Different psychopathological courses between chronic interictal psychosis and schizophrenia.

OBJECTIVE: The clinical course of interictal psychosis (IIP) has not yet been investigated. We aimed to compared the psychopathology and time-relevant indices between chronic IIP (CIIP) and schizophrenia (SC) METHODS: In this comprehensive psychopathological study, patients with chronic psychosis with and without epilepsy (127 with CIIP and 187 with SC) were compared. Psychopathology was measured using the Brief Psychiatric Rating Scale (BPRS): total, negative symptoms (NSs), positive symptoms (PSs), and anxiety-depressive symptoms (ADSs). Time-relevant indices included age at the time of evaluation, age at the onset of psychosis, and duration of psychosis. The psychopathology of psychosis types and time-relevant indices were analyzed using Pearson's correlation coefficient analysis of covariance. RESULTS: 　Age at the time of evaluation was significantly correlated with NS, and ADS scores. Age-relevant trajectories significantly interacted with psychosis types. As age advanced, patients with SC exhibited increased scores, whereas patients with CIIP often exhibited decreased (or unchanged) scores. Age at onset of psychosis was significantly correlated with NS and ADS outcomes in patients with CIIP, whereas it was not correlated in patients with SC. There were significant interactions between age at onset and psychosis types. Patients with early-onset CIIP exhibited higher NS and lower ADS scores, whereas patients with SC exhibited no particular trajectory. The duration of psychosis significantly interacted with the psychosis types in the BPRS total, NSs and PSs. As duration increased, patients with CIIP exhibited no significant relationship, whereas patients with SC exhibited significantly higher psychotic scores. CONCLUSION: Psychopathological courses differ between patients with CIIP and SC. Although patients with SC often exhibit deteriorations in psychotic symptoms, patients with CIIP exhibit no distinct deterioration. These findings can contribute psychiatric nosology, treatment strategies, and prediction outcomes.

Psychoses after an antiepileptic drug administration: Frequency, timing, and duration.

OBJECTIVES: To clarify the pathophysiology of psychoses after the new administration of antiepileptic drugs (AED), we analyzed the annual incidence, timing of development, and duration of episodes. METHODS: Psychotic outcomes in the first 6-month period after an AED or non-AED administration in patients with focal epilepsy were exhaustively reviewed in eight Japanese neuropsychiatry institutions. In cases with psychotic episodes, the subtype of psychosis, timing of development, previous history of psychosis, and duration of the episode were evaluated. RESULTS: Between 1981 and 2015, 5018 new drugs (4402 AED and 616 non-AED) were administered to 2067 patients with focal epilepsy. In the first 6-month period, 105 psychotic episodes occurred (81 interictal psychosis [IIP] and 24 postictal psychosis). Furthermore, 55 cases were first episodes and 50 were recurrent episodes. The frequency of psychoses is significantly higher after AED administration (n = 102) compared with non-AED administration (n = 3). Psychosis occurred most frequently in the initial 1-month period after new-AED administration and tended to decrease with increasing time. The estimated annual incidence of all psychoses after a new AED administration was 3.5% (2.0% for first-episode psychosis and 1.8% for first-episode IIP). Duration of psychoses (mean, 38.5 weeks) was equivalent to overall IIP. Duration of IIP did not shorten with discontinuation of newly administered AED. SIGNIFICANCE: Patients with epilepsy exhibit psychosis more frequently after new AED administration than after non-AED administration. This study shows the pathophysiology of psychoses after AED administration with annual incidence, the timing of development, and the duration of PAP, which have rarely been reported.

Quantitative psychopathology of interictal psychosis in epilepsy; interaction between epilepsy-related and psychosis-general effects.

OBJECTIVE: There is a historical debate whether psychopathology of epilepsy psychosis is unique to epilepsy or common to other psychoses. However, a large comprehensive studies on this issue are scarce. To clarify the characteristics of interictal psychosis (IIP), we evaluated psychopathology quantitatively. METHODS: This study included 150 patients with IIP (epilepsy+/psychosis+), 187 patients with schizophrenia (SC: epilepsy-/psychosis+), 182 patients with epilepsy (EP: epilepsy+/psychosis-), and 172 non-clinical individuals (NC: epilepsy-/psychosis-). The IIP group comprised 127 chronic and 23 brief psychoses. Age, sex, and years of education, onset and duration of psychosis, and onset and duration of epilepsy were matched among the groups. The psychopathology was evaluated using the 16-item Brief Psychiatric Rating Scale (BPRS), which comprises three symptom factors namely negative symptoms (NS), positive symptoms (PS), and anxiety-depressive symptoms (ADS). RESULTS: For overall 16-BPRS and NS factor scores, there were significant interactions between epilepsy-related (epilepsy+/-) and psychosis-general (psychosis+/-) effects. The EP exhibited higher scores than did the NC, whereas the IIP exhibited lower scores than did the SC. For PS and ADS factor scores, the IIP and SC exhibited a significant psychosis-general effect. Chronic IIP was associated with more serious psychopathologies than was brief IIP. However, limited with chronic IIP, there was a significant interaction between epilepsy-related and psychosis-general effects on the overall 16-BPRS and NS factor scores. CONCLUSION: These findings demonstrate the first large quantitative evidence on the unique psychopathology of IIP which has been only narratively described. The psychopathology is associated with the interaction between epilepsy-related and psychosis-general effects.

Increased frequency of psychosis after second-generation antiepileptic drug administration in adults with focal epilepsy.

OBJECTIVE: Many studies show psychoses after some antiepileptic drug (AED) administrations (post-AED administration psychoses [PAP]). It remains uncertain about psychogenetic potential of each AED and effects of clinical state factors on PAP. We examined the relations between AED-related factors (types, generations, dosages, and concomitant AED) and PAP. METHODS: The clinical records of patients with focal epilepsy were retrospectively reviewed from eight adult epilepsy clinics, for every six-month period after administration of a new drug (either AED or non-AED) between 1981 and 2015. Characteristics of psychotic episodes, AED-related factors (type, daily dosage, and concomitant AED), and other state-related risk factors to psychosis (age, duration of epilepsy, history of psychosis, and seizure frequency) were examined. Psychogenetic risks of AED-related and state-related factors were analyzed with multifactorial procedures. RESULTS: Of 2067 patients with focal epilepsy, 5018 new drugs (4402 AEDs and 616 non-AEDs) were administered. Within the first six-month period, 89 patients exhibited 105 psychotic episodes (81 interictal and 24 postictal psychoses: 55 first episodes and 50 recurrences). With second-generation AED (SAED) administration, particularly topiramate and lamotrigine, frequency of psychosis was significantly increased. Daily dosage of AED was not significantly associated with psychosis. Psychosis tended to occur with a higher number of concomitant AED. Subsequent analysis with AED-related and general factors showed that SAED administrations and previous psychotic history were the most significant risks for PAP. CONCLUSION: Post-AED administration psychoses is associated with type of AED (SAED), rather than its dosage. Individual vulnerabilities are also associated with PAP.

Dissociative experiences in epilepsy: effects of epilepsy-related factors on pathological dissociation.

Psychogenic nonepileptic seizures (PNESs) in patients with epilepsy can be categorized as dissociative disorders. The prevalence of PNESs in patients with epilepsy appears to be much higher than that of dissociative experiences in nonclinical subjects. In order to clarify as to whether epilepsy-related factors were associated with pathological dissociation, we conducted a controlled study with 225 patients with epilepsy and 334 nonclinically matched individuals. All participants completed the Japanese version of the Dissociative Experiences Scale (DES). There was no significant difference in the DES score (DES-S) between the group with epilepsy and the control group. The group with epilepsy showed a significantly higher DES taxon (DES-T; a subset of DES-S and an index of pathological dissociation) than the control group. Thirty-one out of the 225 patients with epilepsy (13.8%) had PNESs. Because of its strong association with the DES-S and DES-T, PNESs can be regarded as a symptom of dissociation. With multiple regression analysis, the patients with a shorter duration of epilepsy, higher seizure frequency, or shorter period in education tend to suffer from pathological dissociation. These findings demonstrate that patients with epilepsy are more prone to experiencing pathological dissociation when having certain clinical factors.

[Deceased Schizophrenic Patients--Focus on QT Prolongation].

We retrospectively evaluated factors affecting the lifespan of schizophrenic patients, who are known to have a shorter life expectancy than healthy people, focusing on the relationship with QT prolongation associated with antipsychotics. In a total of 406 patients who died at Asai Hospital the mean age at death was compared between schizophrenic patients and nonpsychiatric patients. In deceased schizophrenic patients, drug-related factors, hematology results, and electrocardiographic findings for 3 years before death were compared with those for the same period in age-matched surviving schizophrenic patients. In addition, QT values in schizophrenic patients and healthy controls were evaluated by age group. The mean age at death was significantly younger in schizophrenic patients (63.4 +/- 2.63 years) than in nonpsychiatric patients (84.0 +/- 0.57 years) (p<0.001). Bivariate analysis between deceased and surviving schizophrenic patients showed significant differences in QT values at 2 years, 1 year, and 0.5 years before death and in AST and ALT values at 0.5.years before death. The incidence of QT prolongation in deceased schizophrenic patients (52.0%) was about twice as high as that in surviving schizophrenic patients (24.5%). Multiple logistic regression analysis suggested that the proportion of deceased patients was higher when QT intervals were longer and ALT values were relatively higher, even if within the normal range. In both schizophrenic patients and medical checkup examinees, QT values were positively correlated with the age (R2 = 0.9061 and 0.9276, respectively), and QT intervals in schizophrenic patients were significantly longer in the 30- to 70-year age groups. In both schizophrenic patients and medical checkup examinees, QT values were positively correlated with the age, and QT intervals in schizophrenic patients were significantly longer than those in medical checkup examinees in the same age groups. Deceased schizophrenic patients showed significantly longer QT intervals from 2 years before death than age-matched surviving schizophrenic patients. QT prolongation may influence the lifespan of schizophrenic patients, which are shorter than those of nonpsychiatric patients. This highlights the importance of following electrocardiographic findings and hematology results of schizophrenic patients over time.

Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection in Japan 2023: Executive Summary.

Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in developed countries. Although a standard therapy has not yet been established, evidence for the management of cCMV infection has been accumulating. The first edition of the "Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection" was published in Japan in 2023. This summary outlines the clinical questions (CQs) in the guidelines, with reference to the Japanese Medical Information Distribution Service Manual. Overall, 20 CQs with statements regarding prenatal risk assessment, prevention and management at diagnosis (CQs 1-1-1-3), diagnosis (CQs 2-1-2-6), treatment (CQs 3-1-3-7) and follow-up requirements (CQs 4-1-4-4) have been discussed. For each statement, the levels of recommendation, evidence and consensus rates were determined. These guidelines will assist in the management of patients with cCMV infection.

Effects of antipsychotic drugs on the duration of interictal psychotic episodes in patients with epilepsy.

Treatment protocols for interictal psychosis (IIP) of patients with epilepsy have not yet been established. We aimed to clarify the effects of antipsychotic drugs (APDs) on duration of IIP episodes. We studied 393 IIP episodes in 200 patients with epilepsy in accordance with our empirical treatment protocol. The duration of all the episodes and APD treatments were reviewed. Antipsychotic drugs were used in 338 episodes and not used in 55 episodes (non-APD group). The APDs used in the treatment of IIP episodes were divided into the following three groups: first-generation APDs (FAPD, n=252), second-generation APDs (SAPD, n=44), and the combination of first- and second-generation APDs (CAPD, n=42). The non-APD group showed a significantly shorter episode duration than did the APD group (F=6.05, p=0.014). Among the 3 APD groups (FAPD, SAPD, and CAPD), there was a significant difference in duration of IIP episode (F=8.65, p=0.000). Whereas the duration of episodes was significantly longer in the CAPD group than in the other two groups, it was not significantly different between the FAPD and SAPD groups. Our findings further to clarify the nature of IIP and add further perspectives on treatment protocols for IIP.

Procalcitonin-Based Antibiotic Use for Neonatal Early-Onset Bacterial Infections: Pre- and Post-Intervention Clinical Study.

We previously reported the 95th percentile cutoff value of the serum procalcitonin (PCT) reference curve for diagnosing early-onset bacterial infection. We aimed to verify the effectivity of these novel diagnostic criteria by comparing antibiotic use and incidence of early-onset bacterial infection between pre- and post-introduction periods. We included newborns admitted to our neonatal intensive care unit who underwent blood tests within 72 h after birth between 2018 and 2022. The neonates were divided into the pre-intervention (admitted before the introduction, n = 737) or post-intervention (admitted after the introduction, n = 686) group. The days of antibiotics therapy (DOT) per 1000 patient days up to 6 days after birth, percentage of antibiotic use, and incidence of early-onset bacterial infection were compared between the groups. The post-intervention group had significantly lower DOT per 1000 patient days (82.0 days vs. 211.3 days, p < 0.01) and percentage of newborns receiving antibiotics compared with the pre-intervention group (79 (12%) vs. 280 (38%), respectively, p < 0.01). The incidence of early-onset bacterial infections did not differ between the groups (2% each, p = 0.99). In conclusion, our diagnostic criteria using the 95th percentile cutoff value of the serum PCT reference curve for early-onset bacterial infection were proven safe and effective, promoting appropriate use of antibiotics.

Association of umbilical cord insulin-like growth factor 1 levels with severe retinopathy in extremely preterm infants.

BACKGROUND: The association between umbilical cord blood insulin-like growth factor 1 (IGF-1) levels and retinopathy of prematurity (ROP) remains unclear. This study aimed to investigate whether umbilical cord blood IGF-1 levels can predict the development of severe ROP in extremely preterm infants. METHODS: This hospital-based retrospective cohort study included infants born at <37 weeks gestational age (GA) between 2019 and 2021 and then classified them into the two GA groups: extremely preterm, <28 weeks and preterm infants, 28-36 weeks. Extremely preterm infants were further subclassified into two groups according to the laser treatment as follows: the severe ROP (ROP-Tx) and ROP (No ROP-Tx) groups. Median umbilical cord blood IGF-1 values were compared between the groups. Perinatal risk factors were identified by univariate and multivariate analyses. Finally, umbilical cord IGF-1 cut-off values requiring ROP treatment with laser were determined by receiver operating characteristic (ROC) curve analyses. RESULTS: A total of 205 infants were enrolled, with 32 being extremely preterm (ROP-Tx: n = 11; No ROP-Tx: n = 21) and 173 being preterm. IGF-1 levels were significantly lower in extremely preterm (13.5 ng/mL) than preterm infants (36 ng/mL, p < 0.001). In extremely preterm infants, IGF-1 levels were significantly lower in the ROP-Tx group than the No ROP-Tx group (10 vs. 19 ng/mL, respectively, p = 0.024). Only GA, umbilical cord blood IGF-1 levels, birth head circumference, and birth chest circumference were identified as risk factors by univariate analysis (p < 0.05). Multivariate analysis showed that only umbilical cord blood IGF-1 was an independent risk factor (odds ratio: 1.26, p = 0.021). ROC curves revealed an IGF-1 cut-off value of 14 ng/mL. CONCLUSION: The need of laser treatment for ROP was found to be associated with low umbilical cord blood IGF-1 levels in extremely preterm infants. Umbilical cord blood IGF-1 can be used as a biomarker for the risk of developing severe ROP.