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Schizophrenia

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Description: Schizophrenia is a chronic mental disorder characterized by delusions, hallucinations, disorganized thinking, and impaired cognitive function.
Type: Schizophrenia is a complex, multifactorial disorder primarily characterized as a psychotic illness. The genetic transmission of schizophrenia is not straightforward; it is considered to be polygenic, involving multiple genes with small effects, as well as interactions with environmental factors. There is no single gene responsible for the disorder, but family, twin, and adoption studies indicate a significant genetic component, with heritability estimates around 70-80%. This means that individuals with a family history of schizophrenia have a higher risk of developing the disorder.
Signs And Symptoms: Schizophrenia is a mental disorder characterized by significant alterations in perception, thoughts, mood and behavior. Symptoms are described in terms of positive, negative and cognitive symptoms. The positive symptoms of schizophrenia are the same for any psychosis and are sometimes referred to as psychotic symptoms. These may be present in any of the different psychoses and are often transient, making early diagnosis of schizophrenia problematic. Psychosis noted for the first time in a person who is later diagnosed with schizophrenia is referred to as a first-episode psychosis (FEP).
Prognosis: Schizophrenia has great human and economic costs. It decreases life expectancy by between 20 and 28 years. This is primarily because of its association with heart disease, diabetes, obesity, poor diet, a sedentary lifestyle, and smoking, with an increased rate of suicide playing a lesser role. Side effects of antipsychotics may also increase the risk.Almost 40% of those with schizophrenia die from complications of cardiovascular disease which is seen to be increasingly associated. An underlying factor of sudden cardiac death may be Brugada syndrome (BrS) – BrS mutations that overlap with those linked with schizophrenia are the calcium channel mutations. BrS may also be drug-induced from certain antipsychotics and antidepressants. Primary polydipsia, or excessive fluid intake, is relatively common in people with chronic schizophrenia. This may lead to hyponatremia which can be life-threatening. Antipsychotics can lead to a dry mouth, but there are several other factors that may contribute to the disorder; it may reduce life expectancy by 13 percent. Barriers to improving the mortality rate in schizophrenia are poverty, overlooking the symptoms of other illnesses, stress, stigma, and medication side effects.Schizophrenia is a major cause of disability. In 2016, it was classed as the 12th most disabling condition. Approximately 75% of people with schizophrenia have ongoing disability with relapses. Some people do recover completely and others function well in society. Most people with schizophrenia live independently with community support. About 85% are unemployed. In people with a first episode of psychosis in schizophrenia a good long-term outcome occurs in 31%, an intermediate outcome in 42% and a poor outcome in 31%. Males are affected more often than females, and have a worse outcome. Studies showing that outcomes for schizophrenia appear better in the developing than the developed world have been questioned. Social problems, such as long-term unemployment, poverty, homelessness, exploitation, stigmatization and victimization are common consequences, and lead to social exclusion.There is a higher than average suicide rate associated with schizophrenia estimated at 5% to 6%, most often occurring in the period following onset or first hospital admission. Several times more (20 to 40%) attempt suicide at least once. There are a variety of risk factors, including male sex, depression, a high IQ, heavy smoking, and substance use. Repeated relapse is linked to an increased risk of suicidal behavior. The use of clozapine can reduce the risk of suicide, and of aggression.A strong association between schizophrenia and tobacco smoking has been shown in worldwide studies. Smoking is especially high in those diagnosed with schizophrenia, with estimates ranging from 80 to 90% being regular smokers, as compared to 20% of the general population. Those who smoke tend to smoke heavily, and additionally smoke cigarettes with high nicotine content. Some propose that this is in an effort to improve symptoms. Among people with schizophrenia use of cannabis is also common.Schizophrenia leads to an increased risk of dementia.
Onset: Schizophrenia typically has its onset in late adolescence to early adulthood, usually between the ages of 16 and 30. Onset before adolescence or after the age of 40 is less common.
Prevalence: The prevalence of schizophrenia is approximately 0.25% to 0.64% of the population. This means that, globally, around 1 in 200 to 1 in 400 people may be affected by this chronic mental disorder.
Epidemiology: In 2017, the Global Burden of Disease Study estimated there were 1.1 million new cases; in 2022 the World Health Organization (WHO) reported a total of 24 million cases globally. Schizophrenia affects around 0.3–0.7% of people at some point in their life. In areas of conflict this figure can rise to between 4.0 and 6.5%. It occurs 1.4 times more frequently in males than females and typically appears earlier in men.Worldwide, schizophrenia is the most common psychotic disorder. The frequency of schizophrenia varies across the world, within countries, and at the local and neighborhood level; this variation in prevalence between studies over time, across geographical locations, and by gender is as high as fivefold.Schizophrenia causes approximately one percent of worldwide disability adjusted life years and resulted in 17,000 deaths in 2015.In 2000, WHO found the percentage of people affected and the number of new cases that develop each year is roughly similar around the world, with age-standardized prevalence per 100,000 ranging from 343 in Africa to 544 in Japan and Oceania for men, and from 378 in Africa to 527 in Southeastern Europe for women.
Intractability: Schizophrenia is often considered an intractable or chronic condition because it typically requires long-term management and has no cure. However, with appropriate treatment involving antipsychotic medications, psychotherapy, and social support, many individuals with schizophrenia can manage their symptoms effectively and lead a functional life. The complexity and variability of the disease make it challenging to treat, necessitating personalized care plans.
Disease Severity: Schizophrenia is a chronic and severe mental disorder that affects how a person thinks, feels, and behaves. It can be very disabling and often requires lifelong treatment. The severity of schizophrenia can vary widely among individuals, but it generally has significant impacts on daily functioning, social interactions, and quality of life. Early diagnosis and treatment, which often include medication and psychotherapy, can help manage symptoms and improve outcomes.
Healthcare Professionals: Disease Ontology ID - DOID:5419
Pathophysiology: Schizophrenia is a complex psychiatric disorder characterized by disruptions in thought processes, perceptions, emotional responsiveness, and social interactions. The exact pathophysiology remains unclear, but several factors are implicated:

1. **Neurotransmitter Imbalance**: Abnormal levels of neurotransmitters, particularly an overactive dopamine system in certain brain pathways (mesolimbic pathway), and dysfunctions in serotonin, glutamate, and gamma-aminobutyric acid (GABA) transmission.

2. **Brain Structure Abnormalities**: Structural brain changes are often present, such as enlarged ventricles, reduced gray matter volume, and alterations in the hippocampus, thalamus, and prefrontal cortex.

3. **Genetic Factors**: Schizophrenia has a heritable component, with multiple genes contributing to increased susceptibility. These genetic factors may affect neurotransmitter pathways and brain development.

4. **Developmental/Cognitive Factors**: Abnormalities in brain development and cognitive processes during critical developmental periods might contribute to the onset of symptoms.

5. **Environmental Factors**: Prenatal stressors, infections, malnutrition, and psychosocial stress during critical periods of brain development are considered potential environmental triggers.

These elements interact in complex, not fully understood ways, leading to the symptoms characteristic of schizophrenia.
Carrier Status: Schizophrenia is not a condition typically described in terms of carrier status because it is not a single-gene disorder inherited in a simple Mendelian fashion. Instead, schizophrenia is considered a complex, multifactorial disorder influenced by a combination of genetic and environmental factors. Multiple genes are involved, and certain genetic variations can increase the risk of developing the condition, but having these variations does not guarantee that a person will have schizophrenia.
Mechanism: Schizophrenia is a complex psychiatric disorder characterized by a range of symptoms including hallucinations, delusions, disorganized thinking, and impaired daily functioning. The exact mechanism of schizophrenia is not fully understood, but it involves a combination of genetic, neurobiological, and environmental factors.

### Mechanism
1. **Genetic Factors**: Schizophrenia has a high heritability rate, with multiple genes implicated. Variations in specific genes may increase susceptibility.
2. **Neurodevelopmental Factors**: Abnormal brain development during prenatal and early postnatal life may play a role.
3. **Neurotransmitter Dysregulation**: Imbalances in key neurotransmitters, particularly dopamine and glutamate, are strongly associated with schizophrenia.
4. **Structural Brain Abnormalities**: MRI and other imaging studies often reveal abnormalities in brain structure, including enlarged ventricles and reduced gray matter volume.
5. **Environmental Factors**: Prenatal exposures, infections, stress, and substance abuse may contribute to the onset and progression of the disorder.

### Molecular Mechanisms
1. **Dopaminergic System**:
- Hyperactivity of the mesolimbic dopamine pathway is often linked to positive symptoms (hallucinations, delusions).
- Hypoactivity of the mesocortical dopamine pathway is associated with negative symptoms (apathy, reduced social engagement) and cognitive dysfunction.

2. **Glutamatergic System**:
- Dysfunction in the N-methyl-D-aspartate (NMDA) receptors impacts glutamate signaling, which is thought to contribute to both positive and negative symptoms.

3. **GABAergic System**:
- GABAergic interneurons, particularly those expressing parvalbumin, show dysfunction in schizophrenia, leading to disorganized neural circuits.

4. **Synaptic Dysfunction**:
- Aberrant synaptic pruning during adolescence may lead to changes in connectivity and communication among neurons.

5. **Inflammation and Immune System**:
- Elevated levels of pro-inflammatory cytokines and microglial activation have been observed, indicating a role for the immune system in the pathology of the disease.

6. **Oxidative Stress**:
- Increased oxidative stress and decreased antioxidant defenses have been implicated in neuronal damage and dysfunction in schizophrenia.

These molecular mechanisms reflect the complexity of schizophrenia and underscore the interplay between various biological systems in its etiology and progression.
Treatment: For schizophrenia, treatment typically involves:

1. **Antipsychotic Medications**: These are the cornerstone of schizophrenia treatment, helping to manage symptoms such as hallucinations and delusions.

2. **Psychotherapy**: Cognitive Behavioral Therapy (CBT) and supportive therapy can help patients cope with symptoms and improve functioning.

3. **Social Skills Training**: Helps individuals improve their communication and social interactions.

4. **Family Therapy**: Engages family members in treatment to support the patient's recovery and improve family dynamics.

5. **Rehabilitation and Vocational Training**: Assists patients in gaining skills to lead meaningful lives and find suitable employment.

6. **Hospitalization**: May be necessary during severe episodes to ensure safety and provide intensive treatment.

7. **Community Support and Services**: Includes case management and social support services to ensure ongoing care and integration into the community.

A comprehensive and individualized treatment plan is essential for effective management of schizophrenia.
Compassionate Use Treatment: For schizophrenia, compassionate use treatments and off-label or experimental treatments may include:

1. **Clozapine:** Although FDA-approved for treatment-resistant schizophrenia, it is sometimes used on a compassionate basis for patients not responding to other medications.

2. **Cannabidiol (CBD):** Research is ongoing, but CBD has shown some potential in small studies to reduce symptoms of schizophrenia.

3. **NMDA Receptor Modulators:** Experimental drugs like Glycine, D-Serine, and D-Cycloserine aim to enhance NMDA receptor function, which is implicated in schizophrenia.

4. **Cognitive Remediation Therapy (CRT):** This non-pharmacological approach focuses on improving cognitive deficits through targeted exercises and is being explored as a supplementary treatment.

5. **Deep Brain Stimulation (DBS):** Though primarily used for movement disorders, DBS is being investigated for its potential benefits in treating severe schizophrenia.

6. **Anti-inflammatory Agents:** Medications like minocycline or aspirin are being studied for their role in reducing inflammation, which may play a role in schizophrenia.

These treatments are still under investigation, and their efficacy and safety are not fully established. They are usually considered when standard treatments have not been effective.
Lifestyle Recommendations: Lifestyle recommendations for managing schizophrenia include:

1. **Medication Adherence**: Regularly take prescribed antipsychotic medications.
2. **Healthy Diet**: Maintain a balanced diet rich in fruits, vegetables, whole grains, and lean proteins.
3. **Regular Exercise**: Engage in regular physical activity like walking, jogging, or yoga.
4. **Avoid Substance Abuse**: Steer clear of alcohol and recreational drugs as they can worsen symptoms.
5. **Routine**: Establish a daily routine to provide structure and predictability.
6. **Sleep Hygiene**: Prioritize a regular sleep schedule to help stabilize mood and energy levels.
7. **Stress Management**: Practice relaxation techniques such as mindfulness, meditation, or deep-breathing exercises.
8. **Social Support**: Stay connected with supportive friends, family, or support groups.
9. **Therapy**: Participate in cognitive-behavioral therapy or other forms of psychotherapy.
10. **Regular Medical Check-Ups**: Maintain regular appointments with healthcare providers to monitor overall health.
Medication: The first-line treatment for schizophrenia is an antipsychotic. The first-generation antipsychotics, now called typical antipsychotics like Flupentixol, are dopamine antagonists that block D2 receptors, and affect the neurotransmission of dopamine. Those brought out later, the second-generation antipsychotics known as atypical antipsychotics, including olanzapine and risperidone, can also have an effect on another neurotransmitter, serotonin. Antipsychotics can reduce the symptoms of anxiety within hours of their use but for other symptoms they may take several days or weeks to reach their full effect. They have little effect on negative and cognitive symptoms, which may be helped by additional psychotherapies and medications. There is no single antipsychotic suitable for first-line treatment for everyone, as responses and tolerances vary between people. Stopping medication may be considered after a single psychotic episode where there has been a full recovery with no symptoms for twelve months. Repeated relapses worsen the long-term outlook and the risk of relapse following a second episode is high, and long-term treatment is usually recommended.About half of those with schizophrenia will respond favourably to antipsychotics, and have a good return of functioning. However, positive symptoms persist in up to a third of people. Following two trials of different antipsychotics over six weeks, that also prove ineffective, they will be classed as having treatment resistant schizophrenia (TRS), and clozapine will be offered. Clozapine is of benefit to around half of this group although it has the potentially serious side effect of agranulocytosis (lowered white blood cell count) in less than 4% of people.About 30 to 50 percent of people with schizophrenia do not accept that they have an illness or comply with their recommended treatment. For those who are unwilling or unable to take medication regularly, long-acting injections of antipsychotics may be used, which reduce the risk of relapse to a greater degree than oral medications. When used in combination with psychosocial interventions, they may improve long-term adherence to treatment.
Repurposable Drugs: Repurposable drugs potentially useful for treating schizophrenia include:

1. **Minocycline** - An antibiotic that may reduce symptoms due to its anti-inflammatory properties.
2. **Memantine** - Commonly used for Alzheimer's, it has potential benefits for cognitive symptoms in schizophrenia.
3. **Raloxifene** - Typically used for osteoporosis, it may help with negative and cognitive symptoms in postmenopausal women.
4. **Sodium Benzoate** - A food preservative that can have antioxidative and NMDA receptor-modulating effects, potentially beneficial in schizophrenia.

N-Acetylcysteine (NAC) - An antioxidant supplement that might help reduce some symptoms due to its glutathione-boosting properties.
Metabolites: For schizophrenia, research indicates alterations in certain metabolites, which can serve as potential biomarkers or therapeutic targets. Key metabolites involved include glutamate, GABA, and dopamine. These neurotransmitters and their metabolic pathways are often dysregulated in individuals with schizophrenia, contributing to the disorder's symptoms. Additionally, studies have reported altered levels of metabolites like lactate and various amino acids in patients with schizophrenia. Understanding these metabolic changes is crucial for developing more effective treatments and diagnostic tools for the disorder.
Nutraceuticals: Nutraceuticals are food-derived products that provide health benefits, including the prevention and treatment of disease. For schizophrenia, certain nutraceuticals have shown potential in managing symptoms and improving overall mental health. Key examples include:

1. Omega-3 Fatty Acids: Found in fish oil, these have anti-inflammatory properties and may help alleviate some symptoms of schizophrenia, especially in the early stages.
2. B Vitamins: Particularly B6, B9 (folate), and B12, these vitamins can help in reducing psychiatric symptoms and improving neural function.
3. Antioxidants: Vitamins C and E, along with other antioxidants, may help reduce oxidative stress, which is noted to be higher in individuals with schizophrenia.
4. N-Acetylcysteine (NAC): This antioxidant has shown promise in reducing negative symptoms and improving overall cognitive function.

These nutraceuticals may serve as adjuncts to traditional pharmacological treatments but should always be integrated into a treatment plan under professional supervision.
Peptides: Schizophrenia is a complex mental disorder characterized by disruptions in thought processes, perceptions, emotional responsiveness, and social interactions. The exact causes of schizophrenia are not fully understood, but both genetic and environmental factors are believed to play a role.

Peptides: There is ongoing research examining the role of neuropeptides in schizophrenia. Neuropeptides such as neurotensin, oxytocin, and tachykinins are being studied for their potential involvement in the regulation of neurotransmission and the development of schizophrenia. Abnormal levels of certain neuropeptides have been detected in individuals with schizophrenia, suggesting they may play a role in the disease's pathophysiology.

Nanotechnology (nan): Nanotechnology is being explored as a potential avenue for improving schizophrenia treatment. This includes the development of nanoparticle-based drug delivery systems that can target specific areas of the brain, which could enhance the efficacy and reduce the side effects of antipsychotic medications. Additionally, nanotechnology might be used in the future for more precise imaging and diagnostics to better understand the disease and its progression.