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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.
Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms
- J. Ferri, J. M. Ford, B. J. Roach, J. A. Turner, T. G. van Erp, J. Voyvodic, A. Preda, A. Belger, J. Bustillo, D. O'Leary, B. A. Mueller, K. O. Lim, S. C. McEwen, V. D. Calhoun, M. Diaz, G. Glover, D. Greve, C. G. Wible, J. G. Vaidya, S. G. Potkin, D. H. Mathalon
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- Journal:
- Psychological Medicine / Volume 48 / Issue 15 / November 2018
- Published online by Cambridge University Press:
- 15 February 2018, pp. 2492-2499
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Background
Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.
MethodResting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.
ResultsHC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.
ConclusionsThalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium
- E. Walton, D. P. Hibar, T. G. M. van Erp, S. G. Potkin, R. Roiz-Santiañez, B. Crespo-Facorro, P. Suarez-Pinilla, N. E. M. van Haren, S. M. C. de Zwarte, R. S. Kahn, W. Cahn, N. T. Doan, K. N. Jørgensen, T. P. Gurholt, I. Agartz, O. A. Andreassen, L. T. Westlye, I. Melle, A. O. Berg, L. Morch-Johnsen, A. Færden, L. Flyckt, H. Fatouros-Bergman, Karolinska Schizophrenia Project Consortium (KaSP), E. G. Jönsson, R. Hashimoto, H. Yamamori, M. Fukunaga, N. Jahanshad, P. De Rossi, F. Piras, N. Banaj, G. Spalletta, R. E. Gur, R. C. Gur, D. H. Wolf, T. D. Satterthwaite, L. M. Beard, I. E. Sommer, S. Koops, O. Gruber, A. Richter, B. Krämer, S. Kelly, G. Donohoe, C. McDonald, D. M. Cannon, A. Corvin, M. Gill, A. Di Giorgio, A. Bertolino, S. Lawrie, T. Nickson, H. C. Whalley, E. Neilson, V. D. Calhoun, P. M. Thompson, J. A. Turner, S. Ehrlich
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- Journal:
- Psychological Medicine / Volume 48 / Issue 1 / January 2018
- Published online by Cambridge University Press:
- 26 May 2017, pp. 82-94
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Background
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
MethodsThis study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
ResultsMeta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
ConclusionsUsing an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Multidimensional assessment of impulsivity in schizophrenia, bipolar disorder, and major depressive disorder: testing for shared endophenotypes
- R. G. Fortgang, C. M. Hultman, T. G. M. van Erp, T. D. Cannon
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- Journal:
- Psychological Medicine / Volume 46 / Issue 7 / May 2016
- Published online by Cambridge University Press:
- 22 February 2016, pp. 1497-1507
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Background
Impulsivity is associated with bipolar disorder as a clinical feature during and between manic episodes and is considered a potential endophenotype for the disorder. Schizophrenia and major depressive disorder share substantial genetic overlap with bipolar disorder, and these two disorders have also been associated with elevations in impulsivity. However, little is known about the degree of overlap among these disorders in discrete subfacets of impulsivity and whether any overlap is purely phenotypic or due to shared genetic diathesis.
MethodWe focused on five subfacets of impulsivity: self-reported attentional, motor, and non-planning impulsivity, self-reported sensation seeking, and a behavioral measure of motor inhibition (stop signal reaction time; SSRT). We examined these facets within and across disorder proband and co-twin groups, modeled heritability, and tested for endophenotypic patterning in a sample of twin pairs recruited from the Swedish Twin Registry (N = 420).
ResultsWe found evidence of moderate to high levels of heritability for all five subfacets. All three proband groups and their unaffected co-twins showed elevations on attentional, motor, and non-planning impulsivity. Schizophrenia probands (but not their co-twins) showed significantly lower sensation seeking, and schizophrenia and bipolar disorder probands (but not in their co-twins) had significantly longer SSRTs, compared with healthy controls and the other groups.
ConclusionsAttentional, motor, and non-planning impulsivity emerged as potential shared endophenotypes for the three disorders, whereas sensation seeking and SSRT were associated with phenotypic affection but not genetic loading for these disorders.