INTRODUCTION: Both maternal depression problems during pregnancy and prenatal exposure to air pollution have been associated with changes in the brain as well as worse mood and anxiety in the offspring in adulthood. However, it is not clear whether these effects are independent or whether and how they might interact and impact the brain age and mental health of the young adult offspring. METHODS: A total of 202 mother-child dyads from a prenatal birth cohort were assessed for maternal depression during pregnancy through self-report questionnaires administered in the early 90s, exposure to air pollutants (Sulfur dioxide [SO2], nitrogen oxides [NOx], and suspended particle matter [SPM]) during each trimester based on maternal address and air quality data, mental health of the young adult offspring (28-30 years of age; 52% men, all of European ancestry) using self-report questionnaires for depression (Beck Depression Inventory), mood dysregulation (Profile of Mood States), anxiety (State-Trait Anxiety Inventory), and psychotic symptoms (Schizotypal Personality Questionnaire), and brain age, estimated from structural magnetic resonance imaging (MRI) and previously published neuroanatomical age prediction model using cortical thickness maps. The brain age gap estimate (BrainAGE) was computed by subtracting structural brain age from chronological age. Trajectories of exposure to air pollution during pregnancy were assessed using Growth Mixture Modeling. The interactions of prenatal depression and prenatal exposure to air pollutants on adult mental health and BrainAGE were assessed using hierarchical linear regression. RESULTS: We revealed two distinct trajectories of exposure to air pollution during pregnancy: "early exposure," characterized by high exposure during the first trimester, followed by a steady decrease, and "late exposure," characterized by low exposure during the first trimester, followed by a steady increase in the exposure during the subsequent trimesters. Maternal depression during the first half of pregnancy interacted with NOX exposure trajectory, predicting mood dysregulation and schizotypal symptoms in young adults. In addition, maternal depression during the second half of pregnancy interacted with both NOx and SO2 exposure trajectories, respectively, and predicted BrainAGE in young adults. In those with early exposure to NOx, maternal depression during pregnancy was associated with worse mental health and accelerated brain aging in young adulthood. In contrast, in those with early exposure to SO2, maternal depression during pregnancy was associated with slower brain aging in young adulthood. CONCLUSIONS: Our findings provide the first evidence of the combined effects of prenatal exposure to air pollution and maternal depression on mental health outcomes and brain age in young adult offspring. Moreover, they point out the importance of the timing and trajectory of the exposure during prenatal development.

• Klíčová slova
• Air pollution, Brain aging, Longitudinal, Maternal antenatal depression, Prenatal birth cohort,
• MeSH
• deprese * chemicky indukované   MeSH
• dospělí MeSH
• duševní zdraví MeSH
• kohortové studie MeSH
• látky znečišťující vzduch škodlivé účinky   toxicita   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek * účinky léků   růst a vývoj   diagnostické zobrazování   MeSH
• stárnutí MeSH
• těhotenství MeSH
• znečištění ovzduší * škodlivé účinky   MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   psychologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• látky znečišťující vzduch MeSH

Maternal depression during pregnancy is associated with elevated risk of anxiety and depression in offspring, but the mechanisms are incompletely understood. Here we conducted a neuroimaging follow-up of a prenatal birth cohort from the European Longitudinal Study of Pregnancy and Childhood (n = 131; 53% women, age 23-24) to test whether deviations from age-normative structural brain development in young adulthood may partially underlie this link. Structural brain age was calculated based on previously published neuroanatomical age prediction models using cortical thickness maps from healthy controls aged 6-89. Brain age gap was computed as the difference between chronological and structural brain age. Participants also completed self-report measures of anxiety and mood dysregulation. Further, mothers of a subset of participants (n = 103, 54% women) answered a self-report questionnaire in 1990-1992 about depressive symptoms during pregnancy. Higher exposure to maternal depressive symptoms in utero showed a linear relationship with elevated brain age gap, which showed a quadratic relationship with anxiety and mood dysregulation in the young adult offspring. Our findings suggest that exposure to maternal depressive symptoms in utero may be associated with accelerated brain maturation and that deviations from age-normative structural brain development in either direction predict more anxiety and dysregulated mood in young adulthood.

• Klíčová slova
• anxiety, brain age gap, dysregulated mood, magnetic resonance imaging, maternal depression during pregnancy,
• MeSH
• deprese * MeSH
• dítě MeSH
• dospělí MeSH
• komplikace těhotenství * MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozek diagnostické zobrazování   MeSH
• poruchy nálady diagnostické zobrazování   psychologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stárnutí * MeSH
• těhotenství MeSH
• tloušťka mozkové kůry MeSH
• úzkost diagnostické zobrazování   psychologie   MeSH
• zpožděný efekt prenatální expozice diagnostické zobrazování   psychologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Methamphetamine (MA), as a psychostimulant drug that crosses the placental barrier, may disrupt the development of social play. The present study aims to examine the effect of prenatal MA (5 mg/kg) exposure during the first (gestational day (GD) 1-11) or second (GD 12-22) halves of prenatal development of rats on social play behavior. To investigate an acute effect of MA on social play in adulthood, juvenile rats were exposed to a dose of 1 mg/kg MA or saline on the test day and tested for social play for 15 min. Prenatal exposure to MA during GD 1-11 increased social play behavior during 5-10 min interval of the test in males but not females. Prenatal MA during GD 12-22 did not influence social play in males nor females. However, social play occurred to a greater extent in GD 12-22 groups compared with GD 1-11. Acute exposure to MA eliminated playful behavior in all groups and decreased social exploration in GD 1-11. Our results suggest that manipulation of prenatal development during the first half of the gestational period has a greater impact on social play behavior than during the second half.

• MeSH
• gestační stáří MeSH
• hra a hračky psychologie   MeSH
• krysa rodu Rattus MeSH
• methamfetamin toxicita   MeSH
• novorozená zvířata MeSH
• potkani Wistar MeSH
• sociální chování * MeSH
• stimulanty centrálního nervového systému toxicita   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   psychologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• methamfetamin MeSH
• stimulanty centrálního nervového systému MeSH

Depression is the leading cause of years lost due to disability worldwide. Still, the mechanisms underlying its development are not well understood. This study aimed to evaluate white-matter properties associated with depressive symptomatology in young adulthood and their developmental origins. Diffusion tensor imaging and assessment of depressive symptomatology were conducted in 128 young adults (47% male, age 23-24) from a prenatal birth cohort (European Longitudinal Study of Pregnancy and Childhood). For a subset of these individuals, the database included information on prenatal stress (n = 93) and depressive symptoms during adolescence (assessed repeatedly at age 15 and 19). Depressive symptoms in young adulthood were associated with lower fractional anisotropy in the left and right cingulum and higher fractional anisotropy in the right corticospinal tract and superior longitudinal fasciculus. Further analyses revealed that prenatal stress and depressive symptomatology during adolescence were independent predictors of altered white-matter properties in the cingulum in young adulthood. We conclude that typically developing young adults with more depressive symptoms already exhibit tract-specific alterations in white-matter properties and that prenatal stress and depressive symptomatology during adolescence might contribute to their development.

• Klíčová slova
• adolescence, cohort studies, depression, diffusion tensor imaging, life stress, prenatal development, white matter,
• MeSH
• bílá hmota patologie   MeSH
• deprese etiologie   patologie   MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozek patologie   MeSH
• psychický distres MeSH
• těhotenství MeSH
• zobrazování difuzních tenzorů MeSH
• zpožděný efekt prenatální expozice patologie   psychologie   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

This study aimed to determine whether prenatal stress, measured by the number of stressful life events during the first 20 weeks of pregnancy, might relate to mood dysregulation and altered brain structure in young adulthood. Participants included 93 young adults from a community-based birth cohort from the Czech Republic. Information on prenatal stress exposure was collected from their mothers in 1990-1992. Magnetic resonance imaging (MRI) and mood-related data were collected from the young adults in 2015. MRI analyses focused on overall gray matter (GM) volume and GM volume of cortical regions previously associated with major depression. Higher prenatal stress predicted more mood dysregulation, lower overall GM volume, and lower GM volume in mid-dorsolateral frontal cortex, anterior cingulate cortex, and precuneus in young adulthood. We observed no prenatal stress by sex interactions for any of the relations. We conclude that prenatal stress is an important risk factor that relates to worse mood states and altered brain structure in young adulthood irrespective of sex. Our results point to the importance and long-lasting effects of prenatal programming and suggest that offspring of mothers who went through substantial stress during pregnancy might benefit from early intervention that would reduce the odds of mental illness in later life.

• MeSH
• afekt fyziologie   MeSH
• dospělí MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladý dospělý MeSH
• mozek patologie   MeSH
• pohlavní dimorfismus MeSH
• psychický stres patologie   psychologie   MeSH
• šedá hmota patologie   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice patologie   psychologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

It has been shown that early life traumatic events strongly alter the physiology and behavior in adult rats. In the present study, the effect of postnatal stressor on the spontaneous behavior of adult male rats was evaluated. A method of positive habituation based on a detailed analysis of behavioral patterns and attention of animals to a stimulus object was used. Twenty-four dams and twenty-four of their male progeny were used. Pups were divided into three groups (n = 8): controls (C); maternal social stressor (S); maternal social and physical stressors (SW). Animals (postnatal day 70-80) were individually placed in the open field arena in two habituation sessions with a 24-h delay between them (Test day 1 and Test day 2). Before the start of third session (Test day 3) a solid object was fixed in the center of the arena. Each test lasted 10 min. Our results showed the habituation effect in both stressed-groups. Although there were no significant differences in the number of investigations of the novel object among all tested groups, stress-exposed rats spent less time investigating the object. In conclusion, our findings indicate that long-term neonatal stress may impair an animal's ability to sustain attention to stimuli.

• Klíčová slova
• Attention, Habituation, Open field, Rat, Stress,
• MeSH
• fyziologický stres * MeSH
• habituace (psychofyziologie) * MeSH
• krysa rodu Rattus MeSH
• pátrací chování * MeSH
• psychický stres psychologie   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice psychologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Methamphetamine (MA) is an addictive psychostimulant with significant potential for abuse. Previous rat studies have demonstrated that MA use during pregnancy impairs maternal behavior and induced delayed development of affected pups. The offspring of drug-addictive mothers were often neglected and exposed to neonatal stressors. The present study therefore examines the effect of perinatal stressors combined with exposure to prenatal MA on the development of pups and maternal behavior. Dams were divided into three groups according to drug treatment during pregnancy: controls (C); saline (SA, s.c., 1 ml/kg); MA (s.c., 5 mg/ml/kg). Litters were divided into four groups according to postnatal stressors: controls (N); maternal separation (S); maternal cold-water stress (W); maternal separation plus cold-water stress (SW). The pup-retrieval test showed differences among postnatally stressed mothers and non-stressed controls. The righting reflex on a surface revealed delayed development of pups prenatally exposed to MA/SA and postnatal stress. Negative geotaxis and Rotarod results confirmed that the MA group was the most affected. Overall, our data suggests that a combination of perinatal stress and prenatal MA can have a detrimental effect on maternal behavior as well as on the sensorimotor development of pups. However, MA exposure during pregnancy seems to be the decisive factor for impairment.

• MeSH
• krysa rodu Rattus MeSH
• maternální deprivace MeSH
• mateřské chování účinky léků   fyziologie   psychologie   MeSH
• methamfetamin toxicita   MeSH
• metoda rotující tyčky metody   psychologie   MeSH
• náhodné rozdělení MeSH
• novorozená zvířata MeSH
• poruchy spojené s užíváním psychoaktivních látek komplikace   patofyziologie   psychologie   MeSH
• potkani Wistar MeSH
• psychický stres komplikace   patofyziologie   psychologie   MeSH
• psychomotorický výkon účinky léků   fyziologie   MeSH
• stimulanty centrálního nervového systému toxicita   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patofyziologie   psychologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• methamfetamin MeSH
• stimulanty centrálního nervového systému MeSH

Olfactory bulbectomy in rodents is considered a putative model of depression. Depression is often associated with drug addiction. Our previous studies demonstrated that methamphetamine (MA) administration to rat mothers affects both, mothers and their pups. The aim of the present study was to examine the effect of bulbectomy, as a model of depression, and MA administration on behavior of rat mothers and postnatal development of their pups. Adult female Wistar rats were randomly divided into two groups: bulbectomized (OBX) and sham-operated (SH). A period of 20 days was allowed for the development of the depressive-like phenotype. Animals were tested in the motor activity test and 2 % sucrose preference for anhedonia and hyperactive locomotor response to a novel environment, respectively. After then females were impregnated. Pregnant females were exposed to daily subcutaneous (s.c.) injection of MA (5 mg/kg) or saline (SA) during the entire gestation period. Postnatally, maternal behavior and pup development was examined. The effect of a challenge dose of MA (1 mg/kg, s.c.) on behavior was further examined in adult male offspring. Our results showed no differences in the maternal behavior as a matter of bulbectomy, only OBX rats slept more than all the SH controls. Pups from OBX mothers were born with lower birthweight and gained less weight during the postnatal development than pups from SH controls. Both, bulbectomy and MA administration, delayed the eyes opening. As a matter of functional development of the pups, maternal OBX procedure impaired the performance in the Bar-holding test, but only in saline group. OBX/SA group was the worst in the Bar-holding test relative to all the other groups. In addition, pups from OBX mothers dropped more boluses during the Bar-holding test, suggesting that they were more stressed. In adult male offspring, bulbectomy increased immobility only in the SA/SA group. Prenatal MA exposure increased locomotion, while decreasing immobility. In addition, challenge dose of MA in adulthood increased distance traveled, locomotion, rearing, and average and maximal velocity, while decreasing immobility and grooming. In conclusion, our results suggest that depressive-like phenotype of rat mothers induces impairment in somatic and functional development of their male offspring.

• MeSH
• bulbus olfactorius chirurgie   MeSH
• krysa rodu Rattus MeSH
• lokomoce MeSH
• methamfetamin toxicita   MeSH
• náhodné rozdělení MeSH
• novorozená zvířata MeSH
• potkani Wistar MeSH
• stimulanty centrálního nervového systému toxicita   MeSH
• těhotenství MeSH
• tělesná hmotnost účinky léků   fyziologie   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patofyziologie   psychologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• methamfetamin MeSH
• stimulanty centrálního nervového systému MeSH

Behavioral sensitization is defined as augmented psychomotor activity, which can be observed after drug re-administration following withdrawal of repeated drug exposure. It has been shown that abuse of one drug can lead to increased sensitivity to certain other drugs. This effect of developed general drug sensitivity is called cross-sensitization and has been reported between drugs with similar as well as different mechanisms of action. There is growing evidence that exposure to drugs in utero not only causes birth defects and delays in infant development, but also impairs the neural reward pathways, in the brains of developing offspring, in such a way that it can increase the tendency for drug addiction later in life. This review summarizes the results of preclinical studies that focused on testing behavioral cross-sensitization, after prenatal Methamphetamine exposure, to drugs administered in adulthood, with both similar and different mechanisms of action. Traditionally, behavioral sensitization has been examined using the Open field or the Laboras Test to record locomotor activity, and the Conditioned Place Preference and Self-administration test to examine drug-seeking behavior. However, it seems that prenatal drug exposure can sensitize animals not only to the locomotor-stimulating and conditioning effects of drugs, but may also be responsible for modified responses to various drug effects.

• MeSH
• lidé MeSH
• lokomoce účinky léků   fyziologie   MeSH
• methamfetamin aplikace a dávkování   škodlivé účinky   MeSH
• modely u zvířat * MeSH
• poruchy spojené s užíváním psychoaktivních látek etiologie   metabolismus   psychologie   MeSH
• stimulanty centrálního nervového systému aplikace a dávkování   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   metabolismus   psychologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• methamfetamin MeSH
• stimulanty centrálního nervového systému MeSH

Social behavior involves complex of different forms of interactions between individuals that is essential for healthy mental and physical development throughout lifespan. Psychostimulants, including methamphetamine (MA), have neurotoxic effect, especially, if they are targeting CNS during its critical periods of development. The present study was aimed on evaluation of changes in social interactions (SI) following scheduled prenatal/neonatal MA treatment in combination with acute application in adulthood. Eight groups of male and eight groups of female rats were tested in adulthood: rats, whose mothers were exposed to MA (5mg/ml/kg) or saline (SA, 1ml/kg) during the first half of gestation (ED 1-11), the second half of gestation (ED 12-22) and neonatal period (PD 1-11). To do this, we compared indirect neonatal applications via the exposed dams with group of rat pups that received MA or SA directly through injections. In adulthood, half animals from each group were injected with MA (1mg/kg), second half with saline 45min prior to the Social Interaction Test. Females and males were observed for social and nonsocial activities of two unfamiliar individuals of the same sex and treatment in a familiar Open field arena. The present study demonstrated that prenatal/neonatal MA exposure leads to decrease the time spent in genital investigation, following and nonsocial activity. Acute dose of MA leads to a decrease in all SI patterns and to an increase in nonsocial activities relative to acute SA. Females were more active than males. Animals exposed to prenatal/neonatal treatment during the second half of gestation (ED 12-22) and throughout lactation period (PD 1-11 indirect/direct) had fewer SI and greater exploratory behavior than animals exposed during the first half of gestation (ED 1-11).

• Klíčová slova
• Methamphetamine, Sex differences, Social interaction, Trimesters,
• MeSH
• estrální cyklus účinky léků   MeSH
• methamfetamin toxicita   MeSH
• modely nemocí na zvířatech MeSH
• náhodné rozdělení MeSH
• novorozená zvířata MeSH
• pohlavní dimorfismus * MeSH
• pohybová aktivita účinky léků   MeSH
• potkani Wistar MeSH
• sociální chování * MeSH
• stimulanty centrálního nervového systému toxicita   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice psychologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• methamfetamin MeSH
• stimulanty centrálního nervového systému MeSH