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

BUTLER HOSPITAL of Rhode Island … plus connections

By Steve Lippmann, M.D.

Well, seems like maybe we are getting over the pandemic. We have lessened coronavirus fears, attenuation of COVID-19 illness severity, and my wife and I are fully vaccinated. Great. With restrictions on travel eased in April 2021, we visited our eldest daughter in Rhode Island. A Brown University emergency medicine faculty member, she was our tour guide; Butler Hospital was among the first things she showed us in Providence. Yes, she took us to the beach, town, medical school, and other affiliated hospitals, too.

Butler Hospital is a very old psychiatric facility and now affiliated with Brown University. What about Butler?

The hospital was founded in 1884 as one of the earliest mental health facilities in this country. It is a huge institution sitting on a surprisingly massive, yet attractive campus that houses numerous buildings, a park-like environment, and even a two-century old farmhouse. Besides the expected many in-patient facilities for psychiatry and addiction medicine, it also hosts a day hospital, and services for social work, a wide variety of offices for other out-patient medical specialties, research facilities, and legal aspects, that include a courthouse. A network of campus roads and parking lots link the numerous buildings.Butler is a base for Brown University’s Psychiatry Department and remains a famous, award-winning mental health hospital. The focus is on psychiatry, addiction medicine, research, and movement disorders, like Parkinson’s disease. They serve adolescents and adults; children, too, had been included, but kids these days go to another affiliated facility. The hospital campus also has a psychiatry emergency evaluation and treatment center with close ties to Brown’s two main Emergency Medicine Departments. Butler Hospital also has an interesting history.

One prominent story is about Dr. William Halsted. He was a famous, early leader in aseptic surgery, use of anesthesia during operations, and numerous innovative surgical techniques. Dr. Halsted was admitted as a patient to the Butler Hospital because of his being addicted to cocaine. At Butler, physicians back then prescribed opiates to attenuate cocaine drug withdrawal, as was the accepted medical practice in those days. Thus, Dr. Halsted got “switched” from cocaine dependance to became opiate addicted; hard to imagine now adays … sad, but true.

Together with the Oxford internist, Sir William Osler, Dr. William Halsted was one of the founders of Johns Hopkins Medical School. It offered excellent, up-to-date physician education. Here now follows a Louisville connection.

Back in those days American medical schools were generally not up to European scientific standards. They were unregulated, often proprietary, and without academic requirements, faculty, or credentialing. Our own Louisvillian, Abraham Flexner was part of a movement that evaluated all American medical schools, closed them, and only allowed reopening only if they met the Johns Hopkins role model for educating new doctors. That included having faculty on-staff in all specialties, providing clinical care to patients, while actually teaching medical students. This reform greatly improved US medical training. Oh, Abraham Flexner Way, a road named in his honor, is in Louisville, running between Jewish Hospital and the University of Louisville of School of Medicine.

By the way, Johns Hopkins Medical School was originally conceived in the 1890s to be built with a big economic donation of railroad stock shares. It was to be a public hospital without race or other restrictions for patient admissions. However, a stock market decline left insufficient funds. The donor’s daughters agreed to help fund the new school, but IF and ONLY if women students were to be admitted under the same criteria as men. The administrators initially refused, but short on money, they finally agreed. Johns Hopkins was then established offering a top-quality medical education as the national role model for all US medical schools to copy. Hopkins also helped begin the concept of admitting women to study medicine in this country. So be it.                                                                

Rescheduled: KPMA 2020 Annual Meeting

Please join us virtually on Thursday, October 15th and 22nd, for our 2020 Annual Meeting. This meeting will be free for all KPMA members.

On October 15th, from 6:30pm – 8:30pm we will have a panel discussion on addiction featuring Dr. Allan Brenzel, Dr. Lon Hays, Dr. Chris Stewart, and Dr. Michelle Lofwall. A Q&A/live discussion will take place from 8:30pm – 9:00pm.

On October 22nd, from 7pm – 8:30pm we will have a panel discussion addressing social justice issues and health disparities featuring Dr. Julio Ramirez, Dr. Cheryl Willis and Dr. Stephanie White. A Q&A/live discussion will take place from 8:30pm – 9:00pm.

Register Now

KPMA Town Hall

Please join us Monday, June 1st, from 6pm – 7pm for a discussion with Dr. Allen Brenzel regarding the climate of mental health in Kentucky and what psychiatry can do to help. We will also be discussing current changes in our practice systems and what we anticipate needing in the future to provide quality patient care. We will offer two breakout sessions led by Dr. Randy Schrodt and Dr. Kathy Vincent. Dr. Schrodt will moderate conversation around ambulatory/outpatient psychiatry while Dr. Vincent moderates conversation around academic/inpatient psychiatry. Registration is required. This town hall is open to members only.

Register Now