […] The acetylcholine neurotransmitter system cholinergic muscarinic receptors have been connected to psychosis neurobiological. […] Psychosis in AD is thought to be related to abnormalities in cholinergic neurotransmission. […] Significant progress has been made in recent years in determining the genetic correlates of psychosis in AD.

• #19 Psychosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK546579/

  Psychosis is a loose description of an amalgamation of psychological symptoms resulting in a loss of contact with reality. […] Psychosis is a common feature of many psychiatric, neuropsychiatric, neurologic, neurodevelopmental, and medical conditions. […] Psychosis may result from a primary psychiatric illness, substance use, or another neurologic or medical condition. Brain abnormalities have correlated with first-episode psychotic disorders, including reduced prefrontal, superior, and medial temporal grey matter. […] There is significant evidence for genetic risk factors in the pathogenesis of psychotic disorders. […] Most strongly linked to the pathophysiology of psychotic disorders is the neurotransmitter dopamine. The positive symptoms of psychotic disorders are believed to be caused by excess dopamine in the mesolimbic tract.

• #20 Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience | Translational Psychiatry

  https://www.nature.com/articles/s41398-017-0071-9

  Clinical studies have confirmed that dopamine abnormalities are also present prior to the onset of psychosis in schizophrenia and thus are not a consequence of psychotic episodes or antipsychotic exposure. […] We propose a network model whereby dysfunction in a central circuit, including the associative striatum, prefrontal cortex and thalamus, is critical for the expression of psychotic symptoms in schizophrenia. […] Overall, these findings in UHR subjects are congruent with those observed in schizophrenia and provide evidence indicating that presynaptic dopaminergic abnormalities are present prior to the onset of psychosis. […] Central to the networks involved in psychosis and schizophrenia, the thalamus acts as a relay for most information going to the cortex. […] This raises important questions as to how antipsychotic drugs exert their effects. In most individuals with schizophrenia, antipsychotic treatment is effective in reducing positive symptoms; therefore, excessive D2 signalling in the associative striatum appears to be critical.

• #21 Two key brain systems are central to psychosis, Stanford Medicine-led study finds | News Center

  https://med.stanford.edu/news/all-news/2024/04/brain-systems-psychosis.html

  When the brain has trouble filtering incoming information and predicting what’s likely to happen, psychosis can result, Stanford Medicine-led research shows. […] Inside the brains of people with psychosis, two key systems are malfunctioning: a „filter” that directs attention toward important external events and internal thoughts, and a „predictor” composed of pathways that anticipate rewards. […] Dysfunction of these systems makes it difficult to know what’s real, manifesting as hallucinations and delusions. […] The findings, observed in individuals with a rare genetic disease called 22q11.2 deletion syndrome who experience psychosis as well as in those with psychosis of unknown origin, advance scientists’ understanding of the underlying brain mechanisms and theoretical frameworks related to psychosis.

• #22 Two key brain systems are central to psychosis, Stanford Medicine-led study finds | News Center

  https://med.stanford.edu/news/all-news/2024/04/brain-systems-psychosis.html

  When the brain has trouble filtering incoming information and predicting what’s likely to happen, psychosis can result, Stanford Medicine-led research shows. […] Inside the brains of people with psychosis, two key systems are malfunctioning: a „filter” that directs attention toward important external events and internal thoughts, and a „predictor” composed of pathways that anticipate rewards. […] Dysfunction of these systems makes it difficult to know what’s real, manifesting as hallucinations and delusions. […] The findings, observed in individuals with a rare genetic disease called 22q11.2 deletion syndrome who experience psychosis as well as in those with psychosis of unknown origin, advance scientists’ understanding of the underlying brain mechanisms and theoretical frameworks related to psychosis.

• #23 Two key brain systems are central to psychosis, Stanford Medicine-led study finds | News Center

  https://med.stanford.edu/news/all-news/2024/04/brain-systems-psychosis.html

  The brain patterns we identified support our theoretical models of how cognitive control systems malfunction in psychosis. […] Thoughts that are not linked to reality can capture the brain’s cognitive control networks. […] This process derails the normal functioning of cognitive control, allowing intrusive thoughts to dominate, culminating in symptoms we recognize as psychosis. […] Comparing brain scans from 22q11.2 deletion syndrome patients who had and did not have psychosis, the researchers showed that the brain areas contributing most to psychosis are the anterior insula (a key part of the salience network or „filter”) and the ventral striatum (the „reward predictor”); this was true for different cohorts of patients. […] A second mathematical model, trained to distinguish all subjects with 22q11.2 deletion syndrome and psychosis from those who have the genetic syndrome but without psychosis, selected brain scans from people with idiopathic psychosis with 77.5% accuracy, again supporting the idea that the brain’s filtering and predicting centers are key to psychosis.

• #24 Cerebellum models of psychosis implicate association nuclei in the pathogenesis of psychosis and mechanisms of cognitive impairment | bioRxiv

  https://www.biorxiv.org/content/10.1101/2020.11.06.372300v1

  Cerebellum models of psychosis implicate association nuclei in the pathogenesis of psychosis and mechanisms of cognitive impairment. […] The present findings suggested that the voxel-wise WM integrity analysis might was the more sensitive way to investigate the structural abnormalities in schizophrenia patients. […] Middle cerebellar peduncles and inferior cerebellar peduncles may be a crucial neurobiological substrate of cognition and thus might be regarded as a biomarker for treatment.

• #25

  https://link.springer.com/article/10.1007/s00415-014-7242-x

  Psychotic symptoms have previously been reported following right hemisphere brain injury. […] We provide clinical evidence from patients with structural brain lesions implicating damage to the right inferior frontal lobe in the generation of persistent psychosis following stroke. […] The main cortical region involved was the inferior frontal gyrus (IFG). […] Our findings are consistent with observations of patients with degenerative disease, where psychotic symptoms are associated with right-sided atrophy. […] Impaired functional connectivity, especially of right inferior frontal lobe, appears to be a key factor in the pathogenesis of psychosis. […] Our study provides the most precise lesion data to date corroborating existing structural and functional studies that right IFG damage is a critical component in the development of clinical psychosis in at-risk individuals.

• #26 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11200831/

  An inflammatory response characterized by elevated pro-inflammatory cytokine concentrations is characteristic of many psychiatric disorders, and the finding that neuroinflammation tends to precede psychosis symptomology implicates it as part of the psychotic pathogenesis. […] Elevated concentrations of these cytokines are implicated in chronic immune activation which disturbs the physiological pathways involved in neurotransmission. […] Oxidative stress is often described as the result of an imbalance between the production of reactive species, or free radicals, and the inability of the body to detoxify these reactive products. […] Research to date strongly suggests that interactions among mitochondrial deficits, neurotransmitter dysfunction, oxidative stress, and inflammation produce the symptoms of schizophrenia.

• #27 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11200831/

  An inflammatory response characterized by elevated pro-inflammatory cytokine concentrations is characteristic of many psychiatric disorders, and the finding that neuroinflammation tends to precede psychosis symptomology implicates it as part of the psychotic pathogenesis. […] Elevated concentrations of these cytokines are implicated in chronic immune activation which disturbs the physiological pathways involved in neurotransmission. […] Oxidative stress is often described as the result of an imbalance between the production of reactive species, or free radicals, and the inability of the body to detoxify these reactive products. […] Research to date strongly suggests that interactions among mitochondrial deficits, neurotransmitter dysfunction, oxidative stress, and inflammation produce the symptoms of schizophrenia.

• #28 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11200831/

  An inflammatory response characterized by elevated pro-inflammatory cytokine concentrations is characteristic of many psychiatric disorders, and the finding that neuroinflammation tends to precede psychosis symptomology implicates it as part of the psychotic pathogenesis. […] Elevated concentrations of these cytokines are implicated in chronic immune activation which disturbs the physiological pathways involved in neurotransmission. […] Oxidative stress is often described as the result of an imbalance between the production of reactive species, or free radicals, and the inability of the body to detoxify these reactive products. […] Research to date strongly suggests that interactions among mitochondrial deficits, neurotransmitter dysfunction, oxidative stress, and inflammation produce the symptoms of schizophrenia.

• #29 Protocol for the Psychosis Immune Mechanism Stratified Medicine (PIMS) trial: a randomised double-blind placebo-controlled trial of single-dose tocilizumab in patients with psychosis | BMJ Open

  https://bmjopen.bmj.com/content/13/3/e067944

  Evidence suggests a potentially causal role of interleukin 6 (IL-6), a pleiotropic cytokine that generally promotes inflammation, in the pathogenesis of psychosis. […] The primary objective of this study is to test whether IL-6 contributes to the pathogenesis of first episode psychosis and to examine potential mechanisms by which IL-6 affects psychotic symptoms. […] The neuroimmune hypothesis of schizophrenia proposes that mild peripheral immune activation gives rise to an inflammatory response in the brain and neurobiological changes associated with psychotic illness. […] These Mendelian randomisation studies eliminate the possibility that raised IL-6 concentrations are a consequence of environmental exposures associated with schizophrenia, such as obesity and smoking and instead suggest that IL-6 has a causal role in psychosis.

• #30 Protocol for the Psychosis Immune Mechanism Stratified Medicine (PIMS) trial: a randomised double-blind placebo-controlled trial of single-dose tocilizumab in patients with psychosis | BMJ Open

  https://bmjopen.bmj.com/content/13/3/e067944

  Evidence suggests a potentially causal role of interleukin 6 (IL-6), a pleiotropic cytokine that generally promotes inflammation, in the pathogenesis of psychosis. […] The primary objective of this study is to test whether IL-6 contributes to the pathogenesis of first episode psychosis and to examine potential mechanisms by which IL-6 affects psychotic symptoms. […] The neuroimmune hypothesis of schizophrenia proposes that mild peripheral immune activation gives rise to an inflammatory response in the brain and neurobiological changes associated with psychotic illness. […] These Mendelian randomisation studies eliminate the possibility that raised IL-6 concentrations are a consequence of environmental exposures associated with schizophrenia, such as obesity and smoking and instead suggest that IL-6 has a causal role in psychosis.

• #31 Protocol for the Psychosis Immune Mechanism Stratified Medicine (PIMS) trial: a randomised double-blind placebo-controlled trial of single-dose tocilizumab in patients with psychosis | BMJ Open

  https://bmjopen.bmj.com/content/13/3/e067944

  Evidence suggests a potentially causal role of interleukin 6 (IL-6), a pleiotropic cytokine that generally promotes inflammation, in the pathogenesis of psychosis. […] The primary objective of this study is to test whether IL-6 contributes to the pathogenesis of first episode psychosis and to examine potential mechanisms by which IL-6 affects psychotic symptoms. […] The neuroimmune hypothesis of schizophrenia proposes that mild peripheral immune activation gives rise to an inflammatory response in the brain and neurobiological changes associated with psychotic illness. […] These Mendelian randomisation studies eliminate the possibility that raised IL-6 concentrations are a consequence of environmental exposures associated with schizophrenia, such as obesity and smoking and instead suggest that IL-6 has a causal role in psychosis.

• #32 Role of Immunity in Pathogenesis of Psychosis | IntechOpen

  https://www.intechopen.com/chapters/76999

  The involvement of immunity in the pathogenesis of schizophrenia and related psychoses was suspected a century ago but was shadowed by the dopaminergic hypothesis after the discovery of antipsychotics. […] The immune-inflammatory theory is now one of the most promising axes of research in terms of pathogenesis of several mental health conditions. Immunity and inflammation play a role at least in a subgroup of patients with psychosis. […] All immune system components can have effects on the brain cells and thus they can produce psychiatric symptoms. […] All these findings allow to conclude that immunity plays a role in pathophysiology of psychosis at least in a subgroup of patients. […] There is evidence for inflammation dysfunction in psychosis. […] An increase in the production of proinflammatory cytokines such as Interleukin 6 (IL-6) was detected in patients with schizophrenia and patients at high risk for psychosis and predicted development of adult schizophrenia when detected in children.

• #33 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11200831/

  An inflammatory response characterized by elevated pro-inflammatory cytokine concentrations is characteristic of many psychiatric disorders, and the finding that neuroinflammation tends to precede psychosis symptomology implicates it as part of the psychotic pathogenesis. […] Elevated concentrations of these cytokines are implicated in chronic immune activation which disturbs the physiological pathways involved in neurotransmission. […] Oxidative stress is often described as the result of an imbalance between the production of reactive species, or free radicals, and the inability of the body to detoxify these reactive products. […] Research to date strongly suggests that interactions among mitochondrial deficits, neurotransmitter dysfunction, oxidative stress, and inflammation produce the symptoms of schizophrenia.

• #34 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://www.mdpi.com/2076-3921/13/6/709

  An inflammatory response characterized by elevated pro-inflammatory cytokine concentrations is characteristic of many psychiatric disorders, and the finding that neuroinflammation tends to precede psychosis symptomology implicates it as part of the psychotic pathogenesis. […] Elevated concentrations of these cytokines are implicated in chronic immune activation which disturbs the physiological pathways involved in neurotransmission. […] Oxidative stress is often described as the result of an imbalance between the production of reactive species, or free radicals, and the inability of the body to detoxify these reactive products. […] Reactive oxygen species (ROS) can block the dopamine transporters (DATs) which regulate dopamine degradation. […] Mitochondria, which play crucial roles in energy metabolism, oxidative stress, and modulation of synaptic activity, produce almost all of the cellular ATP in the body, via oxidative phosphorylation carried out by complexes I through IV of the electron transport chain. […] This paper has reviewed several important facets of interest in psychosis, namely neurotransmitter dysregulation, neuroinflammation, oxidative stress, and mitochondrial dysfunction, which are implicated in psychosis pathogenesis.

• #35 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11200831/

  An inflammatory response characterized by elevated pro-inflammatory cytokine concentrations is characteristic of many psychiatric disorders, and the finding that neuroinflammation tends to precede psychosis symptomology implicates it as part of the psychotic pathogenesis. […] Elevated concentrations of these cytokines are implicated in chronic immune activation which disturbs the physiological pathways involved in neurotransmission. […] Oxidative stress is often described as the result of an imbalance between the production of reactive species, or free radicals, and the inability of the body to detoxify these reactive products. […] Research to date strongly suggests that interactions among mitochondrial deficits, neurotransmitter dysfunction, oxidative stress, and inflammation produce the symptoms of schizophrenia.

• #36 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://www.mdpi.com/2076-3921/13/6/709

  An inflammatory response characterized by elevated pro-inflammatory cytokine concentrations is characteristic of many psychiatric disorders, and the finding that neuroinflammation tends to precede psychosis symptomology implicates it as part of the psychotic pathogenesis. […] Elevated concentrations of these cytokines are implicated in chronic immune activation which disturbs the physiological pathways involved in neurotransmission. […] Oxidative stress is often described as the result of an imbalance between the production of reactive species, or free radicals, and the inability of the body to detoxify these reactive products. […] Reactive oxygen species (ROS) can block the dopamine transporters (DATs) which regulate dopamine degradation. […] Mitochondria, which play crucial roles in energy metabolism, oxidative stress, and modulation of synaptic activity, produce almost all of the cellular ATP in the body, via oxidative phosphorylation carried out by complexes I through IV of the electron transport chain. […] This paper has reviewed several important facets of interest in psychosis, namely neurotransmitter dysregulation, neuroinflammation, oxidative stress, and mitochondrial dysfunction, which are implicated in psychosis pathogenesis.

• #37 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://www.mdpi.com/2076-3921/13/6/709

  An inflammatory response characterized by elevated pro-inflammatory cytokine concentrations is characteristic of many psychiatric disorders, and the finding that neuroinflammation tends to precede psychosis symptomology implicates it as part of the psychotic pathogenesis. […] Elevated concentrations of these cytokines are implicated in chronic immune activation which disturbs the physiological pathways involved in neurotransmission. […] Oxidative stress is often described as the result of an imbalance between the production of reactive species, or free radicals, and the inability of the body to detoxify these reactive products. […] Reactive oxygen species (ROS) can block the dopamine transporters (DATs) which regulate dopamine degradation. […] Mitochondria, which play crucial roles in energy metabolism, oxidative stress, and modulation of synaptic activity, produce almost all of the cellular ATP in the body, via oxidative phosphorylation carried out by complexes I through IV of the electron transport chain. […] This paper has reviewed several important facets of interest in psychosis, namely neurotransmitter dysregulation, neuroinflammation, oxidative stress, and mitochondrial dysfunction, which are implicated in psychosis pathogenesis.

• #38 Psychosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK546579/

  Psychosis is a loose description of an amalgamation of psychological symptoms resulting in a loss of contact with reality. […] Psychosis is a common feature of many psychiatric, neuropsychiatric, neurologic, neurodevelopmental, and medical conditions. […] Psychosis may result from a primary psychiatric illness, substance use, or another neurologic or medical condition. Brain abnormalities have correlated with first-episode psychotic disorders, including reduced prefrontal, superior, and medial temporal grey matter. […] There is significant evidence for genetic risk factors in the pathogenesis of psychotic disorders. […] Most strongly linked to the pathophysiology of psychotic disorders is the neurotransmitter dopamine. The positive symptoms of psychotic disorders are believed to be caused by excess dopamine in the mesolimbic tract.

• #39 What is Psychosis? | Vanderbilt Early Psychosis Program

  https://www.vumc.org/early-psychosis-program/what-psychosis

  Psychosis includes experiences such as hallucinations, unusual beliefs and disorganized thoughts and behavior. […] The mechanism of psychosis remains obscure. […] Recently, several risk genes have been identified, but they do not determine the illness. […] The complex and often changing abnormalities of behavior have been associated with abnormal brain function, but they are not a consistent finding and do not define psychosis.

• #40 Advances in the understanding of the pathophysiology of schizophrenia and bipolar disorder through induced pluripotent stem cell models | JPN

  https://www.jpn.ca/content/49/2/E109

  The pathophysiology of schizophrenia and bipolar disorder involves a complex interaction between genetic and environmental factors that begins in the early stages of neurodevelopment. […] Recent advancements in the field of induced pluripotent stem cells (iPSCs) offer a promising tool for understanding the neurobiological alterations involved in these disorders and, potentially, for developing new treatment options. […] The neurodevelopmental hypothesis postulates that disturbances in neurogenesis, occurring both during embryonic development and the postnatal period, can functionally alter neural circuitry and lead to the onset of schizophrenia and bipolar disorder. […] Molecular biology, neuroimaging, and postmortem studies have supported the hypothesis of disturbances in neurogenesis, showing that several genes associated with schizophrenia and bipolar disorder are expressed prenatally and are involved in cell differentiation, leading to alterations in cortical structures during early neurodevelopmental stages or at the onset of the disease.

• #41 Advances in the understanding of the pathophysiology of schizophrenia and bipolar disorder through induced pluripotent stem cell models | JPN

  https://www.jpn.ca/content/49/2/E109

  The pathophysiology of schizophrenia and bipolar disorder involves a complex interaction between genetic and environmental factors that begins in the early stages of neurodevelopment. […] Recent advancements in the field of induced pluripotent stem cells (iPSCs) offer a promising tool for understanding the neurobiological alterations involved in these disorders and, potentially, for developing new treatment options. […] The neurodevelopmental hypothesis postulates that disturbances in neurogenesis, occurring both during embryonic development and the postnatal period, can functionally alter neural circuitry and lead to the onset of schizophrenia and bipolar disorder. […] Molecular biology, neuroimaging, and postmortem studies have supported the hypothesis of disturbances in neurogenesis, showing that several genes associated with schizophrenia and bipolar disorder are expressed prenatally and are involved in cell differentiation, leading to alterations in cortical structures during early neurodevelopmental stages or at the onset of the disease.

• #42 The role of neurotransmitter receptors in antipsychotic medication efficacy for Alzheimer’s-related psychosis | The Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Full Text

  https://ejnpn.springeropen.com/articles/10.1186/s41983-024-00848-2

  The first single nucleotide polymorphism [SNP]-based genome-wide association study (GWAS) to assess the heritability of psychosis in AD was published in 2021 and involved over 12,000 individuals with AD. […] The study focuses on the complex interactions that exist between neurotransmitter receptors and the effectiveness of antipsychotic medications in treating psychosis associated with AD. […] The intricate nature of psychosis in AD is highlighted by the neuropathological alterations in neurotransmitter systems, specifically in glutamate, serotonin, and dopamine, which calls for focused therapeutic interventions.

• #43

  https://link.springer.com/article/10.1007/s11920-012-0260-4

  The stress vulnerability model has proven to be a politically important model for two reasons. […] Mechanisms within the process of repressive coping are consistent with evidence and mechanisms supporting the stress vulnerability models and existing cognitive-behavioral theories regarding development of paranoid delusions. […] Historically, within the psychoanalytic school there has been debate regarding the role of repressive coping mechanisms in schizophrenia development.

• #44 [Stress and psychosis: is sensitisation the underlying mechanism?]

  https://lirias.kuleuven.be/396469?limo=0

  Epidemiological research has shown that stressful environmental factors can play an aetiological role in the development of psychosis. However, the mechanism underlying the link between stress and psychosis is still not fully understood. […] In this article it is argued that the interaction between stressful environmental factors and epigenetic factors can bring about psychological and biological changes. Both types of change can be referred to as 'sensitisation’. The underlying mechanism of sensitisation can be interpreted on the one hand as cognitive misinterpretations (psychological sensitisation) and on the other hand as altered dopaminergic neurotransmission (biological sensitisation). Both of these deviations can facilitate the onset and persistence of psychotic symptoms. […] With the help of epidemiological research at psychometric level sensitisation can be quantified as (i) stress-induced persistence (indicating continuous sensitisation) of the normally transient expression of subclinical psychotic experiences during adolescence and early adulthood and as (ii) the increased risk of transition from gradually more persistent subclinical psychotic experiences to a clinical psychotic disorder.

• #45 [Stress and psychosis: is sensitisation the underlying mechanism?]

  https://lirias.kuleuven.be/396469?limo=0

  Epidemiological research has shown that stressful environmental factors can play an aetiological role in the development of psychosis. However, the mechanism underlying the link between stress and psychosis is still not fully understood. […] In this article it is argued that the interaction between stressful environmental factors and epigenetic factors can bring about psychological and biological changes. Both types of change can be referred to as 'sensitisation’. The underlying mechanism of sensitisation can be interpreted on the one hand as cognitive misinterpretations (psychological sensitisation) and on the other hand as altered dopaminergic neurotransmission (biological sensitisation). Both of these deviations can facilitate the onset and persistence of psychotic symptoms. […] With the help of epidemiological research at psychometric level sensitisation can be quantified as (i) stress-induced persistence (indicating continuous sensitisation) of the normally transient expression of subclinical psychotic experiences during adolescence and early adulthood and as (ii) the increased risk of transition from gradually more persistent subclinical psychotic experiences to a clinical psychotic disorder.

• #46 Stress and GABA in the pathogenesis of psychosis

  https://wellcome.org/grant-funding/people-and-projects/grants-awarded/stress-gaba-pathogenesis-psychosis

  Psychosis is the fourth leading cause of disability in the world. […] These symptoms result from interactions between genes and environmental risk factors like stress. […] Psychosis is associated with producing too much of the brain chemical dopamine, but little is known about what causes this. […] Research in experimental animals shows that problems in regulating the response to stress lead to deficits in another brain chemical called GABA. […] This produces an excess of dopamine in the brain. […] When adolescent rats are given a drug that improves GABA function, the response to stress is reduced. […] This prevents an excess of dopamine. […] These studies will help us to use the stress response to identify people who are most at risk of psychosis, and new ways of preventing psychosis by reducing the response to stress.

• #47 Stress and GABA in the pathogenesis of psychosis

  https://wellcome.org/grant-funding/people-and-projects/grants-awarded/stress-gaba-pathogenesis-psychosis

  Psychosis is the fourth leading cause of disability in the world. […] These symptoms result from interactions between genes and environmental risk factors like stress. […] Psychosis is associated with producing too much of the brain chemical dopamine, but little is known about what causes this. […] Research in experimental animals shows that problems in regulating the response to stress lead to deficits in another brain chemical called GABA. […] This produces an excess of dopamine in the brain. […] When adolescent rats are given a drug that improves GABA function, the response to stress is reduced. […] This prevents an excess of dopamine. […] These studies will help us to use the stress response to identify people who are most at risk of psychosis, and new ways of preventing psychosis by reducing the response to stress.

• #48 Psychosis in adults: Epidemiology, clinical manifestations, and diagnostic evaluation – UpToDate

  https://www.uptodate.com/contents/psychosis-in-adults-epidemiology-clinical-manifestations-and-diagnostic-evaluation

  Psychosis is a condition of the mind broadly defined as a loss of contact with reality. Psychotic symptoms can increase patients’ risk for harming themselves or others or being unable to meet their basic needs. […] Psychosis may be seen in many psychiatric disorders. It is commonly seen in schizophrenia and other conditions in the schizophrenia spectrum, and mood disorders including bipolar disorder and major depression with psychotic features. However, psychosis may also be a manifestation of substance use or underlying medical disease. […] This topic will characterize different aspects of psychosis including epidemiology, pathogenesis, clinical manifestations, comorbid conditions, and initial diagnostic evaluation of psychosis in adults.

• #49 Amphetamine-Induced Psychosis – BrightQuest Treatment Centers

  https://www.brightquest.com/drug-induced-psychosis/amphetamine-induced-psychosis/

  Amphetamine-induced psychosis refers to the presence of psychotic symptoms in the context of amphetamine usage, without a more obvious cause. A high percentage of amphetamine users experience psychotic symptoms, which manifest as paranoia, auditory, visual, and other types of hallucinations, delusions, ideas of reference, and agitation. […] To understand how and why the symptoms of psychosis develop during or after amphetamine use, it is important to understand the basic mechanism of amphetamines on the central nervous system (CNS). Like all stimulants, amphetamines increase the activity of the sympathetic nervous system, which is responsible for the “fight or flight” response that all animals experience to aid survival. This confers the treatment benefits of stimulants, as it results in increased focus and alertness, improved concentration, higher energy levels, and higher rates of metabolism. Amphetamines in particular accomplish these benefits by increasing the availability of the chemical messengers called monoamines to the CNS, allowing acceleration or amplification of the processes that the CNS normally controls. The primary monoamines that are amplified by amphetamines are dopamine and norepinephrine.

• #50 Amphetamine-Induced Psychosis – BrightQuest Treatment Centers

  https://www.brightquest.com/drug-induced-psychosis/amphetamine-induced-psychosis/

  Psychotic symptoms can occur when such information is either corrupted, overloaded, or poorly integrated, and researchers generally believe this phenomenon occurs when excess dopamine over stimulates the dopamine receptors of the midbrain and forebrain. The primary evidence for this mechanism of action is that most antipsychotic medications block or limit the activity of these dopamine receptors.

• #51 Cannabis-Induced Psychosis: A Review

  https://www.psychiatrictimes.com/view/cannabis-induced-psychosis-review

  Numerous lines of evidence suggest a correlation between cannabis consumption and a variety of psychiatric conditions, including cannabis-induced psychosis (CIP). […] Cannabis is considered an environmental risk factor that increases the odds of psychotic episodes, and longer exposure is associated with greater risk of psychosis in a dose-dependent fashion. The drug acts as a stressor that leads to the emergence and persistence of psychosis. […] Findings from a study that examined presynaptic dopaminergic function in patients who have experienced CIP indicate that dopamine synthesis in the striatum has an inverse relationship with cannabis use. Long-term users had reduced dopamine synthesis, although no association was seen between dopaminergic function and CIP. […] There has been much controversy surrounding the validity of a CIP diagnosis and whether it is a distinct clinical entity or an early manifestation of schizophrenia.

• #52 d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology.

  https://vivo.weill.cornell.edu/display/pubid27886063

  d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. […] The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. […] LSD’s mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT2A receptor as a partial agonist and 5-HT1A as an agonist. […] More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. […] LSD’s effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR receptors.

• #53 Managing Psychosis in Parkinson Disease: Challenges and Opportunities

  https://www.neurologylive.com/view/managing-psychosis-in-parkinson-disease-challenges-and-opportunities

  Although the indication of pimavanserin has provided some relief, more work remains to improve how physicians diagnose, treat, and manage psychosis symptoms. […] Parkinson disease psychosis (PDP) is thought to be a result of an increase in the numbers of 5-HT2A receptors and dopaminergic hyperactivity. […] The clinical approach for treating PDP traditionally relies on initially reducing the dopaminergic agent and considering an add-on therapy for psychiatric symptom management. […] Definition and formal criteria for PDP as a distinct disease entity have been established. PDP symptoms are believed to progress and can include hallucinations involving all 5 senses (most commonly, sight), illusions, and delusions. […] Once a patient starts having psychosis symptoms, they will progress.

• #54 Managing Psychosis in Parkinson Disease: Challenges and Opportunities

  https://www.neurologylive.com/view/managing-psychosis-in-parkinson-disease-challenges-and-opportunities

  Although the indication of pimavanserin has provided some relief, more work remains to improve how physicians diagnose, treat, and manage psychosis symptoms. […] Parkinson disease psychosis (PDP) is thought to be a result of an increase in the numbers of 5-HT2A receptors and dopaminergic hyperactivity. […] The clinical approach for treating PDP traditionally relies on initially reducing the dopaminergic agent and considering an add-on therapy for psychiatric symptom management. […] Definition and formal criteria for PDP as a distinct disease entity have been established. PDP symptoms are believed to progress and can include hallucinations involving all 5 senses (most commonly, sight), illusions, and delusions. […] Once a patient starts having psychosis symptoms, they will progress.

• #55

  https://eurekaselect.com/public/article/122669

  Behavioral and psychotic manifestations, including aggression, delusions, and hallucinations, are frequent comorbidities in patients with debilitating nervous illnesses such as Alzheimers disease (AD), Amyotrophic Lateral Sclerosis, Multiple Sclerosis, and Parkinsons disease. […] The mechanisms behind neurodegeneration-related psychosis are complex and are not fully understood, imposing a burden on researchers to find appropriate management modalities. Familial history and some genetic disturbances may have a determinant role in these delusions and hallucinations in cases with AD. The loss of neuronal cells, atrophy in some regions of the central nervous, and synaptic dysfunction may also contribute to these comorbidities. Furthermore, inflammatory disturbances triggered by pro-inflammatory agents such as interleukins and tumor necrosis factors are stratified among the potential risk factors for the onset of numerous psychotic symptoms in Alzheimers patients. […] This review summarizes the current findings regarding the AD-related psychosis symptoms, pathological features, assessment, and management.

• #56 Psychosis of Epilepsy: An Update on Clinical Classification and Mechanism

  https://www.mdpi.com/2218-273X/15/1/56

  Psychosis is a prevalent comorbidity among patients with epilepsy, significantly diminishing their quality of life. […] The pathogenic mechanism of POE has not been conclusively established, but a number of studies have investigated its neuroimaging, neurobiology, and genetic mechanisms. […] The alterations in brain structure and function, neurotransmitters, neuroinflammatory mediators, and genetic factors discussed in this review may offer insights into the onset and progression of psychotic symptoms in epilepsy patients and are anticipated to inform the identification of novel therapeutic targets in the future. […] This review will center around the clinical classification and possible pathophysiological mechanisms of POE, with a focus on the mechanisms, and will elaborate on the possible relevant mechanisms from the perspectives of neuroimaging, neurobiology, and genetics.

• #57 Psychosis secondary to thyrotoxicosis that persisted post-thyroidectomy: a case report | BMC Psychiatry | Full Text

  https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-023-05227-4

  There is a prevalence of data that suggests beta-adrenergic activation would help explain the similarity of thyrotoxicosis to symptoms such as mania, aggression or anxiety. However, the connection of thyrotoxicosis to psychosis is less clear. It is thought that, in Graves Disease, the increase in TSH receptor (TSHR) antibodies activates TSH receptors in the hippocampus and cerebrum, producing neuropsychiatric symptoms. […] Treating thyrotoxicosis-induced psychosis typically involves a combination of medical and psychiatric treatment. The primary goal is to reduce the thyroid hormone levels to normal ranges with antithyroid medications such as Methimazole and Propyluracil, but those effects may not be seen for several weeks. […] This cases acute psychosis after thyroidectomy is not fully understood, and more research on Graves Disease complications post-thyroidectomy needs to be performed to understand the etiology of this rebound acute psychosis.

• #58 When Steroids Cause Psychosis – The Rheumatologist

  https://www.the-rheumatologist.org/article/when-steroids-cause-psychosis/?singlepage=1%26theme=print-friendly

  Corticosteroids are used to treat inflammatory manifestations of many rheumatologic conditions. […] In this setting, one out of every two to three patients prescribed steroids may develop psychiatric symptoms including psychosis, mania, delirium, and depression. The most common symptoms reported with corticosteroid therapy are hypomania, mania, and psychosis. […] Corticosteroid-induced psychosis refers to a spectrum of psychiatric symptoms ranging from subtle mood changes to memory deficits to frank psychosis that can occur at any time during treatment. […] The pathophysiology of corticosteroid-induced psychosis remains poorly understood, although it is generally accepted that abnormalities of the hypothalamopituitaryadrenal (HPA) axis can result in mood disorders. […] Whether corticosteroid-associated psychiatric symptoms are related to hippocampal effects, suppression of the HPA by dopamine neurotransmission, or other direct or indirect effects of corticosteroids is not well understood.

• #59 Frontiers | Psychosis as an Evolutionary Adaptive Mechanism to Changing Environments

  https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2018.00237/full

  Psychotic symptoms may not be viewed as an illness but as an adaptation phenomenon, which can become out of control due to different underlying brain vulnerabilities and external stressors, leading to social exclusion. […] Psychotic symptoms may be explained as a natural defense mechanism or protective response to stressful environments. […] Psychotic symptoms may be considered as an evolutionary maintained phenomenon. Research investigating psychotic disorders may benefit from a focus on underlying general brain vulnerabilities or prevention of social exclusion, instead of psychotic symptoms. […] Psychosis could be a natural defense mechanism that is necessary to survive as an individual or a group in specific social circumstances. […] When this natural response to a new environment becomes too extreme or gets out of control, it is not functional anymore.

• #60 Frontiers | Psychosis as an Evolutionary Adaptive Mechanism to Changing Environments

  https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2018.00237/full

  Psychotic symptoms may not be viewed as an illness but as an adaptation phenomenon, which can become out of control due to different underlying brain vulnerabilities and external stressors, leading to social exclusion. […] Psychotic symptoms may be explained as a natural defense mechanism or protective response to stressful environments. […] Psychotic symptoms may be considered as an evolutionary maintained phenomenon. Research investigating psychotic disorders may benefit from a focus on underlying general brain vulnerabilities or prevention of social exclusion, instead of psychotic symptoms. […] Psychosis could be a natural defense mechanism that is necessary to survive as an individual or a group in specific social circumstances. […] When this natural response to a new environment becomes too extreme or gets out of control, it is not functional anymore.

• #61 Frontiers | Psychosis as an Evolutionary Adaptive Mechanism to Changing Environments

  https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2018.00237/full

  The control or inhibiting system for psychosis could be the capacity and speed of adaptation to a new environment. […] Psychosis, as a normal phenomenon, could become problematic when higher cognitive functioning, like executive functioning, social competence, consciousness/self-reflection, and/or abstract thinking are not developed solidly, leading to difficulties in adaptation when someone is in a situation of being a social outsider.

• #62 The psychodynamics of psychosis | Advances in Psychiatric Treatment | Cambridge Core

  https://www.cambridge.org/core/journals/advances-in-psychiatric-treatment/article/psychodynamics-of-psychosis/95DD237908479A2E17BE3215AD0AF4F1

  This article outlines common psychodynamics in psychosis. We consider psychosis as a response to unbearable aspects of reality and illustrate how psychodynamic concepts of psychological defence can be used as a framework for understanding this. […] Psychosis is commonly described as a mental state in which there is an altered relation to reality. […] In the psychodynamic approach to psychosis, attention is paid to clarifying experiences of reality that the person has found unmanageable and which have, through the psychosis, been dispensed with or altered, rather than contained, digested and integrated as in non-psychotic states. […] Psychotic symptoms often function as a defence against unbearable aspects of reality. […] Psychotic symptoms will contain meaningful personal information disguised to varying extents, including elements of both the avoided reality and the processes by which the patient’s mind has changed this.

• #63 Drug Abuse and Psychosis: New Insights into Drug-induced Psychosis

  https://www.en-journal.org/journal/view.html?uid=330

  Addictive drug use or prescribed medicine abuse can cause psychosis. Some representative symptoms frequently elicited by patients with psychosis are hallucination, anhedonia, and disrupted executive functions. These psychoses are categorized into three classifications of symptoms: positive, negative, and cognitive. The symptoms of DIP are not different from the symptoms of schizophrenia, and it is difficult to distinguish between them. […] Environmental factors such as maternal stress, traumatic brain injury, psychosocial stress, and drug abuse can instigate psychosis. Among these factors, it has been shown in multiple studies that drug use can lead to psychosis without the involvement of genetic factors, especially in adult animals. The representative drugs that can cause psychosis are amphetamine, scopolamine, ketamine, phencyclidine (PCP), and lysergic acid diethylamide (LSD).

• #64 Drug Abuse and Psychosis: New Insights into Drug-induced Psychosis

  https://www.en-journal.org/journal/view.html?uid=330

  Addictive drug use or prescribed medicine abuse can cause psychosis. Some representative symptoms frequently elicited by patients with psychosis are hallucination, anhedonia, and disrupted executive functions. These psychoses are categorized into three classifications of symptoms: positive, negative, and cognitive. The symptoms of DIP are not different from the symptoms of schizophrenia, and it is difficult to distinguish between them. […] Environmental factors such as maternal stress, traumatic brain injury, psychosocial stress, and drug abuse can instigate psychosis. Among these factors, it has been shown in multiple studies that drug use can lead to psychosis without the involvement of genetic factors, especially in adult animals. The representative drugs that can cause psychosis are amphetamine, scopolamine, ketamine, phencyclidine (PCP), and lysergic acid diethylamide (LSD).

• #65 Drug Abuse and Psychosis: New Insights into Drug-induced Psychosis

  https://www.en-journal.org/journal/view.html?uid=330

  While DIP is a result of environmental factors, schizophrenia is highly heritable and a considerable number of genetic components are involved in the development of schizophrenia. Therefore, we defined schizophrenia models as models that incorporated altered genes, many of which were identified from schizophrenic patients.

• #66 [2103.13924] Computational Mechanism for the Effect of Psychosis Community Treatment: A Conceptual Review from Neurobiology to Social Interaction

  https://arxiv.org/abs/2103.13924

  The computational underpinnings of positive psychotic symptoms have recently received significant attention. Candidate mechanisms include some combination of maladaptive priors and reduced updating of these priors during perception. […] A potential benefit of models with such mechanisms is their ability to link multiple levels of explanation. This is key to improving how we understand the experience of psychosis. Moreover, it points us towards more comprehensive avenues for therapeutic research by providing a putative mechanism that could allow for the generation of new treatments from first principles. […] We develop the argument that this structure and predictability directly counteract the relatively low precision afforded to sensory information in psychosis, while also providing the patient more access to external cognitive resources in the form of providers and the structure of the programs themselves.

• #67 Advances in the understanding of the pathophysiology of schizophrenia and bipolar disorder through induced pluripotent stem cell models | JPN

  https://www.jpn.ca/content/49/2/E109

  Overall, these results suggest that alterations in both glutamate and GABA neurotransmission may contribute to the pathophysiology of schizophrenia. […] Overall, the evidence from iPSC studies of bipolar disorder on the dysfunctions linked to the glutamatergic, GABAergic and dopaminergic systems or on the excitatory-inhibitory imbalance is still scarce and further studies are required to improve knowledge on the topic. […] The advances in the development of iPSC models have allowed more detailed characterization of these 2 disorders, including a series of aberrations in neurogenesis, axon development, neurotransmission, and mitochondrial functionality.

• #68 Psychosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK546579/

  Glutamate, an excitatory neurotransmitter, is also implicated. Multiple studies have found a decreased function of the N-methyl-D-aspartate (NMDA) glutamate receptor. […] Studies have also pointed to gamma-amino-butyric acid (GABA), an important inhibitory neurotransmitter. […] Lastly, implications point to an imbalance in acetylcholine. […] Antipsychotic medications are the gold-standard treatment for psychotic episodes and disorders, and the choice, dosing, and administration of the medication will largely depend on the scenario. […] Antipsychotics have been shown to be more efficacious in treating positive symptoms. […] There is potential for positive outcomes in patients with psychotic disorders. […] Early intervention is essential for good long-term outcomes.

• #69 Antipsychotic Medications: What They Are, Uses & Side Effects

  https://my.clevelandclinic.org/health/treatments/24692-antipsychotic-medications

  Antipsychotic medications are drugs that mainly treat psychosis-related conditions and symptoms. […] Antipsychotics work by changing how certain signals in your brain called neurotransmitters affect how you feel and act. If these chemicals are out of balance, you may develop symptoms of psychosis like hallucinations and delusions. […] By changing the balance of the chemicals in your brain, you may start to have fewer symptoms.

• #70 Psychosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK546579/

  Glutamate, an excitatory neurotransmitter, is also implicated. Multiple studies have found a decreased function of the N-methyl-D-aspartate (NMDA) glutamate receptor. […] Studies have also pointed to gamma-amino-butyric acid (GABA), an important inhibitory neurotransmitter. […] Lastly, implications point to an imbalance in acetylcholine. […] Antipsychotic medications are the gold-standard treatment for psychotic episodes and disorders, and the choice, dosing, and administration of the medication will largely depend on the scenario. […] Antipsychotics have been shown to be more efficacious in treating positive symptoms. […] There is potential for positive outcomes in patients with psychotic disorders. […] Early intervention is essential for good long-term outcomes.

• #71 Protocol for the Psychosis Immune Mechanism Stratified Medicine (PIMS) trial: a randomised double-blind placebo-controlled trial of single-dose tocilizumab in patients with psychosis | BMJ Open

  https://bmjopen.bmj.com/content/13/3/e067944

  Previous attempts of testing the inflammatory hypothesis in therapeutic clinical trials have been attempted. However, little evidence of overall efficacy has been found. […] A trial using tocilizumab, a humanised monoclonal antibody (mAb) against the IL-6 receptor, currently licensed in the UK for treatment of rheumatoid arthritis (RA) and severe COVID-19, reported no improvements in any clinical measure in a small sample of 36 patients with established schizophrenia. […] Meta-analysis suggests that evidence of immune activation, defined by elevated CRP levels, is present in a quarter to one-third of patients with schizophrenia. […] The primary aim of this trial is to examine potential mechanisms by which IL-6 affects anhedonia, psychotic symptoms and cognition. […] This will provide further evidence for a potential causal role of inflammation in psychosis. […] Our secondary hypothesis is that reduction in peripheral inflammation after tocilizumab infusion in patients with psychosis and evidence of inflammation will be associated with central measures of oxidative stress and relevant resting state brain function.

• #72 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11200831/

  An inflammatory response characterized by elevated pro-inflammatory cytokine concentrations is characteristic of many psychiatric disorders, and the finding that neuroinflammation tends to precede psychosis symptomology implicates it as part of the psychotic pathogenesis. […] Elevated concentrations of these cytokines are implicated in chronic immune activation which disturbs the physiological pathways involved in neurotransmission. […] Oxidative stress is often described as the result of an imbalance between the production of reactive species, or free radicals, and the inability of the body to detoxify these reactive products. […] Research to date strongly suggests that interactions among mitochondrial deficits, neurotransmitter dysfunction, oxidative stress, and inflammation produce the symptoms of schizophrenia.

• #73 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://www.mdpi.com/2076-3921/13/6/709

  An inflammatory response characterized by elevated pro-inflammatory cytokine concentrations is characteristic of many psychiatric disorders, and the finding that neuroinflammation tends to precede psychosis symptomology implicates it as part of the psychotic pathogenesis. […] Elevated concentrations of these cytokines are implicated in chronic immune activation which disturbs the physiological pathways involved in neurotransmission. […] Oxidative stress is often described as the result of an imbalance between the production of reactive species, or free radicals, and the inability of the body to detoxify these reactive products. […] Reactive oxygen species (ROS) can block the dopamine transporters (DATs) which regulate dopamine degradation. […] Mitochondria, which play crucial roles in energy metabolism, oxidative stress, and modulation of synaptic activity, produce almost all of the cellular ATP in the body, via oxidative phosphorylation carried out by complexes I through IV of the electron transport chain. […] This paper has reviewed several important facets of interest in psychosis, namely neurotransmitter dysregulation, neuroinflammation, oxidative stress, and mitochondrial dysfunction, which are implicated in psychosis pathogenesis.

• #74 The role of neurotransmitter receptors in antipsychotic medication efficacy for Alzheimer’s-related psychosis | The Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Full Text

  https://ejnpn.springeropen.com/articles/10.1186/s41983-024-00848-2

  The review article summarizes the most recent findings regarding the contribution of neurotransmitter receptors to the effectiveness of antipsychotic drugs in the management of ADP. […] The difficulties of treating Alzheimers with antipsychotics are also covered in this study, including the potential for cognitive impairment to worsen, the emergence of extrapyramidal symptoms, and other unfavorable effects. […] New approaches to studying and treating ARP including neuroinflammation-targeting medicines, transcranial magnetic stimulation (TMS), cerebrospinal fluid (CSF) biomarkers, and muscarinic acetylcholine receptor (mAChR) agonists like xanomeline. […] Reducing psychosis through treatment options could be improved by knowledge of N-methyl-D-aspartate glutamate receptors (NMDAR) hypofunction processes in gamma-aminobutyric acid (GABAergic) neurons.

• #75 GtR

  https://gtr.ukri.org/projects?ref=MR%2FS037675%2F1

  The PIMS project will focus on the IL-6/IL-6R pathway and immune markers up and downstream of IL-6 (e.g. IL-1B, TNF-a, CRP) as potential therapeutic targets for schizophrenia. […] Our experimental medicine study will be the first conducted within an immune selected patient group. […] Successful completion of this proposal will provide significant insight into the neurobiological changes that occur in psychosis and how these relate to inflammation. […] PIMS will result in a group of expertise across discipline working together with a focus on a novel area of drug development: focussing on immune dysfunction in schizophrenia.

• #76 Psychosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK546579/

  Glutamate, an excitatory neurotransmitter, is also implicated. Multiple studies have found a decreased function of the N-methyl-D-aspartate (NMDA) glutamate receptor. […] Studies have also pointed to gamma-amino-butyric acid (GABA), an important inhibitory neurotransmitter. […] Lastly, implications point to an imbalance in acetylcholine. […] Antipsychotic medications are the gold-standard treatment for psychotic episodes and disorders, and the choice, dosing, and administration of the medication will largely depend on the scenario. […] Antipsychotics have been shown to be more efficacious in treating positive symptoms. […] There is potential for positive outcomes in patients with psychotic disorders. […] Early intervention is essential for good long-term outcomes.

• #77 Pathophysiologic Mechanisms in the Pathogenesis and Clinical Course of Schizophrenia

  https://www.psychiatrist.com/jcp/pathophysiologic-mechanisms-pathogenesis-clinical/

  It is widely accepted that schizophrenia originates from abnormalities occurring during the early stages of neural development. […] This review presents evidence of neurodevelopmental and neurodegenerative mechanisms for the development of schizophrenia. […] These data indicate the importance of effective treatment at the first onset of schizophrenia to improve patient outcome. […] In addition, animal studies suggest that treatment with clozapine may prevent the neurodegenerative component responsible for the development of treatment resistance.

• #78 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11200831/

  Psychosis, defined as a set of symptoms that results in a distorted sense of reality, is observed in several psychiatric disorders in addition to schizophrenia. […] The dopamine hypothesis has been a major influence in the study of the neurochemistry of psychosis and in development of antipsychotic drugs. However, it became clear early on that other factors must be involved in the dysfunction involved in psychosis. In the current review, it is reported how several of these factors, namely dysregulation of neurotransmitters [dopamine, serotonin, glutamate, and -aminobutyric acid (GABA)], neuroinflammation, glia (microglia, astrocytes, and oligodendrocytes), the hypothalamic-pituitary-adrenal axis, the gut microbiome, oxidative stress, and mitochondrial dysfunction contribute to psychosis and interact with one another.

• #79 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11200831/

  This paper has reviewed several important facets of interest in psychosis, namely neurotransmitter dysregulation, neuroinflammation, oxidative stress, and mitochondrial dysfunction, which are implicated in psychosis pathogenesis. […] The exciting and innovative research that has been performed on psychosis in the past few decades has greatly increased our knowledge of factors involved in the etiology of psychosis, but has also made us acutely aware of how complex psychotic disorders are.

• #80 The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11200831/

  This paper has reviewed several important facets of interest in psychosis, namely neurotransmitter dysregulation, neuroinflammation, oxidative stress, and mitochondrial dysfunction, which are implicated in psychosis pathogenesis. […] The exciting and innovative research that has been performed on psychosis in the past few decades has greatly increased our knowledge of factors involved in the etiology of psychosis, but has also made us acutely aware of how complex psychotic disorders are.

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