Hypothesis: Schizophrenia results from an underactivation of glutamate receptors.

- Origin of Hypothesis

The Glutamate Hypothesis of Antipsychotics

While the discovery of antipsychotic drugs helped with the treatment of schizophrenia, there were quite significant side effects.

- Dyskinesia
- Tardive Dyskinesia
- Supersensitivity psychosis
- Involuntary movements of the arms, legs, tongue and facial muscles, resulting in Parkinson’s-like tremors

Long-Term Effects of Antipsychotic Drugs

These are a class of antipsychotic drugs that have a high affinity for other types of receptors and not dopamine receptors. They are also known as 2nd Generation Antipsychotics. They can be prescribed for Schizophrenia and other types of severe thought disorders. They can target dopamine and serotonin receptors to treat schizophrenia's negative symptoms, such as withdrawal and apathy; newer drugs may treat both positive and negative symptoms.

Atypical Antipsychotics include: 
- Aripiprazole (Abilify)

- Clozapine (Clozaril)

- Olanzapine (Zyprexa)

- Quetiapine (Seroquel)

- Risperidone (Risperdal)

- Ziprasidone (Geodon)

Atypical Antipsychotics

Typical Antipsychotic are separated into 1st Generation and 2nd Generation.

1st Generation Antipsychotics include:  
- Chlorpromazine

- Mesoridazine 

- Perphenazine 

- Thioridazine 

- Trifluoperazine 

- Butyrophenone 

- Haloperidol 

- Others:  Loxapine, Molindone, Thiothixene 


Typical Antipsychotics

Both typical and atypical antipsychotics appear to inhibit the release of pro-inflammatory cytokines and potentially promote regular neurogenesis in schizophrenia patients by decreasing oxidative stress. Studies of prenatal administration of some antipsychotics in mice models have demonstrated a decrease in psychosis-like behaviors in the offspring. Given that the microglial inflammatory mechanisms are particularly pronounced in schizophrenia, this is a particular area of interest for future pharmacological research.

Effects of Antipsychotics on Microglia

The dopamine hypothesis posits that schizophrenia is linked to irregularities in the dopamine system. The original theory suggested that the disorder was caused by a general excess of dopamine or an overabundance of dopamine receptors. However, this view has been refined. More recent research indicates that dopamine abnormalities are specific to different brain regions. An oversupply of dopamine in the limbic system is thought to be responsible for positive symptoms like hallucinations and delusions, while a deficit of dopamine in the prefrontal cortex is associated with negative symptoms such as avolition and alogia.

The Dopamine Hypothesis of Schizophrenia

A class of drugs that typically alleviate symptoms of schizophrenia. (Also called neuroleptics)

- The Dopamine Hypothesis

- Typical Antipsychotics

- Long-Term Effects of Antipsychotic Drugs

- Atypical Antipsychotics

- The Glutamate Hypothesis

University of Rochester

Syracuse University

Scripps College

New York University

University of Michigan - Ann Arbor

The study of the effects of drugs on the brain and behavior.

Psychopharmacology 

Empirically supported treatments for psychotic disorders. 

Psychotic Disorder Treatments

Individuals with serious mental illness die 25 years earlier than the general population often from cardiovascular disease caused by factors like:
- Side effects from 2nd generation antipsychotics 
- High rates of obesity, hypertension, diabetes, & dyslipidemia
- Poor nutrition habits 
- Lack of exercise 
- Smoking 

Those suffering from severe mental illness typically do not consume a healthy diet due to barriers such as:
- Increased appetite from psychiatric medications
- Convenience of unhealthy foods 
- Difficulties eating a healthy diet 

Researchers suggest that by changing individuals' dietary behaviors, they will be able to live longer and healthier lives. 

Background of Nutrition & Mental Illness Study 

Breedlove, S. & Watson, N. (2017). Behavioral neuroscience, eighth edition. Oxford University Press.

Behavioral Neuroscience 8th Edition

Psychopharmacology Library

Microdosing is the administration of a psychedelic drug/medication at one-tenth of the dose that would cause hallucinogenic effects.

Microdosing

Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs used to treat conditions like depression, which is often associated with low serotonin levels. Unlike agonists or antagonists that bind to receptors, SSRIs work by blocking the reuptake process. This action prevents unused serotonin from being reabsorbed by the presynaptic neuron, allowing it to remain in the synaptic cleft for a longer period. The extended presence of serotonin enhances its interaction with postsynaptic receptors, thereby strengthening its overall effect. Common examples of SSRIs include Prozac, Paxil, and Zoloft.

SSRIs and SNRIs

Antipsychotic Drugs

Tricyclic (or heterocyclic) antidepressants inhibit the reuptake of serotonin and/or norepinephrine, and are thus called due to their three (or more)-ring chemical structure. Some examples include:

- Amitriptyline (Elavil) 
- Nortriptyline (Aventyl)
- Maprotiline hydrochloride (Ludiomil)
- Desipramine hydrochloride (Norpramin)
- Clomipramine (Anafranil)

A similar drug is Bupropion (Wellbutrin), which is an aminoketone that weakly blocks norepinephrine, serotonin, and dopamine reuptake.

Tricyclic Antidepressants

MAOIs inhibit the breakdown of the enzyme that breaks down monoamine neurotransmitters. Some MAOIs have antidepressant effects, including:

- Phenelzine (Nardil)
- Isocarboxazid (Marplan)
- Tranylcypromine (Parnate)

Monoamine Oxidase Inhibitors (MAOIs)

Psychoplastogens class of compounds that take effect on neural plasticity in key circuits involved in brain health. Psychoplastogens include psychadelics, and produce a quantifiable change in plasticity within a short time frame (>72 h) post administration.

Psychoplastogens 

The study of the use of extracts and compounds obtained from mushrooms as medicines or health-promoting agents. Mycotherapy, also known as fungal or mushroom therapy, is a branch of natural medicine exploring the therapeutic properties and potential health benefits of various mushrooms. The practice of using mushrooms for medicinal purposes has been observed in different cultures throughout history, and it continues to gain recognition and scientific interest in modern times.

Mycotherapy

Medications that have Anticholinergic effects are associated with central and peripheral side effects. These include constipation, confusion, sedation, and dry mouth. Increased Anticholinergic exposure increases adverse risks.

Anticholinergic Medicines

Psychomotor stimulant drugs, such as amphetamines, are a primary treatment for narcolepsy. These medications function by increasing overall levels of neural activity to combat daytime sleepiness. Examples include modafinil, armodafinil, and various amphetamines.

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