Neuroinflammation After COVID-19 With Persistent Depressive and Cognitive Symptoms.

Importance: Persistent depressive symptoms, often accompanied by cognitive symptoms, commonly occur after COVID-19 illness (hereinafter termed COVID-DC, DC for depressive and/or cognitive symptoms). In patients with COVID-DC, gliosis, an inflammatory change, was suspected, but measurements of gliosis had not been studied in the brain for this condition. Objective: To determine whether translocator protein total distribution volume (TSPO VT), a marker of gliosis that is quantifiable with positron emission tomography (PET), is elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of persons with COVID-DC. Design, Setting, and Participants: This case-control study conducted at a tertiary care psychiatric hospital in Canada from April 1, 2021, to June 30, 2022, compared TSPO VT of specific brain regions in 20 participants with COVID-DC with that in 20 healthy controls. The TSPO VT was measured with fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA) PET. Main Outcomes and Measures: The TSPO VT was measured in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus. Symptoms were measured with neuropsychological and psychological tests, prioritizing outcomes related to striatal function. Results: The study population included 40 participants (mean [SD] age, 32.9 [12.3] years). The TSPO VT across the regions of interest was greater in persons with COVID-DC (mean [SD] age, 32.7 [11.4] years; 12 [60%] women) compared with healthy control participants (mean [SD] age, 33.3 [13.9] years; 11 [55%] women): mean (SD) difference, 1.51 (4.47); 95% CI, 0.04-2.98; 1.51 divided by 9.20 (17%). The difference was most prominent in the ventral striatum (mean [SD] difference, 1.97 [4.88]; 95% CI, 0.36-3.58; 1.97 divided by 8.87 [22%]) and dorsal putamen (mean difference, 1.70 [4.25]; 95% CI, 0.34-3.06; 1.70 divided by 8.37 [20%]). Motor speed on the finger-tapping test negatively correlated with dorsal putamen TSPO VT (r, -0.53; 95% CI, -0.79 to -0.09), and the 10 persons with the slowest speed among those with COVID-DC had higher dorsal putamen TSPO VT than healthy persons by 2.3 (2.30 divided by 8.37 [27%]; SD, 2.46; 95% CI, 0.92-3.68). Conclusions and Relevance: In this case-control study, TSPO VT was higher in patients with COVID-DC. Greater TSPO VT is evidence for an inflammatory change of elevated gliosis in the brain of an individual with COVID-DC. Gliosis may be consequent to inflammation, injury, or both, particularly in the ventral striatum and dorsal putamen, which may explain some persistent depressive and cognitive symptoms, including slowed motor speed, low motivation or energy, and anhedonia, after initially mild to moderate COVID-19 illness.

Monoamine Oxidase B Total Distribution Volume in the Prefrontal Cortex of Major Depressive Disorder: An [11C]SL25.1188 Positron Emission Tomography Study.

Importance: Monoamine oxidase B (MAO-B) is an important, high-density enzyme in the brain that generates oxidative stress by hydrogen peroxide production, alters mitochondrial function, and metabolizes nonserotonergic monoamines. Recent advances in positron emission tomography radioligand development for MAO-B in humans enable highly quantitative measurement of MAO-B distribution volume (MAO-B VT), an index of MAO-B density. To date, this is the first investigation of MAO-B in the brain of major depressive disorder that evaluates regions beyond the raphe and amygdala. Objective: To investigate whether MAO-B VT is elevated in the prefrontal cortex in major depressive episodes (MDEs) of major depressive disorder. Design, Setting, and Participants: This case-control study was performed at a tertiary care psychiatric hospital from April 1, 2014, to August 30, 2018. Twenty patients with MDEs without current psychiatric comorbidities and 20 age-matched controls underwent carbon 11-labeled [11C]SL25.1188 positron emission tomography scanning to measure MAO-B VT. All participants were drug and medication free, nonsmoking, and otherwise healthy. Main Outcomes and Measures: The MAO-B VT in the prefrontal cortex (PFC). The second main outcome was to evaluate the association between MAO-B VT in the PFC and duration of major depressive disorder illness. Results: Twenty patients with MDEs (mean [SD] age, 34.2 [13.2] years; 11 women) and 20 healthy controls (mean [SD] age, 33.7 [13.1] years; 10 women) were recruited. Patients with MDEs had significantly greater MAO-B VT in the PFC (mean, 26%; analysis of variance, F1,38 = 19.6, P < .001). In individuals with MDEs, duration of illness covaried positively with MAO-B VT in the PFC (analysis of covariance, F1,18 = 15.2, P = .001), as well as most other cortex regions and the thalamus. Conclusions and Relevance: Fifty percent (10 of 20) of patients with MDEs had MAO-B VT values in the PFC exceeding those of healthy controls. Greater MAO-B VT is an index of MAO-B overexpression, which may contribute to pathologies of mitochondrial dysfunction, elevated synthesis of neurotoxic products, and increased metabolism of nonserotonergic monoamines. Hence, this study identifies a common pathological marker associated with downstream consequences poorly targeted by the common selective serotonin reuptake inhibitor treatments. It is also recommended that the highly selective MAO-B inhibitor medications that are compatible for use with other antidepressants and have low risk for hypertensive crisis should be developed or repurposed as adjunctive treatment for MDEs.

Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis.

Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case-control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capacity) in immigrants compared to nonimmigrants were performed in Canada and the United Kingdom. The Canadian dopamine release study included 25 immigrant and 31 nonmigrant Canadians. These groups included 23 clinical high risk (CHR) subjects, 9 antipsychotic naïve patients with schizophrenia, and 24 healthy volunteers. The UK dopamine synthesis study included 32 immigrants and 44 nonimmigrant British. These groups included 50 CHR subjects and 26 healthy volunteers. Both striatal stress-induced dopamine release and dopamine synthesis capacity were significantly elevated in immigrants compared to nonimmigrants, independent of clinical status. These data provide the first evidence that the effect of migration on the risk of developing psychosis may be mediated by an elevation in brain dopamine function.

Dopamine response to psychosocial stress in humans and its relationship to individual differences in personality traits.

BACKGROUND: Previous studies have reported inter-individual variability in the dopamine (DA) response to stress. This variability might be related to individual differences in the vulnerability to experience the negative effect of stress. OBJECTIVE: To investigate whether personality traits as measured by the revised NEO personality inventory explain variability in DA response to a psychosocial stress task. METHODS: Eleven healthy adults, mean age of 26 ± 3.87 underwent two positron emission tomography (PET) scans using the dopamine D(2/3) agonist, [11C]-(+)-PHNO under a control and stress condition. The simplified reference tissue model (SRTM) was used to obtain [11C]-(+)-PHNO binding potential (BP(ND)). Stress-induced DA response was indexed as a percent change in [11C]-(+)-PHNO BP(ND) between control and stress conditions. The regions of interest were defined into D2-rich regions, which included the Associative and Sensorimotor Striatum (AST and SMST); D(2/3) mixed regions, which included the limbic striatum (LST) and globus pallidus (GP); and D3-rich region, which included the Substantia Nigra (SN). RESULTS: Several personality traits within the Neuroticism and Openness to Experience domain were significantly correlated with blunted DA response to stress. Specifically, the Angry-Hostility, Vulnerability, and Depression trait were associated with blunted DA stress response in the AST (r = -0.645, p = 0.032), LST (r = -0.677, p = 0.022) and GP (r = -0.736, p = 0.010), respectively. The Openness to Values was correlated with a decreased DA release in the SN (r = -0.706, p = 0.015). CONCLUSION: Variability in DA stress response might be related to individual differences in personality.

Utility of the MMPI-2-RF in detecting non-credible somatic complaints.

We examined the utility of the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) validity scales (infrequent responses (F-r), infrequent psychopathology responses (Fp-r), infrequent somatic responses (Fs), symptom validity (FBS-r), and response bias (RBS)) in differentiating individuals who were asked to feign physical health problems from a group of somatoform disorder patients and genuine medical patients with no history of mental health problems. A large group of undergraduate students were instructed to feign physical health problems as if they were participating in a disability evaluation for a work-related injury. Comparison groups were drawn from archival databases and consisted of non-litigating medical patients or individuals carefully diagnosed with somatoform disorder. The Fs and Fp-r scales were associated with the best differentiation between the three groups; the Fs scale was the most sensitive to somatic malingering, whereas the Fp-r scale was the most specific. Both scales were associated with high likelihood ratios in differentiating the somatic malingering group from the somatoform and medical illness groups. Although the FBS-r scale was overall the most sensitive in differentiating non-credible somatic complaints from genuine medical illness, it could not differentiate well between the somatic malingering and somatoform patient conditions. The MMPI-2-RF appears to have considerable promise in detecting individuals who feign physical health problems. Not surprisingly, differentiating somatic malingering from somatoform disorder with the MMPI-2-RF was less accurate than differentiating somatic malingering from bona-fide medical patients.

The Observer-Rated Scale for Mania (ORSM): development, psychometric properties and utility.

BACKGROUND: The diagnosis of mania largely depends on the quality of information the physician is provided with. Often, the patient cannot give an accurate account of the symptom development and thus information from relatives and friends is required. No systematic rating instrument is available, however, to facilitate this. OBJECTIVE: In this study, the psychometric properties of the 49-item Observer-Rated Scale for Mania (ORSM) are reported. METHODS: The scale was used in 113 inpatients and the following psychometric aspects were assessed: reliability, test-retest reliability, construct validity (factor analysis, discriminant analysis, comparison of means), extreme-group validity, prognostic validity, sensitivity, specificity, positive and negative predictive values. RESULTS: The ORSM proved highly valid and reliable. Factor analysis revealed three factors which were labelled euphoric mania, instable mania and psychotic mania. CONCLUSION: The ORSM is a useful instrument to help non-professionals who are in regular contact with the patient diagnosed a manic/mixed episode. It thus complements existing rating scales for mania, which are either designed for professionals or are self-rating instruments.

Alexithymia and pathological gambling.

The purpose of this study was to study the relationship between alexithymia and gambling in a community sample of pathological gamblers. Pathological, problem and non-problem gamblers were recruited from the community via advertisements and completed an assessment of their gambling behavior and the Toronto Alexithymia Scale. Alexithymia was higher among male pathological gamblers who identified slot machines, cards, and lotteries as their primary gambling problem. High alexithymics scored higher on Diagnostic and Statistical Manual symptoms related to poor self-regulation, communication, and problem-solving skills. Although a correlational study, the evidence suggests that further investigation of the clinical significance of alexithymia in individuals with severe gambling pathology is indicated.

A comparison of evaluations of male and female psychiatry supervisors.

OBJECTIVE: To assess whether male and female psychiatry supervisors are evaluated differently by psychiatry residents. METHODS: The University of Toronto Department of Psychiatry compiled anonymous supervisor evaluations completed semiannually by psychiatry residents over a period of 3 years. Male and female psychiatry supervisors' ratings were compared by using t-tests, effect estimates, and chi-square analyses. Results from these ratings were discussed in a resident focus group. RESULTS: Female psychiatry supervisors (n=76) were rated significantly lower than male supervisors (n=222), both overall (P<0.05) and in the areas of enthusiasm (P<0.05), clarity (P<0.05), and knowledge (P<0.001). CONCLUSIONS: Future studies comparing evaluations of supervision by male and female psychiatrists must control for academic rank, numbers of publications, and hours of teaching. Comparing evaluations of the various male-female supervisory pairs will be useful to assess for gender biases.