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Background Prior studies have shown that young people “not in education, employment or training” (“NEET”) are at higher risk for psychopathology and substance abuse. Similar studies are lacking in Southern European populations. We aimed to examine the associations of anxiety and depressive symptoms, and substance use with NEET status in a large, randomized population-based sample in Greece. Methods A telephone structured questionnaire was conducted in a representative sample of 2771 young Greeks aged 15–24 years. Anxiety and depressive symptoms were assessed with GAD-7 and PHQ-9 scales, respectively. Substances use and several sociodemographic parameters were also examined. Results In our sample 16.4% were NEETs. In multivariate analyses, NEETs compared to non-NEETs were older, with lower family income, without insurance and more likely to be married and smoke. Furthermore, NEET status was associated with a higher GAD-7 score among older NEETs and long-term NEETs (NEETs unemployed for more than a year). Moreover, being NEET among older participants was associated with severe symptoms of anxiety and moderate/severe symptoms of depression. Limitations This was a telephone survey and a clinical evaluation of the patients was not performed. Furthermore, the structured interview was not designed to detect the level of substance use or the reasons for being NEET. Conclusions NEET status is frequent among young Greeks. Older, and long-term NEETs appear to be at higher risk for presenting anxiety/depression symptoms. Whether NEET status is associated with adverse outcomes later in life requires longitudinal studies.

The present study examines whether attitudes of mental health professionals (MHPs) towards severe mental illness are associated with professional quality of life. The Attitudes towards Severe Mental Illness (ASMI), the Maslach Burnout Inventory (MBI), and the Professional Quality of Life Scale-5 (ProQOL-5) were completed by 287 MHPs in Greece (25.4% males, 74.6% females). The results indicate that MHPs hold predominantly positive attitudes towards people with severe mental illness. Nonetheless, MHPs' attitudes are deemed to be stereotypical according to ASMI concerning treatment duration, prospects of recovery, and whether patients are similar to other people. Higher scores in emotional exhaustion, depersonalization, compassion fatigue and ProQOL-5 burn out dimension were significantly associated with MHPs' unfavorable attitudes, whereas higher scores in compassion satisfaction and personal accomplishment were associated with MHPs' positive attitudes. Assessing compassion fatigue, compassion satisfaction and burnout levels could help identify the processes involved in the development or maintenance of MHPs' stigmatizing attitudes.

BackgroundMaternal thyroid hormones’ supply is crucial for fetal neurodevelopment; however, the role of maternal mild thyroid dysfunction is not clear. We aimed to assess the association of maternal mild thyroid dysfunction with child neuropsychological development from infancy to early childhood.MethodsWe included 757 mother–child pairs from the prospective ‘Rhea’ cohort on Crete, Greece. Maternal thyroid functioning was assessed by quantitative analysis of serum thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies and thyroglobulin antibodies at early gestation (mean=14 weeks). Neuropsychological assessment was based on Bayley Scales of Infant Development (18 months of age), McCarthy Scales of Children’s Abilities (4 years of age), Raven’s Coloured Progressive Matrices, Trail Making Test and Finger Tapping Test (6 years of age).ResultsIn multivariate adjusted linear regression analyses, maternal hypothyroxinemia was associated with decreased verbal scores at 4 years and reduced motor speed at 6 years of age. Maternal thyroid autoimmunity was associated with decreased child perceptual and motor ability at 4 years of age. Four trajectories of longitudinal non-verbal cognitive development were identified and children exposed to maternal thyroid autoimmunity had increased risk for belonging to an adverse trajectory (‘low’: adjusted relative risk ratio (RRR) = 2.7 95% CI: (1.4, 5.2), ‘high-decreasing’: adjusted RRR = 2.2 95% CI: (1.2, 4.0), ‘low-increasing’: adjusted RRR = 1.8 95% CI: (1.0, 3.2)).ConclusionMaternal hypothyroxinemia is associated with reduced offspring verbal and motor ability. Maternal thyroid autoimmunity is associated with decreased offspring perceptual performance and motor ability and increased risk for adverse non-verbal cognitive development from infancy to childhood.

BACKGROUND/AIM: Inflammation provides a substrate for mechanisms that underlie the association of maternal diet during pregnancy with Attention Deficit-Hyperactivity Disorder (ADHD) symptoms in childhood. However, no previous study has quantified the proinflammatory potential of maternal diet as a risk factor for ADHD. Thus, we evaluated the association of maternal dietary inflammatory index (DII(®)) scores during pregnancy with ADHD symptoms in 4 year-old children born in two Mediterranean regions. METHODS: We analyzed data from two population-based birth cohort studies – INMA (Environment and Childhood) four subcohorts in Spain (N=2,097), and RHEA study in Crete (Greece) (N=444). The DII score of maternal diet was calculated based on validated food frequency questionnaires completed during pregnancy (12(th) and/or 32(nd) week of gestation). ADHD symptoms were assessed by ADHD-DSM-IV in INMA cohort and by ADHDT test in RHEA cohort, with questionnaires filled-out by teachers and parents, respectively. The associations between maternal DII and ADHD symptoms were analysed using multivariable-adjusted zero-inflated negative binomial regression models in each cohort study separately. Meta-analysis was conducted to combine data across the cohorts for fitting within one model. RESULTS: The DII was significantly higher in RHEA (RHEA=2.09 [1.94, 2.24]) in comparison to INMA subcohorts (Asturias=−1.52 [−1.67,−1.38]; Gipuzkoa=−1.48 [−1.64,−1.33]; Sabadell=−0.95 [−1.07,−0.83]; Valencia= −0.76 [−0.90,−0.62]). Statistically significant reduced risk of inattention symptomatology (OR = 0.86; CI 95% = 0.77–0.96), hyperactivity symptomatology (OR = 0.82; CI 95% = 0.72–0.92) and total ADHD symptomatology (OR = 0.82; CI 95%= −0.72–0.93) were observed with increased maternal DII in boys. No statistically significant associations were observed in girls between maternal DII and inattention, hyperactivity and total ADHD symptomatology. CONCLUSIONS: We found reduced risk of ADHD symptomatology with increased DII only in boys. This relationship requires further exploration in other settings.

Animal studies suggest that prenatal vitamin D status may affect fetal brain growth. However, human studies are scarce with conflicting results. We aimed to investigate the association of maternal 25-hydroxyvitamin D [25(OH) D] levels with multiple neurodevelopmental outcomes at 4 years of age. We included 487 mother–child pairs from the prospective pregnancy cohort, “Rhea” in Crete, Greece. Maternal serum 25(OH) D concentrations were measured at the first prenatal visit (13 ± 2.4 weeks). Cognitive functions at 4 years were assessed by means of the McCarthy Scales of Children’s Abilities. Behavioral difficulties were assessed by means of Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Children of women in the high 25(OH) D tertile (>50.7 nmol/l) had 37% decreased number of hyperactivity–impulsivity symptoms (IRR 0.63, 95% CI 0.39, 0.99, p trend = 0.05) and 40% decreased number of total ADHD-like symptoms (IRR 0.60, 95% CI 0.37, 0.95, p trend = 0.03) at 4 years of age, compared to children of women in the low 25(OH) D tertile (

Background: Persistent Organic Pollutants (POPs) are highly-resistant compounds to environmental degradation and due to fat solubility they bioaccumulate through the food chain. As they cross the placenta, in utero exposure to POPs could disrupt child neurodevelopment as they are considered to be neurotoxic. Aims: We examined whether in utero exposure to levels of different POPs is associated with offspring cognitive and behavioral outcomes at 4 years of age in a mother-child cohort in Crete, Greece (Rhea study). Methods: We included 689 mother-child pairs. Concentrations of several polychlorinated biphenyls (PCBs) and other organochlorine compounds (dichlorodiphenyl dichloroethene [DDE], hexachlorobenzene [HCB]) were determined in maternal serum collected in the first trimester of pregnancy by triple quadrupole mass spectrometry. Neurodevelopment at 4 years was assessed by means of the McCarthy Scales of Children's Abilities. Behavioral difficulties were assessed by Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Linear regression analyses were used to estimate the associations between the exposures and outcomes of interest after adjustment for potential confounders. Results: Children with “high” HCB concentrations (≥90th percentile) in maternal serum, demonstrated decreased scores in perceptual performance (adjusted β = −6.07; 95% CI: −10.17, −1.97), general cognitive (adjusted β = −4.97; 95% CI: −8.99, −0.96), executive function (adjusted β = −6.24; 95% CI: −10.36, −2.11) and working memory (adjusted β = −4.71; 95% CI: −9.05, −0.36) scales at 4 years of age. High exposure to PCBs (≥90th percentile) during pregnancy was associated with a 4.62 points reduction in working memory score at 4 years of age (95% CI: −9.10, −0.14). Prenatal exposure to DDE, HCB and PCBs was not associated with child behavioral difficulties. Conclusions: The findings suggest that prenatal exposure to HCB and PCBs may contribute to reduced cognitive development at preschool age. Our results raise the possibility that exposure to HCB may play a more important role in child cognition than previously considered. Keywords: Persistent organic pollutants, PCBs, HCB, Neuropsychological development, Cognition, McCarthy Scales for Children’s Abilities

Background Viral infections of the central nervous system may have detrimental effects for the developing brain, but the effects of less virulent common infections are unclear. We aim to investigate the impact of common viral infections of early childhood on neuropsychological performance of children at age four. Methods We used cross-sectional data on 674 children participating at the 4 years of age follow-up of the Rhea birth cohort in Crete, Greece. Blood levels of IgG antibodies to 10 polyomaviruses (BKPyV, JCPyV, KIPyV, WUPyV, HPyV6, HPyV7, TSPyV, MCPyV, HPyV9, and HPyV10) and four herpesviruses [Epstein–Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), and herpes simplex virus-2 (HSV-2)] were measured using multiplex serology. Child's neuropsychological development at age four was assessed using the McCarthy Scales of Children's Abilities, the Attention-Deficit Hyperactivity Disorder Test (ADHDT), and the Strengths and Difficulties Questionnaire (SDQ). Multiple linear regression models were used to explore the associations. Results Seroprevalence to polyomaviruses ranged from 21% for HPyV9 to 82% for HPyV10. Seroprevalence for EBV was 53%, for CMV 26%, for HSV-1 3.6%, and for HSV-2 1.5%. Children seropositive to ≥8 polyomaviruses had lower score in ADHDT inattention subscale [β = −1.28 (95% CI: −2.56, −0.001)] and lower score in SDQ hyperactivity–inattention subscale [β = −.99 (95% CI: −1.60, −0.37)] versus children seropositive to ≤3 polyomaviruses. Seropositivity to BKPyV, a potential neurotropic virus, was associated with higher score in ADHDT inattention subscale [β = .87 (95% CI: 0.03, 1.71)]. Conclusions These findings suggest that acquisition of polyomaviruses during development may influence behavioral outcomes in early childhood.

The evidence regarding a potential link of low-to-moderate iodine deficiency, selenium status, and cadmium exposure during pregnancy with neurodevelopment is either contradicting or limited. We aimed to assess the prenatal impact of cadmium, selenium, and iodine on children's neurodevelopment at 4 years of age. The study included 575 mother-child pairs from the prospective "Rhea" cohort on Crete, Greece. Exposure to cadmium, selenium and iodine was assessed by concentrations in the mother's urine during pregnancy (median 13 weeks), measured by ICPMS. The McCarthy Scales of Children's Abilities was used to assess children's general cognitive score and seven different sub-scales. In multivariable-adjusted regression analysis, elevated urinary cadmium concentrations (≥0.8 µg/L) were inversely associated with children's general cognitive score [mean change: -6.1 points (95 % CI -12; -0.33) per doubling of urinary cadmium; corresponding to ~0.4 SD]. Stratifying by smoking status (p for interaction 0.014), the association was restricted to smokers. Urinary selenium was positively associated with children's general cognitive score [mean change: 2.2 points (95 % CI -0.38; 4.8) per doubling of urinary selenium; ~0.1 SD], although the association was not statistically significant. Urinary iodine (median 172 µg/L) was not associated with children's general cognitive score. In conclusion, elevated cadmium exposure in pregnancy of smoking women was inversely associated with the children's cognitive function at pre-school age. The results indicate that cadmium may adversely affect neurodevelopment at doses commonly found in smokers, or that there is an interaction with other toxicants in tobacco smoke. Additionally, possible residual confounding cannot be ruled out. The “Rhea” project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009-single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU-FP7-HEALTH-2012 Proposal No 308333 HELIX) and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011–2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–2015). The present study was also funded by Karolinska Institutet, the Swedish Research Council Formas (Project No. 210-2013-751), and Swedish Research Council

The aim of the present study was to assess the relationship between illness-related characteristics, such as symptom severity and psychosocial functioning, and specific aspects of family functioning both in patients experiencing their first episode of psychosis (FEP) and chronically ill patients. A total of 50 FEP and 50 chronic patients diagnosed with schizophrenia or bipolar disorder (most recent episode manic severe with psychotic features) and their family caregivers participated in the study. Family functioning was evaluated in terms of cohesion and flexibility (FACES IV Package), expressed emotion (FQ), family burden (FBS) and caregivers' psychological distress (GHQ-28). Patients' symptom severity (BPRS) and psychosocial functioning (GAS) were assessed by their treating psychiatrist within 2 weeks from the caregivers' assessment. Increased symptom severity was associated with greater dysfunction in terms of family cohesion and flexibility (β coefficient -0.13; 95 % CI -0.23, -0.03), increased caregivers' EE levels on the form of emotional overinvolvement (β coefficient 1.03; 95 % CI 0.02, 2.03), and psychological distress (β coefficient 3.37; 95 % CI 1.29, 5.45). Family burden was found to be significantly related to both symptom severity (β coefficient 3.01; 95 % CI 1.50, 4.51) and patient's functioning (β coefficient -2.04; 95 % CI -3.55, -0.53). No significant interaction effect of chronicity was observed in the afore-mentioned associations. These findings indicate that severe psychopathology and patient's low psychosocial functioning are associated with poor family functioning. It appears that the effect for family function is significant from the early stages of the illness. Thus, early psychoeducational interventions should focus on patients with severe symptomatology and impaired functioning and their families.

BACKGROUND Limited evidence exists on the association between exposure to Helicobacter pylori infection early in life, including fetal life, and neurodevelopment in childhood. METHODS We used prospective data on 352 mother-child pairs and cross-sectional data on 674 children to assess the association of maternal and child's H. pylori seropositivity correspondingly on child's neurodevelopment at age four in the Rhea birth cohort in Crete, Greece. Blood levels of immunoglobulin G antibodies to 12 H. pylori proteins were measured using multiplex serology. Child's neurodevelopment at age four was assessed using the McCarthy Scales of Children's Abilities. Linear regression models were used to explore the associations after adjusting for potential confounders. RESULTS Helicobacter pylori seroprevalence (95% CI) in cord blood, representing maternal status, was 41.5% (36.3%, 46.8%) and in 4 years old children was 6.5% (95% CI 4.8%, 8.7%). Children of H. pylori seropositive mothers had lower score in the general cognitive (-3.87, 95% CI -7.02, -0.72), verbal (-2.96, 95% CI -6.08, 0.15), perceptual performance (-3.37, 95% CI -6.60, -0.15), quantitative (-2.85, 95% CI -6.28, 0.58), and memory scale (-3.37, 95% CI -6.67, -0.07) compared to those of seronegative mothers. Seropositivity in cord blood specifically to GroEl and NapA - two of the 12 H. pylori proteins investigated - was associated with lower scores in almost all scales. At age four, H. pylori seropositive children performed worst in neurodevelopment assessment compared to their seronegative counterparts although no association reached statistically significant level. CONCLUSIONS Helicobacter pylori infection in early life may be an important but preventable risk factor for poor neurodevelopment.

Antenatal maternal mental health has been identified as an important determinant of postpartum depression (PPD). We investigated the occurrence of depression both antenatally and postnatally and examined whether maternal trait anxiety and depression during pregnancy were associated with PPD at 8 weeks postpartum in a prospective mother–child cohort (Rhea Study) in Crete, Greece. 438 women completed the Edinburgh Postnatal Depression Scale (EPDS) and the Trait subscale of the State-Trait Anxiety Inventory (STAI-Trait) questionnaires assessing antenatal depression and anxiety, respectively, during the third trimester of pregnancy as well as the EPDS at 8 weeks postpartum. The prevalence of women with probable depression (EPDS score ≥13) was 16.7 % at 28–32 weeks of pregnancy and 13.0 % at 8 weeks postpartum. A per 5 unit increase in the STAI-Trait subscale increased the odds for PPD by 70 % (OR = 1.70, 95 % CI 1.41, 2.05), whereas a per unit increase in EPDS during pregnancy increased the odds for PPD by 27 % (OR = 1.27, 95 % CI 1.19, 1.36). Our findings suggest that antenatal maternal psychological well-being has a significant effect on PPD, which might have important implications for early detection during pregnancy of women at risk for postpartum depression.

Aims.Few epidemiological studies evaluated associations between perinatal complications and maternal mood at the early postpartum period and the findings are inconsistent. We aimed at investigating a wide range of complications during pregnancy, at delivery, and at the early postpartum period as determinants of postpartum depression (PPD) at 8 weeks postpartum.Methods.A total of 1037 women who enrolled in the Rhea mother–child cohort in Crete, Greece participated in the present study. Information on pregnancy, perinatal and postpartum complications was obtained from clinical records or by questionnaires. Postpartum depressive symptoms were assessed at 8 weeks postpartum using the Edinburgh Postnatal Depression Scale (EPDS). Multivariable linear and logistic regression models were fit to estimate the association between pregnancy, perinatal and postpartum complications and maternal depressive symptoms, adjusting also for potential confounders.Results.The prevalence of women with probable depression (EPDS score ≥ 13) was 13.6% at 8 weeks postpartum. Gestational hypertension and/or preeclampsia (β coefficient 1.86, 95% CI: 0.32, 3.41) and breastfeeding difficulties (β coefficient 0.77, 95% CI: 0.02, 1.53) were significantly associated with higher PPD symptoms. Sleep patterns during pregnancy, such as sleep deprivation (OR = 3.57, 95% CI: 1.91, 6.67) and snoring (OR = 1.81, 95% CI: 1.11, 2.93), and breastfeeding duration less than 2 months (OR = 1.77, 95% CI: 1.19, 2.64) were significantly associated with increase in the odds for PPD. Some other complications, such as unplanned pregnancy and hospitalisation during pregnancy were also associated with EPDS score, but these associations were explained by socio-demographic characteristics of the mother.Conclusions.We found that several pregnancy, perinatal and postpartum complications may have an adverse effect on maternal mood at the early postpartum period. These findings have considerable implications for developing effective prevention and early psychoeducational intervention strategies for women at risk of developing PPD.

Background Poor perinatal maternal mental health has been linked with negative outcomes on early child development; however, the importance of maternal personality has been neglected thus far. We aimed to examine the effects of antenatal and postnatal maternal mental health, including assessment of maternal personality characteristics, on child neuropsychological and behavioral development at preschool years in a population based mother-child cohort (Rhea Study) in Crete, Greece. Method Self-reported measures of maternal depression (EPDS), trait anxiety (STAI-Trait) and personality traits (EPQ-R) were assessed in a sample of 288 women at 28–32 weeks of gestation. A larger sample of 642 mothers completed the EPDS scale at 8 weeks postpartum. Children's neuropsychological (MSCA) and behavioral (ADHDT and SDQ) development were assessed at 4 years of age. Linear regression analyses were used to estimate the associations between the exposures and outcomes of interest after adjustment for potential confounders. Results Regarding child neuropsychological development, increased postnatal depressive symptoms were associated with child's perceptual performance, whereas increased maternal psychoticism was linked with child's motor ability at 4 years of age. Furthermore, elevated levels of maternal depression during pregnancy and postpartum, and the predisposing personality characteristics of trait anxiety and neuroticism, were associated with children's behavioral difficulties. Limitations A clinical diagnostic instrument for maternal mental health was not used and assessment of children's behavior was based on maternal report. Conclusion These findings suggest that poor perinatal maternal mental health and an adverse personality profile may be associated with impaired child neuropsychological and behavioral development at preschool years.

Studies have suggested an association between maternal obesity pre-pregnancy and gestational diabetes (GDM) with impaired offspring neurodevelopment, but it is not clear if these associations are explained by shared familiar characteristics. We aimed to assess the associations of maternal and paternal obesity, maternal glucose intolerance in early pregnancy and GDM, with offspring neurodevelopment at 4 years of age. We included 772 mother–child pairs from the “Rhea” Mother–Child cohort in Crete, Greece. Data on maternal/paternal body mass index (BMI) and maternal fasting serum samples for glucose and insulin measurements were collected at 12 weeks of gestation. GDM screening was performed at 24–28 weeks. Neurodevelopment at 4 years was assessed using the McCarthy Scales of Children’s Abilities. Behavioral difficulties were assessed by Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Multivariate linear regression analyses showed that maternal obesity was associated with a significant score reduction in general cognitive ability (β-coeff −4.03, 95% CI: −7.08, −0.97), perceptual performance (β-coeff −4.60, 95% CI: −7.74, −1.47), quantitative ability (β-coeff −4.43, 95% CI: −7.68, −1.18), and executive functions (β-coeff −4.92, 95% CI: −8.06, −1.78) at 4 years of age, after adjustment for several confounders and paternal BMI. Maternal obesity was also associated with increased behavioral difficulties (β-coeff 1.22, 95% CI: 0.09, 2.34) and ADHD symptoms (β-coeff 4.28, 95% CI: 1.20, 7.36) at preschool age. Paternal obesity maternal glucose intolerance in early pregnancy and GDM was not associated with child neurodevelopment. These findings suggest that maternal obesity may impair optimal child neurodevelopment at preschool age independently of family shared characteristics.

Background/AimsMaternal personality may increase vulnerability to stress, which could lead to an unfavourable intrauterine environment to the fetus. We sought to investigate the impact of maternal personality traits on adverse birth outcomes such as preterm birth, and fetal growth restriction in the mother-child cohort study (RHEA Study) in Crete, Greece 2007–2009.MethodsFive hundred and eighty pregnant women participating in “Rhea” cohort study completed the Eysenck Personality Questionnaire-Revised (EPQ-R) at 28–32 weeks of gestation. Information on anthropometric measures at birth was obtained from the hospital delivery logs and medical records. Fetal growth restriction was based on a customized model, and multivariate logistic regression models were used adjusting for confounders.ResultsA per unit increase in the EPQ Neuroticism scale increased the risk for fetal weight growth restriction by 9% [Odds Ratio (OR) = 1.09, 95 percent CI: 1.01, 1.19)], and for fetal head circumference growth restriction by 6% [OR = 1.06, 95 percent CI: 1.01, 1.18] after adjusting for maternal age, education, origin, marital status, working status, pre-pregnancy BMI, delivery type, parity, smoking, and alcohol intake during pregnancy.ConclusionsMaternal neuroticism, which predisposes to negative mood, may be a risk factor for fetal growth restriction.

ObjectiveTo investigate whether high doses of folic acid supplementation in early pregnancy are associated with child neurodevelopment at 18 months of age.DesignThe study uses data from the prospective mother–child cohort ‘Rhea’ study. Pregnant women completed an interviewer-administered questionnaire on folic acid supplementation at 14–18 weeks of gestation. Neurodevelopment at 18 months was assessed with the use of the Bayley Scales of Infant and Toddler Development (3rd edition). Red-blood-cell folate concentrations in cord blood were measured in a sub-sample of the study population (n 58).SettingHeraklion, Crete, Greece, 2007–2010.SubjectsFive hundred and fifty-three mother–child pairs participating in the ‘Rhea’ cohort.ResultsSixty-eight per cent of the study participants reported high doses of supplemental folic acid use (5 mg/d), while 24 % reported excessive doses of folic acid (>5 mg/d) in early pregnancy. Compared with non-users, daily intake of 5 mg supplemental folic acid was associated with a 5-unit increase on the scale of receptive communication and a 3·5-unit increase on the scale of expressive communication. Doses of folic acid supplementation higher than 5 mg/d were not associated with additional increase in the neurodevelopmental scales.ConclusionsThis is the first prospective study showing that high doses of supplementary folic acid in early pregnancy may be associated with enhanced vocabulary development, communicational skills and verbal comprehension at 18 months of age. Additional longitudinal studies and trials are needed to confirm these results.

The present study aimed to evaluate a path analytic model accounting for caregivers' psychological distress that takes into account perceived family cohesion and flexibility, expressed emotion and caregiver's burden associated with the presence of mental illness in the family. 50 first-episode and 50 chronic patients diagnosed with schizophrenia or bipolar disorder (most recent episode manic severe with psychotic features) recruited from the Inpatient Psychiatric Unit of the University Hospital of Heraklion, Crete, Greece, and their family caregivers participated in the study. Family functioning was assessed in terms of cohesion and flexibility (FACES-IV), expressed emotion (FQ), family burden (FBS) and caregivers' psychological distress (GHQ-28). Structural equation modelling was used to evaluate the direct and indirect effects of family dynamics on caregivers' psychological distress. The results showed that neither family cohesion nor family flexibility exerted significant direct effects on caregivers' psychological distress. Instead, the effect of flexibility was mediated by caregivers' criticism and family burden indicating an indirect effect on caregivers' psychological distress. These results apply equally to caregivers of first episode and chronic patients. Family interventions aiming to improve dysfunctional family interactions by promoting awareness of family dynamics could reduce the burden and improve the emotional well-being of family caregivers.

Background The aim of the present study was to investigate whether dysfunctional family functioning contributes to relapse over a two-year follow-up period in patients experiencing their first episode of psychosis (FEP) and chronic patients with psychosis. Methods The sample consisted of 100 remitted patients (50 FEP and 50 chronic) diagnosed with schizophrenia (82%) or bipolar disorder with most recent episode manic severe with psychotic features (18%) recruited from the Inpatient Psychiatric Unit of the University Hospital of Heraklion, Crete, Greece, and their family caregivers. Family functioning was assessed in terms of cohesion and flexibility (FACES-IV), expressed emotion (FQ), family burden (FBS) and caregivers’ psychological distress (GHQ-28). Relapse was defined as patient rehospitalisation due to acute psychotic exacerbation, while number, length, and type of hospitalisations were also evaluated. Results Dysfunctional family functioning in terms of cohesion and flexibility was not found to be a significant risk factor for relapse in psychosis. High expressed emotion, as indexed primarily by increased levels of criticism rather than emotional over-involvement, was associated with increased risk of relapse and shorter time to relapse (HR = 0.48, 95% CI: 0.24, 0.98, p = 0.043). Similarly, high levels of family burden were related to shorter time to relapse (HR = 0.47, 95% CI: 0.23, 0.95, p = 0.037), whereas there was no significant difference in survival curves based on caregivers’ psychological distress. No significant interaction effect of illness chronicity was observed in the aforementioned associations. Conclusion These findings highlight caregivers’ criticism and burden of care as long-term predictors of the course of psychosis from the early stages of the illness and later on. In contrast, unbalanced levels of cohesion and flexibility in the family, as well as caregivers’ high emotional over-involvement and psychological distress do not appear to be factors that contribute to patient relapse. Family psychoeducational interventions focusing at ameliorating caregivers’ negativity toward the patient, and easing the burden of care should be considered as means in reducing relapse.

Background:Studies on determinants affecting family functioning of patients with psychosis are still limited in Greece.Aim:The aim of this study was to describe the socio-demographic and clinical characteristics associated with family functioning in patients with schizophrenia and bipolar disorder in Crete, Greece.Methods:A total of 100 patients and their caregivers agreed to participate in the study. Family functioning was assessed in terms of cohesion, adaptability, communication and satisfaction dimensions (Family Adaptability and Cohesion Evaluation Scale IV Package), expressed emotion (Family Questionnaire), family burden (Family Burden Scale) and caregivers’ psychological distress (General Health Questionnaire-28). Multivariate linear regression models were implemented to examine the associations between each one of the family measures and different social and clinical characteristics.Results:With regard to the caregivers’ characteristics, gender, employment status, origin, residence, financial status, relation to the patient, contact with the patient and family structure were among the most significant determinants of family functioning. Also, patients’ socio-demographic characteristics, including age, education, origin, residence and employment status, as well as illness-related factors, such as onset of mental illness, number of hospitalisations, last hospitalisation, longer hospitalisation and clinical diagnosis impacted intrafamilial relationships.Conclusion:The results of this study suggest that a number of social and clinical factors contributed to the family environment of patients with psychosis. Identifying the determinants of family functioning in psychosis is instrumental in developing understandings regarding the factors which may contribute to the rehabilitation or relapse of the patient and the support required to strengthen positive family interactions.

The present study aimed to investigate possible differences in family environment among patients experiencing their First Episode of Psychosis (FEP), chronic patients and controls. Family cohesion and flexibility (FACES-IV) and psychological distress (GHQ-28) were evaluated in families of 50 FEP and 50 chronic patients, as well as 50 controls, whereas expressed emotion (FQ) and family burden (FBS) were assessed in families of FEP and chronic patients. Multivariable linear regression analysis, adjusted for confounders, indicated impaired cohesion and flexibility for families of FEP patients compared to controls, and lower scores for families of chronic patients compared to those of FEP patients. Caregivers of chronic patients scored significantly higher in criticism, and reported higher burden and psychological distress than those of FEP patients. Our findings suggest that unbalanced levels of cohesion and flexibility, high criticism and burden appeared to be the outcome of psychosis and not risk factors triggering the onset of the illness. Furthermore, emotional over-involvement both in terms of positive (i.e. concern) and negative behaviors (i.e. overprotection) is prevalent in Greek families. Psychoeducational interventions from the early stages of the illness should be considered to promote caregivers' awareness regarding the patients' illness, which in turn, may ameliorate dysfunctional family interactions.

Expressed emotion (EE) has proved to be an established factor in short-term relapse in schizophrenia. The aim of the present study was to examine the psychometric properties of the Greek version of the Family Questionnaire (FQ), a brief self-report questionnaire measuring the EE status of relatives of patients with schizophrenia in terms of criticism (CC) and emotional overinvolvement (EOI). The translated and adapted 20-item FQ was administered to 176 family caregivers of patients with schizophrenia and bipolar disorder. Caregivers' burden (Family Burden Scale) and psychological distress (General Health Questionnaire-28) were also evaluated. The findings indicated that the Greek version displays a two-factor structure with two subscales of EE—CC and EOI—with 10 items each, similarly to the original version. The convergent validity of the subscales was highly supported by correlations with caregivers' burden and psychological distress. The Cronbach's α coefficient measuring internal consistency for the two scales were 0.90 for CC and 0.82 for EOI. The test–retest correlation coefficients measuring reproducibility were 0.99 and 0.98 for CC and EOI, respectively. The Greek version of the FQ appears to be a valid and reliable instrument to be used in both research and clinical assessment of family EE.

Background Maternal pre-pregnancy obesity may be associated with impaired infant neuropsychological development; however, there are few studies and it is unclear if reported associations are due to intrauterine mechanisms. Methods We assessed whether maternal pre-pregnancy overweight and obesity were associated with cognitive and psychomotor development scores (mean 100 ± 15) of children aged 11-22 months in two birth cohorts: Environment and Childhood (INMA, Spain; n = 1967) and Mother-Child (RHEA, Greece: n = 412). Paternal body mass index (BMI) was used as a negative control exposure. Results The percentage of overweight and obese mothers was 18% and 8%, respectively, in INMA and 20% and 11% in RHEA, respectively. Maternal pre-pregnancy obesity was associated with reduced infant cognitive development scores in both INMA (score reduction: -2.72; 95% CI: -5.35, -0.10) and RHEA (score reduction: -3.71; 95% CI: -8.45, 1.02), after adjusting for socioeconomic variables and paternal BMI. There was evidence in both cohorts of a dose-response relationship with continuous maternal BMI. Paternal overweight/obesity was not associated with infant cognitive development. Associations with psychomotor scores were not consistent between cohorts, and were stronger for paternal than maternal BMI in RHEA. Conclusions This study in two birth cohorts with moderately high obesity prevalence suggests that maternal pre-pregnancy obesity is associated with reduced child cognitive development at early ages. This association appears more likely to be due to maternal than shared family and social mechanisms, but further research is needed to disentangle a direct intrauterine effect from other maternal confounding factors.

Purpose A growing body of evidence links poor maternal mental health with negative outcomes on early child development. We examined the effect of antenatal and postnatal maternal mental health on infant neurodevelopment at age 18 months in a population-based mother–child cohort (Rhea Study) in Crete, Greece. Methods Self-reported measures of maternal depression (EPDS), trait anxiety (STAI-Trait) and personality traits (EPQ-R) were assessed in a sample of women during pregnancy and at 8 weeks postpartum (n = 223). An additional sample of 247 mothers also completed the EPDS scale at 8 weeks postpartum (n = 470). Neurodevelopment at 18 months was assessed with the use of Bayley Scales of Infant and Toddler Development (3rd edition). Results Multivariable linear regression models adjusted for confounders revealed that antenatal depressive symptoms (EPDS C 13) were associated with decrease in cognitive development independently of postnatal depression. High trait anxiety and extraversion were associated with decrease and increase, respectively, in social–emotional development. Also, high trait anxiety and neuroticism had a positive effect on infants’ expressive communication. Finally, postpartum depressive symptoms (EPDS C 13) were associated with decrease in cognitive and fine motor development independently of antenatal depression. Conclusions These findings suggest that antenatal and postnatal maternal psychological well-being has important consequences on early child neurodevelopment.

The influential role of family in the outcome of chronic schizophrenia is well documented. However, there has been relatively little research on the intrafamilial relationships of people experiencing their first episode of psychosis (FEP), a point in time when most of the changes in family dynamics are observed. The aim of this article is to present a review of the literature focusing on the family environment of FEP patients. We carried out a computerized literature search on MEDLINE and PsycINFO (1990–2013), and a manual search of references of pertinent articles. In total, 27 studies investigating expressed emotion (EE) and family burden (FB) in FEP were identified and fulfilled the inclusion criteria. Similar to chronic patients, a high prevalence of high-EE in carers of FEP patients was reported. High-EE status appears to be independent of the patient’s illness-related characteristics, but dependent of relatives’ attributions. In contrast to chronic patients, low levels of FB and psychological distress among family members of FEP patients were observed indicating that in the early stages of the illness family involvement is not yet associated with significant disruption in their lives. Studies assessing FB in chronic patients have found a well-established link of FB with patient’s illness-related factors, but in FEP patients the families’ appraisal of FB is more closely associated with their coping mechanisms. Further studies evaluating family functioning in terms of cohesion and adaptability will shed light on the intrafamilial relationships in FEP patients which may be associated with the long-term outcome of this chronic illness.

Objective To evaluate the association of second-hand smoke exposure of pregnant mothers using urine cotinine with the neurodevelopment of their children at 18 months of age in the mother-child cohort in Crete (Rhea Study). Study design Selected participants were Greek mothers with singleton pregnancies, had never smoked, and had available urine cotinine measurements in pregnancy, and their children for whom a neurodevelopmental assessment was completed. We performed face-to-face interviews twice during pregnancy and postnatally, and assessed children's neurodevelopment at 18 months of age using the Bayley Scales of Infant and Toddler Development, Third Edition. We used linear regression and generalized additive models. Results Of 599 mothers, 175 (29%) met the inclusion criteria. Maternal urine cotinine levels were low (mean: 10.3 ng/mL, SD: 11.7 ng/mL). Reported passive smoking from different sources was strongly associated with urine cotinine levels. A negative association was observed between cotinine levels in pregnancy and child's gross motor function (beta = −3.22 per 10 ng/mL, 95% CI −5.09 to −1.34) after adjusting for factors potentially associated with neurodevelopment; results were similar in both sexes. A negative association was also observed for cognitive and receptive communication scales but the effect was small and not statistically significant. Conclusions Maternal exposure during pregnancy to second-hand smoke measured through urine cotinine was associated with a decrease in gross motor function among 18-month-old children, even at low levels of exposure.

Introduction Research focused on the intrafamilial environment of people experiencing their first episode of psychosis (FEP) is limited. Objectives To investigate possible differences in family environment between FEP patients, chronic psychotic patients and healthy controls. Aims To compare family variables between relatives of FEP patients, chronic patients and healthy controls. Methods Family cohesion and flexibility (FACES-IV) and psychological well-being (GHQ-28) were evaluated in relatives of 50 FEP patients, 50 chronic patients and 50 controls, whereas expressed emotion (FQ) and family burden (FBS) were assessed between the two clinical groups. Results Multivariable linear regression analysis adjusted for several confounding variables revealed statistically significant differences in the total ratio for family cohesion and flexibility between the three groups indicating poorer family functioning for chronic families as compared to FEP families (β coefficient −0.47, 95% CI: −0.77, −0.18) and lower scores for FEP families as compared to controls (β coefficient −0.59, 95% CI: −0.81, −0.37). Chronic families scored significantly higher in critical comments (β coefficient 7.17, 95% CI: 3.45, 10.89), and reported higher subjective (β coefficient 2.85, 95% CI: 0.69, 5.01) and objective burden (β coefficient 8.25, 95% CI: 4.67, 11.84) as compared to FEP families. Non-significant differences were found in psychological well-being between FEP and chronic families, whereas FEP families reported higher levels of psychological distress as compared to controls. Conclusions Having a family member with a major psychiatric disorder is a general stressor for families and family interventions should be considered to minimize disruption to family life.

Introduction The influential role of family in the outcome of chronic mental illness is well documented; however there has been relatively little research on the intrafamilial relationships of people experiencing their first episode of psychosis (FEP). Objectives To investigate possible differences in family environment between FEP and chronic patients with schizophrenia and bipolar disorder. Aims To compare family measures between relatives of FEP and chronic psychotic patients. Methods Family functioning (FACES-IV), expressed emotion (FQ), family burden (FBS) and psychological well being (GHQ- 28) were assessed in relatives of 30 FEP and 30 chronic patients. Results Multivariable linear regression models adjusted for confounders revealed that relatives of chronic patients scored significantly lower in balanced cohesion (β coefficient -4.27, 95% CI: -08.03, -1.71) and balanced flexibility (β coefficient -4.01, 95% CI: -6.91, -1.10), as well as communication (β coefficient -6.61, 95% CI: -11.70, -1.50) and satisfaction scales (β coefficient -7.32, 95% CI: -13.23, -1.41). Relatives caring for a chronic patient had significantly higher scores in critical comments (β coefficient 7.81, 95% CI: 3.95, 11.68) and emotional overinvolvement (β coefficient 3.70, 95% CI: 0.24, 7.16). They, also, reported higher objective (β coefficient 12.23, 95% CI: 3.76, 20.71) and subjective (β coefficient 2.79, 95% CI: 0.45, 5.14) burden, as well as poorer psychological well being (β coefficient 12.23, 95% CI: 3.76, 20.71). Conclusions These findings suggest that chronicity adversely affects patients’ family. Early intervention strategies are needed to reduce family burden which in turn may adversely affect the course of the patient’s illness.