The period of 1920
During this time frame, psychotic disorders were associated with demonic spirits and the devil. These disorders instilled fear in those around them. These individuals were thought of as someone who "has been maddened by the sin of gods, or been robbed of sense by the Rakshas”.The stereotypes of madness were often synonymous with the symptoms of schizophrenia.
Ancient Egyptian and Chinese medicine suggested the heart as being the central player, controlling the mind and spirit. Hence it was inferred that symptoms of insanity and madness were associated with afflictions of the heart. Emil Kraepelin wrote a paper "The Influence of Acute Illness in the Causation of Mental Disorders." He was working on the classification of mental illness around that time frame. While Kraepelin called these patients as having “Dementia Praecox”, it was Eugene Bleuler who in 1908 coined the term schizophrenia. Bleuler stated that dementia praecox was neither associated with dementia or precociousness and emphasized the splitting of psychic functioning as an essential feature of schizophrenia.
Hence with this backdrop treatments in the early 20th century were crude and lacked evidence. These treatments often involved gas therapy and injection of sulphur or oils to induce fever. At this point, even prefrontal leukotomy or insulin coma therapy were not in use. These approaches came in to use after 1935.
In summary, there were no well-established treatments 100 years ago and patients were housed in asylums and had agricultural duties.
Owen R. Schizophrenia-From devilry to disease. Res Medica 2014;22: 126-132
Fast forward 100 years later the year 2020
Now there are multiple hypotheses as to the cause of schizophrenia. There have been twin and family studies suggesting heritable risk factors account for 80% of the risk of this psychiatric disorder in a population. Now we think on the lines of environmental factors such as obstetric complications, immune system-related factors, and synaptic plasticity and function. These factors are thought to have an interaction with genetic risks to increase the likelihood of schizophrenia.
Sophisticated MRI studies have revealed lower gray matter volumes. Studies reveal there is increased gray matter loss over time in the prefrontal and parahippocampal brain regions amongst those with psychosis. Immunological markers (related to cytokines) have been associated with the rate of gray matter loss. Theories have developed around a lack of coordination between various brain regions such as the prefrontal cortex, temporal cortex, hippocampus, thalamus, and cerebellum. The concept of cognitive dysmetria has been proposed. Animal models using rats, mice, and primates have been developed for the study of this disorder.
There have been various diagnostic classifications of schizophrenia into subtypes (paranoid, undifferentiated, disorganized type) which have been abandoned now in DSM-5 due to lack of consistency, reliability, and to simplify the diagnosis.
Neurochemical models such as the theory that psychosis is related to excessive dopamine activity are established. This theory suggests that medications blocking the D2 receptor cause downstream changes leading to clinical response. These medications, however, block dopamine activity in the basal ganglia leading to neuroleptic-induced parkinsonism. Similarly, effects on the tuberoinfundibular system lead to elevations in prolactin levels and related effects. More recently it is known that dopamine interacts with glutamate and γ-aminobutyric acid (GABA) affecting the functioning of microcircuits modulating the excitatory and inhibitory interneurons in cortical circuits. These neurotransmitters are being targeted more recently for the development of therapeutic agents. We also recognize now that the use of cannabis can precipitate schizophrenia in at-risk individuals.
It is well established that antipsychotic medications are effective in treating psychotic symptoms. We have a wide variety of antipsychotic drugs in 2020. This ranges from chlorpromazine the first antipsychotic available (not much used) to D3/D2 receptor partial agonists (cariprazine). Additionally, we also have clozapine which works for treatment-refractory schizophrenia. This drug also has an FDA indication for suicidality. The side-effects of the conventional antipsychotics include movement disorders such as extrapyramidal side-effects and TD while the atypical antipsychotics predominantly have weight gain and metabolic issues. There is a newer group of medications such as cariprazine, lurasidone, and lumateparone that have minimal if any weight gain.
The use of cognitive-behavioral therapy in schizophrenia has also helped manage this disease especially those who are partially responsive to medications for schizophrenia. Multiple other approaches are available such as family-based services, skills training, supportive employment. There is also the availability of IQ testing which can be helpful.
Long-acting injectable (LAI) antipsychotics have been developed and there are many to choose from in the year 2020. The dosing interval is variable for some of these medications (1-3 months). Side-effects such as tardive dyskinesia now also have FDA approved treatment choices such as valbenazine and deutetrabenazine.
Marder SR and Cannon TD. N Engl J Med 2019;381: 1753-1761