Antipsychotic drugs and risk of newly diagnosed tuberculosis in schizophrenia

Aim

Patients with schizophrenia have a higher incidence of tuberculosis than do people in the general population. Information is limited regarding the association between antipsychotic agents and the risk of tuberculosis in patients with schizophrenia. This exploratory study assessed the risk of tuberculosis among patients with schizophrenia on antipsychotic therapy.

Methods

Among a nationwide schizophrenia cohort derived from the National Health Insurance Research Database in Taiwan (n = 32 399), we identified 284 patients who had developed newly diagnosed tuberculosis after their first psychiatric admission. Ten or fewer matched controls were selected randomly from the cohort for each patient based on risk‐set sampling. We categorized exposure to antipsychotic medications by type and defined daily dose. Using multivariate methods, we explored individual antipsychotic agents for the risk of tuberculosis and employed a propensity‐scoring method in sensitivity analyses to validate any associations.

Results

Among the antipsychotic agents studied and after adjustment for covariates, current use of clozapine was the only antipsychotic agent associated with a 63% increased risk of tuberculosis (adjusted risk ratio = 1.63, P = 0.014). In addition, the association did not show a clear dose‐dependent relationship. Clozapine combined with other antipsychotic agents showed a potential synergistic risk for tuberculosis (adjusted risk ratio = 2.30, P = 0.044).

Conclusion

This exploratory study suggests the potential risk of clozapine on the risk of tuberculosis, especially for those on clozapine in combination with other antipsychotics. Future studies are needed to verify the association.

     

Evaluation of the neutrophil/lymphocyte ratio,platelet/lymphocyte ratio,and mean platelet volume as inflammatory markers in children with attention‐deficit hyperactivity disorder

Aim

The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and mean platelet volume (MPV) have recently been used as indicators of a systemic inflammatory response. The aim of this study was to investigate the relations of the NLR, PLR, MLR, and MPV with attention‐deficit hyperactivity disorder (ADHD).

Methods

The study group consisting of 82 children diagnosed with ADHD was compared with a healthy control (HC) group of 70 age‐, sex‐, and body‐mass‐index‐matched subjects. The NLR, PLR, MLR, and MPV were measured according to the complete blood count.

Results

The NLR, PLR, MLR, MPV, and neutrophil count of the ADHD group were significantly higher than those of the HC group. The lymphocyte counts of the patients were significantly lower than those of the HC group.

Conclusion

Inflammation might play a role in the etiopathogenesis of ADHD. The NLR, PLR, MLR, and MPV may be potential inflammation markers for ADHD in children.

     

Understanding the roles of glutamine synthetase,glutaminase, and glutamate decarboxylase autoantibodies in imbalanced excitatory/inhibitory neurotransmission as etiological mechanisms of autism

Aim

Autism is a heterogeneous neurological disorder that is characterized by impairments in communication and social interactions, repetitive behaviors, and sensory abnormalities. The etiology of autism remains unclear. Animal, genetic, and post‐mortem studies suggest that an imbalance exists in the neuronal excitation and inhibition system in autism. The aim of this study was to determine whether alterations of the measured parameters in children with autism are significantly associated with the risk of a sensory dysfunction.

Methods

The glutamine synthetase (GS), kidney‐type glutaminase (GLS1), and glutamic acid decarboxylase autoantibody levels were analyzed in 38 autistic children and 33 age‐ and sex‐matched controls using enzyme‐linked immunosorbent assays.

Results

The obtained data demonstrated significant alterations in glutamate and glutamine cycle enzymes, as represented by GS and GLS1, respectively. While the glutamic acid decarboxylase autoantibodies levels were remarkably increased, no significant difference was observed compared to the healthy control participants.

Conclusion

The obtained data indicate that GS and GLS1 are promising indicators of a neuronal excitation and inhibition system imbalance and that combined measured parameters are good predictive biomarkers of autism.

     

Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia in Japan: A 6‐week,randomized, double‐blind,placebo‐controlled study

Aim

This study aimed to evaluate the efficacy, safety, and tolerability of brexpiprazole compared to placebo in Japanese patients with acute schizophrenia (SCZ).

Methods

We conducted a 6‐week, multicenter, double‐blind, placebo‐controlled, phase 2/3 study in Japan. Patients with acute SCZ were randomized (1:1:1:1) to receive brexpiprazole 1 mg, 2 mg, 4 mg, or placebo once a day. The primary endpoint was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total scores.

Results

In the 459 patients that were randomized, brexpiprazole 2 mg showed a significant improvement versus placebo (treatment difference: ?7.32, P = 0.0124), although brexpiprazole 4 mg showed numerical improvements (treatment difference: ?3.86, P = 0.1959), and brexpiprazole 1 mg showed only minimal change (treatment difference: ?0.63, P = 0.8330). Treatment‐emergent adverse events with an incidence of ≥5% and ≥2 times the rate of placebo in the brexpiprazole groups were vomiting, elevated blood prolactin, diarrhea, nausea, and dental caries. Most treatment‐emergent adverse events were mild or moderate in severity. There were no clinically significant changes in electrocardiogram parameters, bodyweight, laboratory values, or vital signs in the brexpiprazole groups.

Conclusion

Brexpiprazole was efficacious and well tolerated in Japanese adult patients with acute SCZ.

     

MEF2C mRNA expression and cognitive function in Japanese patients with Alzheimer's disease

Aim

Despite continuing research into Alzheimer's disease (AD), its pathological mechanisms and modulating factors remain unknown. Several genes influence AD pathogenesis by affecting inflammatory pathways. Myocyte‐enhancer factor 2C (MEF2C) is one such candidate gene for AD.

Methods

We examined MEF2C mRNA expression levels and methylation rates of CpG on its promoter region in peripheral leukocytes from Japanese AD patients compared with age‐ and sex‐matched control subjects.

Results

In peripheral leukocytes, MEF2C mRNA expression levels in AD subjects were significantly lower than those in control subjects (0.86 ± 0.25 vs 0.99 ± 0.27, respectively, P = 0.007) and were correlated with the Alzheimer's Disease Assessment Scale (r = ?0.345, P = 0.049) and the Mini Mental State Examination (r = 0.324, P = 0.02). No significant differences were found in methylation rates between AD and control subjects.

Conclusion

MEF2C mRNA expression in leukocytes may be a biological marker for cognitive decline in AD.

     

Ten‐year follow‐up study of Japanese patients with obsessive–compulsive disorder

Aim

Obsessive–compulsive disorder (OCD) is a well‐known chronic illness. This study retrospectively investigated 10‐year outcomes and associated clinical factors in Japanese OCD patients. We focused on the impact of several sociocultural factors, including medical expenses and insurance systems specific to each country, on the differences or biases in follow‐up procedures of OCD.

Methods

Seventy‐nine patients diagnosed with OCD who received a standardized combination of treatments for 10 continuous years were divided into three groups according to their improvement rates on the Yale–Brown Obsessive–Compulsive Scale after 10 years of treatment.

Results

A survival analysis revealed that the rate of patients achieving full remission increased every year. Following 10 years of treatment, 56% of OCD patients experienced ‘full remission’ for at least 1 year. Consequently, 48% exhibited full remission, and 37% exhibited partial remission at the end‐point of this study. We identified several factors that were predictive of poorer outcomes, including lower Global Assessment of Functioning Scale scores and the presence of hoarding symptoms or involvement behaviors. In addition, improvement rates after 1 year significantly predicted better 10‐year outcomes.

Conclusion

Our findings highlight the transcultural nature of long‐term outcomes of OCD treatment, which appear to be independent of sociocultural differences.

     

Altered gray matter volume and disrupted functional connectivity of dorsolateral prefrontal cortex in men with heroin dependence

Aim

Chronic heroin use can cause various neuropathological characteristics that may compromise brain function. The present study evaluated the alteration of gray matter volume (GMV) and its resting‐state functional connectivity (rsFC) over the dorsolateral prefrontal cortex (DLPFC) among male heroin users.

Methods

Thirty heroin‐dependent men undergoing methadone maintenance therapy and 30 educational‐level‐ and age‐matched male controls were recruited for this study. To assess their GMV and rsFC, the participants were evaluated using spoiled gradient echo and gradient‐recalled echo planar imaging sequences with a 3‐Tesla General Electric MR scanner under resting state.

Results

The heroin‐dependent men showed lower GMV over the right DLPFC in comparison with the controls. Further evaluation of the rsFC of the right DLPFC revealed a marked decrease in interhemispheric DLPFC connectivity among those with heroin dependence under control of head movement and GMV of the right DLPFC.

Conclusion

Although the mechanism remains unclear, the present study shows that chronic heroin use is associated with alteration of morphology as well as rsFC over the right DLPFC. As the DLPFC plays an imperative role in various domains of cognitive function, service providers for heroin users should consider the impacts of possible DLPFC‐related cognitive deficits on treatment effectiveness.

     

Relationship between anxious temperament and harm avoidance in medical students and staff

Aim

In order to resolve the equivocal relationship between anxious temperament rated by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego‐Autoquestionnaire (TEMPS‐A) and harm avoidance rated by the Temperament and Character Inventory (TCI), the present study aimed to investigate whether the anxious temperament scale and the harm avoidance scale are significantly associated with adjustment of relevant factors. Our hypothesis was that anxious temperament might be associated with harm avoidance.

Methods

From the database of our previous studies, the data of 111 healthy subjects who had both TCI and TEMPS‐A scores were extracted for the present study. Two multiple regression analyses were performed: one to predict variance in anxious temperament scores without and with harm avoidance scores, and relevant factors; and another to predict variance in harm avoidance scores without and with anxious temperament scores, and relevant factors.

Results

Anxious temperament was significantly and positively associated with depressive temperament, irritable temperament, and Hamilton Rating Scale for Depression whereas harm avoidance was significantly and negatively associated with hyperthymic temperament, novelty seeking, persistence, and self‐directedness, although both were significantly and positively associated with each other.

Conclusion

These findings support our hypothesis and suggest that anxious temperament may have ‘depressive proneness’ whereas harm avoidance may have ‘passive proneness.’

     

Just‐in‐time response to reward as a function of ADHD symptom severity

Aim

Attention‐deficit hyperactivity disorder (ADHD) neuroimaging studies have identified substantial differences in reward‐related circuits on a trial‐by‐trial basis. However, no research to date has evaluated the effect of motivational context on neural activity in settings with intermittent reward in ADHD. The present study was designed to identify neural processes underlying both immediate effects of reward and sustained effects of reward associated with motivational context in adult ADHD patients.

Methods

We used a functional magnetic resonance imaging paradigm, including a time estimation task with constant versus intermittent reward conditions, in a sample of 21 medication‐naïve adults with combined ADHD and 24 healthy adults.

Results

Although no between‐group neural differences were detected, orbitofrontal activity dropped in association with high ADHD symptom severity during the transition from initial non‐reward context blocks to subsequent reward context blocks. In turn, ADHD symptom severity predicted higher orbitofrontal activity in response to immediate reward versus no reward within reward context blocks.

Conclusion

These results suggest that high ADHD symptom severity scorers adopted a ‘just‐in‐time’ strategy, involving the recruitment of reward processing brain areas in the face of immediate reward rather than a sustained response to motivational context.

     

Effect of phase‐encoding direction on group analysis of resting‐state functional magnetic resonance imaging

Aim

Echo‐planar imaging is a common technique used in functional magnetic resonance imaging (fMRI); however, it suffers from image distortion and signal loss because of large susceptibility effects that are related to the phase‐encoding direction of the scan. Despite this relation, the majority of neuroimaging studies has not considered the influence of phase‐encoding direction. Here, we aimed to clarify how phase‐encoding direction can affect the outcome of an fMRI connectivity study of schizophrenia (SCZ).

Methods

Resting‐state fMRI using anterior to posterior (A–P) and posterior to anterior (P–A) directions was used to examine 25 patients with SCZ and 37 matched healthy controls (HC). We conducted a functional connectivity (FC) analysis using independent component analysis and performed three group comparisons: (i) A–P versus P–A (all participants); (ii) SCZ versus HC for the A–P and P–A datasets; and (iii) the interaction between phase‐encoding direction and participant group.

Results

The estimated FC differed between the two phase‐encoding directions in areas that were more extensive than those where signal loss has been reported. Although FC in the SCZ group was lower than that in the HC group for both directions, the A–P and P–A conditions did not exhibit the same specific pattern of differences. Further, we observed an interaction between participant group and the phase‐encoding direction in the left temporoparietal junction and left fusiform gyrus.

Conclusion

Phase‐encoding direction can influence the results of FC studies. Thus, appropriate selection and documentation of phase‐encoding direction will be important in future resting‐state fMRI studies.

     

An open‐label extension long‐term study of the safety and efficacy of aripiprazole for irritability in children and adolescents with autistic disorder in Japan

Aim

The purpose of this study was to evaluate the long‐term safety and efficacy of aripiprazole in treating irritability in pediatric patients (6–17 years) with autistic disorder (AD) in Japan.

Methods

In this open‐label extension study, patients who had completed a previous randomized, double‐blind, placebo‐controlled 8‐week study were enrolled and were flexibly dosed with aripiprazole (1–15 mg/day) until the new indication of irritability in pediatric autism spectrum disorder was approved in Japan.

Results

Seventy (81%) out of 86 enrolled patients completed week‐48 assessments. The mean duration of treatment was 694.9 days. The mean daily dose of aripiprazole over the treatment period was 7.2 mg and the mean of the final dose was 8.5 mg. The most common treatment‐emergent adverse events (TEAE; ≥20%) included nasopharyngitis, somnolence, influenza, and increased weight. The majority of these TEAE were mild or moderate in severity, and there were no deaths, and no clinically relevant findings in laboratory values except prolactin decrease, vital signs, height, or ECG parameters. At week 48 (observed case), the mean change from baseline in the Irritability subscale score for the Aberrant Behavior Checklist Japanese Version was ?6.3 in prior placebo patients and ?2.6 in prior aripiprazole patients.

Conclusion

Aripiprazole was generally safe, well tolerated, and effective in the long‐term treatment of irritability associated with AD in Japanese pediatric patients.

     

Increase of frontal cerebral blood volume during transcranial magnetic stimulation in depression is related to treatment effectiveness: A pilot study with near‐infrared spectroscopy

Aim

Alterations of cerebral blood flow have been reported in studies of depression treated by transcranial magnetic stimulation (TMS). However, the relation between these changes in activity during stimulation and the effectiveness of TMS is not known. The aim of this study was to determine whether changes in frontal cerebral blood volume measured as frontal hemoglobin concentration (fHbC) during TMS are correlated with clinical outcomes of treatment.

Methods

Fifteen drug‐resistant patients with depression underwent a standard treatment regimen of TMS to the left dorsolateral prefrontal cortex. We recorded fHbC during stimulation at the start and end of the TMS treatment series using near‐infrared spectroscopy. Symptom severity was determined using the Montgomery–Åsberg Depression Rating Scale.

Results

At the start of the TMS series, fHbC increased during stimulation in a majority of patients with no relation to symptom severity. However, at the end of the series, fHbC increase during stimulation was negatively correlated with the Montgomery–Åsberg Depression Rating Scale score and positively with the score reduction. Patients showing a decreasing response of fHbC during TMS at the end of the series experienced less clinical improvement.

Conclusion

These results suggest that the maintenance of frontal activation during stimulation in the course of TMS series is related to the effectiveness in the treatment of depression. Measurement of fHbC during stimulation is informative in the clinical use of TMS.

     

Polymorphisms in the microglial marker molecule CX3CR1 affect the blood volume of the human brain

Aim

CX3CR1 , a G‐protein‐coupled receptor, is involved in various inflammatory processes. Two non‐synonymous single nucleotide polymorphisms, V249I (rs3732379) and T280M (rs3732378), are located in the sixth and seventh transmembrane domains of the CX3CR1 protein, respectively. Previous studies have indicated significant associations between T280M and leukocyte functional characteristics, including adhesion, signaling, and chemotaxis, while the function of V249I is unclear. In the brain, microglia are the only proven and widely accepted CX3CR1‐expressing cells. This study aimed to specify whether there were specific brain regions on which these two single nucleotide polymorphisms exert their biological impacts through their functional effects on microglia.

Methods

Associations between the single nucleotide polymorphisms and brain characteristics, including gray and white matter volumes, white matter integrity, resting arterial blood volume, and cerebral blood flow, were evaluated among 1300 healthy Japanese individuals.

Results

The major allele carriers (V249 and T280) were significantly associated with an increased total arterial blood volume of the whole brain, especially around the bilateral precuneus, left posterior cingulate cortex, and left posterior parietal cortex. There were no significant associations between the genotypes and other brain structural indicators.

Conclusion

This finding suggests that the CX3CR1 variants may affect arterial structures in the brain, possibly via interactions between microglia and brain microvascular endothelial cells.

     

Optimal cut‐off score of the Edinburgh Postnatal Depression Scale for major depressive episode during pregnancy in Japan

Aim

Depression during pregnancy adversely affects both mother and child. As antenatal depression is a predictor of postnatal depression, early detection might prevent postnatal depression. The Edinburgh Postnatal Depression Scale (EPDS) is frequently used during the perinatal period, but the cut‐off score during pregnancy has not been verified for the Japanese population. We aimed to clarify the optimal EPDS cut‐off score in mid‐pregnancy in Japan.

Methods

We recruited pregnant women aged 20 years or older at 12–24 gestational weeks and those who scored ≥9 on the EPDS were invited to participate in this study. In parallel with the EPDS, the Japanese version of the Mini‐International Neuropsychiatric Interview was administered to determine diagnosis of major depressive episode. We then calculated the receiver–operator curve, sensitivity and specificity, and positive and negative predictive values for the EPDS.

Results

All 210 participants were in the second trimester except for one (12 gestational weeks). Twenty participants were diagnosed with major depressive episode. With a cut‐off score set at 13 points, the area under the curve was 0.956; sensitivity and specificity were 90.0% and 92.1% [Correction added on 10 November 2017, after first online publication: The percentage for specificity has been corrected from 79.0% to 92.1%.], respectively; and positive and negative predictive values were 54.5% and 98.9%, respectively.

Conclusion

To our knowledge, this is the first study to clarify the optimal EPDS cut‐off score in the second trimester for Japan. This finding will be helpful for appropriate screening for antenatal depression in Japan.

     

Diagnostic consistency and interchangeability of schizophrenic disorders and bipolar disorders: A 7‐year follow‐up study

Aim

The change in psychiatric diagnoses in clinical practice is not an unusual phenomenon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders is a major clinical issue because of the differences in treatment regimens and long‐term prognoses. In this study, we used a nationwide population‐based sample to compare the diagnostic consistency and interchange rate between schizophrenic disorders and bipolar disorders.

Methods

In total, 25 711 and 11 261 patients newly diagnosed as having schizophrenic disorder and bipolar disorder, respectively, were retrospectively enrolled from the Psychiatric Inpatient Medical Claims database between 2001 and 2005. We followed these two cohorts for 7 years to determine whether their diagnoses were consistent throughout subsequent hospitalizations. The interchange between the two diagnoses was analyzed.

Results

In the schizophrenic disorder cohort, the overall diagnostic consistency rate was 87.3% and the rate of change to bipolar disorder was 3.0% during the 7‐year follow‐up. Additional analyses of subtypes revealed that the change rate from schizoaffective disorder to bipolar disorder was 12.0%. In the bipolar disorder cohort, the overall diagnostic consistency rate was 71.9% and the rate of change to schizophrenic disorder was 8.3%.

Conclusion

Changes in the diagnosis of a major psychosis are not uncommon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders might be attributed to the evolution of clinical symptoms and the observation of preserved social functions that contradict the original diagnosis. While making a psychotic diagnosis, clinicians should be aware of the possibility of the change in diagnosis in the future.

     

Reduced prefrontal hemodynamic response in adult attention‐deficit hyperactivity disorder as measured by near‐infrared spectroscopy

Aim

Recent developments in near‐infrared spectroscopy (NIRS) have enabled non‐invasive clarification of brain functions in psychiatric disorders. In pediatric attention‐deficit hyperactivity disorder (ADHD), reduced prefrontal hemodynamic responses have been observed with NIRS repeatedly. However, there are few studies of adult ADHD by multi‐channel NIRS. Therefore, in this study, we used multi‐channel NIRS to examine the characteristics of prefrontal hemodynamic responses during the Stroop Color–Word Task (SCWT) in adult ADHD patients and in age‐ and sex‐matched control subjects.

Methods

Twelve treatment‐naïve adults with ADHD and 12 age‐ and sex‐matched healthy control subjects participated in the present study after giving consent. We used 24‐channel NIRS to measure the oxygenated hemoglobin (oxy‐Hb) changes at the frontal lobes of participants during the SCWT. We compared the oxy‐Hb changes between adults with ADHD and control subjects by t ‐tests with Bonferroni correction.

Results

During the SCWT, the oxy‐Hb changes observed in the ADHD group were significantly smaller than those in the control group in channels 11, 16, 18, 21, 22, 23, and 24, corresponding to the prefrontal cortex. At channels 16, 21, 23, and 24 of the ADHD group, there were negative correlations between the symptomatic severity and the oxy‐Hb changes.

Conclusion

The present study suggests that adults with ADHD have reduced prefrontal hemodynamic response as measured by NIRS.

     

Safety and efficacy from a 6‐week double‐blind study and a 52‐week open‐label extension of aripiprazole in adolescents with schizophrenia in Japan

Aim

The purpose of this study was to evaluate the safety and efficacy of aripiprazole in adolescents with schizophrenia (SCZ) in Japan.

Methods

In a 6‐week, randomized, double‐blind, dose‐comparison study, adolescents (aged 13–17 years) with SCZ were randomized to receive aripiprazole 2, 6–12, or 24–30 mg/day. Patients who completed the 6‐week study participated in a 52‐week, flexible‐dose, open‐label extension (OLE) study of aripiprazole (initial dose: 2 mg/day, maintenance dose: 6–24 mg/day, maximum dose: 30 mg/day).

Results

In the 6‐week study, the percentage of patients completing treatment was: 77.1% (27/35) for 2 mg/day; 80.0% (24/30) for 6–12 mg/day; and 85.4% (35/41) for 24–30 mg/day. The least squares mean change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to endpoint (primary efficacy endpoint, last observation carried forward) was ?19.6 for 2 mg/day, ?16.5 for 6–12 mg/day, and ? 21.6 for 24–30 mg/day. The most common (≥20% patients in any group) treatment‐emergent adverse events (TEAE) were nausea, akathisia, insomnia, and somnolence. Most TEAE were mild or moderate in severity. There were no deaths. In the OLE, 60.3% (41/68) of patients completed treatment, and the PANSS total score decreased by ?7.9 from OLE baseline to week 52. The most common (≥20% patients) TEAE were nasopharyngitis and somnolence. Most TEAE were mild or moderate in severity. There were no deaths.

Conclusion

These study results suggest that aripiprazole would be safe and well tolerated in both short‐ and long‐term treatment for adolescents with SCZ in Japan.

     

Natural regulatory IgM‐mediated autoimmune responses directed against malondialdehyde regulate oxidative and nitrosative pathways and coupled with IgM responses to nitroso adducts attenuate depressive and physiosomatic symptoms at the end of term pregnancy

Aim

We aimed to delineate the effects of immunoglobulin (Ig)M‐mediated autoimmune responses directed against malondialdehyde (MDA) and nitroso (SNO) adducts on nitro‐oxidative stress and depressive and physiosomatic symptoms (DPSS) at the end of term.

Methods

IgM responses to MDA, NO (nitroso) adducts formed by nitrosylation, and NO₂ tyrosine formed by nitration were measured as well as hydroperoxides (ferrous oxidation xylenol orange), advanced protein oxidation products (AOPP), and NO metabolite (NOx) levels in women at the end of term pregnancy and in normal controls.

Results

IgM responses to MDA were significantly and inversely associated with AOPP, ferrous oxidation xylenol orange, and NOx and DPSS. IgM responses to NO adducts were significantly and inversely associated with DPSS and positively with NOx levels. There were significant associations between IgM responses to MDA, NO adducts, and NO₂ tyrosine. The DPSS score was predicted by AOPP and a lifetime history of premenstrual syndrome (both positively) and IgM responses to NO adducts (inversely). Furthermore, 71.8% of the variance in the index of nitro‐oxidative stress was explained by lowered IgM responses to MDA, antioxidant levels (zinc, total radical trapping parameter), and inflammatory mediators.

Conclusion

Lowered levels of IgM responses to MDA during pregnancy are accompanied by a reduced regulation of nitro‐oxidative processes thereby explaining increased oxidative and nitrosative stress biomarkers in association with DPSS. IgM responses to NO adducts, which reflect nitrosylation as a consequence of increased NO production, regulate DPSS symptoms at the end of term and are a trait marker of major depression. IgM responses to MDA are a key part of the compensatory anti‐inflammatory responses system.