Offspring psychopathology following preconception, prenatal and postnatal maternal bereavement stress.

BACKGROUND: Preconception, prenatal and postnatal maternal stress is associated with increased offspring psychopathology, but findings are inconsistent and need replication. We estimated associations between maternal bereavement stress and offspring autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, suicide attempt and completed suicide. METHOD: Using Swedish registers, we conducted the largest population-based study to date examining associations between stress exposure in 738,144 offspring born 1992-2000 for childhood outcomes and 2,155,221 offspring born 1973-1997 for adult outcomes with follow-up to 2009. Maternal stress was defined as death of a first-degree relative during (a) the 6 months before conception, (b) pregnancy or (c) the first two postnatal years. Cox proportional survival analyses were used to obtain hazard ratios (HRs) in unadjusted and adjusted analyses. RESULTS: Marginal increased risk of bipolar disorder and schizophrenia following preconception bereavement stress was not significant. Third-trimester prenatal stress increased the risk of ASD [adjusted HR (aHR) 1.58, 95% confidence interval (CI) 1.15-2.17] and ADHD (aHR 1.31, 95% CI 1.04-1.66). First postnatal year stress increased the risk of offspring suicide attempt (aHR 1.13, 95% CI 1.02-1.25) and completed suicide (aHR 1.51, 95% CI 1.08-2.11). Bereavement stress during the second postnatal year increased the risk of ASD (aHR 1.30, 95% CI 1.09-1.55). CONCLUSIONS: Further research is needed regarding associations between preconception stress and psychopathological outcomes. Prenatal bereavement stress increases the risk of offspring ASD and ADHD. Postnatal bereavement stress moderately increases the risk of offspring suicide attempt, completed suicide and ASD. Smaller previous studies may have overestimated associations between early stress and psychopathological outcomes.

Hearing and speech impairment at age 4 and risk of later non-affective psychosis.

BACKGROUND: Schizophrenia often becomes manifest in late adolescence and young adulthood but deviations in physical and behavioural development may already be present in childhood. We investigated the relationship between hearing impairment (measured with audiometry) and speech impairment (broadly defined) at age 4 years and adult risk of non-affective psychosis. METHOD: We performed a population-based, case­control study in Sweden with 105 cases of schizophrenia or other non-affective psychoses and 213 controls matched for sex, date and place of birth. Information on hearing and speech impairment at age 4, along with potential confounding factors, was retrieved from Well Baby Clinic (WBC) records. RESULTS: Hearing impairment [odds ratio (OR) 6.0, 95% confidence interval (CI) 1.6­23.2] and speech impairment (OR 2.6, 95% CI 1.4­4.9) at age 4 were associated with an increased risk of non-affective psychotic illness. These associations were mutually independent and not explained by parental psychiatric history, occupational class or obstetric complications. CONCLUSIONS: These results support the hypothesis that psychosis has a developmental aspect with presentation of antecedent markers early in childhood, long before the disease becomes manifest. Our findings add to the growing evidence that early hearing impairment and speech impairment are risk indicators for later non-affective psychosis and possibly represent aetiological clues and potentially modifiable risk factors. Notably, speech impairment and language impairment are both detectable with inexpensive, easily accessible screening.

30-day morbidity and mortality after transoral robotic surgery for human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma: A retrospective analysis of two prospective adjuvant de-escalation trials (MC1273 & MC1675).

OBJECTIVE: Dose de-escalation of adjuvant therapy (DART) in patients with HPV(+)OPSCC was investigated in two prospective Phase II and III clinical trials (MC1273 and MC1675). We report the 30-day morbidity and mortality associated with primary TORS resection in patients enrolled in these trials. MATERIALS AND METHODS: Patients with HPV(+)OPSCC, who underwent TORS resection between 2013 and 2020 were considered in this analysis. The severity of postoperative transoral bleeding was graded using both the Hinni Grade (HG) transoral surgery bleeding scale and the Common Terminology for Adverse Events (CTCAE) v5.0. Post-surgical complications within 30 days of surgery, as well as rates of tracheostomy, PEG and nasogastric tube placement. RESULTS: 219 patients were included. A total of 7 (3.2 %) patients had a tracheostomy placed at the time of surgery, and all were decannulated within 26 days (median: 5, range: 2-26). There were 33 (15.1 %) returns to the emergency department (ED) with 10 (4.6 %) patients requiring readmission. Using the HG scale, 10 (4.6 %) patients experienced ≥ Grade 3 bleeding with no Grade 5 or 6 bleeds. In contrast, using the CTCAE scale, 15 patients (6.8 %) experienced ≥ Grade 3 bleeding with no Grade 5 bleeds. There was one post-operative death in a patient withdrawn from the trial, and no deaths related to hemorrhage. CONCLUSION AND RELEVANCE: TORS for HPV(+)OPSCC in carefully selected patients at a high volume center was associated with low morbidity and mortality.

Non-opioid analgesics and post-operative pain following transoral robotic surgery for oropharyngeal cancer.

OBJECTIVE: To investigate associations between multimodal analgesia and post-operative pain among patients undergoing transoral robotic surgery for oropharyngeal squamous cell carcinoma. METHODS: Records of patients who underwent surgery from 5 September 2012 to 30 November 2016 were abstracted. Associations were assessed using multivariable analysis. RESULTS: A total of 216 patients (mean age of 59.1 years, 89.4 per cent male) underwent transoral robotic surgery (92.6 per cent were human papilloma virus positive, 87.5 per cent had stage T1-T2 tumours, and 82.9 per cent had stage N0-N1 nodes). Gabapentin (n = 86) was not associated with a reduction in severe pain. Ibuprofen (n = 72) was administered less often in patients with severe pain. Gabapentin was not associated with increased post-operative sedation (p = 0.624) and ibuprofen was not associated with increased bleeding (p = 0.221). Post-operative opioid usage was not associated with surgical duration, pharyngotomy, bilateral neck dissections, tumour stage, tumour size, subsite or gabapentin. CONCLUSION: Scheduled low-dose gabapentin was not associated with improved pain control or increased respiratory depression. Ibuprofen was not associated with an increased risk of bleeding and may be under-utilised.

Teenage motherhood and risk of premature death: long-term follow-up in the ONS Longitudinal Study.

BACKGROUND: Teenage motherhood is relatively common in the UK, but little is known about related health inequalities in this population. We estimated cause-specific mortality risks over three decades in a nationally representative cohort. METHOD: We examined premature mortality in a 1.1% sample of all women who were teenagers in England and Wales during the 1970s, 1980s and 1990s using data from the Office for National Statistics Longitudinal Study (ONS LS). Our primary outcome was suicide. Long-term follow-up to 31 December 2006, to a potential maximum age of 49 years, was achieved through near-complete routine linkage to national mortality records. We created a time-dependent exposure variable, with relative risks estimated according to age when women first experienced motherhood versus a reference group of those currently without children. RESULTS: Women who were teenage mothers were around 30% more likely to die prematurely by any cause and almost 60% more likely to die unnaturally, whereas first-time motherhood at mature age conferred lower risk compared to women without children. Teenage motherhood was associated with a more than doubled risk of suicide [mortality rate ratio (MRR) 2.23, 95% confidence interval (CI) 1.30-3.83], and elevated risks of fatal cancer of the cervix and lung were also found. Changing the reference category to first-time mothers at 20 years and above also revealed a significant elevation in risk of accidental death. CONCLUSIONS: The complex psychosocial needs of these women require greater attention from clinicians, public health professionals, social services and policymakers. Their elevated risk of poor health outcomes may persist well beyond the actual teenage motherhood years.

Ketamine-induced disruption of verbal self-monitoring linked to superior temporal activation.

INTRODUCTION: Misattribution of distorted self-generated speech in patients with schizophrenia has been associated with increased lateral temporal activation. As a pharmacological model of schizophrenia, we tested whether ketamine would induce the same effects in healthy individuals. METHODS: Participants were 8 healthy male volunteers who were naïve to ketamine (mean age: 28 years). Ketamine (0.23 mg/kg bolus followed by 0.64 mg/kg/h) and placebo infusions were administered in a double-blind, randomised order, during 2 functional magnetic resonance imaging (fMRI) sessions. Each fMRI session consisted of a verbal self-monitoring task in which auditory feedback was experimentally modified. RESULTS: Ketamine was associated with psychotic and dissociative symptoms. Participants made more misattributions of distorted self-generated speech (P < 0.02) during the ketamine infusion. Ketamine led to reduced activation in the left superior temporal cortex during self-distorted speech, regardless of whether the speech was identified correctly or not, as compared to the placebo infusion. Misidentification of speech that had been distorted was not associated with any increase in brain activation in during the placebo infusion, however ketamine-induced misattributions were associated with a relative increase in left superior temporal cortex activation. DISCUSSION: These data are consistent with the notion that self-monitoring impairments underlie psychotic symptoms and suggest that N-methyl-D-aspartate (NMDA) receptor dysfunction may mediate self-monitoring deficits and psychotic phenomena in schizophrenia.

Sex ratio at birth following prenatal maternal exposure to severe life events: a population-based cohort study.

BACKGROUND: A reduction in the sex ratio at birth has been linked to maternal condition during and before pregnancy. A recent study reported an association between maternal exposure to severe life events and sex ratio at birth using the Danish national register. We attempted to replicate that study using a new Danish cohort. METHODS: Mothers of all singleton live births (n = 1.35 million births) in Denmark, between 1 January 1980 and 31 December 2002, were linked to data on their children and partners. The old cohort consisted of babies born between 1980 and 1992 (n = 699 362), whereas the new cohort consisted of babies born between 1993 and 2002 (n = 633 451). We defined exposure as death or serious illness in older children and partners in the first trimester or in the 6 months before conception. Sex ratio at birth was defined as the proportion of male live births. RESULTS: During the study period, there were 1,349,099 singleton live births (692,870 boys and 656,229 girls). The sex ratio at birth in the new cohort was 0.5134. In the new cohort, prenatal exposure to severe life events was not associated with a reduction in the sex ratio at birth [relative risk = 1.00 (95% confidence interval: 0.95-1.05)]. CONCLUSIONS: In the new cohort, we did not find strong evidence that, in a stable western population, prenatal exposure to severe life events is associated with a reduction in the sex ratio at birth.

Rates of preterm birth following antenatal maternal exposure to severe life events: a population-based cohort study.

BACKGROUND: Preterm birth and other pregnancy complications have been linked to maternal stress during pregnancy. We investigated the association between maternal exposure to severe life events and risk of preterm birth. METHODS: Mothers of all singleton live births (n = 1.35 million births) in Denmark between 1 January 1979 and 31 December 2002 were linked to data on their children, parents, siblings and partners. We defined exposure as death or serious illness in close relatives in the first or second trimesters or in the 6 months before conception. Log-linear binomial regression was used to estimate the effect of exposure on preterm birth, very preterm birth and extremely preterm birth. RESULTS: There were 58 626 (4.34%) preterm births (<37 weeks), 11 732 (0.87%) very preterm births and 3288 (0.24%) extremely preterm births in the study cohort. Severe life events in close relatives in the 6 months before conception increased the risk of preterm birth by 16% (relative risk, RR = 1.16, [95% CI: 1.08-1.23]). Severe life events in older children in the 6 months before conception increased the risk of preterm birth by 23% (RR = 1.23, [95% CI: 1.02-1.49]) and the risk of very preterm birth by 59% (RR = 1.59, [95% CI: 1.08-2.35]). CONCLUSIONS: Our population-based cohort study suggests that maternal exposure to severe life events, particularly in the 6 months before pregnancy, may increase the risk of preterm and very preterm birth.

Preliminary evidence for neural responsiveness to infants in mothers with schizophrenia and the implications for healthy parenting.

Schizophrenia is a severe mental illness that may significantly affect maternal sensitive behaviour. Neural correlates of maternal behaviour represent a potentially valuable means of differentiating objectively between healthy mothers expressing variations in maternal sensitivity. As mothers with schizophrenia (MWS) show deficits in behavioural responses to infants compared to healthy mothers, we explored whether maternal brain responses to infant stimuli would be significantly reduced in MWS. We also examined whether differences in maternal behaviour between healthy and ill mothers (during play interactions with own infant) were associated with differences in brain activation to infant stimuli. We found no evidence of differential 'maternal brain' responses or 'maternal behavioural' responses in 11 new MWS compared to 20 healthy new mums; neither were neural responses to infants linked to behavioural or cognitive aspects of the mother's relationship with her infant in MWS. These preliminary findings suggest maternal sensitivity differences between MWS and healthy mothers, suggested in previous studies, may be reversible in stable treated MWS.

Plasma homovanillic acid profile at different phases of the ovulatory cycle in healthy women.

Variation in some central monoamine levels has been shown to be influenced by cyclical changes in gonadal hormones in women; however, there is less consensus about how the human menstrual cycle affects turnover of dopamine. Fluctuations in plasma homovanillic acid (HVA) are thought to represent changes in central dopamine turnover and activity and, some suggest, may be used to monitor the response to neuroleptic medication or to predict those more likely to respond to antipsychotic treatment. We have measured the effect of fluctuations in gonadal hormones on the level of plasma HVA at four consecutive points across the menstrual cycles of 30 healthy volunteers. We found no significant change in plasma HVA over the cycle and there was no correlation with either estradiol or progesterone levels. This study suggests that peripheral markers of central dopamine function do not change significantly with physiological changes in gonadal hormones levels.

Serotonergic function and negative and depressive symptomatology in schizophrenia and major depression.

BACKGROUND: Serotonergic abnormalities are found in both major depressive disorder (MDD) and schizophrenia. Depressive symptoms commonly occur alongside the negative or defect symptoms in schizophrenia and antiserotonergic drugs may be particularly effective in their treatment. We wished to explore whether these symptoms could be distinguished biologically by directly comparing serotonergic function in these two illnesses. METHOD: Fifteen patients with MDD and 13 patients with schizophrenia underwent testing with the specific serotonin releasing agent D-fenfluramine (D-FEN). Prolactin and cortisol responses were measured to ascertain central serotonergic function. Individual patient results were compared with their own carefully matched control to correct for the effect of age, sex, weight and menstrual cycle, before the two patient groups were then compared. RESULTS: Prolactin responses differed significantly between the two patient groups, being lower in MDD patients and higher in schizophrenia patients than their individually matched controls. Cortisol responses did not differ. Within the schizophrenia group, increased serotonergic function correlated positively with depressive symptoms, but there was no such correlation with defect symptoms. Depressive scores were negatively correlated with the presence of negative symptoms in the schizophrenic group. CONCLUSIONS: Schizophrenia and MDD have distinct and opposite neuroendocrine responses to D-FEN. There is no evidence that depressive symptoms in these two conditions have a common serotonergic basis. Moreover, these responses distinguished between negative and depressive symptoms in our schizophrenic group.

Prolactin response to d-fenfluramine in postmenopausal women on and off ERT: comparison with young women.

Estrogen is thought to have an impact on both psychological well being and cognitive function. The biological basis to this is not fully understood, but may involve estrogen's interactions with central serotonergic (5-HT) systems. Therefore, we studied the effect of long-term estrogen hormone replacement therapy (ERT) on central 5-HT tone in healthy postmenopausal women and made comparisons with young women. Prolactin (PRL) responses to the specific 5-HT releasing and re-uptake inhibiting agent, d-fenfluramine, were measured in three groups of healthy women: 11 young, 11 postmenopausal on long-term ERT, and 11 postmenopausal ERT naïve. PRL responses were significantly decreased in ERT naïve women compared to young healthy women. In contrast, PRL responses were not different between estrogen-treated and young women. Overall, there was a significant relationship between older age and lower PRL responsivity. These results suggest that central 5-HT tone is reduced in healthy postmenopausal women who are ERT naïve, but not in postmenopausal women who have received prolonged estrogen treatment. Estrogen may modulate age-related changes in 5-HT tone. This may partly explain why estrogen can decrease vulnerability to mood disorders and cognitive changes in postmenopausal women.

Peripheral hormonal responses to D-fenfluramine as a probe of central serotonergic function in humans.

We tested the hypothesis that D-fenfluramine (DFEN)-elicited cortisol (CORT) release in humans may be mediated by a direct effect on the adrenal gland by pretreating subjects with dexamethasone (DEX), to prevent release of ACTH from the pituitary, followed by a DFEN challenge test. Eight healthy subjects (four males; four female) (mean age = 38.1 +/- 8.4 years (SD)] were studied > 1 week apart (same phase of menstrual cycle) and testing order was randomised. On the with-DEX day (DEX+), subjects took 2 mg DEX orally at 10 p.m.; 30 mg DFEN was then given orally at 9 a.m. and samples were taken at 0-5 h for PRL and CORT. Peak hormone responses (delta values) were calculated by subtracting baseline values from the maximum levels post-DFEN administration. Peak and baseline hormonal values were compared between the two test conditions; DFEN-induced CORT and PRL responses were compared across all time points, with and without DEX. There was no significant difference in delta PRL between the two test conditions (DEX- and DEX+), but delta CORT values were significantly reduced after DEX: mean delta CORT DEX- = 68.4 +/- 26.3 nmol/l; DEX+ = 0.0 nmol/l (all blunted) (df 7,1; P = 0.03). The completely blunted peripheral cortisol response indicates that DFEN cortisol responses are of central origin only.

The neural basis of maternal responsiveness to infants: an fMRI study.

Using fMRI, we examined the neural correlates of maternal responsiveness. Ten healthy mothers viewed alternating blocks of video: (i) 40 s of their own infant; (ii) 20 s of a neutral video; (iii) 40 s of an unknown infant and (iv) 20 s of neutral video, repeated 4 times. Predominant BOLD signal change to the contrasts of infants minus neutral stimulus occurred in bilateral visual processing regions (BA 19,21,37,38); to own infant minus unknown infant in right anterior temporal pole (BA 38), left amygdala and visual cortex (BA 19), and to the unknown infant minus own infant contrast in bilateral orbitofrontal cortex (BA 10,47) and medial prefrontal cortex (BA 8) [corrected] These findings suggest that amygdala and temporal pole may be key sites in mediating a mother's response to her infant and reaffirms their importance in face emotion processing and social behaviour.

The influence of schizotypy traits on prepulse inhibition in young healthy controls.

Deficits in sensorimotor gating or prepulse inhibition (PPI) have been demonstrated repeatedly in patients with schizophrenia or with schizotypal personality disorder, but not consistently in schizotypal non-psychiatric controls. The appearance of normal PPI in this group has been interpreted as reflecting a discontinuous underlying vulnerability to psychosis in high-risk groups. An alternative interpretation is that underlying vulnerability to psychosis is continuously distributed in the normal population (Claridge, 1972, 1987), and therefore that performance on information processing tasks should vary continuously with increasing levels of schizotypy in non-clinical populations. We attempted to examine further the notion of a continuous relationship between PPI and schizotypy in 44 (17 female, 27 male) healthy, non-smoking subjects controlling for menstrual phase. In this selected sample, the findings do not support a continuum model, and suggest that PPI deficits may indeed be the result of a discontinuous neurophysiological change in those with psychotic illness, rather than one continuously distributed in the normal population.

Antipsychotic drugs for non-affective psychosis during pregnancy and postpartum.

BACKGROUND: Antipsychotics are commonly prescribed for women suffering psychotic illnesses during pregnancy and the postpartum period. The potential adverse consequences of these different options are multiple and complex, impacting on the foetus, neonate, infant and early development of the child as well as the woman herself. OBJECTIVES: To establish whether the benefits of taking antipsychotic drugs outweigh the risks for pregnant or post partum women. SEARCH STRATEGY: The Cochrane Schizophrenia Group's Register (January 2003) was searched in order to identify all published trials of women during pregnancy or the postpartum period. We inspected all references of all identified studies. If any studies had been found, the first authors of each included study would have been contacted. SELECTION CRITERIA: Randomised controlled clinical trials investigating the effects of any type of antipsychotic drug compared with any other treatment option (including standard psychosocial care, any other antipsychotic drug, or an alternative therapy such as electro-convulsive therapy or cognitive behavioural therapy) and involving pregnant women and/or women during the postpartum period diagnosed with a non-affective psychotic disorder. DATA COLLECTION AND ANALYSIS: Citations, and where possible, abstracts were independently inspected by reviewers and the papers ordered were scrutinised and quality assessed. Data would have been extracted independently by at least two reviewers. Binary outcomes were to have been analysed using Relative Risks (RR) and their 95% Confidence Intervals (CI). MAIN RESULTS: We found no trials that met the broad inclusion criteria. REVIEWERS' CONCLUSIONS: Current guidelines and clinical practice for the use of antipsychotic drugs in women with non-affective disorders during pregnancy and postpartum are not based on evidence from randomised controlled trials. Although ethical concerns have to date precluded the use of randomised controlled trials to address this research topic, the continued use of antipsychotic drugs in this group of women in itself poses significant clinical and ethical problems. Evidence is required from large pragmatic trials that reflect routine clinical practice, examine a broad range of outcomes and accurately quantify risks and benefits to both mothers and their offspring, so that comparison between different treatment options can be made.

Approaching the biology of human parental attachment: brain imaging, oxytocin and coordinated assessments of mothers and fathers.

Brain networks that govern parental response to infant signals have been studied with imaging techniques over the last 15 years. The complex interaction of thoughts and behaviors required for sensitive parenting enables the formation of each individual's first social bonds and critically shapes development. This review concentrates on magnetic resonance imaging experiments which directly examine the brain systems involved in parental responses to infant cues. First, we introduce themes in the literature on parental brain circuits studied to date. Next, we present a thorough chronological review of state-of-the-art fMRI studies that probe the parental brain with a range of baby audio and visual stimuli. We also highlight the putative role of oxytocin and effects of psychopathology, as well as the most recent work on the paternal brain. Taken together, a new model emerges in which we propose that cortico-limbic networks interact to support parental brain responses to infants. These include circuitry for arousal/salience/motivation/reward, reflexive/instrumental caring, emotion response/regulation and integrative/complex cognitive processing. Maternal sensitivity and the quality of caregiving behavior are likely determined by the responsiveness of these circuits during early parent-infant experiences. The function of these circuits is modifiable by current and early-life experiences, hormonal and other factors. Severe deviation from the range of normal function in these systems is particularly associated with (maternal) mental illnesses - commonly, depression and anxiety, but also schizophrenia and bipolar disorder. Finally, we discuss the limits and extent to which brain imaging may broaden our understanding of the parental brain given our current model. Developments in the understanding of the parental brain may have profound implications for long-term outcomes in families across risk, resilience and possible interventions. This article is part of a Special Issue entitled Oxytocin and Social Behav.

Severe bereavement stress during the prenatal and childhood periods and risk of psychosis in later life: population based cohort study.

OBJECTIVE: To examine the risk of psychosis associated with severe bereavement stress during the antenatal and postnatal period, between conception to adolescence, and with different causes of death. DESIGN: Population based cohort study. SETTING: Swedish national registers including births between 1973 and 1985 and followed-up to 2006. PARTICIPANTS: In a cohort of 1,045,336 Swedish births (1973-85), offspring born to mothers exposed to severe maternal bereavement stress six months before conception or during pregnancy, or exposed to loss of a close family member subsequently from birth to 13 years of age were followed until 2006. Admissions were identified by linkage to national patient registers. MAIN OUTCOME MEASURES: Crude and adjusted odds ratios for all psychosis, non-affective psychosis, and affective psychosis. RESULTS: Maternal bereavement stress occurring preconception or during the prenatal period was not associated with a significant excess risk of psychosis in offspring (adjusted odds ratio, preconception 1.24, 95% confidence interval 0.96 to 1.62; first trimester 0.95, 0.58 to 1.56; second trimester 0.79, 0.46 to 1.33; third trimester 1.14, 0.78 to 1.66). Risks increased modestly after exposure to the loss of a close family member from birth to adolescence for all psychoses (adjusted odds ratio 1.17, 1.04 to 1.32). The pattern of risk was generally similar for non-affective and affective psychosis. Thus estimates were higher after death in the nuclear compared with extended family but remained non-significant for prenatal exposure; the earlier the exposure to death in the nuclear family occurred in childhood (all psychoses: adjusted odds ratio, birth to 2.9 years 1.84, 1.41 to 2.41; 3-6.9 years 1.47, 1.16 to 1.85; 7-12.9 years 1.32, 1.10 to 1.58) and after suicide. Following suicide, risks were especially higher for affective psychosis (birth to 2.9 years 3.33, 2.00 to 5.56; 6.9 years 1.84, 1.04 to 3.25; 7-12.9 years 2.68, 1.84 to 3.92). Adjustment for key confounders attenuated but did not explain associations with risk. CONCLUSIONS: Postnatal but not prenatal bereavement stress in mothers is associated with an increased risk of psychosis in offspring. Risks are especially high for affective psychosis after suicide in the nuclear family, an effect that is not explained by family psychiatric history. Future studies are needed to understand possible sources of risk and resilience so that structures can be put in place to support vulnerable children and their families.

Filicide in offspring of parents with severe psychiatric disorders: a population-based cohort study of child homicide.

OBJECTIVE: Although rare in absolute terms, risk of homicide is markedly elevated among children of parents with mental disorders. Our aims were to examine risk of child homicide if 1 or both parents had a psychiatric history, to compare effects by parental sex and diagnostic group, and to assess likelihood of child homicide being perpetrated by parents according to their psychiatric history. METHOD: A prospective, register-based cohort study using the entire Danish population born between January 1, 1973, and January 1, 2007, was conducted. Follow-up of the cohort members began on their date of birth and ended on January 1, 2007; their 18th birthday; their date of death; or their date of emigration, whichever came first. We used the Danish national registers from 1973 to 2007 to study homicide risk between children whose parents were previously admitted to a psychiatric hospital, including diagnosis-specific analyses, versus their unexposed counterparts. In addition, we used police records during 2000 to 2005 to examine whether or not 1 of the parents was the perpetrator. Rates of homicide were analyzed using survival analysis. RESULTS: Children of parents previously admitted to a psychiatric hospital had an overall higher risk of being homicide victims (MRR = 8.94; 95% CI, 6.56-12.18). The risk differed according to parental sex and psychiatric diagnosis (ICD-8 and ICD-10 criteria). The absolute risk of homicide was 0.009% if neither parent had been admitted before the birth of their child and 0.051% if 1 of the parents had previously been admitted. During 2000 to 2005, 88% of the child homicide cases were filicide victims. This percentage was not significantly different for parents with a previous psychiatric admission versus those without such a history. CONCLUSIONS: In the large majority of Danish child-homicide cases, a parent was the perpetrator, regardless of whether there had been parental admission to a psychiatric hospital. Children of parents previously admitted had a higher risk of being homicide victims, and risks were especially high in young children whose mothers were hospitalized with affective disorders or schizophrenia. However, the relative risks presented in the current study are based on extremely rare events, and the overwhelming majority of children whose parents have a psychiatric history do not become homicide victims.