Our meeting slated for Friday, September 24th, at the Louisville Boat Club has been postponed until the spring. We will announce further plans later this month. If you have already registered, please use the link below to indicate if you prefer a credit or full refund.
Raymond Pary, M.D., VA Hospital, VA Staff Psychiatrist and Steven Lippmann, M.D., Retired PsychiatristLouisville, KY
Schizophrenia has a heterogeneous clinical prodrome and variable outcome. It usually occurs with symptoms of delusions and auditory hallucinations. Sometimes, affective presentations include depression or mania, or less often, catatonia with bradykinesia and mutism. Such presentations are often labeled schizoaffective disorder or catatonia, respectively. Clinical patterns alter over time as do lifetime diagnoses and are unpredictably identified even by accomplished psychiatrists. Agitated and/or violent behavior is occasionally observed.
A historical perspective on schizophrenia starts with Emil Kraepelin. In the early 1900s, he attributed degenerative cells in the brain as being responsible for the deteriorating course of illness. The brain pathology is likely genetic and/or related to gene expression, but there are many unanswered questions about the [RP1] role genes have in the neuropathology. Further understanding is needed to understand how the heterogeneous brain connections and circuits contribute to schizophrenia. Diagnoses, now based on subjective clinical symptoms, will in the future hopefully be determined by documentable brain changes. Some amelioration of clinical severity for many patients followed the 1960s advent of administering antipsychotic medications; yet, responses to these drugs is variable.
Sigmund Freud speculated that schizophrenia resulted from disintegration of the ego and separation from reality. Accordingly, the death of the ego produced a loss of self-identity. Unsuccessful attachment to the opposite sex parent and disordered family patterns were thought to contribute to the psychopathology. Paranoid delusions are stress-induced, based on unconscious homosexual impulses. These theories were further elaborated and included the concept of the “schizophrenogenic mother”. Such concepts might have retarded research progress about neurobiology, and there is a dearth of evidence corroborating that mothers actually cause schizophrenic illnesses in their offspring.
Pneumoencephalographic studies reveal that people with schizophrenia have abnormally large brain ventricles. Computerized tomography corroborates this finding. It also suggests that schizophrenia begins in utero as a neurodevelopmental disorder, and that manifestations vary over the life cycle. Ventricular enlargement is not static and appears to exert influence on the illness pathology.
Magnetic resonance brain imaging research among neonates at high risk for schizophrenia reveals that cortical thickness alterations, diminished gray matter volume, and white matter changes occur in the same regions as where pathology is documented in adults with schizophrenia. This supports a neurodevelopmental abnormality. However, structural investigations document non-specific gray and white matter abnormalities that differ among patients and are not diagnostic.
Positron emission tomography measures blood flow and glucose utilization, depicting abnormalities of brain function. Such investigations evidence deficits in working memory, executive functioning, processing speed, and language production. Imaging studies reveal anatomic abnormalities in the medial frontal cortex, the posterior cingulate cortex, reduced cortical thickness, white matter abnormalities, and enlarged lateral ventricles. The subcortical amygdala, thalamus, hippocampus, and nucleus accumbens are documented to be subnormal in size.
The dopamine hypothesis involving these structures during this illness has undergone refinements over time. In short, the assumption was that hyperactivity of dopamine D2 receptors influence the presence of positive symptoms, while hypofunction of the D1 receptor in the prefrontal cortex may have a role in the negative manifestations of disease. Abnormalities of dopamine may change over different stages of illness and are dependent on other neurochemical systems. These interactive neuronal networks also at least involve glutamate, gamma-aminobutyric acid, and serotonin.
There are progressive alterations in the brains of some patients with schizophrenia. The apparent brain volume changes also might be explained to be imaging artifacts or induced by exposure to antipsychotic pharmaceuticals. The neuropathology leading to hallucinations and delusions remains unexplained. Similar questions apply to the pathological variance among individuals. It is still not established as to whether early detection and treatment mitigate disease progression. Nevertheless, antipsychotic drugs exert a positive influence on the lives of many people with this illness; withdrawing these pharmaceuticals usually yields worsening clinical outcomes for those affected.
Schizophrenia is a disease with genes influencing the development of brain structure and neuronal performance. Alteration of cortical and subcortical structures has pathological consequences for white matter function. These vary between individuals, but abnormalities in neuronal connectivity occurs in many individuals with this illness. Research continues. Antipsychotic medicines generally induce some clinical improvement; yet, there remains no means to cure or fully understand this terrible disease. The neurobiology of schizophrenia is still an enigma.
A Suggested ReadingDelisi, L. The Neurobiology of Schizophrenia. Focus 2020; 18 (4): 368-374