Schizophrenia, clinical and basic research at NIMH: A 75 Year retrospective.

Objective: In 2024, NIMH is celebrating its 75th anniversary. At the Congressional hearings preceding its initial funding in 1949, witnesses stressed the need for NIMH to carry out clinical and basic research to find the causes and better treatments for severe mental illnesses. Patients with schizophrenia alone were said to occupy one quarter of all hospital beds in the U.

The Underuse of Clozapine and Long-Acting Injectable Antipsychotics.

Schizophrenia is among the most devastating and costly human diseases. The public face of the failure to appropriately treat schizophrenia includes approximately 100,000 homeless individuals with schizophrenia and related psychoses and 200,000 incarcerated individuals with similar diagnoses. Clozapine and long-acting injectable antipsychotics are among the most effective treatments, but both are markedly underused.

Did the human genome project affect research on Schizophrenia?

The Human Genome Project was undertaken primarily to discover genetic causes and better treatments for human diseases. Schizophrenia was targeted since three of the project`s principal architects had a personal interest and also because, based on family, adoption, and twin studies, schizophrenia was widely believed to be a genetic disorder. Extensive studies using linkage analysis, candidate genes, genome wide association studies [GWAS], copy number variants, exome sequencing and other approaches have failed to identify causal genes.

Mercury and Parkinson's Disease: Promising Leads, but Research Is Needed.

Environmental toxicants are thought to play a major role in the pathogenesis of Parkinson's disease. In reviewing the literature on heavy metals known to be toxicants, we noted several recent studies on mercury suggesting a possible role in the etiology of some cases of this disease. We therefore undertook a review of this association, focusing especially on peer-reviewed articles to avoid the bias inherent in much of the literature regarding mercury.

The NIMH Research Portfolio: An Update.

To examine the funding priorities of the National Institute of Mental Health (NIMH) since 2016 to assess whether NIMH was continuing to prioritize basic research at the expense of clinical research. Six psychiatric disorders (schizophrenia, bipolar disorder, depression, anxiety disorders, eating disorders, autism) were assessed using 2 publicly available data sources (ClinicalTrials.gov and the National Institutes of Health Research, Condition, and Disease Categorization [RCDC]) to determine the degree of NIMH support for drug trials and research on these disorders in general since 2016.

The Continuing Decline of Clinical Research on Serious Mental Illnesses at NIMH.

It has been claimed that the National Institute of Mental Health (NIMH) budget, which traditionally has been evenly balanced between basic and clinical research, has shifted sharply and that 90% of NIMH resources are funding basic research. The authors used public data sources to assess this claim: the Research Condition and Disease Categorization Database, ClinicalTrials.gov, and the NIMH Strategic Plan for Research for 2020-2024.

Using the NIH Research, Condition and Disease Categorization Database for research advocacy: Schizophrenia research at NIMH as an example.

In 2008 the National Institutes of Health established the Research, Condition and Disease Categorization Database (RCDC) that reports the amount spent by NIH institutes for each disease. Its goal is to allow the public "to know how the NIH spends their tax dollars," but it has been little used. The RCDC for 2018 was used to assess 428 schizophrenia-related research projects funded by the National Institute of Mental Health.

Schizophrenia as a pseudogenetic disease: A call for more gene-environmental studies.

In recent years schizophrenia has been assumed to be largely a genetic disease with heritability estimates, derived primarily from family and twin studies, of 80%-85%. However, the results of genetic research on schizophrenia have not yielded results consistent with that estimate of heritability. In particular, extensive genetic studies have not led to new methods for diagnosis and treatment.

Birth month and later diagnosis of schizophrenia. A population-based cohort study in Sweden.

The objective of the present study was to examine if the monthly variation in births of individuals diagnosed with schizophrenia currently differs from that of unaffected individuals in Sweden. In an extensive linkage of Swedish national and regional population registers we here investigate the birth pattern of the population born 1940-97 (5,995,499 individuals) which included 30,684 individuals diagnosed with schizophrenia in the National Patient Register by December 31, 2016. Among 2,409,862 individuals born since 1973 we investigated potential confounding by co-variates associated with pregnancy and birth.

Familial abnormalities of endocannabinoid signaling in schizophrenia.

Objectives: Epidemiological and experimental evidence suggests that the endocannabinoid system plays a pathophysiological role in schizophrenia. This is reflected by elevated cerebrospinal levels of the endocannabinoid anandamide in schizophrenia and its initial prodromal states.

Methods: We analyzed plasma concentrations of anandamide, 2-arachidonoyl-sn-glycerol, palmitoylethanolamide and oleoylethanolamide from 25 twin pairs discordant for schizophrenia, six discordant for bipolar disorder and eight healthy twin pairs to determine hereditary traits.

Evidence of increased exposure to Toxoplasma gondii in individuals with recent onset psychosis but not with established schizophrenia.

A possible role for Toxoplasma gondii in the etiopathogenesis of schizophrenia is supported by epidemiological studies and animal models of infection. However, recent studies attempting to link Toxoplasma to schizophrenia have yielded mixed results. We performed a nested case-control study measured serological evidence of exposure to Toxoplasma gondii in a cohort of 2052 individuals.

Second Chance.

My second career as a schizophrenia researcher will focus on infectious agents as a cause. It will include the collection of serial sera, cerebrospinal fluid, functional magnetic resonance imaging, and diffusion tensor imaging on a cohort of affected individuals over 20 years. Since I believe that the initial transmission of these agents occurs in childhood, I will also follow a cohort of children from birth to age 20.

Schizophrenia and Infections: The Eyes Have It.

The visual tract is prominently involved in schizophrenia, as evidenced by perceptual distortions and a type of nystagmus found in many individuals affected. Genetic explanations for these abnormalities have been suggested. This study proposes an alternate explanation based on infection.