Update on Neurodegenerative Diseases and Glutamate: A PMHNP Single Case Study Report of a Diagnostically Complex Adult Patient, Interventions, and Unexpected Outcomes.

OBJECTIVE: While dysfunction of serotonin and dopamine neurotransmitters has been studied in depth, in regard to the etiology of mental illness, the neurotransmitter glutamate and its dysfunction is now being explored as contributing to neurodegenerative psychiatric diseases, schizophrenia, autism, depression, and Alzheimer's disease. This article explains its synthesis, neurotransmission, and metabolism within the brain and subsequent dysfunction that is responsible for neurocognitive loss associated with several psychiatric disorders. METHOD: The case study will report on the screening for pseudobulbar affective (PBA) disorder in a 29-year-old male with bipolar disorder, autism spectrum disorder, and intellectual developmental disability who was experiencing extreme, uncontrolled emotional outbursts requiring continuous family isolation (pre-COVID-19) for safety. With the positive screen for PBA, the patient was subsequently treated with a glutamatergic drug, dextromethorphan/quinidine. RESULTS: The patient's unexpected response to this treatment including the acquisition of language, increased cognition, and improved executive functioning is presented. At 2 years post the initiation of treatment, his PBA screening score is reduced, uncontrolled outbursts and aggression have subsided, and the family can spend time outside of their home. CONCLUSIONS: Neurodegeneration and its impact is being researched and treated with medications affecting glutamate. The addition of a glutamatergic medication to this young man's medication regimen has improved both his and his family's quality of life. The psychiatric diagnoses, medications, and treatments associated with glutamate are explained in depth. The importance of nurses' understanding of glutamate, its synthesis, transmission, and dysfunction causing excitotoxicity and brain cell death and its impact on patients' behavior and safety is explained.

Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia in 106,160 Patients Across Four Health Care Systems.

OBJECTIVE: Individuals at high risk for schizophrenia may benefit from early intervention, but few validated risk predictors are available. Genetic profiling is one approach to risk stratification that has been extensively validated in research cohorts. The authors sought to test the utility of this approach in clinical settings and to evaluate the broader health consequences of high genetic risk for schizophrenia. METHODS: The authors used electronic health records for 106,160 patients from four health care systems to evaluate the penetrance and pleiotropy of genetic risk for schizophrenia. Polygenic risk scores (PRSs) for schizophrenia were calculated from summary statistics and tested for association with 1,359 disease categories, including schizophrenia and psychosis, in phenome-wide association studies. Effects were combined through meta-analysis across sites. RESULTS: PRSs were robustly associated with schizophrenia (odds ratio per standard deviation increase in PRS, 1.55; 95% CI=1.4, 1.7), and patients in the highest risk decile of the PRS distribution had up to 4.6-fold higher odds of schizophrenia compared with those in the bottom decile (95% CI=2.9, 7.3). PRSs were also positively associated with other phenotypes, including anxiety, mood, substance use, neurological, and personality disorders, as well as suicidal behavior, memory loss, and urinary syndromes; they were inversely related to obesity. CONCLUSIONS: The study demonstrates that an available measure of genetic risk for schizophrenia is robustly associated with schizophrenia in health care settings and has pleiotropic effects on related psychiatric disorders as well as other medical syndromes. The results provide an initial indication of the opportunities and limitations that may arise with the future application of PRS testing in health care systems.

Predictors of length of stay in an acute psychiatric inpatient facility in a general hospital: a prospective study

Objective: There have been significant reductions in numbers of psychiatric beds and length of stay (LOS) worldwide, making LOS in psychiatric beds an interesting outcome. The objective of this study was to find factors measurable on admission that would predict LOS in the acute psychiatric setting. Methods: This was a prospective, observational study. Results: Overall, 385 subjects were included. The median LOS was 25 days. In the final model, six variables explained 14.6% of the variation in LOS: not having own income, psychiatric admissions in the preceding 2 years, high Clinical Global Impression and Brief Psychiatric Rating Scale scores, diagnosis of schizophrenia, and history of attempted suicide. All variables were associated with longer LOS, apart from history of attempted suicide. Conclusions: Identifying patients who will need to stay longer in psychiatric beds remains a challenge. Improving knowledge about determinants of LOS could lead to improvements in the quality of care in hospital psychiatry.

A Randomized Controlled Trial of Ethyl Glucuronide-Based Contingency Management for Outpatients With Co-Occurring Alcohol Use Disorders and Serious Mental Illness.

OBJECTIVE: The authors examined whether a contingency management intervention using the ethyl glucuronide (EtG) alcohol biomarker resulted in increased alcohol abstinence in outpatients with co-occurring serious mental illnesses. Secondary objectives were to determine whether contingency management was associated with changes in heavy drinking, treatment attendance, drug use, cigarette smoking, psychiatric symptoms, and HIV-risk behavior. METHOD: Seventy-nine (37% female, 44% nonwhite) outpatients with serious mental illness and alcohol dependence receiving treatment as usual completed a 4-week observation period and were randomly assigned to 12 weeks of contingency management for EtG-negative urine samples and addiction treatment attendance, or reinforcement only for study participation. Contingency management included the variable magnitude of reinforcement "prize draw" procedure contingent on EtG-negative samples (<150 ng/mL) three times a week and weekly gift cards for outpatient treatment attendance. Urine EtG, drug test, and self-report outcomes were assessed during the 12-week intervention and 3-month follow-up periods. RESULTS: Contingency management participants were 3.1 times (95% CI=2.2-4.5) more likely to submit an EtG-negative urine test during the 12-week intervention period, attaining nearly 1.5 weeks of additional alcohol abstinence compared with controls. Contingency management participants had significantly lower mean EtG levels, reported less drinking and fewer heavy drinking episodes, and were more likely to submit stimulant-negative urine and smoking-negative breath samples, compared with controls. Differences in self-reported alcohol use were maintained at the 3-month follow-up. CONCLUSIONS: This is the first randomized trial utilizing an accurate and validated biomarker (EtG) to demonstrate the efficacy of contingency management for alcohol dependence in outpatients with serious mental illness.

Interview-based assessment of cognition is a strong predictor of quality of life in patients with schizophrenia and severe negative symptoms

Objective: To analyze the correlation between quality of life, symptoms, and cognition assessed by the interview-based Schizophrenia Cognition Rating Scale (SCoRS). Methods: Seventy-nine outpatients diagnosed with schizophrenia were evaluated with the Quality of Life Scale – Brazilian version (QLS-BR), the SCoRS, and symptoms scales (Positive and Negative Syndrome Scale [PANSS]). After determining the potential explanatory variables using Spearman’s correlation and Student’s t test results, we ran simple, multivariate, and decision-tree regression analyses to assess the impact of SCoRS and PANSS ratings on mean overall quality of life. Results: Cognitive deficits and negative symptoms were the best predictors of quality of life. A low degree of negative symptoms (PANSS negative < 11) was a strong predictor of better quality of life (QLS ∼ 75), regardless of SCoRS rating. Among participants with more severe negative symptoms, elevated cognitive impairment (interviewer SCoRS ∼ 44) was a predictor of worse quality of life (QLS ∼ 44). Conclusions: Cognitive impairment determined by interview-based assessment seems to be a strong predictor of quality of life in subjects with severe negative symptoms. These results support the usefulness of SCoRS for cognitive assessment that is relevant to the everyday life of patients with schizophrenia.

Is semantic verbal fluency impairment explained by executive function deficits in schizophrenia?

Objective: To investigate if verbal fluency impairment in schizophrenia reflects executive function deficits or results from degraded semantic store or inefficient search and retrieval strategies. Method: Two groups were compared: 141 individuals with schizophrenia and 119 healthy age and education-matched controls. Both groups performed semantic and phonetic verbal fluency tasks. Performance was evaluated using three scores, based on 1) number of words generated; 2) number of clustered/related words; and 3) switching score. A fourth performance score based on the number of clusters was also measured. Results: SZ individuals produced fewer words than controls. After controlling for the total number of words produced, a difference was observed between the groups in the number of cluster-related words generated in the semantic task. In both groups, the number of words generated in the semantic task was higher than that generated in the phonemic task, although a significant group vs. fluency type interaction showed that subjects with schizophrenia had disproportionate semantic fluency impairment. Working memory was positively associated with increased production of words within clusters and inversely correlated with switching. Conclusion: Semantic fluency impairment may be attributed to an inability (resulting from reduced cognitive control) to distinguish target signal from competing noise and to maintain cues for production of memory probes.

Association between duration of untreated bipolar disorder and clinical outcome: data from a Brazilian sample

Objective: Bipolar disorder (BD) is often left untreated for long periods, and this delay in treatment correlates with unfavorable prognosis. The present study sought to assess the magnitude of duration of untreated bipolar disorder (DUB) in Brazil. We hypothesized that DUB would be longer in Brazil than in developed countries, and would be associated with poor clinical outcomes. Methods: One hundred and fifty-two psychiatric outpatients were evaluated for BD diagnosis, demographics, DUB, and clinical outcomes. Results: The mean age and mean DUB were, respectively, 38.9±10.8 and 10.4±9.8 years. An extended DUB was associated with early onset of BD (p < 0.001), depression as first mood episode (p = 0.04), and presence of BD in a first-degree relative (p = 0.012). Additionally, a longer DUB was associated with poorer clinical outcomes, such as elevated rates of rapid cycling (p = 0.004) and anxiety disorders (p = 0.016), as well as lower levels of current full remission (p = 0.021). Conclusion: As DUB may be a modifiable variable, better medical education regarding mental health, more structured medical services, and population-wide psychoeducation might reduce the time between onset and proper management of BD, thus improving outcome.

Depressive morbidity among elderly individuals who are hospitalized, reside at long-term care facilities, and are under outpatient care in Brazil: a meta-analysis

Objectives: i) To investigate studies published between 1991 and 2010 on the prevalence of depressive morbidity (major depressive disorder [MDD], dysthymia and clinically significant depressive symptoms [CSDS]) among elderly Brazilians assisted at healthcare facilities; ii) to establish the prevalence of depression and identify its related factors; and iii) to conduct a meta-analysis to assess the prevalence of depressive syndrome among elderly individuals assisted or hospitalized at healthcare facilities. Methods: Studies were selected from articles dated between January 1991 and June 2010 and extracted from the MEDLINE, LILACS, and SciELO databases. Results: The final analysis consisted of 15 studies, distributed as follows: i) four sampled hospitalized patients, totaling 299 individuals, and found a prevalence of CSDS varying between 20 and 56%; ii) four sampled outpatients, totaling 1,454 individuals; the prevalence of CSDS varied between 11 and 65%, and the prevalence of MDD varied between 23 and 42%; and iii) seven sampled elderly individuals residing in long-term care facilities (LTCF), totaling 839 individuals, and the prevalence of CSDS varied between 11 and 65%. Conclusion: The present review indicated a higher prevalence of both MDD and CSDS among elderly Brazilians assisted at healthcare facilities. .

Prevalence of psychiatric comorbidities in temporal lobe epilepsy in a Southern Brazilian population / Prevalência de comorbidades psiquiátricas na epilepsia do lobo temporal em uma população do sul do Brasil

A great prevalence of psychiatric disorders in epilepsy is well demonstrated, although most studies have used unstructured psychiatric interviews for diagnosis. Here we present a study evaluating the prevalence of psychiatric comorbidities in a cohort of Southern Brazilian patients with temporal lobe epilepsy (TLE) using a structured clinical interview. We analyzed 166 patients with TLE regarding neuropsychiatric symptoms through the Structured Clinical Interview for DSM-IV. One hundred-six patients (63.9 percent) presented psychiatric comorbidities. Mood disorders were observed in 80 patients (48.2 percent), anxiety disorders in 51 patients (30.7 percent), psychotic disorders in 14 (8.4 percent), and substance abuse in 8 patients (4.8 percent) respectively. Our results agree with literature data where most authors detected mental disorders in 10 to 60 percent of epileptic patients. This wide variation is probably attributable to different patient groups investigated and to the great variety of diagnostic methods. Structured psychiatric interviews might contribute to a better evaluation of prevalence of psychiatric comorbidities in TLE.

Embora muitos estudos tenham demonstrado uma alta prevalência de transtornos psiquiátricos em pacientes com epilepsia, a maioria utilizou entrevistas psiquiátricas não-estruturadas para o diagnóstico. Este método pode levar a diferenças significativas nos resultados. Nós estudamos a prevalência de comorbidades psiquiátricas em pacientes com epilepsia do lobo temporal (ELT), utilizando uma entrevista clínica estruturada. Foram estudados 166 pacientes com ELT, aos quais foi aplicada a Entrevista Clínica Estruturada para o DSM-IV (SCID). Cento e seis pacientes (63,9 por cento) apresentaram comorbidades psiquiátricas. Transtornos de humor, observados em 80 pacientes (48,2 por cento), foram o transtorno neuropsiquiátrico mais comum. Transtornos de ansiedade, observados em 51 pacientes (30,7 por cento), foram a segunda comorbidade psiquiátrica mais frequente. Transtornos psicóticos foram encontrados em 14 (8,4 por cento), e abuso de substâncias foram observados em 8 pacientes (4,8 por cento), respectivamente. Nossos resultados estão de acordo com os dados da literatura, que demonstra problemas psiquiátricos em 10-60 por cento dos pacientes com epilepsia. A grande variação dos resultados pode ser atribuída aos diferentes grupos de pacientes estudados e à variabilidade de métodos diagnósticos empregados. Entrevistas psiquiátricas estruturadas podem contribuir para uma avaliação mais adequada da real prevalência de comorbidades psiquiátricas na ELT.