Most of people think psychosis is splitting of the mind, is this true? if not, then, what is psychosis, and how it can affect the human being?
Psychosis is a thought disturbance ( psychiatric disorder ) (1) (Dr.Marian Gorge) . since long time ago, psychosis was generally described as significant impairment in the testing of the truth or “ loss of ego boundaries “ witch interfere with the ability to meet ordinary demand (2). Only 1-2% of the population are susceptible to the disease. (1)
The causes of psychosis may be genetic or due to brain changes like changes in the structure of the brain or in the chemicals or due to hormonal effect like in postpartum psychosis, and Psychosis can be divided according to the dominated symptoms into catatonic ( purposeless movement and rigid immobility ), disorganized, paranoid and undifferentiated (1).
Psychosis is a condition consisting of several symptoms. This is not an object which is nosological. Psychosis symptoms occur in a wide range of mental disorders and show a high degree of inter-individual variability among people with different mental disorders and a high degree of intra-individual variability over time but the concept and meaning of psychosis are defined by the central clinical symptoms of delusions, hallucinations, and disorganized thought so, it may include symptoms of mania and depression. (3) (Wolfgang Gaebel)
Psychosis is characterized by three groups of symptoms. The first is the positive symptoms which include Insomnia, Hallucination, catatonic behavior, and paranoid delusion. And the second is the negative symptoms and include amotivation, apathy, asocial, and loss of pleasure in normally happy events. And the third group is the disorganized symptoms including the patient’s thoughts, talks, behavior, and loss of concentration. The patient has to have at least two symptoms that last one month and at least one area if social or occupational function is significantly affected to be diagnose as psychotic patient. (1)
Pharmacotherapy of psychosis can be divided according to mechanism of action into two types, typical and atypical. Typical antipsychotics act mainly as D2 blockers whereas atypical antipsychotics' mechanism is to block both 5HT2A and D2. (1)
An atypical APD is described more precisely and simply as one that produces minimal EPS at clinically effective doses (4) (Meltzer HY. 2000.) which is considered as one of the major side effects found in typical antipsychotics. So, it is preferable to start the treatment with them according to the American psychiatric association (1). Some examples of atypical APD are clozapine (5) (Schulte P. 2003.), risperidone, quetiapine, and olanzapine (6) (Y. Meltzer. 2013) (1), sertindole, sulpiride, and aripiprazole. (1) Clozapine is the gold standard due to its high efficacy in treating positive symptoms in patients with treatment-resistant schizophrenia (TRS) (7) (Kane J,1988)but it has some side effects like agranulocytosis, seizures, and the side effects of atypical APD generally include weight gain, atropine-like effect, orthostatic hypotension, and sedations. (1)
Pharmacotherapy by typical antipsychotics includes three generations which have the same efficacy but different potency so can be classified according to the potency to high potency drugs (eg: Trifluoperazine, Fluphenazine, Haloperidol, and Zuclopenthixol ), moderate potency drugs ( eg: Chlorpromazine and Loxapine ) and low potency drugs (eg: Thioridazine ). These drugs have many side effects which may be due to dopamine blocking like Extrapyramidal side effects [EPS] (dystonia, Akathisia, Pseudo-parkinsonism, Tardive dyskinesia ), neuroleptic malignant syndrome, and endocrine disturbances and may not like sedation and postural hypotension. (1)
The original experiments undertaken to explain the brain pathology of psychosis date back to 1935 and included the study of brain structures of people with psychosis using X-ray imagery by using pneumoencephalography that was very painful. Studies have shown that neurotransmitters can play a role in depression in the brain (e.g. serotonin and dopamine). Some studies reveal that 5-HT2A receptor activation can lead to hallucination. Hallucination and delusion are not the biggest issues in psychosis, but the inability to differentiate between them and reality. In people who have auditory hallucinations, brain scans using PET (positron emission tomography) or fMRI (functional magnetic resonance) imaging indicate that areas of the brain that regulate speech and hearing are impaired.(8)( Dr. Ananya Mandal) Also motor disorders (MAs) are extremely prevalent both before any diagnosis and during treatment with antipsychotic medications in patients with first-episode psychosis. However, it is not understood to what degree such phenomena have predictive value for long-term psychosocial functioning. (9)( Cuesta MJ1…et al, 2019)
A growing body of literature assists in the pathophysiology of psychosis a role for neuroinflammation. Though the underlying relation between these factors and psychosis development is still not clear, A promising target for these factors is a population of N-methyl - d-aspartate receptors (NMDARs)-containing prefrontal cortex and hippocampus parvalbumin interneurons (PVIs), which are likely to be disturbed during major developmental windows. (10)
The genetic studies give an indicator of the importance of inflammation in schizophrenia. Multiple genome-wide association studies have concluded that the main island of histocompatibility (MHC) on chromosome 6, which is a pillar of the immune system, has the greatest allegiance to schizophrenia. In particular, it was found that the complement component 4 (C4 gene) within the island of human leukocyte antigen (HLA) has a strong association with schizophrenia(11) (Purcell SM,2009) . C4 includes both the opsonization of pathogens and synaptic pruning, which can be related to the developmentally timed existence of the risk of schizophrenia (12).
References:
Lecture 7, Dr. Marian gorge, American Psychiatric Association Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders, 4th edition text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association, 2000
Focus on psychosis , Wolfgang Gaebel,. Jürgen Zielasek, , Dialogues Clin Neurosci. 2015 Mar; 17(1): 9–18.
An atypical compound by any other name is still a….. . Meltzer HY. 2000. Psychopharmacology (Berlin) 148(1): 16-19
What is an adequate trial with clozapine? Therapeutic drug monitoring and time to response in treatment-refractory schizophrenia Schulte P. 2003. Clin. Pharmacokinet. 42(7): 607–18
Update on typical and atypical antipsychotics. Y . Meltzer. Vol. 65:393-406 (volume publication date: January 2013) . https://doi.org/10.1146/annurev-med-050911-161504
Clozapine for the treatment-resistant schizophrenia. A double-blind comparison with chlorpromazine. Kane J, Honigfeld G, Singer J, et al. 1988. Arch. Gen. Psychiatry 45(9): 789–96
Psychosis Pathophysiology. Dr. Ananya Mandal.
Motor abnormalities in first-episode psychosis patients and long-term psychosocial functioning. Cuesta MJ1, García de Jalón E2, Campos MS3, Moreno-Izco L4, Lorente-Omeñaca R4, Sánchez-Torres AM4, Peralta V2. 201 . 2018 Oct;200:97-103.doi: 10.1016/j.schres.2017.08.050. Epub 2017 Sep 8.
Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis. Hardingham GE, Do KQ. Nat Rev Neurosci. 2016 Feb; 17(2):125-34.
Common polygenic variation contributes to the risk of schizophrenia and bipolar disorder. International, Schizophrenia Consortium., Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P. Nature. 2009 Aug 6; 460(7256):748-52.
Schizophrenia risk from complex variation of complement component 4.