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Interruption of oxygen availability and re-oxygenation at birth implies a severe metabolic insult, affecting the development of the central nervous system (CNS), increasing its vulnerability to challenges occurring at adult stages. It has been reported that perinatal asphyxia produces regionally specific neuronal decrease and neurite atrophy in basal ganglia, and hippocampus. In hippocampus, a concomitant increase of neurogenesis and neurite hypertrophy has also been observed. The potential neuroprotection of nicotinamide, a non-selective inhibitor of poly(ADP-ribose) polymerase (PARP-1), has been investigated, finding functional and morphological improvements when administered 24h after the insult (0.8 mmol/kg, i.p., 24, 48 and 72 h after birth.). The main effect of nicotinamide has been seen in neostriatum, preventing an asphyxia-induced decrease of the number of nNoS cells, and nNoS- and dopamine-like neurite atrophy. The present results support the idea that nicotinamide can prevent the effects elicited by a sustained energy-failure condition, as occurring during perinatal asphyxia, enlightening the enzyme PARP-1 as a novel target for neuronal protection. [ABSTRACT FROM AUTHOR]

Dopamine replacement therapy (DRT) of Parkinson's disease (PD) may trigger non-motor complications, some of which affect hedonic homeostatic regulation. Management of iatrogenic alterations in the affective state in PD is unsatisfactory, partly because of the limitations in the experimental models that are used in the preclinical investigation of the neurobiology and therapy of these alterations. In this connection, we recently employed a new experimental approach consisting in measuring the emission of 50-kHz ultrasonic vocalizations (USVs), a marker of positive affect, in hemiparkinsonian rats treated with drugs used in the DRT of PD. To further strengthen our approach, we here evaluated how the acute and repeated (× 5, on alternate days) administration of apomorphine (2 mg/kg, i.p.) or L-3,4-dihydroxyphenilalanine (L-DOPA, 12 mg/kg, i.p.) modified the immunoreactivity for Zif-268, a marker of neuronal activation, in the nucleus accumbens (NAc), caudate-putamen (CPu) and medial prefrontal cortex (mPFC), which are brain regions that regulate emotional states and drugs' affective properties. Acute and repeated treatment with either apomorphine or L-DOPA stimulated the emission of 50-kHz USVs in hemiparkinsonian rats, and this effect was paired with increased Zif-268 immunoreactivity in the NAc and CPu, but not mPFC. These findings indicate that subcortical and cortical regions may differently regulate the emission of 50-kHz USVs in hemiparkinsonian rats treated with dopaminergic drugs used in the DRT of PD. Moreover, they provide further evidence that measuring 50-kHz USV emissions in hemiparkinsonian rats may be a relevant approach to investigate at the preclinical level the affective properties of antiparkinsonian drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Grandparental support may protect mothers from depression, particularly mothers who separate and enter single parenthood. Using longitudinal Finnish register data on 116,917 separating and 371,703 non-separating mothers with young children, we examined differences in mothers' antidepressant purchases by grandparental characteristics related to provision of support. Grandparents' younger age (<70 years), employment, and lack of severe health problems predicted a lower probability of maternal depression. Depression was also less common if grandparents lived close to the mother and if the maternal grandparents' union was intact. Differences in maternal depression by grandparental characteristics were larger among separating than among non-separating mothers, particularly during the years before separation. Overall, maternal grandmothers' characteristics appeared to matter most, while the role of paternal grandparents was smaller. The findings suggest that grandparental characteristics associated with increased potential for providing support and decreased need of receiving support predict a lower likelihood of maternal depression, particularly among separating mothers.

Hospitals at home are increasingly offering outpatient parenteral antimicrobial therapy (OPAT) in an attempt to reduce costly inpatient care, but these settings favour broad-spectrum antibiotics that require less frequent dosing than penicillin. Benzyl penicillin could be delivered via continuous infusion pumps (eCIPs), but studies on their safety and efficacy in OPAT are scarce, and it remains unclear how much the availability of eCIPs increases penicillin use in real-life settings. We examined 462 electronic healthcare records of erysipelas patients treated between January 2018 and January 2022 in a large Finnish OPAT clinic. Average marginal effects from logistic models were estimated to assess how the introduction of eCIPs in December 2020 affected penicillin use and to compare clinical outcomes between patients with and without eCIPs. Introduction of eCIPs increased the predicted probability of penicillin treatment by 36.0 percentage points (95% confidence interval 25.5-46.5). During eCIP implementation, patients who received an eCIP had 73.1 (58.0-88.2) percentage points higher probability than patients without an eCIP to receive penicillin treatment. They also had about 20 percentage points higher probability to be cured at the time of discharge and 3 months after it. Patient and nurse satisfaction regarding eCIPs was very high. Benzyl penicillin eCIP treatment is effective and safe, and substantially increases the use of penicillin instead of broad-spectrum antibiotics. To reduce the risk of antimicrobial resistance, eCIPs could increasingly be promoted for use in OPAT clinics, and there should be adequate education and support in their implementation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Preclinical and clinical studies indicate that psychostimulants, in addition to having abuse potential, may elicit brain dysfunctions and/or neurotoxic effects. Central toxicity induced by psychostimulants may pose serious health risks since the recreational use of these substances is on the rise among young people and adults. The present review provides an overview of recent research, conducted between 2018 and 2023, focusing on brain dysfunctions and neurotoxic effects elicited in experimental models and humans by amphetamine, cocaine, methamphetamine, 3,4-methylenedioxymethamphetamine, methylphenidate, caffeine, and nicotine. Detailed elucidation of factors and mechanisms that underlie psychostimulant-induced brain dysfunction and neurotoxicity is crucial for understanding the acute and enduring noxious brain effects that may occur in individuals who use psychostimulants for recreational and/or therapeutic purposes., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

The number of people who undergo medically assisted reproduction (MAR) to conceive has increased considerably in recent decades. However, existing research into the demographics and the partnership histories of this growing subgroup is limited. Using unique data from Finnish population registers on nulliparous women born in Finland in 1971-77 ( n  = 21,129; ∼10 per cent of all women) who had undergone MAR treatment, we created longitudinal partnership histories from age 16 until first MAR treatment. We identified six typical partnership trajectories and used relative frequency sequence plots to investigate heterogeneity in partnership transitions within and between these groups. The majority of women (60.7 per cent) underwent MAR with their first partner, followed by women who underwent MAR in a second (21.5 per cent) or higher-order partnership (7.1 per cent), while 10.7 per cent underwent MAR without a partner. On average, women undergoing MAR were relatively young (with around half starting treatment before age 30) and were highly educated with high incomes.

Background: The proliferation of novel psychoactive substances (NPS) in the drug market raises concerns about uncertainty on their pharmacological profile and the health hazard linked to their use. Within the category of synthetic stimulant NPS, the phenethylamine 2-Cl-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) has been linked to severe intoxication requiring hospitalization. Thereby, the characterization of its pharmacological profile is urgently warranted., Methods: By in vivo brain microdialysis in adolescent and adult male rats we investigated the effects of 2-Cl-4,5-MDMA on dopamine (DA) and serotonin (5-HT) neurotransmission in two brain areas critical for the motivational and rewarding properties of drugs, the nucleus accumbens (NAc) shell and the medial prefrontal cortex (mPFC). Moreover, we evaluated the locomotor and stereotyped activity induced by 2-Cl-4,5-MDMA and the emission of 50-kHz ultrasonic vocalizations (USVs) to characterize its affective properties., Results: 2-Cl-4,5-MDMA increased dialysate DA and 5-HT in a dose-, brain area-, and age-dependent manner. Notably, 2-Cl-4,5-MDMA more markedly increased dialysate DA in the NAc shell and mPFC of adult than adolescent rats, while the opposite was observed on dialysate 5-HT in the NAc shell, with adolescent rats being more responsive. Furthermore, 2-Cl-4,5-MDMA stimulated locomotion and stereotyped activity in both adolescent and adult rats, although to a greater extent in adolescents. Finally, 2-Cl-4,5-MDMA did not stimulate the emission of 50-kHz USVs., Conclusions: This is the first pharmacological characterization of 2-Cl-4,5-MDMA demonstrating that its neurochemical and behavioral effects may differ between adolescence and adulthood. These preclinical data could help understanding the central effects of 2-Cl-4,5-MDMA by increasing awareness on possible health damage in users., (© The Author(s) 2024. Published by Oxford University Press on behalf of CINP.)

Background: Grey divorce and later remarriage have become increasingly common in high-income countries, but previous evidence on their impacts on mental health is scarce. Even less is known about the effects of non-marital separation and re-partnering in later life., Methods: Using Finnish registry data from 1996 to 2018 on 228 644 individuals aged 50-70 in 2000-2014, trajectories of antidepressant (AD) use 4 years before and 4 years after divorce, non-marital separation, bereavement and subsequent re-partnering were examined using individual fixed-effects (FE) linear probability models., Results: In adjusted FE models, for both genders AD use increased during the 4 years before divorce (men: 5.00 percentage points (95% CI 4.50 to 5.50); women: 6.96 (95% CI 6.34 to 7.59)), non-marital separation (men: 3.20 (95% CI 2.72 to 3.69); women: 5.98 (95% CI 5.30 to 6.66)) and bereavement (men: 4.53 (95% CI 3.97 to 5.09); women: 5.64 (95% CI 5.25 to 6.04)), with the increase accelerating immediately before the event. AD use gradually declined after union dissolution, after which it stabilised on a persistently higher level compared with pre-dissolution. Re-partnering was only associated with a small and transitory reduction in AD use (0.1-1.5 percentage points). The increases in AD use associated with union dissolution were larger in women than in men, whereas the small reductions in AD use associated with re-partnering were particularly short-lived among women., Conclusions: Our results suggest that union dissolution in later life is associated with large and persistent increases in AD use, whereas the reductions associated with re-partnering are limited both in magnitude and duration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Prior studies suggest that poor physical health, accompanied by functional disability, is associated with increased divorce risk. However, this association may depend on gender, the socioeconomic resources of the couple, as well as the social policy and social (in)equality context in which the illness is experienced. This study focuses on neurological conditions, which often have substantial functional consequences., Methods: We used longitudinal population-wide register data from the years 2007-2016 (Denmark, Sweden) or 2008-2017 (Finland, Norway) to follow 2 809 209 married couples aged 30-64 for neurological conditions, identified using information on specialised healthcare for diseases of the nervous system and subsequent divorce. Cox regression models were estimated in each country, and meta-analysis used to calculate across-country estimates., Results: During the 10-year follow-up period, 22.2% of couples experienced neurological conditions and 12.0% of marriages ended in divorce. In all countries, divorce risk was elevated among couples where at least one spouse had a neurological condition, and especially so if both spouses were ill. The divorce risk was either larger or similar for husband's illness, compared with wife's illness, in all educational categories. For the countries pooled, the weighted average HR was 1.21 (95% CI 1.20 to 1.23) for wives' illness, 1.27 (95% CI 1.25 to 1.29) for husbands' illness and 1.38 (95% CI 1.34 to 1.42) for couples where both spouses were ill., Conclusions: Despite some variation by educational resources and country context, the results suggest that the social consequences of illness are noticeable even in Nordic welfare states, with the husband's illness being at least as important as the wife's., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Rats emit 50-kHz ultrasonic vocalizations (USVs) in response to nonpharmacological and pharmacological stimuli, with addictive psychostimulants being the most effective drugs that elicit calling behavior in rats. Earlier investigations found that dopamine D1-like and D2-like receptors modulate the emission of 50-kHz USVs stimulated in rats by the acute administration of addictive psychostimulants. Conversely, information is lacking on how dopamine D1-like and D2-like receptors modulate calling behavior in rats that are repeatedly treated with addictive psychostimulants., Methods: We evaluated the emission of 50-kHz USVs in rats repeatedly treated (×5 on alternate days) with amphetamine (1 mg/kg, i.p.) either alone or together with (1) SCH 23390 (0.1-1 mg/kg, s.c.), a dopamine D1 receptor antagonist; (2) raclopride (0.3-1 mg/kg, s.c.), a selective dopamine D2 receptor antagonist; or (3) a combination of SCH 23390 and raclopride (0.1 + 0.3 mg/kg, s.c.). Calling behavior of rats was recorded following pharmacological treatment, as well as in response to the presentation of amphetamine-paired cues and to amphetamine challenge (both performed 7 days after treatment discontinuation)., Results: Amphetamine-treated rats displayed a sensitized 50-kHz USV emission during repeated treatment, as well as marked calling behavior in response to amphetamine-paired cues and to amphetamine challenge. Antagonism of D1 or D2 receptors either significantly suppressed or attenuated the emission of 50-kHz USVs in amphetamine-treated rats, with a maximal effect after synergistic antagonism of both receptors., Conclusions: These results shed further light on how dopamine transmission modulates the emission of 50-kHz USVs in rats treated with psychoactive drugs., (© The Author(s) 2024. Published by Oxford University Press on behalf of CINP.)

Background: Maternal mental illness appears to increase the risk of unintentional childhood injuries, which are a common cause of morbidity and mortality in early childhood. However, little is known about the variations in this association by type of injury and child's age, and studies on the effects of maternal somatic illness on children's injury risk are scarce., Methods: We used Finnish total population register data from 2000 to 2017 to link 1 369 325 children to their biological mothers and followed them for maternal illness and childhood injuries until the children's sixth birthday. Cox regression models were used to examine the associations between maternal illness and children's injuries by type of illness (neurological, psychiatric and cancer), type of injury (transport injuries, falls, burns, drowning or suffocations, poisonings, exposure to inanimate and animate mechanical forces) and child's age (<1 year-olds, 1-2 year-olds, 3-5 year-olds)., Results: After adjustment for family structure, maternal age at birth, maternal education, income, child's gender, native language and region of residence, children of unwell mothers showed a higher risk of injuries (HR: 1.21, 95% CI: 1.19 to 1.23). This association was clear for maternal neurological (HR: 1.31, 95% CI: 1.26 to 1.36) and psychiatric illnesses (HR: 1.20, 95% CI: 1.18 to 1.23) but inconsistent for cancer. Maternal illness predicted an increased risk of injury across all age groups., Conclusions: Maternal mental and somatic illness may both increase children's injury risk. Adequate social and parenting support for families with maternal illness may reduce childhood injury., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Mice and rats emit ultrasonic vocalizations (USVs), which may express their arousal and emotional states, to communicate with each other. There is continued scientific effort to better understand the functions of USVs as a central element of the rodent behavioral repertoire. However, studying USVs is not only important because of their ethological relevance, but also because they are widely applied as a behavioral readout in various fields of biomedical research. In mice and rats, a large number of experimental models of brain disorders exist and studying the emission of USVs in these models can provide valuable information about the health status of the animals and the effectiveness of possible interventions, both environmental and pharmacological. This review (i) provides an updated overview of the contexts in which ultrasonic calling behaviour of mice and rats has particularly high translational value, and (ii) gives some examples of novel approaches and tools used for the analysis of USVs in mice and rats, combining qualitative and quantitative methods. The relevance of age and sex differences as well as the importance of longitudinal evaluations of calling and non-calling behaviour is also discussed. Finally, the importance of assessing the communicative impact of USVs in the receiver, that is, through playback studies, is highlighted., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Medically assisted reproduction can negatively affect women's mental health, particularly when the treatments do not result in a live birth. Although the number of women relying on medically assisted reproduction to conceive has grown rapidly, our knowledge about the mental health effects before, during, and after treatment is limited., Objective: This study aimed to understand the long-term association between medically assisted reproduction and mental health outcomes for women before, during, and after their treatments, and according to whether the treatment resulted in a live birth., Study Design: Using Finnish register data for the period from 1995 to 2018, we estimated the probability of psychotropic purchases (antidepressants, anxiolytics, hypnotics, and sedatives) for 3 groups of women who: (1) gave birth after natural conception, (2) gave birth after medically assisted reproduction treatments, or (3) underwent medically assisted reproduction but remained childless. We followed up women for up to 12 years before and 12 years after the reference date, which corresponded to the conception date for women who had a first live birth either after a natural or a medically assisted conception, or the date of the last medically assisted reproduction treatment for women with no live birth by the end of 2017. We estimated linear probability models before and after adjustment for sociodemographic characteristics., Results: The results show that women who did not have a live birth after undergoing medically assisted reproduction treatments purchased more psychotropics than women who gave birth after conceiving naturally or through medically assisted reproduction, and that these differences did not attenuate over time. Twelve years after the reference date, 17.73% (95% confidence interval, 16.82-18.63) of women who underwent medically assisted reproduction but remained childless purchased psychotropics vs 11.11% of women who gave birth after natural conception (95% confidence interval, 10.98-11.26) and 12.17% (95% confidence interval, 11.65-12.69) of women who gave birth after medically assisted reproduction treatments. In addition, women who conceived naturally and through medically assisted reproduction had very similar psychotropic use patterns from 3 years before conception to 4 years after, and over the long term. Adjustment for women's sociodemographic characteristics did not change the results., Conclusion: The similarities in psychotropic purchases of women who had a live birth, whether naturally or through medically assisted reproduction, suggest that the higher psychotropic use among women who remained childless after undergoing medically assisted reproduction were likely driven more by involuntary childlessness than by treatment-related stress. The results highlight the importance of counseling for women undergoing medically assisted reproduction treatments, especially if their attempts to conceive are unsuccessful., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Single motherhood is known to be distressing, and to be associated with poor mental health. However, less is known about the pathways into and out of single motherhood, or about the mental health trajectories of single mothers. We used total population registry data on Finnish women who experienced the life events of separation (616,762), widowhood (43,355), or child birth (515,756) during the 1995-2018 period while between the ages of 15-64. Single mothers were compared with women who experienced the same life event, but without becoming a single mother. The results for women who separated showed that among single mothers, there was a substantial increase in antidepressant use at the time of separation, and only a moderate decline after separation. Among women who experienced widowhood, those who had underage children initially had lower antidepressant use than women without children, but this gap narrowed in the post-widowhood period. In addition, single women experienced more unfavorable mental health trajectories than partnered women around the time they gave birth. Re-partnering was associated with more favorable mental health among all groups of single mothers. Given the growing prevalence of single-parent households, our results underscore the need for context-specific interventions to support single mothers' mental health., (© 2022. The Author(s).)

Background: A recent study has suggested that labor epidural analgesia may be associated with increased rates of offspring autism spectrum disorder. Subsequent replication attempts have lacked sufficient power to confidently exclude the possibility of a small effect, and the causal nature of this association remains unknown., Objective: This study aimed to investigate the extent to which exposure to labor epidural analgesia is associated with offspring autism spectrum disorder and attention-deficit/hyperactivity disorder following adjustments for unmeasured familial confounding., Study Design: We identified 4,498,462 singletons and their parents using the Medical Birth Registers in Finland (cohorts born from 1987-2005), Norway (1999-2015), and Sweden (1987-2011) linked with population and patient registries. These cohorts were followed from birth until they either had the outcomes of interest, emigrated, died, or reached the end of the follow-up (at mean ages 13.6-16.8 years), whichever occurred first. Cox regression models were used to estimate country-specific associations between labor epidural analgesia recorded at birth and outcomes (eg, at least 1 secondary care diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder or at least 1 dispensed prescription of medication used for the treatment of attention-deficit/hyperactivity disorder). The models were adjusted for sex, birth year, birth order, and unmeasured familial confounders via sibling comparisons. Pooled estimates across all the 3 countries were estimated using inverse variance weighted fixed-effects meta-analysis models., Results: A total of 4,498,462 individuals (48.7% female) were included, 1,091,846 (24.3%) of which were exposed to labor epidural analgesia. Of these, 1.2% were diagnosed with autism spectrum disorder and 4.0% with attention-deficit/hyperactivity disorder. On the population level, pooled estimates showed that labor epidural analgesia was associated with increased risk of offspring autism spectrum disorder (adjusted hazard ratio, 1.12; 95% confidence interval, 1.10-1.14, absolute risks, 1.20% vs 1.07%) and attention-deficit/hyperactivity disorder (adjusted hazard ratio, 1.20; 95% confidence interval, 1.19-1.21; absolute risks, 3.95% vs 3.32%). However, when comparing full siblings who were differentially exposed to labor epidural analgesia, the associations were fully attenuated for both conditions with narrow confidence intervals (adjusted hazard ratio [autism spectrum disorder], 0.98; 95% confidence interval, 0.93-1.03; adjusted hazard ratio attention-deficit/hyperactivity disorder, 0.99; 95% confidence interval, 0.96-1.02)., Conclusion: In this large cross-national study, we found no support for the hypothesis that exposure to labor epidural analgesia causes either offspring autism spectrum disorder or attention-deficit/hyperactivity disorder., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: Changes in mental health at the time of widowhood may depend on the expectedness of spousal death, but scant evidence is available for spousal deaths attributable to stroke. Methods: Using register-linkage data for Finland, we assessed changes in antidepressant use before and after spousal death for those whose spouses died suddenly of stroke between 1998 and 2003 ( N =1820) and for those whose spouses died expectedly of stroke, with prior hospitalisation for cerebrovascular disease ( N =1636). We used both population-averaged logit models and individual fixed-effects linear probability models. The latter models control for unobserved time-invariant heterogeneity between the individuals. Results: Our study indicates that the suddenness of a spouse's death from stroke plays a role in the well-being of the surviving spouse. Increases in antidepressant use appeared larger following widowhood for those whose spouses died suddenly of stroke relative to those whose spouses had a medical history of cerebrovascular disease. Conclusions: The suddenness of a spouse's death from stroke plays a role for the surviving spouse. The results suggest multifaceted timings of distress surrounding spousal death, depending on the suddenness of a spouse's death from stroke.

Objective: This study analyzes the victimization trajectories of partner violence against women surrounding divorce, depending on whether the couple has children together., Background: Prior studies have found that partner violence is associated with an increased risk of divorce. No study has assessed the victimization trajectories surrounding divorce for women with and without children, although women with children may remain at higher risk of violence following divorce., Method: Using Finnish record-linkage data of 22,468 divorced and 333,542 continuously married women and their husbands, we used repeated-measures logistic regression analyses to assess changes in victimization for partner violence before and after divorce. The outcomes considered were police-reported crimes committed by husbands against their wives and hospital-treated assault injuries recorded for wives., Results: The risk of crime victimization for partner assault was already elevated from 2 to 3 years before divorce, peaked in the year prior to divorce, and then mainly leveled off 1-2 years after divorce. Hospital data show that the time of the greatest risk was from 6 to 12 months before divorce, when divorce is usually filed for. Women with younger children experienced elevated risks of physical violence shortly before divorce and remained at higher risk of menace than women without children for a year after divorce., Conclusion: Divorcing women committed assaults against their husbands, but these were mostly accompanied by victimization, suggesting that resistant violence was common for women as perpetrators. Women with a history of victimization need support, especially at the starts of their divorce processes., (© 2022 The Authors. Journal of Marriage and Family published by Wiley Periodicals LLC on behalf of National Council on Family Relations.)