Risk Of Psychiatric Illness Research Articles

Effect of Schizophrenia Risk Variants On Mating and Fecundity

The polygenic risk score for schizophrenia (SZ-PRS) is associated with creativity and psychiatric disorders, including cannabis use. We have investigated the selection pressures on sequence variants that predispose to schizophrenia in the Icelandic population and find no evidence of selective advantage of a high SZ-PRS. Rare copy-number variants conferring moderate to high risk of psychiatric illness are, however, associated with having fewer children and are under negative selection. We also examined the correlation between SZ-PRS and the number of relationships producing offspring in 81,713 adult Icelanders without diagnosis of schizophrenia. SZ-PRS is associated with increased likelihood of having offspring with more than one mate (P = 7.9 x 10-12). Thus, while common variants that increase schizophrenia risk may not be under strong selection they influence mating behaviour in adults who do not have the disorder.

Childhood seizures and risk of psychiatric disorders in adolescence and early adulthood: a Danish nationwide cohort study

Paediatric seizures have been linked to psychiatric disorders in childhood, but there is a paucity of large-scale population-based studies of psychiatric comorbidity in later life. We aimed to examine the relation between childhood seizures and the risk of psychiatric disorders in adolescence and early adulthood. We did a register-based cohort study of all individuals born in Denmark in 1978-2002. Using diagnostic information from the Danish National Patient Register, all cohort members were categorised according to occurrence of febrile seizures and epilepsy, before entering the follow-up period on their 10th birthday. Individuals were followed up until onset of mental illness, death, emigration, or the end of the study period on Dec 31, 2012. Cox regression analyses were used to estimate the risk of five predefined groups of psychiatric disorders (substance abuse disorders, schizophrenia, mood disorder, anxiety, and personality disorder), separately and combined. Models were adjusted for relevant confounders. Between Jan 1, 1978, and Dec 31, 2002, 1 291 679 individuals were born in Denmark and followed up in our population cohort (approximately 15 million person-years). 43 148 individuals had a history of febrile seizures, 10 355 had epilepsy, and 1696 had both these disorders. 83 735 (6%) cohort members were identified with at least one of the psychiatric disorders of interest. The risk of any psychiatric disorder was raised in individuals with a history of febrile seizures (hazard ratio [HR] 1·12, 95% CI 1·08-1·17), epilepsy (1·34, 1·25-1·44), or both disorders (1·50, 1·28-1·75). Excess risk of psychiatric illness associated with childhood seizures was present across a range of different disorders, most notably schizophrenia but also anxiety and mood disorders. Associations did not differ between males and females (p=0·30) but increased with a growing number of admissions for febrile seizures (p<0·0001) and with later onset of childhood epilepsy (p<0·0001). Children with epilepsy and febrile seizures-with and without concomitant epilepsy-are at increased risk of developing a broad range of psychiatric disorders in later life. Clarification of the underlying mechanisms attributable to these associations is needed to identify potential options for prevention. Novo Nordisk Foundation, Danish Epilepsy Association, Central Denmark Region, Lundbeck Foundation, and Stanley Medical Research Institute.

Dissociable Disruptions in Thalamic and Hippocampal Resting-State Functional Connectivity in Youth with 22q11.2 Deletions.

The 22q11.2 deletion syndrome (22q11DS) is a recurrent copy number variant with high penetrance for developmental neuropsychiatric disorders. Study of individuals with 22q11DS therefore may offer key insights into neural mechanisms underlying such complex illnesses. Resting-state functional connectivity MRI studies in idiopathic schizophrenia have consistently revealed disruption of thalamic and hippocampal circuitry. Here, we sought to test whether this circuitry is similarly disrupted in the context of this genetic high-risk condition. To this end, resting-state functional connectivity patterns were assessed in a sample of human youth with 22q11DS (n = 42; 59.5% female) and demographically matched healthy controls (n = 39; 53.8% female). Neuroimaging data were acquired via single-band protocols and analyzed in line with methods provided by the Human Connectome Project. We computed functional relationships between individual-specific anatomically defined thalamic and hippocampal seeds and all gray matter voxels in the brain. Whole-brain Type I error protection was achieved through nonparametric permutation-based methods. The 22q11DS patients displayed dissociable disruptions in thalamic and hippocampal functional connectivity relative to control subjects. Thalamocortical coupling was increased in somatomotor regions and reduced across associative networks. The opposite effect was observed for the hippocampus in regards to somatomotor and associative network connectivity. The thalamic and hippocampal dysconnectivity observed in 22q11DS suggests that high genetic risk for psychiatric illness is linked with disruptions in large-scale corticosubcortical networks underlying higher-order cognitive functions. These effects highlight the translational importance of large-effect copy number variants for informing mechanisms underlying neural disruptions observed in idiopathic developmental neuropsychiatric disorders.SIGNIFICANCE STATEMENT Investigation of neuroimaging biomarkers in highly penetrant genetic syndromes represents a more biologically tractable approach to identify neural circuit disruptions underlying developmental neuropsychiatric conditions. The 22q11.2 deletion syndrome confers particularly high risk for psychotic disorders and is thus an important translational model in which to investigate systems-level mechanisms implicated in idiopathic illness. Here, we show resting-state fMRI evidence of large-scale sensory and executive network disruptions in youth with 22q11DS. In particular, this study provides the first evidence that these networks are disrupted in a dissociable fashion with regard to the functional connectivity of the thalamus and hippocampus, suggesting circuit-level dysfunction.

Maternal experience and adult neurogenesis in mammals: Implications for maternal care, cognition, and mental health.

The transition to motherhood encompasses physiological and behavioral adaptations essential for the initiation and maintenance of offspring care and feeding and includes widespread changes throughout the brain. The growth of new neurons occurs across the lifespan in distinct regions of mammalian brains and changes dynamically across reproductive events in female mammals. The subventricular zone (SVZ) and dentate gyrus (DG) of the hippocampus undergo high rates of neurogenesis in adulthood and are sensitive to hormonal fluctuations. Pregnancy and the postpartum period are associated with increased cell proliferation in the SVZ and interneuron survival in the olfactory bulb. In mice, peripartum prolactin signaling mediates SVZ neurogenesis and is important for enhanced olfactory recognition of offspring and maternal care. In contrast, cell proliferation and immature neuron survival decrease in the DG during the postpartum period. High baseline glucocorticoid concentrations suppress hippocampal neurogenesis, potentially representing an energetic trade-off accompanying a reduced need for spatial navigation early postpartum. In women, hippocampal volume decline during pregnancy and partial recovery during the postpartum period could contribute to the risk of psychiatric illness. New evidence indicates that the dorsal raphe nucleus (DR) is an additional site for adult neurogenesis sensitive to reproductive experience and offspring contact. In this review, we discuss the initial and lasting impact of maternal experience on adult neurogenesis. Because neurogenesis has been implicated in a variety of psychiatric and neurodegenerative illnesses, understanding how reproductive experience alters new neuron production in maternal mammals has far-reaching implications for women's health and wellness across the lifespan.

Review makes case for supplementation in pregnancy to prevent mental illness

A review of the effect of using prenatal nutritional supplements on mental health outcomes in children has concluded that evidence suggests supplementation as part of a maternal health strategy to decrease children's risk of psychiatric illness. The review, published online March 21 in the American Journal of Psychiatry, examined trials involving folic acid, phosphatidylcholine, omega‐3 fatty acids, and vitamins A and D.

The Immediate Early Gene Egr3 Is Required for Hippocampal Induction of Bdnf by Electroconvulsive Stimulation.

Early growth response 3 (Egr3) is an immediate early gene (IEG) that is regulated downstream of a cascade of genes associated with risk for psychiatric disorders, and dysfunction of Egr3 itself has been implicated in schizophrenia, bipolar disorder, and depression. As an activity-dependent transcription factor, EGR3 is poised to regulate the neuronal expression of target genes in response to environmental events. In the current study, we sought to identify a downstream target of EGR3 with the goal of further elucidating genes in this biological pathway relevant for psychiatric illness risk. We used electroconvulsive stimulation (ECS) to induce high-level expression of IEGs in the brain, and conducted expression microarray to identify genes differentially regulated in the hippocampus of Egr3-deficient (-/-) mice compared to their wildtype (WT) littermates. Our results replicated previous work showing that ECS induces high-level expression of the brain-derived neurotrophic factor (Bdnf) in the hippocampus of WT mice. However, we found that this induction is absent in Egr3-/- mice. Quantitative real-time PCR (qRT-PCR) validated the microarray results (performed in males) and replicated the findings in two separate cohorts of female mice. Follow-up studies of activity-dependent Bdnf exons demonstrated that ECS-induced expression of both exons IV and VI requires Egr3. In situ hybridization demonstrated high-level cellular expression of Bdnf in the hippocampal dentate gyrus following ECS in WT, but not Egr3-/-, mice. Bdnf promoter analysis revealed eight putative EGR3 binding sites in the Bdnf promoter, suggesting a mechanism through which EGR3 may directly regulate Bdnf gene expression. These findings do not appear to result from a defect in the development of hippocampal neurons in Egr3-/- mice, as cell counts in tissue sections stained with anti-NeuN antibodies, a neuron-specific marker, did not differ between Egr3-/- and WT mice. In addition, Sholl analysis and counts of dendritic spines in golgi-stained hippocampal sections revealed no difference in dendritic morphology or synaptic spine density in Egr3-/-, compared to WT, mice. These findings indicate that Egr3 is required for ECS-induced expression of Bdnf in the hippocampus and suggest that Bdnf may be a downstream gene in our previously identified biologically pathway for psychiatric illness susceptibility.

Gene expression links functional networks across cortex and striatum

The human brain is comprised of a complex web of functional networks that link anatomically distinct regions. However, the biological mechanisms supporting network organization remain elusive, particularly across cortical and subcortical territories with vastly divergent cellular and molecular properties. Here, using human and primate brain transcriptional atlases, we demonstrate that spatial patterns of gene expression show strong correspondence with limbic and somato/motor cortico-striatal functional networks. Network-associated expression is consistent across independent human datasets and evolutionarily conserved in non-human primates. Genes preferentially expressed within the limbic network (encompassing nucleus accumbens, orbital/ventromedial prefrontal cortex, and temporal pole) relate to risk for psychiatric illness, chloride channel complexes, and markers of somatostatin neurons. Somato/motor associated genes are enriched for oligodendrocytes and markers of parvalbumin neurons. These analyses indicate that parallel cortico-striatal processing channels possess dissociable genetic signatures that recapitulate distributed functional networks, and nominate molecular mechanisms supporting cortico-striatal circuitry in health and disease.

Interaction of childhood urbanicity and variation in dopamine genes alters adult prefrontal function as measured by functional magnetic resonance imaging (fMRI).

Brain phenotypes showing environmental influence may help clarify unexplained associations between urban exposure and psychiatric risk. Heritable prefrontal fMRI activation during working memory (WM) is such a phenotype. We hypothesized that urban upbringing (childhood urbanicity) would alter this phenotype and interact with dopamine genes that regulate prefrontal function during WM. Further, dopamine has been hypothesized to mediate urban-associated factors like social stress. WM-related prefrontal function was tested for main effects of urbanicity, main effects of three dopamine genes—catechol-O-methyltransferase (COMT), dopamine receptor D1 (DRD1), and dopamine receptor D2 (DRD2)—and, importantly, dopamine gene-by-urbanicity interactions. For COMT, three independent human samples were recruited (total n = 487). We also studied 253 subjects genotyped for DRD1 and DRD2. 3T fMRI activation during the N-back WM task was the dependent variable, while childhood urbanicity, dopamine genotype, and urbanicity-dopamine interactions were independent variables. Main effects of dopamine genes and of urbanicity were found. Individuals raised in an urban environment showed altered prefrontal activation relative to those raised in rural or town settings. For each gene, dopamine genotype-by-urbanicity interactions were shown in prefrontal cortex–COMT replicated twice in two independent samples. An urban childhood upbringing altered prefrontal function and interacted with each gene to alter genotype-phenotype relationships. Gene-environment interactions between multiple dopamine genes and urban upbringing suggest that neural effects of developmental environmental exposure could mediate, at least partially, increased risk for psychiatric illness in urban environments via dopamine genes expressed into adulthood.

O12.1. EXAMINING THE NEUROBIOLOGICAL IMPACT OF CHILDHOOD TRAUMA: AN IMPORTANT ROLE FOR FRONTAL AND INSULAR REGIONS

BackgroundChildhood trauma may increase the risk for psychiatric illness by its negative impact on brain development. Studies investigating the association between childhood trauma and deviations in gray matter volume have shown inconsistent findings, often restricted by a region-of interest approach with a sole focus on the amygdala and hippocampus and without controlling for the presence of psychiatric illness.MethodsFirst, using a whole-brain approach in a large cross-diagnostic sample (n=554) of healthy individuals and patients with a bipolar type-I or psychotic disorder, we investigated the neurobiological correlates of childhood trauma by evaluating gray matter volume. Follow-up analyses were conducted to evaluate the effect of psychiatric illness. Second, we investigated to what extent these trauma-related structural correlates could be observed in both groups separately (healthy individuals versus patients). Participants were recruited as part of three different studies, all conducted in the University Medical Center Utrecht (the Netherlands) between 2007 and 2016. We included 554 participants: 220 healthy individuals without a psychiatric history, 250 patients with a bipolar-I disorder and 84 patients with a psychotic disorder. Childhood trauma was evaluated with the Childhood Trauma Questionnaire (CTQ-SF). Anatomical T1 MRI scans were acquired at 3T. FreeSurfer was used to assess regional brain morphology.ResultsIn the total sample, childhood trauma severity was associated with bilateral reductions in frontal and insular gray matter volumes. In the right hemisphere, medial orbitofrontal and superior frontal volume reductions were related to childhood trauma. These associations remained when adjusting for psychiatric illness, with the exception of the right superior frontal subregion. However, when evaluating both groups separately, these structural correlates of childhood trauma were mainly observed in patients. Healthy controls did show trauma related reductions in right medial orbitofrontal region, while this association was not significant in the patient group.DiscussionOur results suggest that gray matter reductions in the frontal and insular regions are important neurobiological correlates of childhood trauma. For future research, a whole brain approach should be applied, as cortical rather than subcortical areas may be the main correlate of childhood trauma contributing to the development of psychopathology.

Maternal Immune Activation During the Third Trimester Is Associated with Neonatal Functional Connectivity of the Salience Network and Fetal to Toddler Behavior.

Prenatal maternal immune activation (MIA) is associated with altered brain development and risk of psychiatric disorders in offspring. Translational human studies of MIA are few in number. Alterations of the salience network have been implicated in the pathogenesis of the same psychiatric disorders associated with MIA. If MIA is pathogenic, then associated abnormalities in the salience network should be detectable in neonates immediately after birth. We tested the hypothesis that third trimester MIA of adolescent women who are at risk for high stress and inflammation is associated with the strength of functional connectivity in the salience network of their neonate. Thirty-six women underwent blood draws to measure interleukin-6 (IL-6) and C-reactive protein (CRP) and electrocardiograms to measure fetal heart rate variability (FHRV) at 34-37 weeks gestation. Resting-state imaging data were acquired in the infants at 40-44 weeks postmenstrual age (PMA). Functional connectivity was measured from seeds placed in the anterior cingulate cortex and insula. Measures of cognitive development were obtained at 14 months PMA using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Both sexes were studied. Regions in which the strength of the salience network correlated with maternal IL-6 or CRP levels included the medial prefrontal cortex, temporoparietal junction, and basal ganglia. Maternal CRP level correlated inversely with FHRV acquired at the same gestational age. Maternal CRP and IL-6 levels correlated positively with measures of cognitive development on the BSID-III. These results suggest that MIA is associated with short- and long-term influences on offspring brain and behavior.SIGNIFICANCE STATEMENT Preclinical studies in rodents and nonhuman primates and epidemiological studies in humans suggest that maternal immune activation (MIA) alters the development of brain circuitry and associated behaviors, placing offspring at risk for psychiatric illness. Consistent with preclinical findings, we show that maternal third trimester interleukin-6 and C-reactive protein levels are associated with neonatal functional connectivity and with both fetal and toddler behavior. MIA-related functional connectivity was localized to the salience, default mode, and frontoparietal networks, which have been implicated in the pathogenesis of psychiatric disorders. Our results suggest that MIA alters functional connectivity in the neonatal brain, that those alterations have consequences for cognition, and that these findings may provide pathogenetic links between preclinical and epidemiological studies associating MIA with psychiatric risk in offspring.

Community violence exposure correlates with smaller gray matter volume and lower IQ in urban adolescents

Adolescents' exposure to community violence is a significant public health issue in urban settings and has been associated with poorer cognitive performance and increased risk for psychiatric illnesses, including PTSD. However, no study to date has investigated the neural correlates of community violence exposure in adolescents. Sixty-five healthy adolescents (age = 14-18 years; 36 females, 29 males) from moderate- to high-crime neighborhoods in Los Angeles reported their violence exposure, parents' education level, and free/reduced school lunch status (socio-economic status, SES), and underwent structural neuroimaging and intelligence testing. Violence exposure negatively correlated with measures of SES, IQ, and gray matter volume. Above and beyond the effect of SES, violence exposure negatively correlated with IQ and with gray matter volume in the left inferior frontal gyrus and anterior cingulate cortex, regions involved in high-level cognitive functions and autonomic modulation, and previously shown to be reduced in PTSD and combat-exposed military populations. The current results provide first evidence that frontal brain regions involved in cognition and affect appear to be selectively affected by exposure to community violence, even in healthy nondelinquent adolescents who are not the direct victims or perpetrators of violence.

Can Chronic Probiotic Intake Modulate Psychological Profile, Gut Microbiota and Body Composition of Women Affected by Normal Weight Obese Syndrome and Obesity? A Double-Blind Randomized Clinical Trial

Background: Evidence of probiotics effects on gut function, brain activity and emotional behaviour were provided. Aim: Given the link between gut microbiota, body composition, and the risk of psychiatric illness, we investigated whether chronic probiotic intake could modulate psychological state, eating behavior, and body composition of normal weight obese (NWO) and preobese-obese (PreOB/OB) compared to normal weight lean women (NWL). Methods: 60 women were enrolled. We categorized the subjects according to BMI, and % of total body fat (TBFat) into three groups: NWL, (BMI 2, %TBFat2, %TBFat ≥30); PreOB/OB, (BMI ≥25 kg/m2, %TBFat ≥30). At baseline and after 4 week of a probiotic oral suspension (POS) intake all subjects underwent to: anthropometric evaluation (body weight, height, waist and hip circumferences); body composition by dual X-ray absorptiometry (DXA); gut microbiota evaluation by Glucose Breath Hydrogen test (GHBT). Moreover, all patients were also assessed by means of self-report questionnaries (i.e. Eating Disorder Inventory, Beck Depression Inventory, State and Trait Anxiety inventory, and Body Uneasiness Test). POS contained Streptococcus thermophilus, Bifidobacterium animalis subsp Lactis, Streptococcus thermophiles, Lactobacillus bulgaricus, Lactococcus lactis subsp Lactis, Lactobacillus acidophilus, Lactobacillus Plantarum, Lactobacillus Reuteri (1.5 ×1010 colony-forming unit CFU for each/day). Multivariate of interest analyses, Pearson or Spearman's rank correlation, and Partial Least Squares (PLS) were performed. Trial Registraton: ClinicalTrials.gov Id: NCT01890070. Results: Of the 60 women initially recruited, 8 did not meet inclusion criteria, 4 dropped out of the study voluntarily. We found a 22% of NWO, 26% of NWL, and 48% of PreOB/OB women. Significant differences (p). Conclusion: Four-week intake of selected probiotic, by modulating body composition, bacterial contamination, psychopathological scores and eating behavior of women affected by NWO syndrome and obesity, offers a tractable approach to problems related to obesity, psychological state and unhealthy eating. Further research is needed on a larger population and for longer period of treatment before definitive conclusions can be made.Table: Table. Results of lactulose breath testTable: Table. Symptoms in patients before and after therapy

Continuity and discontinuity between psychopathology of childhood and adulthood: a review on retrospective and prospective studies.

The knowledge of the possible development of a psychiatric disorder, diagnosed for the first time in childhood, is very crucial for all specialists in helping professions working with children and adults. Recent longitudinal studies have demonstrated the possibility that disturbances in childhood may increase the risk of psychiatric illnesses in adulthood, through a homotypic or heterotypic continuity. The aim of this study is to perform a systematic review of existing literature on the psychopathological progression from childhood to adulthood, taking into account both prospective and retrospective studies, and the antecedents and conditions that may encourage/disadvantage the process of continuity of psychopathological syndromes. The study of the possible trajectories of psychopathological disorders is considered fundamental, as it allows the clinician to configure prevention strategies and evaluate interventions, but also to offer to the parent a more concrete vision of the possible risks of their child’s disorders to minimize them.

Reproductive fitness and genetic risk of psychiatric disorders in the general population

The persistence of common, heritable psychiatric disorders that reduce reproductive fitness is an evolutionary paradox. Here, we investigate the selection pressures on sequence variants that predispose to schizophrenia, autism, bipolar disorder, major depression and attention deficit hyperactivity disorder (ADHD) using genomic data from 150,656 Icelanders, excluding those diagnosed with these psychiatric diseases. Polygenic risk of autism and ADHD is associated with number of children. Higher polygenic risk of autism is associated with fewer children and older age at first child whereas higher polygenic risk of ADHD is associated with having more children. We find no evidence for a selective advantage of a high polygenic risk of schizophrenia or bipolar disorder. Rare copy-number variants conferring moderate to high risk of psychiatric illness are associated with having fewer children and are under stronger negative selection pressure than common sequence variants.

Further evidence for the association between LRP8 and schizophrenia

Previous studies (including genome-wide association study (GWAS) and candidate gene studies) have revealed the important roles of genetic risk factors in schizophrenia, and RELN has been identified as a risk gene for this illness. We recently found that the low-density lipoprotein receptor-related protein 8 (LRP8), a receptor of Reelin (the protein encoded by RELN), was significantly associated with schizophrenia and bipolar disorder in European populations. To further enhance our understanding of its role in the risk of psychiatric illnesses, we conducted meta-analyses of a higher density of single nucleotide polymorphisms (SNPs, N=173) in LRP8 to understand their associations with schizophrenia in much larger samples (39,400 cases and 50,357 controls) from populations of European, Chinese and African American ancestries. The significant risk SNPs then underwent further analyses to understand their correlations with bipolar disorder and anxiety disorders, as well as LRP8 expression. We observed that rs5177 in the 3′ untranslated region (3’UTR) of LRP8 was associated with schizophrenia and other psychiatric disorders, and rs5177 was also associated with LRP8 mRNA expression. These data further support LRP8 as a schizophrenia susceptibility gene, and suggest that this variant is likely a risk locus in general populations.

499. Disrupted Activity in Prefrontal Microcircuits in a Mouse Model of Genetic Risk for Psychiatric Illness

499. Disrupted Activity in Prefrontal Microcircuits in a Mouse Model of Genetic Risk for Psychiatric Illness

Illuminating the clinical significance of alexithymia subtypes: A cluster analysis of alexithymic traits and psychiatric symptoms

BackgroundAlexithymia is a personality construct involving difficulties identifying and verbalizing feelings, and an externally oriented thinking style. There is preliminary evidence for alexithymia subtypes that may carry different risk profiles for psychiatric illness. The aim of this study was to gain support for the existence of alexithymia subtypes and further characterize their clinical relevance. MethodsTo identify possible subtypes, a cluster analysis was conducted for individuals with high alexithymic traits (N=113). Current depressive and anxiety symptoms, self-reported psychiatric medical history, and self-reported early life adversity were compared between subtypes. The cluster analysis was replicated with the low (N=2471) and moderate (N=290) alexithymia groups. ResultsWe identified two alexithymia subtypes. Compared to type A, type B alexithymia was associated with higher levels of difficulties in identifying feelings, and was more strongly associated with current depressive (Cohen's d=0.77, p<0.001) and anxiety symptoms (Cohen's d=0.82, p<0.001), and self-reported early life adversity (Cohen's d 0.42, p=0.048). Compared to type A, type B alexithymia was also associated with a higher prevalence of self-reported diagnosis of major depressive- (30.2% vs. 8.3%) and anxiety disorder (18.9% vs. 3.3%). ConclusionsThe results of this study support the hypothesis of alexithymia subtypes, and add support to the growing evidence showing that alexithymia is likely a heterogeneous and dimensional phenomenon. The subtype (type B) with most pronounced difficulties in identifying feelings may be associated with a higher risk for psychiatric illness compared to type A alexithymia, and may exhibit a more severe history of early life adversity.

Hippocampal development in youth with a history of childhood maltreatment

Childhood maltreatment (CM) is associated with enhanced risk of psychiatric illness and reduced subcortical grey matter in adulthood. The hippocampus and amygdala, due to their involvement in stress and emotion circuitries, have been subject to extensive investigations regarding the effect of CM. However, the complex relationship between CM, subcortical grey matter and mental illness remains poorly understood partially due to a lack of longitudinal studies. Here we used segmentation and linear mixed effect modelling to examine the impact of CM on hippocampal and amygdala development in young people with emerging mental illness. A total of 215 structural magnetic resonance imaging (MRI) scans were acquired from 123 individuals (age: 14–28 years, 79 female), 52 of whom were scanned twice or more. Hippocampal and amygdala volumes increased linearly with age, and their developmental trajectories were not moderated by symptom severity. However, exposure to CM was associated with significantly stunted right hippocampal growth. This finding bridges the gap between child and adult research in the field and provides novel evidence that CM is associated with disrupted hippocampal development in youth. Although CM was associated with worse symptom severity, we did not find evidence that CM-induced structural abnormalities directly underpin psychopathology. This study has important implications for the psychiatric treatment of individuals with CM since they are clinically and neurobiologically distinct from their peers who were not maltreated.

Risk of Psychiatric Illness From Advanced Paternal Age Is Not Predominantly From De Novo Mutations

(Abstracted from Nat Genet 2016;48:718–724) Epidemiologic studies have reported an increased risk of schizophrenia, autism, and other psychiatric disorders among offspring of older fathers. It is widely assumed that paternal age–related de novo mutations are the primary underlying causal mechanism.

Depression impacts the physiological responsiveness of mother-daughter dyads during social interaction

Maternal depression is associated with increased risk of psychiatric illness in offspring. While risk may relate to depressed mothers' difficulties regulating emotions in the context of interacting with offspring, physiological indicators of emotion regulation have rarely been examined during mother-child interactions-and never among mother-adolescent dyads in which both mother and adolescent have histories of major depressive disorder (MDD). We examined changes in high-frequency heart rate variability (HF-HRV), an indicator of parasympathetic (vagal) function that has been related to depression, stress, social engagement, and emotion regulation, in 46 mother-daughter dyads (23 in which both mother and daughter had an MDD history and 23 never-depressed controls). Hierarchical linear models evaluated changes in HF-HRV while mother-daughter dyads engaged in discussions about shared pleasant events and relationship conflicts. While control dyads displayed positive slopes (increases) in HF-HRV during both discussions, MDD dyads displayed minimal change in HF-HRV across discussions. Among controls, HF-HRV slopes were positively correlated between mothers and daughters during the pleasant events' discussion. In contrast, HF-HRV slopes were negatively correlated between MDD mothers and daughters during both discussions. Vagal responses observed in control mother-daughter dyads suggest a pattern of physiological synchrony and reciprocal positive social engagement, which may play a role in adolescent development of secure social attachments and healthy emotion regulation. In contrast, MDD mothers and daughters displayed diminished and discordant patterns of vagal responsiveness. More research is needed to understand the development and consequences of these patterns of parasympathetic responses among depressed mother-daughter dyads.