Longitudinal structural MRI studies have shown that patients with schizophrenia have progressive brain tissue loss after onset. Recurrent relapses are believed to play a role in this loss, but the ...relationship between relapse and structural MRI measures has not been rigorously assessed. The authors analyzed longitudinal data to examine this question.
The authors studied data from 202 patients drawn from the Iowa Longitudinal Study of first-episode schizophrenia for whom adequate structural MRI data were available (N=659 scans) from scans obtained at regular intervals over an average of 7 years. Because clinical follow-up data were obtained at 6-month intervals, the authors were able to compute measures of relapse number and duration and relate them to structural MRI measures. Because higher treatment intensity has been associated with smaller brain tissue volumes, the authors also examined this countereffect in terms of dose-years.
Relapse duration was related to significant decreases in both general (e.g., total cerebral volume) and regional (e.g., frontal) brain measures. Number of relapses was unrelated to brain measures. Significant effects were also observed for treatment intensity.
Extended periods of relapse may have a negative effect on brain integrity in schizophrenia, suggesting the importance of implementing proactive measures that may prevent relapse and improve treatment adherence. By examining the relative balance of effects, that is, relapse duration versus antipsychotic treatment intensity, this study sheds light on a troublesome dilemma that clinicians face. Relapse prevention is important, but it should be sustained using the lowest possible medication dosages that will control symptoms.
Background Schizophrenia has a characteristic onset during adolescence or young adulthood but also tends to persist throughout life. Structural magnetic resonance studies indicate that brain ...abnormalities are present at onset, but longitudinal studies to assess neuroprogression have been limited by small samples and short or infrequent follow-up intervals. Methods The Iowa Longitudinal Study is a prospective study of 542 first-episode patients who have been followed up to 18 years. In this report, we focus on those patients ( n = 202) and control subjects ( n = 125) for whom we have adequate structural magnetic resonance data ( n = 952 scans) to provide a relatively definitive determination of whether progressive brain change occurs over a time interval of up to 15 years after intake. Results A repeated-measures analysis showed significant age-by-group interaction main effects that represent a significant decrease in multiple gray matter regions (total cerebral, frontal, thalamus), multiple white matter regions (total cerebral, frontal, temporal, parietal), and a corresponding increase in cerebrospinal fluid (lateral ventricles and frontal, temporal, and parietal sulci). These changes were most severe during the early years after onset. They occur at severe levels only in a subset of patients. They are correlated with cognitive impairment but only weakly with other clinical measures. Conclusions Progressive brain change occurs in schizophrenia, affects both gray matter and white matter, is most severe during the early stages of the illness, and occurs only in a subset of patients. Measuring severity of progressive brain change offers a promising new avenue for phenotype definition in genetic studies of schizophrenia.
Background A standardized quantitative method for comparing dosages of different drugs is a useful tool for designing clinical trials and for examining the effects of long-term medication side ...effects such as tardive dyskinesia. Such a method requires establishing dose equivalents. An expert consensus group has published charts of equivalent doses for various antipsychotic medications for first- and second-generation medications. These charts were used in this study. Methods Regression was used to compare each drug in the experts' charts to chlorpromazine and haloperidol and to create formulas for each relationship. The formulas were solved for chlorpromazine 100 mg and haloperidol 2 mg to derive new chlorpromazine and haloperidol equivalents. The formulas were incorporated into our definition of dose-years such that 100 mg/day of chlorpromazine equivalent or 2 mg/day of haloperidol equivalent taken for 1 year is equal to one dose-year. Results All comparisons to chlorpromazine and haloperidol were highly linear with R2 values greater than .9. A power transformation further improved linearity. Conclusions By deriving a unique formula that converts doses to chlorpromazine or haloperidol equivalents, we can compare otherwise dissimilar drugs. These equivalents can be multiplied by the time an individual has been on a given dose to derive a cumulative value measured in dose-years in the form of (chlorpromazine equivalent in mg) × (time on dose measured in years). After each dose has been converted to dose-years, the results can be summed to provide a cumulative quantitative measure of lifetime exposure.
Abstract
Objective
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related thyroiditis is increasingly recognized. The role of thyroid autoimmunity and SARS-CoV-2 viral load in ...SARS-CoV-2–related thyroid dysfunction is unclear. We evaluated the thyroid function of a cohort of coronavirus disease 2019 (COVID-19) patients, in relation to their clinical features, and biochemical, immunological, and inflammatory markers.
Methods
Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for COVID-19 from July 21 to August 21, 2020, were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine (fT3), and antithyroid antibodies were measured on admission.
Results
Among 191 patients with COVID-19 (mean age 53.5 ± 17.2 years; 51.8% male), 84.3% were mild, 12.6% were moderate, and 3.1% were severe. Abnormal thyroid function was seen in 13.1%. Ten patients had isolated low TSH, suggestive of subclinical thyrotoxicosis due to thyroiditis, although the contribution of autoimmunity was likely in 2 of them. Autoimmune thyroiditis probably also contributed to subclinical hypothyroidism in another patient. Ten patients had isolated low fT3, likely representing nonthyroidal illness syndrome. Lower SARS-Cov-2 polymerase chain reaction cycle threshold values and elevated C-reactive protein were independently associated with occurrence of low TSH (P = .030) and low fT3 (P = .007), respectively. A decreasing trend of fT3 with increasing COVID-19 severity (P = .032) was found. Patients with low fT3 had more adverse COVID-19-related outcomes.
Conclusion
Around 15% of patients with mild to moderate COVID-19 had thyroid dysfunction. There may be a direct effect of SARS-CoV-2 on thyroid function, potentially leading to exacerbation of pre-existing autoimmune thyroid disease. Low fT3, associated with systemic inflammation, may have a prognostic significance.
Objective
Baseline circulating thrombospondin‐2 (TSP2) level was identified as a potential novel hepatic fibrosis biomarker that associates with development and progression of hepatic fibrosis in ...patients with nonalcoholic fatty liver disease and type 2 diabetes. Here, we investigated whether circulating TSP2 levels changed with improvement in liver stiffness (LS), which reflects liver fibrosis on transient elastography.
Design
Serum TSP2 levels were measured in participants from a randomized, open‐label intervention study, at baseline and after 24‐weeks treatment of either dapagliflozin 10 mg (N = 30) or sitagliptin 100 mg daily (N = 30). Vibration‐controlled transient elastography was performed to evaluate the severity of hepatic fibrosis and steatosis using LS and controlled attenuation parameter (CAP), respectively.
Patients and Measurements
Among all 60 participants with similar clinical characteristics at baseline (mean HbA1c 8.9%, CAP 289 dB/m and LS 5.8 kPa), despite similar HbA1c lowering, treatment with dapagliflozin, but not sitagliptin, led to significant improvements in body weight (BW) (p = .012), CAP (p = .015) and LS (p = .011) after 24 weeks.
Results
Serum TSP2 level decreased significantly from baseline in dapagliflozin‐treated participants (p = .035), whereas no significant change was observed with sitagliptin. In correlation analysis, change in serum TSP2 levels only positively correlated with change in LS (r = .487, p = .006), but not with changes in BW, CAP or HbA1c after dapagliflozin treatment.
Conclusions
Serum TSP2 level decreased with LS after dapagliflozin treatment, and was independent of improvements in BW, glycemic control and hepatic steatosis, further supporting the potential of serum TSP2 level as a novel hepatic fibrosis biomarker in type 2 diabetes.
The relationship between cognition and outcome in people with schizophrenia has been established in studies that, for the most part, examined chronic patients and were cross-sectional in design. The ...purpose of this study was to analyze the relationships between neurocognitive variables assessed at illness onset and functional outcome in a longitudinal design. An additional area of interest was whether the severity of negative symptoms would predict outcome independently from neurocognitive variables or whether there would be an overlap in their predictive power.
The authors administered a comprehensive cognitive battery and clinical assessments to 99 subjects who were in their first episode of illness and analyzed the relationship of cognition and symptom severity at intake with community outcome after an average follow-up period of 7 years.
Verbal memory, processing speed and attention, and the severity of negative symptoms at intake were related to subsequent outcome. Global psychosocial functioning was predicted by negative symptoms and attention. Verbal memory was the significant predictor of the degree of impairment in recreational activities. Impairment in relationships was predicted by negative symptoms and memory, whereas attention and negative symptoms were predictive of work performance. There was an overlap in the variance in outcome explained by cognitive variables and negative symptoms.
Verbal memory and processing speed and attention are potential targets for psychosocial interventions to improve outcome. Results from cross-sectional or chronic patient studies do not necessarily correspond to the findings of this prospective first-episode study in which cognition appears to explain less of the variance in outcome.
Schizophrenia (SZ) patients and their biological relatives are more impulsive than controls. Although greater impulsivity in SZ has been associated with dysfunction in prefrontal neural circuits ...implicated in reward processing, little is known regarding brain structural correlates of heightened impulsivity in unaffected adolescent relatives of SZ patients.
Impulsive decision-making was assessed using the delay discounting task in 174 adolescents: 36 first-degree relatives (FDR) and 50 second-degree relatives (SDR) of SZ patients, and 88 healthy controls with no SZ family history (NSFH). We contrasted MRI brain gray matter cortical thickness-discounting constant (k) relationships between these 3 comparison groups using well-validated statistical approaches.
FDR had a distinct pattern in cortical thickness-k associations when compared to NSFH and SDR. Preference for immediate rewards (i.e. greater impulsivity) among FDR correlated with less cortical thickness within diffuse brain regions, including dorsolateral prefrontal (cognitive control network and motor/premotor cortex) and lateral temporal (auditory and visual association cortex) brain areas.
Adolescent impulsive decision-making may serve as an informative phenotype of underlying brain circuitry dysfunction associated with SZ risk. Future research focusing on impulsivity in SZ will likely help advance understanding how dysfunctional interactions between cognitive and reward neural circuits contribute to the neurobiological basis of SZ.
Objective
Existing studies reported the potential prognostic role of non‐thyroidal illness syndrome (NTIS), characterized by low triiodothyronine (T3) with normal/low thyroid‐stimulating hormone ...(TSH), mainly in severe COVID‐19. None considered the significant impact of SARS‐CoV‐2 viral load on adverse outcomes. We aimed to clarify the prognostic role of NTIS among predominantly mild‐to‐moderate COVID‐19 patients.
Design
A prospective study of COVID‐19 patients.
Patients and Measurements
Consecutive adults admitted to Queen Mary Hospital for confirmed COVID‐19 from July to December 2020 were prospectively recruited. SARS‐CoV‐2 viral load was represented by cycle threshold (Ct) values from real‐time reverse transcription‐polymerase chain reaction of the respiratory specimen on admission. Serum TSH, free thyroxine and free T3 were measured on admission. The outcome was deterioration in clinical severity, defined as worsening in ≥1 category of clinical severity according to the Chinese National Health Commission guideline.
Results
We recruited 367 patients. At baseline, 75.2% had mild disease, and 27 patients (7.4%) had NTIS. Fifty‐three patients (14.4%) had clinical deterioration. Patients with NTIS were older, had more comorbidities, worse symptomatology, higher SARS‐CoV‐2 viral loads and worse profiles of inflammatory and tissue injury markers. They were more likely to have clinical deterioration (p < .001). In multivariable stepwise logistic regression analysis, NTIS independently predicted clinical deterioration (adjusted odds ratio 3.19, p = .017), in addition to Ct value <25 (p < .001), elevated C‐reactive protein (p = .004), age >50 years (p = .011) and elevated creatine kinase (p = .017).
Conclusions
Non‐thyroidal illness syndrome was not uncommon even in mild‐to‐moderate COVID‐19 patients. NTIS on admission could predict clinical deterioration in COVID‐19, independent of SARS‐CoV‐2 viral load, age and markers of inflammation and tissue injury.
Abstract
Context
Reports of thyroid dysfunction following COVID-19 vaccination included cases of relapse of Graves' disease and worsening of pre-existing Graves' disease. Little is known about the ...thyroid-specific outcomes among patients treated for hyperthyroidism who have received COVID-19 vaccination.
Objective
Among patients treated for hyperthyroidism, we evaluated factors associated with not receiving the COVID-19 vaccination and whether COVID-19 vaccination was associated with thyroid function instability.
Methods
We included consecutive patients treated for hyperthyroidism attending the thyroid clinic at a teaching hospital between January and September 2021. They were categorized into vaccinated and unvaccinated groups. The index date was the date of first-dose vaccination for the vaccinated group, and the first date of attendance in the inclusion period for the unvaccinated group. They were followed up until March 2022 or occurrence of thyroid function instability (worsening of thyroid function/increase in antithyroid drug dosage), whichever was earlier.
Results
A total of 910 patients were included (mean age 51.6 years; 82.1% female). Of these, 86.2% had Graves disease and 67.3% were vaccinated (67.3% BNT162b2; 30.6% CoronaVac; 2.1% heterologous). Abnormal thyroid function and cardiovascular comorbidities were independently associated with unvaccinated status. Upon median follow-up of 5.3 months, thyroid function instability occurred in 15.9% of patients. COVID-19 vaccination did not increase risks of thyroid function instability (hazard ratio 0.78, 95% CI 0.56-1.09, P = .151); this was consistent in Graves disease, both types of vaccines, and regardless of whether baseline thyroid function was normal. Twenty-seven patients overtly thyrotoxic at the time of vaccination received COVID-19 vaccines without triggering a thyroid storm or difficulty in subsequent thyroid function control.
Conclusion
Among patients treated for hyperthyroidism, abnormal thyroid function was a factor predicting unvaccinated status. Our results should encourage patients treated for hyperthyroidism to receive COVID-19 vaccination to protect themselves from adverse outcomes and potential long-term sequelae of COVID-19.
Factors underlying progressive brain volume changes in schizophrenia remain poorly understood. The authors investigated whether a gene polymorphism influencing neuroplasticity may contribute to ...longitudinal brain volume alterations.
High-resolution magnetic resonance (MR) images of the whole brain were obtained for 119 patients with recent-onset schizophrenia spectrum disorders. Changes in brain volumes over an average of 3 years were compared between brain-derived neurotrophic factor (BDNF) val66met genotype groupings. Exploratory analyses were conducted to examine relationships between antipsychotic treatment and brain volume changes as well as the effects of BDNF genotype on changes in cognition and symptoms.
Significant genotype effects were observed on within-subject changes in volumes of frontal lobe gray matter, lateral ventricles, and sulcal CSF. Met allele carriers had significantly greater reductions in frontal gray matter volume, with reciprocal volume increases in the lateral ventricles and sulcal (especially frontal and temporal) CSF than Val homozygous patients. Independent of BDNF genotype, more antipsychotic exposure between MRI scans correlated with greater volume reductions in frontal gray matter, particularly among patients who were initially treatment naive. There were no statistically significant genotype effects on within-subject changes in cognition or symptoms.
BDNF(Met) variant may be one of several factors affecting progressive brain volume changes in schizophrenia.
PDF
