The association between childhood maltreatment and thermal pain sensitivity in a high-risk adolescent population

Background – research on childhood maltreatment and pain sensitivity has produced opposing hypothesis. One line of research proposes maltreatment leads to developmental impairment of the central nervous system and thus more sensitivity to pain. Another posits childhood maltreatment leads to habituation of pain and thus lower sensitivity. Empirical research in adolescents so far has relied on potentially biased self-report measures or on highly selective populations. Methods – a sample (n =187) from a population-based cohort of adolescents at high-risk for psychopathology (ages 16.7 to 20.5) completed the Childhood Trauma Questionnaire short form (CTQ-SF) to assess emotional, physical, sexual abuse, and emotional and physical neglect. To asses pain sensitivity, a thermal quantitative sensory testing procedure was used which measured when adolescents felt pain from hot and cold stimuli. Multilevel ordered beta regressions were used to estimate the associations adjusted for age, sex and internalizing problems. Results – individuals reporting childhood emotional abuse or neglect and physical neglect could on average withstand hot and cold pain of 1.03°C [0.13, 1.84] to 3.20°C [0.62, 5.97] more across different types of abuse compared to those with no emotional abuse or (physical) neglect history. Physical abuse was not associated with pain sensitivity. Sexual abuse was only associated with cold and not with hot pain sensitivity. Discussion – the current findings suggest that childhood maltreatment might lead to habituation to painful stimuli as opposed to increased pain sensitivit

Lithium exposure during pregnancy increases fetal growth

Background:Lithium is an effective treatment in pregnancy and postpartum for the prevention of relapse in bipolar disorder, but there is a lack of knowledge about the potential adverse impact on fetal development.Aims:To investigate the impact of lithium exposure on early fetal growth.Methods:In this retrospective observational cohort study, we included all singleton pregnancies of women using lithium and referred for advanced fetal ultrasound scanning between 1994 and 2018 to the University Medical Centers in Leiden and Rotterdam, the Netherlands (n=119). The Generation R study, a population-based cohort, served as a non-exposed control population from the same geographic region (n=8184). Fetal head circumference, abdominal circumference, femur length, and transcerebellar diameter were measured by ultrasound at 18–22 weeks of gestation.Results:Lithium use during pregnancy was associated with an average increase in head circumference of 1.77 mm (95% confidence interval: 0.53, 3.01), in abdominal circumference of 5.54 mm (95% confidence interval: 3.95, 7.12) and in femur length of 0.59 mm (95% confidence interval: 0.22, 0.96) at 18–22 weeks gestation. Furthermore, lithium use during pregnancy was associated with an average increase in birth weight of 142.43 grams (95% confidence interval: 58.01, 226.89), whereas it was associated with an average decrease of 1.41 weeks in gestational duration (95% confidence interval: −1.78, −1.05).Conclusions:Lithium use during pregnancy was associated with increased fetal growth parameters at 18–22 weeks gestational age and increased birth weight. Further research is needed to evaluate both short- and long-term implications, as well as the mechanisms driving this difference in growth

Lithium exposure during pregnancy increases fetal growth

Background:Lithium is an effective treatment in pregnancy and postpartum for the prevention of relapse in bipolar disorder, but there is a lack of knowledge about the potential adverse impact on fetal development.Aims:To investigate the impact of lithium exposure on early fetal growth.Methods:In this retrospective observational cohort study, we included all singleton pregnancies of women using lithium and referred for advanced fetal ultrasound scanning between 1994 and 2018 to the University Medical Centers in Leiden and Rotterdam, the Netherlands (n=119). The Generation R study, a population-based cohort, served as a non-exposed control population from the same geographic region (n=8184). Fetal head circumference, abdominal circumference, femur length, and transcerebellar diameter were measured by ultrasound at 18–22 weeks of gestation.Results:Lithium use during pregnancy was associated with an average increase in head circumference of 1.77 mm (95% confidence interval: 0.53, 3.01), in abdominal circumference of 5.54 mm (95% confidence interval: 3.95, 7.12) and in femur length of 0.59 mm (95% confidence interval: 0.22, 0.96) at 18–22 weeks gestation. Furthermore, lithium use during pregnancy was associated with an average increase in birth weight of 142.43 grams (95% confidence interval: 58.01, 226.89), whereas it was associated with an average decrease of 1.41 weeks in gestational duration (95% confidence interval: −1.78, −1.05).Conclusions:Lithium use during pregnancy was associated with increased fetal growth parameters at 18–22 weeks gestational age and increased birth weight. Further research is needed to evaluate both short- and long-term implications, as well as the mechanisms driving this difference in growth

A Sustained Depressive State Promotes a Guanfacine Reversible Susceptibility to Alcohol Seeking in Rats

High rates of comorbidity between alcohol use disorder (AUD) and major depressive disorder (MDD) are reported. Preclinical models examining effects of primary depression on secondary AUD are currently absent, preventing adequate testing of drug treatment. Here, we combined social defeat-induced persistent stress (SDPS) and operant alcohol self-administration (SA) paradigms to assess causality between these two neuropsychiatric disorders. We then exploited guanfacine, an FDA-approved adrenergic agent reported to reduce drug craving in humans, against SDPS-induced modulation of operant alcohol SA. Wistar rats were socially defeated and isolated for a period of ≥9 weeks, during which depression-like symptomatology (cognitive and social behavioral symptoms) was assessed. Subsequently, animals were subjected to a 5-month operant alcohol SA paradigm, examining acquisition, motivation, extinction, and cue-induced reinstatement of alcohol seeking. The effects of guanfacine on motivation and relapse were measured at >6 months following defeat. SDPS rats exhibited significant disruption of social and cognitive behavior, including short-term spatial and long-term social memory, several months following defeat. Notably, SDPS increased motivation to obtain alcohol, and cue-induced relapse vulnerability. Guanfacine reversed the SDPS-induced effects on motivation and relapse. Together, our model mimics core symptomatology of a sustained depressive-like state and a subsequent vulnerability to alcohol abuse. We show that SDPS is strongly associated with an enhanced motivation for alcohol intake and relapse. Finally, we show that the clinically employed drug guanfacine has potential as a novel treatment option in comorbid patients, as it effectively reduced the enhanced sensitivity to alcohol and alcohol-associated stimuli. © 2014 American College of Neuropsychopharmacology

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials.

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD