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Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Comorbidity within mental disorders: a comprehensive analysis based on 145 990 survey respondents from 27 countries
- J. J. McGrath, C. C. W. Lim, O. Plana-Ripoll, Y. Holtz, E. Agerbo, N. C. Momen, P. B. Mortensen, C. B. Pedersen, J. Abdulmalik, S. Aguilar-Gaxiola, A. Al-Hamzawi, J. Alonso, E. J. Bromet, R. Bruffaerts, B. Bunting, J. M. C. de Almeida, G. de Girolamo, Y. A. De Vries, S. Florescu, O. Gureje, J. M. Haro, M. G. Harris, C. Hu, E. G. Karam, N. Kawakami, A. Kiejna, V. Kovess-Masfety, S. Lee, Z. Mneimneh, F. Navarro-Mateu, R. Orozco, J. Posada-Villa, A. M. Roest, S. Saha, K. M. Scott, J. C. Stagnaro, D. J. Stein, Y. Torres, M. C. Viana, Y. Ziv, R. C. Kessler, P. de Jonge
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 29 / 2020
- Published online by Cambridge University Press:
- 12 August 2020, e153
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Aims
Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys.
MethodsThe WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women.
ResultsEach prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2–110.8, interquartile range = 6.0–19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1–2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs.
ConclusionsSurvey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.
Intermittent explosive disorder subtypes in the general population: association with comorbidity, impairment and suicidality
- K. M. Scott, Y. A. de Vries, S. Aguilar-Gaxiola, A. Al-Hamzawi, J. Alonso, E. J. Bromet, B. Bunting, J. M. Caldas-de-Almeida, A. Cía, S. Florescu, O. Gureje, C-Y. Hu, E. G. Karam, A. Karam, N. Kawakami, R. C. Kessler, S. Lee, J. McGrath, B. Oladeji, J. Posada-Villa, D. J. Stein, Z. Zarkov, P. de Jonge
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 29 / 2020
- Published online by Cambridge University Press:
- 23 June 2020, e138
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Aims
Intermittent explosive disorder (IED) is characterised by impulsive anger attacks that vary greatly across individuals in severity and consequence. Understanding IED subtypes has been limited by lack of large, general population datasets including assessment of IED. Using the 17-country World Mental Health surveys dataset, this study examined whether behavioural subtypes of IED are associated with differing patterns of comorbidity, suicidality and functional impairment.
MethodsIED was assessed using the Composite International Diagnostic Interview in the World Mental Health surveys (n = 45 266). Five behavioural subtypes were created based on type of anger attack. Logistic regression assessed association of these subtypes with lifetime comorbidity, lifetime suicidality and 12-month functional impairment.
ResultsThe lifetime prevalence of IED in all countries was 0.8% (s.e.: 0.0). The two subtypes involving anger attacks that harmed people (‘hurt people only’ and ‘destroy property and hurt people’), collectively comprising 73% of those with IED, were characterised by high rates of externalising comorbid disorders. The remaining three subtypes involving anger attacks that destroyed property only, destroyed property and threatened people, and threatened people only, were characterised by higher rates of internalising than externalising comorbid disorders. Suicidal behaviour did not vary across the five behavioural subtypes but was higher among those with (v. those without) comorbid disorders, and among those who perpetrated more violent assaults.
ConclusionsThe most common IED behavioural subtypes in these general population samples are associated with high rates of externalising disorders. This contrasts with the findings from clinical studies of IED, which observe a preponderance of internalising disorder comorbidity. This disparity in findings across population and clinical studies, together with the marked heterogeneity that characterises the diagnostic entity of IED, suggests that it is a disorder that requires much greater research.
Cortisol plasma levels are associated with serotonin - 1A receptor binding in postmenopausal women
- G. Kranz, A. Hahn, J. Ungersböck, U. Kaufmann, P. Stein, P. Baldinger, A. Höflich, S. Zgud, M. Mitterhauser, W. Wadsak, S. Kasper, R. Lanzenberger
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- Journal:
- European Psychiatry / Volume 26 / Issue S2 / March 2011
- Published online by Cambridge University Press:
- 16 April 2020, p. 933
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Introduction
Alterations of the serotonin-1A receptor (5-HT1A) and the hypothalamic-pituitary-adrenal (HPA) axis have been reported in depression and anxiety disorders. We previously showed a strong negative correlation between cortisol plasma levels and 5-HT1A receptor binding potential (BP) in patients with social anxiety disorder but not in healthy controls using PET [1].
ObjectivesTo investigate the relationship of cortisol and the 5-HT1A BP in postmenopausal women, a population that is at increased risk of suffering from depressive symptoms.
MethodsSubjects: 19 postmenopausal women, aged 55.26 ± 4.98, medication free, no current substance abuse or hormone replacement therapy.
PETDynamic measurements (50 frames, 90 min) were performed using the radioligand [carbonyl-11C]WAY100635 and a GE-Advance scanner. PET data were normalized to a ligand-specific template [2]. Regions-of-interest (ROI) were defined as given in [3]. TACs within ROIs were averaged and the 5-HT1A receptor BP was quantified using Logan-plot and PMOD 3.1. Measurement of total cortisol plasma levels was done using electrochemoluminescence.
ResultsWe found negative correlations between cortisol and 5-HT1A BP in the midbrain (Spearman's rs = −0.54, p = 0.02), the median raphe nucleus (rs = −0.47, p = 0.04) and the nucleus accumbens (rs = −0.505, p = 0.03).
ConclusionsIn line with our previous findings [1], the observed negative association between cortisol plasma levels and 5-HT1A BP might reflect an increased vulnerability for mood disorders in postmenopausal women.
740 – All About ‘U’: Associations between Prenatal Depression, and Foetal and Infant Stress Responses in the Developing World
- M.C. Fernandes, A. Stein, K. Srinivasan, G. Menezes, P. Ramchandani
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- Journal:
- European Psychiatry / Volume 28 / Issue S1 / 2013
- Published online by Cambridge University Press:
- 15 April 2020, 28-E241
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Introduction:
Prenatal maternal depression predicts disturbances in stress responses and an increased risk of psychopathology in offspring. However the foetal origins of these programming influences on the offspring's stress response mechanism are unclear. Furthermore, there are no inquiries into this issue from the developing world, where high rates of prenatal depression (25-45%) are reported.
Aim:To explore associations between prenatal depression and, foetal and infant responsivity, in a sample from rural South India.
Methods:67 pregnant women in their third trimester with high prenatal depression scores and 66 controls were assessed for their foetus’ responsivity to repeated vibroacoustic stimulation by measuring foetal heart rate responses. At 1.5-3 months postbirth, infant cortisol responses to immunisation and infant temperament were measured.
Results:A curvilinear relationship existed between prenatal depression and foetal responsivity to a potential stressor (R2=0.98, p=0.02). Foetuses of mothers with both very high and very low levels of depression showed elevated responses compared to the foetuses of mothers with moderate levels of depression.
Prenatal depression predicted elevated infant cortisol responsivity independent of postnatal depression and other confounders (B=13.08, p=0.02). Quintile analysis revealed this relationship to be U shaped (R2=0.20, p=0.02), similar to the relationship between prenatal depression and foetal responsivity.
There were no associations between prenatal depression and difficult infant temperament.
Conclusions:The findings provide the first evidence of a curvilinear relationship between prenatal depression and offspring stress responsivity from the developing world suggesting that intra-uterine exposure to moderate stress levels may be beneficial in the context of socio-economic disadvantage.
Influence of birth cohort on age of onset cluster analysis in bipolar I disorder
- M. Bauer, T. Glenn, M. Alda, O.A. Andreassen, E. Angelopoulos, R. Ardau, C. Baethge, R. Bauer, F. Bellivier, R.H. Belmaker, M. Berk, T.D. Bjella, L. Bossini, Y. Bersudsky, E.Y.W. Cheung, J. Conell, M. Del Zompo, S. Dodd, B. Etain, A. Fagiolini, M.A. Frye, K.N. Fountoulakis, J. Garneau-Fournier, A. Gonzalez-Pinto, H. Harima, S. Hassel, C. Henry, A. Iacovides, E.T. Isometsä, F. Kapczinski, S. Kliwicki, B. König, R. Krogh, M. Kunz, B. Lafer, E.R. Larsen, U. Lewitzka, C. Lopez-Jaramillo, G. MacQueen, M. Manchia, W. Marsh, M. Martinez-Cengotitabengoa, I. Melle, S. Monteith, G. Morken, R. Munoz, F.G. Nery, C. O’Donovan, Y. Osher, A. Pfennig, D. Quiroz, R. Ramesar, N. Rasgon, A. Reif, P. Ritter, J.K. Rybakowski, K. Sagduyu, A.M. Scippa, E. Severus, C. Simhandl, D.J. Stein, S. Strejilevich, A. Hatim Sulaiman, K. Suominen, H. Tagata, Y. Tatebayashi, C. Torrent, E. Vieta, B. Viswanath, M.J. Wanchoo, M. Zetin, P.C. Whybrow
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- Journal:
- European Psychiatry / Volume 30 / Issue 1 / January 2015
- Published online by Cambridge University Press:
- 15 April 2020, pp. 99-105
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Purpose:
Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.
Methods:The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.
Results:There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.
Conclusion:These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.
Everolimus for cardiac rhabdomyomas in children with tuberous sclerosis. The ORACLE study protocol (everOlimus for caRdiac rhAbdomyomas in tuberous sCLErosis): a randomised, multicentre, placebo-controlled, double-blind phase II trial
- Erica V. Stelmaszewski, Daniella B. Parente, Alberto Farina, Anna Stein, Anthony Gutierrez, Antonio F. Raquelo-Menegassio, Carla Manterola, Carolina F. de Sousa, Carolina Victor, Dina Maki, Elias M. Morón, Fabiano F. de Abrantes, Fatima Iqbal, Jazmin Camacho-Vilchez, Joanna Jimenez-Pavón, Juan P. Polania, Lorenzo Thompson, Lygia Bonanato, Matthias Diebold, Maria V. C. P. Da Silva, Mariam W. J. Nashwan, Marianna A. G. Galvani, Osama E. A. Idris, Pierina Danos, Rocio Ortiz-Lopez, Rofida A. A. Mahmoud, Sergio Gresse, Jr, Karla L. Loss
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- Journal:
- Cardiology in the Young / Volume 30 / Issue 3 / March 2020
- Published online by Cambridge University Press:
- 27 January 2020, pp. 337-345
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Introduction:
Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.
Methods:ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.
Conclusions:ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
Interactive impact of childhood maltreatment, depression, and age on cortical brain structure: mega-analytic findings from a large multi-site cohort
- Leonardo Tozzi, Lisa Garczarek, Deborah Janowitz, Dan J. Stein, Katharina Wittfeld, Henrik Dobrowolny, Jim Lagopoulos, Sean N. Hatton, Ian B. Hickie, Angela Carballedo, Samantha J. Brooks, Daniella Vuletic, Anne Uhlmann, Ilya M. Veer, Henrik Walter, Robin Bülow, Henry Völzke, Johanna Klinger-König, Knut Schnell, Dieter Schoepf, Dominik Grotegerd, Nils Opel, Udo Dannlowski, Harald Kugel, Elisabeth Schramm, Carsten Konrad, Tilo Kircher, Dilara Jüksel, Igor Nenadić, Axel Krug, Tim Hahn, Olaf Steinsträter, Ronny Redlich, Dario Zaremba, Bartosz Zurowski, Cynthia H.Y. Fu, Danai Dima, James Cole, Hans J. Grabe, Colm G. Connolly, Tony T. Yang, Tiffany C. Ho, Kaja Z. LeWinn, Meng Li, Nynke A. Groenewold, Lauren E. Salminen, Martin Walter, Alan N Simmons, Theo G.M. van Erp, Neda Jahanshad, Bernhard T. Baune, Nic J.A. van der Wee, Marie-Jose van Tol, Brenda W.J.H. Penninx, Derrek P. Hibar, Paul M. Thompson, Dick J. Veltman, Lianne Schmaal, Thomas Frodl, ‘for the ENIGMA-MDD Consortium’
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- Journal:
- Psychological Medicine / Volume 50 / Issue 6 / April 2020
- Published online by Cambridge University Press:
- 14 May 2019, pp. 1020-1031
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Background
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
MethodsWithin the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
ResultsCM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
ConclusionsSeverity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Recovery from DSM-IV post-traumatic stress disorder in the WHO World Mental Health surveys
- A. J. Rosellini, H. Liu, M. V. Petukhova, N. A. Sampson, S. Aguilar-Gaxiola, J. Alonso, G. Borges, R. Bruffaerts, E. J. Bromet, G. de Girolamo, P. de Jonge, J. Fayyad, S. Florescu, O. Gureje, J. M. Haro, H. Hinkov, E. G. Karam, N. Kawakami, K. C. Koenen, S. Lee, J. P. Lépine, D. Levinson, F. Navarro-Mateu, B. D. Oladeji, S. O'Neill, B.-E. Pennell, M. Piazza, J. Posada-Villa, K. M. Scott, D. J. Stein, Y. Torres, M. C. Viana, A. M. Zaslavsky, R. C. Kessler
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- Journal:
- Psychological Medicine / Volume 48 / Issue 3 / February 2018
- Published online by Cambridge University Press:
- 19 July 2017, pp. 437-450
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Background
Research on post-traumatic stress disorder (PTSD) course finds a substantial proportion of cases remit within 6 months, a majority within 2 years, and a substantial minority persists for many years. Results are inconsistent about pre-trauma predictors.
MethodsThe WHO World Mental Health surveys assessed lifetime DSM-IV PTSD presence-course after one randomly-selected trauma, allowing retrospective estimates of PTSD duration. Prior traumas, childhood adversities (CAs), and other lifetime DSM-IV mental disorders were examined as predictors using discrete-time person-month survival analysis among the 1575 respondents with lifetime PTSD.
Results20%, 27%, and 50% of cases recovered within 3, 6, and 24 months and 77% within 10 years (the longest duration allowing stable estimates). Time-related recall bias was found largely for recoveries after 24 months. Recovery was weakly related to most trauma types other than very low [odds-ratio (OR) 0.2–0.3] early-recovery (within 24 months) associated with purposefully injuring/torturing/killing and witnessing atrocities and very low later-recovery (25+ months) associated with being kidnapped. The significant ORs for prior traumas, CAs, and mental disorders were generally inconsistent between early- and later-recovery models. Cross-validated versions of final models nonetheless discriminated significantly between the 50% of respondents with highest and lowest predicted probabilities of both early-recovery (66–55% v. 43%) and later-recovery (75–68% v. 39%).
ConclusionsWe found PTSD recovery trajectories similar to those in previous studies. The weak associations of pre-trauma factors with recovery, also consistent with previous studies, presumably are due to stronger influences of post-trauma factors.
Post-traumatic stress disorder associated with sexual assault among women in the WHO World Mental Health Surveys
- K. M. Scott, K. C. Koenen, A. King, M. V. Petukhova, J. Alonso, E. J. Bromet, R. Bruffaerts, B. Bunting, P. de Jonge, J. M. Haro, E. G. Karam, S. Lee, M. E. Medina-Mora, F. Navarro-Mateu, N. A. Sampson, V. Shahly, D. J. Stein, Y. Torres, A. M. Zaslavsky, R. C. Kessler
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- Journal:
- Psychological Medicine / Volume 48 / Issue 1 / January 2018
- Published online by Cambridge University Press:
- 19 June 2017, pp. 155-167
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Background
Sexual assault is a global concern with post-traumatic stress disorder (PTSD), one of the common sequelae. Early intervention can help prevent PTSD, making identification of those at high risk for the disorder a priority. Lack of representative sampling of both sexual assault survivors and sexual assaults in prior studies might have reduced the ability to develop accurate prediction models for early identification of high-risk sexual assault survivors.
MethodsData come from 12 face-to-face, cross-sectional surveys of community-dwelling adults conducted in 11 countries. Analysis was based on the data from the 411 women from these surveys for whom sexual assault was the randomly selected lifetime traumatic event (TE). Seven classes of predictors were assessed: socio-demographics, characteristics of the assault, the respondent's retrospective perception that she could have prevented the assault, other prior lifetime TEs, exposure to childhood family adversities and prior mental disorders.
ResultsPrevalence of Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) PTSD associated with randomly selected sexual assaults was 20.2%. PTSD was more common for repeated than single-occurrence victimization and positively associated with prior TEs and childhood adversities. Respondent's perception that she could have prevented the assault interacted with history of mental disorder such that it reduced odds of PTSD, but only among women without prior disorders (odds ratio 0.2, 95% confidence interval 0.1–0.9). The final model estimated that 40.3% of women with PTSD would be found among the 10% with the highest predicted risk.
ConclusionsWhether counterfactual preventability cognitions are adaptive may depend on mental health history. Predictive modelling may be useful in targeting high-risk women for preventive interventions.
Psychological autopsy study comparing suicide decedents, suicide ideators, and propensity score matched controls: results from the study to assess risk and resilience in service members (Army STARRS)
- M. K. Nock, C. L. Dempsey, P. A. Aliaga, D. A. Brent, S. G. Heeringa, R. C. Kessler, M. B. Stein, R. J. Ursano, D. Benedek,
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- Journal:
- Psychological Medicine / Volume 47 / Issue 15 / November 2017
- Published online by Cambridge University Press:
- 18 May 2017, pp. 2663-2674
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Background
The suicide rate has increased significantly among US Army soldiers over the past decade. Here we report the first results from a large psychological autopsy study using two control groups designed to reveal risk factors for suicide death among soldiers beyond known sociodemographic factors and the presence of suicide ideation.
MethodsInformants were next-of-kin and Army supervisors for: 135 suicide cases, 137 control soldiers propensity-score-matched on known sociodemographic risk factors for suicide and Army history variables, and 118 control soldiers who reported suicide ideation in the past year.
ResultsResults revealed that most (79.3%) soldiers who died by suicide have a prior mental disorder; mental disorders in the prior 30-days were especially strong risk factors for suicide death. Approximately half of suicide decedents tell someone that they are considering suicide. Virtually all of the risk factors identified in this study differed between suicide cases and propensity-score-matched controls, but did not significantly differ between suicide cases and suicide ideators. The most striking difference between suicides and ideators was the presence in the former of an internalizing disorder (especially depression) and multi-morbidity (i.e. 3+ disorders) in the past 30 days.
ConclusionsMost soldiers who die by suicide have identifiable mental disorders shortly before their death and tell others about their suicidal thinking, suggesting that there are opportunities for prevention and intervention. However, few risk factors distinguish between suicide ideators and decedents, pointing to an important direction for future research.
Early life stress and the anxious brain: evidence for a neural mechanism linking childhood emotional maltreatment to anxiety in adulthood
- G. A. Fonzo, H. J. Ramsawh, T. M. Flagan, A. N. Simmons, S. G. Sullivan, C. B. Allard, M. P. Paulus, M. B. Stein
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- Journal:
- Psychological Medicine / Volume 46 / Issue 5 / April 2016
- Published online by Cambridge University Press:
- 16 December 2015, pp. 1037-1054
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Background
Childhood emotional maltreatment (CEM) increases the likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms.
MethodOne hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion-processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray-matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood.
ResultsDuring processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray-matter volumes also partially mediated the CEM-anxiety relationship.
ConclusionsActivation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes.
The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium
- C. Benjet, E. Bromet, E. G. Karam, R. C. Kessler, K. A. McLaughlin, A. M. Ruscio, V. Shahly, D. J. Stein, M. Petukhova, E. Hill, J. Alonso, L. Atwoli, B. Bunting, R. Bruffaerts, J. M. Caldas-de-Almeida, G. de Girolamo, S. Florescu, O. Gureje, Y. Huang, J. P. Lepine, N. Kawakami, Viviane Kovess-Masfety, M. E. Medina-Mora, F. Navarro-Mateu, M. Piazza, J. Posada-Villa, K. M. Scott, A. Shalev, T. Slade, M. ten Have, Y. Torres, M. C. Viana, Z. Zarkov, K. C. Koenen
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- Journal:
- Psychological Medicine / Volume 46 / Issue 2 / January 2016
- Published online by Cambridge University Press:
- 29 October 2015, pp. 327-343
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Background
Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs.
MethodGeneral population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure.
ResultsOver 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types – witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury – accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events.
ConclusionsGiven the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization.
Maternal depression and anxiety predicts the pattern of offspring symptoms during their transition to adulthood
- H. Gonçalves, R. M. Pearson, B. L. Horta, D. A. González-Chica, E. Castilho, M. Damiani, R. C. Lima, D. P. Gigante, F. C. Barros, A. Stein, C. G. Victora
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- Journal:
- Psychological Medicine / Volume 46 / Issue 2 / January 2016
- Published online by Cambridge University Press:
- 12 October 2015, pp. 415-424
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Background
Episodes of depression and anxiety (D&A) during the transition from late adolescence to adulthood, particularly when persistent, are predictive of long-term disorders and associated public health burden. Understanding risk factors at this time is important to guide intervention. The current objective was to investigate the associations between maternal symptoms of D&A with offspring symptoms during their transition to adulthood.
MethodData from a large population-based birth cohort study, in South Brazil, were used. Prospective associations between maternal D&A and offspring risk of these symptoms during the transition to adulthood (18/19, 24 and 30 years) were estimated.
ResultsMaternal D&A in adolescence was associated with offspring symptoms across the transition to adulthood, associations were consistently stronger for females than for males. Daughters whose mothers reported D&A were 4.6 times (95% confidence interval 2.71–7.84) as likely to report D&A at all three time-points, than daughters of symptom-free mothers.
ConclusionsMaternal D&A is associated with persistent D&A during the daughter's transition to adulthood. Intervention strategies should consider the mother's mental health.
Predicting non-familial major physical violent crime perpetration in the US Army from administrative data
- A. J. Rosellini, J. Monahan, A. E. Street, S. G. Heeringa, E. D. Hill, M. Petukhova, B. Y. Reis, N. A. Sampson, P. Bliese, M. Schoenbaum, M. B. Stein, R. J. Ursano, R. C. Kessler
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- Journal:
- Psychological Medicine / Volume 46 / Issue 2 / January 2016
- Published online by Cambridge University Press:
- 06 October 2015, pp. 303-316
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Background.
Although interventions exist to reduce violent crime, optimal implementation requires accurate targeting. We report the results of an attempt to develop an actuarial model using machine learning methods to predict future violent crimes among US Army soldiers.
Method.A consolidated administrative database for all 975 057 soldiers in the US Army in 2004–2009 was created in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). Of these soldiers, 5771 committed a first founded major physical violent crime (murder-manslaughter, kidnapping, aggravated arson, aggravated assault, robbery) over that time period. Temporally prior administrative records measuring socio-demographic, Army career, criminal justice, medical/pharmacy, and contextual variables were used to build an actuarial model for these crimes separately among men and women using machine learning methods (cross-validated stepwise regression, random forests, penalized regressions). The model was then validated in an independent 2011–2013 sample.
Results.Key predictors were indicators of disadvantaged social/socioeconomic status, early career stage, prior crime, and mental disorder treatment. Area under the receiver-operating characteristic curve was 0.80–0.82 in 2004–2009 and 0.77 in the 2011–2013 validation sample. Of all administratively recorded crimes, 36.2–33.1% (male-female) were committed by the 5% of soldiers having the highest predicted risk in 2004–2009 and an even higher proportion (50.5%) in the 2011–2013 validation sample.
Conclusions.Although these results suggest that the models could be used to target soldiers at high risk of violent crime perpetration for preventive interventions, final implementation decisions would require further validation and weighing of predicted effectiveness against intervention costs and competing risks.
Occupational differences in US Army suicide rates
- R. C. Kessler, M. B. Stein, P. D. Bliese, E. J. Bromet, W. T. Chiu, K. L. Cox, L. J. Colpe, C. S. Fullerton, S. E. Gilman, M. J. Gruber, S. G. Heeringa, L. Lewandowski-Romps, A. Millikan-Bell, J. A. Naifeh, M. K. Nock, M. V. Petukhova, A. J. Rosellini, N. A. Sampson, M. Schoenbaum, A. M. Zaslavsky, R. J. Ursano
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- Journal:
- Psychological Medicine / Volume 45 / Issue 15 / November 2015
- Published online by Cambridge University Press:
- 20 July 2015, pp. 3293-3304
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Background
Civilian suicide rates vary by occupation in ways related to occupational stress exposure. Comparable military research finds suicide rates elevated in combat arms occupations. However, no research has evaluated variation in this pattern by deployment history, the indicator of occupation stress widely considered responsible for the recent rise in the military suicide rate.
MethodThe joint associations of Army occupation and deployment history in predicting suicides were analysed in an administrative dataset for the 729 337 male enlisted Regular Army soldiers in the US Army between 2004 and 2009.
ResultsThere were 496 suicides over the study period (22.4/100 000 person-years). Only two occupational categories, both in combat arms, had significantly elevated suicide rates: infantrymen (37.2/100 000 person-years) and combat engineers (38.2/100 000 person-years). However, the suicide rates in these two categories were significantly lower when currently deployed (30.6/100 000 person-years) than never deployed or previously deployed (41.2–39.1/100 000 person-years), whereas the suicide rate of other soldiers was significantly higher when currently deployed and previously deployed (20.2–22.4/100 000 person-years) than never deployed (14.5/100 000 person-years), resulting in the adjusted suicide rate of infantrymen and combat engineers being most elevated when never deployed [odds ratio (OR) 2.9, 95% confidence interval (CI) 2.1–4.1], less so when previously deployed (OR 1.6, 95% CI 1.1–2.1), and not at all when currently deployed (OR 1.2, 95% CI 0.8–1.8). Adjustment for a differential ‘healthy warrior effect’ cannot explain this variation in the relative suicide rates of never-deployed infantrymen and combat engineers by deployment status.
ConclusionsEfforts are needed to elucidate the causal mechanisms underlying this interaction to guide preventive interventions for soldiers at high suicide risk.
Common and disorder-specific neural responses to emotional faces in generalised anxiety, social anxiety and panic disorders
- Gregory A. Fonzo, Holly J. Ramsawh, Taru M. Flagan, Sarah G. Sullivan, Andrea Letamendi, Alan N. Simmons, Martin P. Paulus, Murray B. Stein
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- Journal:
- The British Journal of Psychiatry / Volume 206 / Issue 3 / March 2015
- Published online by Cambridge University Press:
- 02 January 2018, pp. 206-215
- Print publication:
- March 2015
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Background
Although evidence exists for abnormal brain function across various anxiety disorders, direct comparison of neural function across diagnoses is needed to elicit abnormalities common across disorders and those distinct to a particular diagnosis.
AimsTo delineate common and distinct abnormalities within generalised anxiety (GAD), panic and social anxiety disorder (SAD) during affective processing.
MethodFifty-nine adults (15 with GAD, 15 with panic disorder, 14 with SAD, and 15 healthy controls) underwent functional magnetic resonance imaging while completing a facial emotion matching task with fearful, angry and happy faces.
ResultsGreater differential right amygdala activation to matching fearful v. happy facial expressions related to greater negative affectivity (i.e. trait anxiety) and was heightened across all anxiety disorder groups compared with controls. Collapsing across emotional face types, participants with panic disorder uniquely displayed greater posterior insula activation.
ConclusionsThese preliminary results highlight a common neural basis for clinical anxiety in these diagnoses and also suggest the presence of disorder-specific dysfunction.
An examination of the bidirectional relationship between functioning and symptom levels in patients with anxiety disorders in the CALM study
- L. A. Brown, J. L. Krull, P. Roy-Byrne, C. D. Sherbourne, M. B. Stein, G. Sullivan, R. D. Rose, A. Bystritsky, M. G. Craske
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- Journal:
- Psychological Medicine / Volume 45 / Issue 3 / February 2015
- Published online by Cambridge University Press:
- 02 October 2014, pp. 647-661
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Background
Patients with anxiety disorders suffer marked functional impairment in their activities of daily living. Many studies have documented that improvements in anxiety symptom severity predict functioning improvements. However, no studies have investigated how improvements in functioning simultaneously predict symptom reduction. We hypothesized that symptom levels at a given time point will predict functioning at the subsequent time point, and simultaneously that functioning at a given time point will predict symptom levels at a subsequent time point.
MethodPatients were recruited from primary-care centers for the Coordinated Anxiety Learning and Management (CALM) study and were randomized to receive either computer-assisted cognitive-behavioral therapy and/or medication management (ITV) or usual care (UC). A cross-lagged panel design examined the relationship between functional impairment and anxiety and depression symptom severity at baseline, 6-, 12-, and 18-month follow-up assessments.
ResultsProspective prediction of functioning from symptoms and symptoms from functioning were both important in modeling these associations. Anxiety and depression predicted functioning as strongly as functioning predicted anxiety and depression. There were some differences in these associations between UC and ITV. Where differences emerged, the UC group was best modeled with prospective paths predicting functioning from symptoms, whereas symptoms and functioning were both important predictors in the ITV group.
ConclusionsTreatment outcome is best captured by measures of functional impairment as well as symptom severity. Implications for treatment are discussed, as well as future directions of research.
Contributors
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- By Lenard A. Adler, Pinky Agarwal, Rehan Ahmed, Jagga Rao Alluri, Fawaz Al-Mufti, Samuel Alperin, Michael Amoashiy, Michael Andary, David J. Anschel, Padmaja Aradhya, Vandana Aspen, Esther Baldinger, Jee Bang, George D. Baquis, John J. Barry, Jason J. S. Barton, Julius Bazan, Amanda R. Bedford, Marlene Behrmann, Lourdes Bello-Espinosa, Ajay Berdia, Alan R. Berger, Mark Beyer, Don C. Bienfang, Kevin M. Biglan, Thomas M. Boes, Paul W. Brazis, Jonathan L. Brisman, Jeffrey A. Brown, Scott E. Brown, Ryan R. Byrne, Rina Caprarella, Casey A. Chamberlain, Wan-Tsu W. Chang, Grace M. Charles, Jasvinder Chawla, David Clark, Todd J. Cohen, Joe Colombo, Howard Crystal, Vladimir Dadashev, Sarita B. Dave, Jean Robert Desrouleaux, Richard L. Doty, Robert Duarte, Jeffrey S. Durmer, Christyn M. Edmundson, Eric R. Eggenberger, Steven Ender, Noam Epstein, Alberto J. Espay, Alan B. Ettinger, Niloofar (Nelly) Faghani, Amtul Farheen, Edward Firouztale, Rod Foroozan, Anne L. Foundas, David Elliot Friedman, Deborah I. Friedman, Steven J. Frucht, Oded Gerber, Tal Gilboa, Martin Gizzi, Teneille G. Gofton, Louis J. Goodrich, Malcolm H. Gottesman, Varda Gross-Tsur, Deepak Grover, David A. Gudis, John J. Halperin, Maxim D. Hammer, Andrew R. Harrison, L. Anne Hayman, Galen V. Henderson, Steven Herskovitz, Caitlin Hoffman, Laryssa A. Huryn, Andres M. Kanner, Gary P. Kaplan, Bashar Katirji, Kenneth R. Kaufman, Annie Killoran, Nina Kirz, Gad E. Klein, Danielle G. Koby, Christopher P. Kogut, W. Curt LaFrance, Patrick J.M. Lavin, Susan W. Law, James L. Levenson, Richard B. Lipton, Glenn Lopate, Daniel J. Luciano, Reema Maindiratta, Robert M. Mallery, Georgios Manousakis, Alan Mazurek, Luis J. Mejico, Dragana Micic, Ali Mokhtarzadeh, Walter J. Molofsky, Heather E. Moss, Mark L. Moster, Manpreet Multani, Siddhartha Nadkarni, George C. Newman, Rolla Nuoman, Paul A. Nyquist, Gaia Donata Oggioni, Odi Oguh, Denis Ostrovskiy, Kristina Y. Pao, Juwen Park, Anastas F. Pass, Victoria S. Pelak, Jeffrey Peterson, John Pile-Spellman, Misha L. Pless, Gregory M. Pontone, Aparna M. Prabhu, Michael T. Pulley, Philip Ragone, Prajwal Rajappa, Venkat Ramani, Sindhu Ramchandren, Ritesh A. Ramdhani, Ramses Ribot, Heidi D. Riney, Diana Rojas-Soto, Michael Ronthal, Daniel M. Rosenbaum, David B. Rosenfield, Durga Roy, Michael J. Ruckenstein, Max C. Rudansky, Eva Sahay, Friedhelm Sandbrink, Jade S. Schiffman, Angela Scicutella, Maroun T. Semaan, Robert C. Sergott, Aashit K. Shah, David M. Shaw, Amit M. Shelat, Claire A. Sheldon, Anant M. Shenoy, Yelizaveta Sher, Jessica A. Shields, Tanya Simuni, Rajpaul Singh, Eric E. Smouha, David Solomon, Mehri Songhorian, Steven A. Sparr, Egilius L. H. Spierings, Eve G. Spratt, Beth Stein, S.H. Subramony, Rosa Ana Tang, Cara Tannenbaum, Hakan Tekeli, Amanda J. Thompson, Michael J. Thorpy, Matthew J. Thurtell, Pedro J. Torrico, Ira M. Turner, Scott Uretsky, Ruth H. Walker, Deborah M. Weisbrot, Michael A. Williams, Jacques Winter, Randall J. Wright, Jay Elliot Yasen, Shicong Ye, G. Bryan Young, Huiying Yu, Ryan J. Zehnder
- Edited by Alan B. Ettinger, Albert Einstein College of Medicine, New York, Deborah M. Weisbrot, State University of New York, Stony Brook
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- Book:
- Neurologic Differential Diagnosis
- Published online:
- 05 June 2014
- Print publication:
- 17 April 2014, pp xi-xx
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Maternal depression and foetal responses to novel stimuli: insights from a socio-economically disadvantaged Indian cohort
- M. Fernandes, A. Stein, K. Srinivasan, G. Menezes, M. Renton, J. Zani, P. G. Ramchandani
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- Journal:
- Journal of Developmental Origins of Health and Disease / Volume 5 / Issue 3 / June 2014
- Published online by Cambridge University Press:
- 11 March 2014, pp. 178-182
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Maternal stress during pregnancy has pervasive effects on stress responsivity in children. This study is the first to test the hypothesis that maternal prenatal depression, as observed in South India, may be associated with how foetuses respond to a potentially stressful stimulus. We employed measures of foetal heart rate at baseline, during exposure to a vibroacoustic stimulus, and post-stimulation, to study patterns of response and recovery in 133 third trimester foetuses of depressed and non-depressed mothers. We show that the association between maternal depression and foetal stress responsivity is U-shaped with foetuses of mothers with high and low depression scores demonstrating elevated responses, and poorer recovery, than foetuses of mothers with moderate levels. The right amount of intra-uterine stimulation is important in conditioning foetuses towards optimal regulation of their stress response. Our results imply that, in certain environmental contexts, exposure to moderate amounts of intra-uterine stress may facilitate this process.