Vulnerabilities in sequencing and task switching in healthy youth offspring of parents with mood disorders

Introduction: Visuospatial processing and task switching are impaired in individuals with mood disorders. It is unknown whether early deficits are present before mood symptom on set or are related to risk for a specific type of mood disorder. To investigate, we compared visual attention and task switching during sequencing among never-disordered youth with parental family histories of bipolar (BD) and major depressive disorders (MDD) and healthy controls (HC) with no personal or family history of psychopathology.

Method: 8–17-year-old youth of parents with BD (n = 31, “BD-risk”), youth of parents with MDD (n = 49, “MDD-risk”), and demographically similar HC (n = 31, “HC”) were examined using the Delis–Kaplan Executive Functioning System Trail Making Test. Seed-based resting-state functional connectivity (RSFC) was collected from a subset of 88 participants (25 BD-risk, 37 MDD-risk, 26 HC) to investigate group differences in RSFC related to visuospatial processing.

Results: BD-risk and MDD-risk offspring had impaired sequencing and task switching, demonstrated by reduced scores on visual scanning, F(2, 108) = 4.12, p = .02, number sequencing, F(2, 88) = 4.75, p = .01, letter sequencing, F(2, 108) = 4.24, p = .02, and number–letter sequencing, F(2, 108) = 4.66, p = .01, compared to scores in HC. RSFC between the posterior cingulate (PCC) and clusters in the subcallosal cortex, amygdala, and hippocampus significantly differed among HC, BD-risk, and MDD-risk groups. PCC-subcallosal/limbic RSFC was positively coupled in the MDD-risk and BD-risk groups and negatively coupled in HCs.

Conclusions: Youth at familial risk for mood disorders demonstrate visuospatial deficits early in the processing stream. Improved methods for identifying at-risk children with the earliest possible neurocognitive impairments may inform remediation strategies that could prevent mood disorders.     

Clinical staging model in offspring of parents with bipolar disorder: a systematic review

Objective

We sought to systematically review the literature on the psychiatric risk of offspring of parents with bipolar disorder (OPBD) using a developmental psychopathology framework. The review also sought to establish the utility of clinical stage modelling as a framework for identifying precursor disorders to later onset of bipolar disorder (BD) in OPBD.

Methods

A systematic search was performed using EMBASE, PsychINFO and Medline. Reference lists of included studies and previous reviews were also searched. Studies were included if they reported diagnostic outcomes for child, adolescent and young adult offspring of parents diagnosed with BD.

Results

Twenty‐six studies were identified representing 21 individual cohorts. The review identified that OBPD present as a high‐risk group for a range of mood and non‐mood disorders in childhood, adolescence and young adulthood. The trajectory of risk was from non‐mood disorders in childhood via non‐bipolar mood disorders in early adolescence towards mania/hypomania in late adolescence and early adulthood. From a clinical staging perspective, childhood anxiety disorders were associated with later onset of BD. Recurrent substance use disorder was identified as a risk in OPBD during late adolescence and early adulthood. Quality ratings indicated that studies were methodologically robust.

Conclusions

Our review provides evidence for a developmental psychopathology trajectory of precursor risks to BD in OPBD. There is support for clinical stage modelling as a conceptual framework for understanding developmental risk in OPBD and as a tool for developing early and individualized intervention strategies.     

肾虚对雄性小鼠及其雄性仔鼠精子DNA损伤的影响

目的：观察肾虚对雄性小鼠及其雄性仔鼠精子DNA损伤的影响。方法：将30只雄性昆明小鼠用计算机取随机数法随机分为正常对照组、模型组和补肾组3组。其中模型组和补肾组采用房劳加惊恐的复合伤肾法制造肾精亏虚模型。从造模结束次日起,所有小鼠与正常发情雌鼠配对饲养5天后,处死,取附睾精子,同时进行精子单细胞凝胶电泳（Single cell gel electropherosis,SCGE）、精子染色体结构分析（sperm chromosome structure analysis,SCSA）检测其精子DNA损伤。取出雌鼠待其分娩。仔鼠饲养至6周龄时每组随机取出10只雄性仔鼠,用SCGE和SCSA检测其精子DNA损伤。结果：模型组小鼠与正常组相比精子细胞拖尾率（40.51±11.21vs23.64±9.86,P〈0.01）和DFI（37.42±7.19vs17.11±4.98,P〈0.01）均明显升高,补肾组（拖尾细胞率25.31±8.59,DFI24.31±7.99,P〉0.05）虽然存在DNA损伤,但与正常组相比没有明显差异。模型组仔鼠精子细胞拖尾率（24.59±9.45vs18.53±8.51P〈0.05）及DFI（32.18±9.90vs17.29±5.14,P〈0.01）亦明显较正常组高,但补肾组仔鼠精子DNA损伤程度较轻（拖尾细胞率20.61±6.34,DFI15.22±7.49,P〉0.05）,与正常组相比没有明显差异。结论：经＂惊恐、房劳＂方法造模后,模型组小鼠精子DNA损伤程度明显上升,而补肾疗法则能较好地保护精子DNA完整性。肾虚雄性仔鼠精子DNA完整性有类似于父代的改变,但程度较轻。说明肾虚造成的生殖系统损害,可能通过DNA损伤影响了其仔鼠的生殖健康。     

Offspring of rats with cerebral hypoxia-ischemia manifest cognitive dysfunction in learning and memory abilities

Neonatal hypoxic-ischemic encephalopathy is a serious neurological disease,often resulting in long-term neurodevelopmental disorders among surviving children.However,whether these neurodevelopmental issues can be passed to offspring remains unclear.The right common carotid artery of 7-day-old parental-generation rats was subjected to permanent ligation using a vessel electrocoagulator.Neonatal hypoxic-ischemic rat models were established by subjecting the rats to 8%O2–92%N2 for 2 hours.The results showed that 24 hours after hypoxia and ischemia,pathological damage,cerebral atrophy,liquefaction,and impairment were found,and Zea-Longa scores were significantly increased.The parental-generation rats were propagated at 3 months old,and offspring were obtained.No changes in the overall brain structures of these offspring rats were identified by magnetic resonance imaging.However,the escape latency was longer and the number of platform crossings was reduced among these offspring compared with normal rats.These results indicated that the offspring of hypoxic-ischemic encephalopathy model rats displayed cognitive impairments in learning and memory.This study was approved by the Animal Care&Welfare Committee of Kunming Medical University,China in 2018(approval No.kmmu2019072).     

Formation of DNA adducts in tissues of mouse progeny through transplacental contamination and/or lactation after administration of a single dose of ochratoxin A to the pregnant mother

Ochratoxin A (OTA) is a mycotoxin which has been detected in foods of plant origin, in edible animal tissues, and in human sera, urine, and milk in many countries. OTA is nephrotoxic and carcinogenic in mice and rats and is suspected to play a key role in the etiology of Balkan endemic nephropathy and/or associated urinary tract tumors. In the present study, some early signs of genetic impairment, including the presence of DNA adducts in target tissues from the progeny of mice after administration of a single OTA dose during late pregnancy, have been investigated. By the ³²P-postlabeling method, several characteristic DNA adducts with the same R_f values were detected in kidney and liver of both the OTA-treated mice and their progeny—the fetus and the offspring. No adduct was found in tissues from control animals. Different adducts were most important in kidney and liver DNA and some were organ-specific. High levels of DNA adducts were detected in the kidneys of male progeny, whereas in the female progeny and the mothers they were detected almost exclusively in the liver. This result correlates well with the carcinogenicity in mice: the target organ for males is the kidney, while for females it is the liver. High levels of DNA adducts were also found in fetuses. These results provide evidence for a direct genotoxic action of OTA in the progeny through transplacental contamination, which constitutes a new serious health hazard of exposure to this toxin. Environ. Mol. Mutagen. 32:155–162, 1998 © 1998 Wiley-Liss, Inc.     

Male proportion in offspring of parents exposed to strong static and extremely low-frequency electromagnetic fields in Norway

Reduced male proportion in offspring of male carbon setters prompted a study into whether offspring of workers exposed to strong static and extremely low-frequency electromagnetic fields (ELF) had a deviant sex ratio. The study was based on all births in Norway 1970–1993. The reference population was offspring of parents not exposed to ELF. The male proportion in offspring of men in aluminum works was 50.38%, RR 0.98 (0.94–1.03), in manganese works 47.32%, RR 0.92 (0.83–1.02), in factories producing iron 50.03%, RR 0.97 (0.93–1.02), in nickel works 48.27%, RR 0.94 (0.84–1.05), and in electric wire production 47.20%, RR 0.92 (0.80–1.05). In the offspring of women in aluminum works, the male proportion was 37.04%, RR 0.72 (0.59–0.90), in all smelter works grouped together, 45.13%, RR 0.88 (0.79–0.99). The male proportion in the reference population was 51.42%. The male proportion in offspring of men in industries with ELF, was slightly reduced, while offspring of women was significantly reduced. Am. J. Ind. Med. 32:557–561, 1997. © 1997 Wiley-Liss, Inc.     

Zinc deficiency and a high-fat diet during growth: Metabolic and adipocyte alterations in rats

Background and aimsTo evaluate the effects of a high-fat diet during post-weaning growth on intermediate metabolism and retroperitoneal adipose tissue, in adult male rats exposed to adequate or deficient zinc intake during prenatal and postnatal life.Methods and resultsFemale Wistar rats were fed low- or control-zinc diets from pregnancy to offspring weaning. Male offspring born from control mothers were fed either control or high-fat, control-zinc diets for 60 days. Male offspring born from zinc deficient mothers were fed either low-zinc or high-fat, low-zinc diets for 60 days. At 74 days of life, oral glucose tolerance test was performed. In 81-day-old offspring, blood pressure, lipid profile, plasmatic lipid peroxidation and serum adiponectin level were determined. In retroperitoneal adipose tissue, we evaluated oxidative stress, morphology and adipocytokines mRNA expression. Low-zinc diet induced adipocytes hypertrophy, increased oxidative stress, and decreased adiponectin mRNA expression in adipose tissue. Low-zinc diet increased systolic blood pressure, triglyceridemia, plasmatic lipid peroxidation and glycemia at 3 h after glucose overload. Animals fed high-fat or high-fat, low-zinc diets showed adipocytes hypertrophy, decreased adiponectin mRNA expression, and increased leptin mRNA expression and oxidative stress in adipose tissue. They also exhibited decreased serum adiponectin levels, increased triglyceridemia, plasmatic lipid peroxidation and area under the oral glucose tolerance curve. High-fat, low-zinc diet induced greater alterations in adipocyte hypertrophy, leptin mRNA expression and glucose tolerance test than high-fat diet.ConclusionZinc deficiency since early stages of intrauterine life could increase susceptibility to metabolic alterations induced by high-fat diets during postnatal life.     

Risk of genetic and epigenetic alteration in children conceived following ART: Is it time to return to nature whenever possible?

Assisted reproductive technology may influence epigenetic signature as the procedures coincide with the extensive epigenetic modification occurring from fertilization to embryo implantation. However, it is still unclear to what extent ART alters the embryo epigenome. In vivo fertilization occurs in the fallopian tube, where a specific and natural environment enables the embryo's healthy development. During this dynamic period, major waves of epigenetic reprogramming, crucial for the normal fate of the embryo, take place. Over the past decade, concerns relating to the raised incidence of epigenetic anomalies and imprinting following ART have been raised by several authors. Epigenetic reprogramming is particularly susceptible to environmental conditions during the periconceptional period; therefore, unphysiological conditions, including ovarian stimulation, in vitro fertilization, embryo culture, cryopreservation of gametes and embryos, parental lifestyle, and underlying infertility, have the potential to contribute to epigenetic dysregulation independently or collectively. This review critically appraises the evidence relating to the association between ART and genetic and epigenetic modifications that may be transmitted to the offspring.     

Maternal obesity and offspring health: Adapting metabolic changes through autophagy and mitophagy

Maternal obesity leads to obstetric complications and a high prevalence of metabolic anomalies in the offspring. Among various contributing factors for maternal obesity-evoked health sequelae, developmental programming is considered as one of the leading culprit factors for maternal obesity-associated chronic comorbidities. Although a unified theory is still lacking to systematically address multiple unfavorable postnatal health sequelae, a cadre of etiological machineries have been put forward, including lipotoxicity, inflammation, oxidative stress, autophagy/mitophagy defect, and cell death. Hereinto, autophagy and mitophagy play an essential housekeeping role in the clearance of long-lived, damaged, and unnecessary cell components to maintain and restore cellular homeostasis. Defective autophagy/mitophagy has been reported in maternal obesity and negatively impacts fetal development and postnatal health. This review will provide an update on metabolic disorders in fetal development and postnatal health issues evoked by maternal obesity and/or intrauterine overnutrition and discuss the possible contribution of autophagy/mitophagy in metabolic diseases. Moreover, relevant mechanisms and potential therapeutic strategies will be discussed in an effort to target autophagy/mitophagy and metabolic disturbances in maternal obesity.