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Psychotic Disorder

Disease Details

Family Health Simplified

Description
A psychotic disorder is a mental health condition characterized by a disconnection from reality, often including symptoms such as hallucinations, delusions, and disorganized thinking.
Type
Psychotic disorders, such as schizophrenia and schizoaffective disorder, are primarily psychiatric conditions. They exhibit a complex pattern of genetic transmission, often described as multifactorial inheritance. This means that multiple genes, along with environmental factors, contribute to the risk of developing these disorders. No single gene is solely responsible, but a combination of genetic variations increases susceptibility.
Signs And Symptoms
Signs and symptoms of psychotic disorders can include:

1. **Delusions:** Strongly held false beliefs that are resistant to reasoning or contrary evidence.
2. **Hallucinations:** Sensing things that aren't there, commonly hearing voices.
3. **Disorganized Thinking:** Incoherent or tangential speech and difficulty organizing thoughts.
4. **Grossly Disorganized or Abnormal Motor Behavior:** Unpredictable agitation, silliness, or catatonic behavior.
5. **Negative Symptoms:** Reduced emotional expression, lack of motivation, withdrawal from social activities, and inability to experience pleasure.
Prognosis
The prognosis for psychotic disorders varies widely depending on the specific type, the individual's overall health, the timeliness and effectiveness of treatment, and support systems. Many individuals with psychotic disorders can lead fulfilling lives with proper medical management, including medication and therapy. However, the course of the disease can be chronic and relapsing for some, necessitating ongoing treatment and support. Early intervention and a comprehensive treatment plan typically improve the outlook significantly.
Onset
Psychotic disorders, such as schizophrenia, typically onset in late adolescence to early adulthood, though they can occur at any age. The term "nan" needs clarification as it is not directly related to the onset of psychotic disorders. If you meant "not a number" (NaN), it might be a placeholder and not applicable in this context.
Prevalence
The prevalence of psychotic disorders varies, but it is estimated that approximately 3% of the population will experience a psychotic episode in their lifetime. Schizophrenia, a common type of psychotic disorder, affects about 1% of the global population.
Epidemiology
Psychotic disorders, such as schizophrenia, usually have a lifetime prevalence of approximately 1% globally. These conditions typically manifest in late adolescence or early adulthood. The incidence can vary based on geographical location, with slightly higher rates in urban areas compared to rural ones. Risk factors include genetic predisposition, early life stressors, and prenatal or perinatal complications. Environmental factors, such as substance abuse and social adversity, also play a significant role in the development of psychotic disorders. Ethnicity and socioeconomic status may influence prevalence and access to treatment, although these patterns can differ widely between populations.
Intractability
Psychotic disorders are generally not considered intractable. While they can be severe and chronic, many individuals with psychotic disorders can experience significant improvement with appropriate treatment, which typically includes a combination of medication (such as antipsychotics), psychotherapy, and psychosocial support. Early intervention and ongoing management are crucial for better outcomes. However, some cases may be more resistant to treatment and could require more intensive and individualized approaches.
Disease Severity
Psychotic disorders are severe mental health conditions characterized by distortions in thinking and perception. These disorders can significantly impact an individual's ability to function in daily life. The severity of psychotic disorders can vary, ranging from brief and mild episodes to chronic and debilitating conditions that require ongoing treatment.
Healthcare Professionals
Disease Ontology ID - DOID:2468
Pathophysiology
Psychotic disorders, including schizophrenia, are primarily characterized by disruptions in thought processes, perceptions, emotional responsiveness, and social interactions. The exact pathophysiology is complex and not fully understood, but several key factors are involved:

1. **Neurotransmitter Dysregulation**: Dopamine dysregulation, particularly hyperactivity in the mesolimbic pathway and hypoactivity in the mesocortical pathway, is strongly implicated. Imbalances in glutamate and serotonin also play roles.

2. **Structural Brain Abnormalities**: Enlarged ventricles, reduced gray matter volume, and abnormalities in various brain regions such as the prefrontal cortex, temporal lobes, and hippocampus have been observed.

3. **Genetic Factors**: Genetic predisposition significantly increases the risk, with multiple genes potentially involved, including those related to neurotransmitter function and synaptic plasticity.

4. **Neurodevelopmental Issues**: Abnormal brain development during prenatal or early life stages, possibly due to genetic and environmental factors such as infections, malnutrition, and exposure to toxins, may contribute.

5. **Immune System Dysregulation**: Inflammatory processes and autoimmune reactions have also been suggested to play a role.

The interplay of these factors results in the behavioral and cognitive symptoms characteristic of psychotic disorders.
Carrier Status
Psychotic disorders, including schizophrenia, do not have a "carrier status" in the way that genetic disorders do. Psychotic disorders are influenced by a combination of genetic, biological, environmental, and psychological factors rather than being transmitted in a simple Mendelian inheritance pattern. While genetic predispositions can increase the risk, there isn't a specific carrier status designation.
Mechanism
Psychotic disorders, such as schizophrenia, involve complex mechanisms and molecular pathways that are not fully understood but have been extensively studied.

## Mechanisms:
Psychotic disorders are characterized by disruptions in thought processes, perceptions, emotions, and behavior. The exact mechanisms are multifactorial and include genetic, neurobiological, and environmental factors.

1. **Neurotransmitter Imbalance**:
- **Dopamine Hypothesis**: Increased dopamine activity in certain brain pathways (mesolimbic pathway) is thought to contribute to positive symptoms (e.g., hallucinations, delusions), while decreased dopamine activity in the mesocortical pathway is related to negative symptoms (e.g., apathy, social withdrawal).
- **Glutamate Hypothesis**: Dysregulation of glutamatergic signaling, particularly hypofunction of NMDA receptors, is implicated in psychotic symptoms.
- **Serotonin Involvement**: Abnormal serotonin activity is also suggested, particularly given the efficacy of atypical antipsychotics that target serotonin receptors.

2. **Brain Structural Abnormalities**:
- Structural imaging studies show alterations in brain regions such as the prefrontal cortex, hippocampus, and thalamus.

3. **Neurodevelopmental Factors**:
- Disruptions in brain development during prenatal or early postnatal life, such as maternal infections or malnutrition, can increase risk.

## Molecular Mechanisms:
1. **Genetic Factors**:
- Numerous genes have been associated with increased risk for psychotic disorders, including those involved in dopamine regulation (e.g., DRD2) and glutamate signaling (e.g., GRIN2A).
- Copy number variations and other genetic anomalies also contribute.

2. **Inflammatory Pathways**:
- Elevated levels of pro-inflammatory cytokines and immune dysregulation have been observed in individuals with psychotic disorders.
- Studies suggest microglial activation in the brain, indicating neuroinflammation.

3. **Oxidative Stress**:
- Increased oxidative stress and reduced antioxidant defenses are implicated, potentially leading to neuronal damage.

4. **Epigenetic Modifications**:
- Epigenetic factors such as DNA methylation and histone modification, possibly influenced by environmental stressors, may contribute to the onset and progression of psychotic disorders by altering gene expression.

Understanding these mechanisms helps in developing targeted therapies and provides insight into potential preventative measures for psychotic disorders.
Treatment
Early civilizations considered madness a supernaturally inflicted phenomenon. Archaeologists have unearthed skulls with clearly visible drillings, some datable back to 5000 BC suggesting that trepanning was a common treatment for psychosis in ancient times. Written record of supernatural causes and resultant treatments can be traced back to the New Testament. Mark 5:8–13 describes a man displaying what would today be described as psychotic symptoms. Christ cured this "demonic madness" by casting out the demons and hurling them into a herd of swine. Exorcism is still utilized in some religious circles as a treatment for psychosis presumed to be demonic possession. A research study of out-patients in psychiatric clinics found that 30 percent of religious patients attributed the cause of their psychotic symptoms to evil spirits. Many of these patients underwent exorcistic healing rituals that, though largely regarded as positive experiences by the patients, had no effect on symptomology. Results did, however, show a significant worsening of psychotic symptoms associated with exclusion of medical treatment for coercive forms of exorcism.
The medical teachings of the fourth-century philosopher and physician Hippocrates of Cos proposed a natural, rather than supernatural, cause of human illness. In Hippocrates' work, the Hippocratic corpus, a holistic explanation for health and disease was developed to include madness and other "diseases of the mind". Hippocrates writes:

Men ought to know that from the brain, and from the brain only, arise our pleasures, joys, laughter, and jests, as well as our sorrows, pains, griefs and tears. Through it, in particular, we think, see, hear, and distinguish the ugly from the beautiful, the bad from the good, the pleasant from the unpleasant.... It is the same thing which makes us mad or delirious, inspires us with dread and fear, whether by night or by day, brings sleeplessness, inopportune mistakes, aimless anxieties, absentmindedness, and acts that are contrary to habit.
Hippocrates espoused a theory of humoralism wherein disease is resultant of a shifting balance in bodily fluids including blood, phlegm, black bile, and yellow bile. According to humoralism, each fluid or "humour" has temperamental or behavioral correlates. In the case of psychosis, symptoms are thought to be caused by an excess of both blood and yellow bile. Thus, the proposed surgical intervention for psychotic or manic behavior was bloodletting.18th-century physician, educator, and widely considered "founder of American psychiatry", Benjamin Rush, also prescribed bloodletting as a first-line treatment for psychosis. Although not a proponent of humoralism, Rush believed that active purging and bloodletting were efficacious corrections for disruptions in the circulatory system, a complication he believed was the primary cause of "insanity". Although Rush's treatment modalities are now considered antiquated and brutish, his contributions to psychiatry, namely the biological underpinnings of psychiatric phenomenon including psychosis, have been invaluable to the field. In honor of such contributions, Benjamin Rush's image is in the official seal of the American Psychiatric Association.
Early 20th-century treatments for severe and persisting psychosis were characterized by an emphasis on shocking the nervous system. Such therapies include insulin shock therapy, cardiazol shock therapy, and electroconvulsive therapy. Despite considerable risk, shock therapy was considered highly efficacious in the treatment of psychosis including schizophrenia. The acceptance of high-risk treatments led to more invasive medical interventions including psychosurgery.
In 1888, Swiss psychiatrist Gottlieb Burckhardt performed the first medically sanctioned psychosurgery in which the cerebral cortex was excised. Although some patients showed improvement of symptoms and became more subdued, one patient died and several developed aphasia or seizure disorders. Burckhardt would go on to publish his clinical outcomes in a scholarly paper. This procedure was met with criticism from the medical community and his academic and surgical endeavors were largely ignored. In the late 1930s, Egas Moniz conceived the leucotomy (AKA prefrontal lobotomy) in which the fibers connecting the frontal lobes to the rest of the brain were severed. Moniz's primary inspiration stemmed from a demonstration by neuroscientists John Fulton and Carlyle's 1935 experiment in which two chimpanzees were given leucotomies and pre- and post-surgical behavior was compared. Prior to the leucotomy, the chimps engaged in typical behavior including throwing feces and fighting. After the procedure, both chimps were pacified and less violent. During the Q&A, Moniz asked if such a procedure could be extended to human subjects, a question that Fulton admitted was quite startling. Moniz would go on to extend the controversial practice to humans with various psychotic disorders, an endeavor for which he received a Nobel Prize in 1949. Between the late 1930s and early 1970s, the leucotomy was a widely accepted practice, often performed in non-sterile environments such as small outpatient clinics and patient homes. Psychosurgery remained standard practice until the discovery of antipsychotic pharmacology in the 1950s.The first clinical trial of antipsychotics (also commonly known as neuroleptics) for the treatment of psychosis took place in 1952. Chlorpromazine (brand name: Thorazine) passed clinical trials and became the first antipsychotic medication approved for the treatment of both acute and chronic psychosis. Although the mechanism of action was not discovered until 1963, the administration of chlorpromazine marked the advent of the dopamine antagonist, or first generation antipsychotic. While clinical trials showed a high response rate for both acute psychosis and disorders with psychotic features, the side effects were particularly harsh, which included high rates of often irreversible Parkinsonian symptoms such as tardive dyskinesia. With the advent of atypical antipsychotics (also known as second generation antipsychotics) came a dopamine antagonist with a comparable response rate but a far different, though still extensive, side-effect profile that included a lower risk of Parkinsonian symptoms but a higher risk of cardiovascular disease. Atypical antipsychotics remain the first-line treatment for psychosis associated with various psychiatric and neurological disorders including schizophrenia, bipolar disorder, major depressive disorder, anxiety disorders, dementia, and some autism spectrum disorders.Dopamine is now one of the primary neurotransmitters implicated in psychotic symptomology. Blocking dopamine receptors (namely, the dopamine D2 receptors) and decreasing dopaminergic activity continues to be an effective but highly unrefined effect of antipsychotics, which are commonly used to treat psychosis. Recent pharmacological research suggests that the decrease in dopaminergic activity does not eradicate psychotic delusions or hallucinations, but rather attenuates the reward mechanisms involved in the development of delusional thinking; that is, connecting or finding meaningful relationships between unrelated stimuli or ideas. The author of this research paper acknowledges the importance of future investigation:

The model presented here is based on incomplete knowledge related to dopamine, schizophrenia, and antipsychotics—and as such will need to evolve as more is known about these.
Freud's former student Wilhelm Reich explored independent insights into the physical effects of neurotic and traumatic upbringing, and published his holistic psychoanalytic treatment with a schizophrenic. With his incorporation of breathwork and insight with the patient, a young woman, she achieved sufficient self-management skills to end the therapy.Lacan extended Freud's ideas to create a psychoanalytic model of psychosis based upon the concept of "foreclosure", the rejection of the symbolic concept of the father.
Psychiatrist David Healy has criticised pharmaceutical companies for promoting simplified biological theories of mental illness that seem to imply the primacy of pharmaceutical treatments while ignoring social and developmental factors that are known important influences in the etiology of psychosis.
Compassionate Use Treatment
Compassionate use treatments and off-label or experimental treatments for psychotic disorders can be considered under specific circumstances, usually when standard treatments have failed, are not suitable, or are unavailable.

**Compassionate Use Treatment:**
1. **Clozapine**: Often used for treatment-resistant schizophrenia under compassionate use programs.
2. **Ketamine**: In some cases, ketamine infusions have been used experimentally for depression with psychotic features.

**Off-label or Experimental Treatments:**
1. **Cannabidiol (CBD)**: Some studies are exploring the use of CBD, a non-psychoactive component of cannabis, for reducing psychotic symptoms.
2. **Transcranial Magnetic Stimulation (TMS)**: This is being researched for its potential to alleviate negative and positive symptoms of psychotic disorders.
3. **N-acetylcysteine (NAC)**: Used off-label for its antioxidant properties that may help with symptoms of schizophrenia.
4. **Glycine**: Being investigated for its role as a co-agonist at NMDA receptors, potentially improving symptoms in schizophrenia.
5. **Anti-inflammatory agents**: Some trials are examining the effects of anti-inflammatory medications like aspirin or minocycline on psychotic symptoms.
6. **Psilocybin**: Currently under investigation for its potential therapeutic effects on various mental health conditions, including psychosis alleviation.

Patients should always be monitored closely by healthcare professionals when undergoing these treatments given their experimental nature and potential side effects.
Lifestyle Recommendations
For managing psychotic disorder, consider the following lifestyle recommendations:

1. **Medication Adherence**: Consistently take prescribed medications as directed by a healthcare professional.
2. **Regular Medical Checkups**: Schedule and attend regular follow-up appointments with mental health providers.
3. **Healthy Diet**: Maintain a balanced diet rich in fruits, vegetables, whole grains, and lean proteins.
4. **Exercise**: Engage in regular physical activity to help improve overall mental and physical health.
5. **Sleep Hygiene**: Establish a consistent sleep routine, aiming for 7-9 hours of quality sleep per night.
6. **Stress Management**: Utilize stress-reduction techniques such as mindfulness, meditation, and deep breathing exercises.
7. **Avoid Substance Abuse**: Refrain from using recreational drugs and limit alcohol consumption, as these can exacerbate symptoms.
8. **Social Support**: Build and maintain a strong support network of friends, family, or support groups.
9. **Routine**: Maintain a consistent daily routine to promote stability and structure.
10. **Healthy Environment**: Create a safe and supportive living environment that reduces stressors and triggers.

Consult with a healthcare provider to tailor these recommendations to individual needs.
Medication
The choice of which antipsychotic to use is based on benefits, risks, and costs. It is debatable whether, as a class, typical or atypical antipsychotics are better. Tentative evidence supports that amisulpride, olanzapine, risperidone and clozapine may be more effective for positive symptoms but result in more side effects. Typical antipsychotics have equal drop-out and symptom relapse rates to atypicals when used at low to moderate dosages. There is a good response in 40–50%, a partial response in 30–40%, and treatment resistance (failure of symptoms to respond satisfactorily after six weeks to two or three different antipsychotics) in 20% of people. Clozapine is an effective treatment for those who respond poorly to other drugs ("treatment-resistant" or "refractory" schizophrenia), but it has the potentially serious side effect of agranulocytosis (lowered white blood cell count) in less than 4% of people.Most people on antipsychotics get side effects. People on typical antipsychotics tend to have a higher rate of extrapyramidal side effects while some atypicals are associated with considerable weight gain, diabetes and risk of metabolic syndrome; this is most pronounced with olanzapine, while risperidone and quetiapine are also associated with weight gain. Risperidone has a similar rate of extrapyramidal symptoms to haloperidol.
Repurposable Drugs
In the context of repurposable drugs for psychotic disorders, some existing medications used for other conditions have shown potential benefits. For instance:

1. **Minocycline**: Originally an antibiotic, it has anti-inflammatory properties and has shown some promise in reducing negative symptoms in schizophrenia.
2. **Metformin**: Commonly used for diabetes, it might help in managing weight gain side effects from antipsychotic medications.
3. **Aspirin**: Known for its anti-inflammatory effects, it may help reduce some psychotic symptoms when used alongside traditional antipsychotics.
4. **N-Acetylcysteine (NAC)**: An antioxidant often used as a supplement, NAC has been studied for its potential to alleviate certain symptoms of schizophrenia.

Note that these should only be considered under the supervision of a healthcare professional.
Metabolites
Psychotic disorders, such as schizophrenia, involve various metabolic abnormalities observed in patients. Some commonly studied metabolites related to psychotic disorders include:

1. **Dopamine:** Dysregulation of dopamine pathways is a well-known factor in psychotic disorders. Elevated dopamine activity, particularly in the mesolimbic pathway, is associated with positive symptoms like hallucinations and delusions.

2. **Glutamate:** Abnormalities in glutamatergic neurotransmission are also implicated. Reduced function of NMDA (N-methyl-D-aspartate) receptors may lead to cognitive and negative symptoms.

3. **Serotonin:** Altered serotonin levels and receptor functioning have been linked to both positive and negative symptoms of psychotic disorders.

4. **Gamma-Aminobutyric Acid (GABA):** Imbalances in GABAergic neurotransmission can contribute to the dysregulation of neural circuits involved in psychotic symptoms.

5. **Neuroactive Steroids:** Changes in levels of neuroactive steroids (e.g., allopregnanolone) have been observed, potentially affecting neurotransmission and stress response.

Monitoring these and other metabolites provides insights into the biochemical underpinnings of psychotic disorders, aiding in the development of targeted treatments.
Nutraceuticals
For psychotic disorders, there is limited clinical evidence supporting the efficacy of nutraceuticals. Some commonly studied nutraceuticals include omega-3 fatty acids, N-acetylcysteine, and certain vitamins and minerals such as vitamin D and magnesium. However, none of these have been conclusively proven to be effective as a primary treatment. It is important to consult healthcare professionals before using any nutraceuticals as a part of the treatment plan.
Peptides
Psychotic disorders, such as schizophrenia, are primarily characterized by impaired thinking, emotional regulation, and perception. While peptides are not typically the main focus in the treatment of psychotic disorders, there is ongoing research into their potential roles. For instance, neuropeptides like oxytocin and vasopressin have been studied for their effects on social cognition and may offer future therapeutic avenues.

The term "nan" appears to be unclear within this context. If it refers to "nanotechnology," this field also holds promise for psychotic disorders by providing innovative methods for drug delivery systems that could enhance the efficacy and reduce the side effects of current treatments. This primarily involves the use of nanoparticles to cross the blood-brain barrier and deliver medications more effectively to target sites within the brain.