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Vaccine-induced protection of the population against severe COVID-19, hospitalization and death is of utmost importance, especially in the elderly. However, limited data are available on humoral immune responses following COVID-19 vaccination in the general population across a broad age range. We performed an integrated analysis of the effect of age, sex and prior SARS-CoV-2 infection on Spike S1-specific (S1) IgG concentrations up to three months post BNT162b2 vaccination. 1·735 persons, eligible for COVID-19 vaccination through the national program, were recruited from the general population (12 to 92 years old). Sixty percent were female and the median vaccination interval was 35 days (interquartile range, IQR: 35-35). All participants had seroconverted to S1 one month after two doses of vaccine. S1 IgG was higher in participants with a history of SARS-CoV-2 infection (median: 4·535 BAU/ml, IQR: 2·341-7·205) compared to infection-naïve persons (1·842 BAU/ml, 1·019-3·116) after two doses, p

Schizophrenia is a complex brain disease involving several neurotransmitter systems, including aberrant noradrenergic activity, which might underlie cognitive deficits. Clonidine is an α(2A)-agonist and previous research has demonstrated that single dosages of clonidine normalize sensori(motor) gating in schizophrenia. Currently, we investigated whether clonidine is able to normalize mismatch negativity (MMN) and P3a amplitude deficits in this same group of patients. This is important, since reports have shown that MMN amplitude is associated with cognitive functioning and daily life functions in schizophrenia. Twenty chronically ill, male schizophrenia patients were tested with the MMN paradigm from the Copenhagen Psychophysiological Test Battery (CPTB) on 5 occasions, separated by a week. Patients received randomized, yet balanced, either a placebo or a single dose (25, 50, 75 or 150 μg) of clonidine (each dose only once) on top of their usual medication on each occasion. Patients were matched on age and gender with 20 healthy controls (HC) who did not receive any treatment. We found decreased MMN and P3a amplitudes in our patients compared to HC. Although clonidine did neither significantly increase MMN nor P3a amplitude in our patients, it did increase certain levels of MMN and P3a amplitude such that these were not significantly different anymore from the healthy controls. Together with our previous reports indicating normalized sensori(motor) gating in the same patients following administration of clonidine, our results could be of potential high clinical relevance in treating schizophrenia. Future studies should focus on longer trial periods to investigate if clonidine also improves cognitive functioning in schizophrenia.

BACKGROUND: Cognitive deficits are a core feature of schizophrenia and are already present at the early stages of the disease. Investigations of early information processing with electroencephalogram (EEG) measures may be a useful method to study the underlying mechanisms of cognitive deficits. Prepulse inhibition of the startle reflex (PPI) and P50 suppression are theorized to be basic inhibitory mechanisms of sensory input into the brain to prevent sensory overload. These sensory gating measures have often been reported to be reduced in schizophrenia, and theoretically, deficits in sensory gating may result in cognitive fragmentation. Previous research from our own lab revealed several associations between P3b amplitudes and working memory, sustained attention and reaction time in a large sample of antipsychotic-naïve, first-episode (AN-FES) patients with schizophrenia and age and gender matched healthy controls (HC). These associations were mainly driven by AN-FES patients, since no such associations were found in the HC sample. In the current study we expected a relationship between sensory gating and cognition and symptomatology in this same large cohort of subjects. METHODS: Seventy-three AN-FES patients and 93 age and gender matched HC were assessed with the PPI and P50 suppression paradigm from the Copenhagen Psychophysiological Test-Battery (CPTB). In addition, both groups performed 6 subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess attention, working memory and executive functioning. To assess symptom severity, the Positive and Negative Symptom Scale (PANSS) was conducted. RESULTS: Our patients scored significantly lower on all cognitive tests (p

Background: Deficits in attention and working memory are already present in early stages of schizophrenia. The P3a and b event related brain potentials (ERPs) are believed to underlie processes of attention and working memory, but, only limited research has been performed on the associations between these psychophysiological and cognitive deficits, particularly in the early stages of schizophrenia. We aimed to investigate associations between P3a and P3b amplitudes and measures of attention and working memory in a large cohort of antipsychotic-naive, first-episode schizophrenia patients (AN-FES) and age and sex-matched healthy controls (HC).

BackgroundCognitive deficits are already present in early stages of schizophrenia. P3a and P3b event-related potentials (ERPs) are believed to underlie the processes of attention and working memory (WM), yet limited research has been performed on the associations between these parameters. Therefore, we explored possible associations between P3a/b amplitudes and cognition in a large cohort of antipsychotic-naïve, first-episode schizophrenia (AN-FES) patients and healthy controls (HC).MethodsSeventy-three AN-FES patients and 93 age- and gender-matched HC were assessed for their P3a/b amplitude with an auditory oddball paradigm. In addition, subjects performed several subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB).ResultsAN-FES patients had significantly reduced P3a/b amplitudes, as well as significantly lower scores on all cognitive tests compared with HC. Total group correlations revealed positive associations between P3b amplitude and WM and sustained attention and negative associations with all reaction time measures. These associations appeared mainly driven by AN-FES patients, where we found a similar pattern. No significant associations were found between P3b amplitude and cognitive measures in our HC. P3a amplitude did not correlate significantly with any cognitive measures in either group, nor when combined.ConclusionsOur results provide further evidence for P3a/b amplitude deficits and cognitive deficits in AN-FES patients, which are neither due to antipsychotics nor to disease progress. Furthermore, our data showed significant, yet weak associations between P3b and cognition. Therefore, our data do not supply evidence for deficient P3a/b amplitudes as direct underlying factors for cognitive deficits in schizophrenia.

Background Schizophrenia is a severe brain disorder with profound deficits in prefrontal cortical cognitive functioning. These cognitive deficits form a core feature in schizophrenia for which treatment has been proven to be clinically challenging. One of the key neurotransmitters involved in cognitive functioning is noradrenaline. Previous research has demonstrated disrupted noradrenergic activity in schizophrenia while several studies report improvements in prefrontal cognitive functioning by a selective α2-agonist. Clonidine is such a selective α2A-agonist and previous research in our lab has demonstrated that a (range of) single dosage(s) of clonidine normalize(s) sensory gating in chronically ill, yet stably medicated patients with schizophrenia. Currently, we investigated if clonidine also normalizes Mismatch Negativity (MMN) deficits in this same group of patients. This is important, since reports have shown that MMN amplitude is associated with negative symptoms and cognitive functioning in schizophrenia. Methods In a pseudo-randomized, double-blind, placebo-controlled experiment twenty chronically ill, yet stably medicated, male patients with schizophrenia were tested with the MMN paradigm from the Copenhagen Psychophysiological Test-Battery (CPTB) on 5 different occasions, each separated by a week. Four hours prior to testing patients were randomized administered either a placebo (non psycho-active compound) or a single dose of 25, 50, 75 or 150 μg of clonidine (Catapresan) on top of their usual medication on each occasion, in such a way that each patient received every dose once. Patients were matched on age and gender with 20 healthy controls (HC), who did not receive any treatment. The MMN paradigm consisted of 1800 stimuli with 4 types of stimuli: 1 standard (1000 Hz, 50 ms) presented 82% of the time and 3 types of deviants, based on either frequency (FreqMMN: 1200 Hz, 50 ms), duration (DurMMN: 1000 Hz, 100 ms) or their combination (FreqDurMMN: 1200 Hz, 100 ms) each with a probability of 6%. All stimuli had an intensity of 75dB and were presented with an interstimulus interval randomized between 300 and 500 ms. Subjects were requested to ignore all stimuli and were therefore watching a (muted) nature documentary. Results In the placebo condition, patients had significantly reduced DurMMN and FreqDurMMN amplitude compared to HC, whereas FreqMMN did not show significant group differences. Furthermore, all doses of clonidine normalized FreqDurMMN amplitude in such a way that it was not significantly different anymore from the HC, while DurMMN only normalized with the highest dose (150ug). Discussion Our results indicate disrupted MMN amplitude in chronically ill patients with schizophrenia in spite of the fact that they were stable on their medical treatment. In addition, our data provide evidence that a single dose of clonidine is able to normalize MMN amplitude in these patients. Furthermore, patients could not distinguish between the placebo and the treatment conditions or reported any side effects of these low doses of clonidine. Together with our previous reports indicating normalized sensory and sensorimotor gating in these patients following administration of clonidine, our results could be of potential high clinical relevance in the treatment of schizophrenia. Future studies should therefore focus on longer trial periods to investigate if clonidine, besides normalizing MMN amplitude and sensory(motor) gating, can also ameliorate negative symptoms and cognitive functioning in schizophrenia.