Generation Scotland: Scottish Family Health Study (GS hereafter) is a population-based cohort of over 24,000 individuals with in-depth phenotyping recruited between 2006 and 2011. A subsample of participants was recontacted in 2015–2019 for neuroimaging and further data collection. This subsample was used as the basis for this study and is described in detail elsewhere [43 (link)–46 (link)]. Cognitive assessments, blood sampling, physical measurements, and clinical questionnaires were also collected from GS participants, including the 28-item CTQ [5 (link)]. The subsample included n = 1,153 participants with CTQ and depression phenotyping, and n = 1,024 also had magnetic resonance imaging (MRI) data.
The 28-item CTQ is a questionnaire validated for self-report of abuse and neglect during childhood [5 (link)]. The questionnaire is made up of five subscales—Emotional Abuse (EA), Emotional Neglect (EN), Physical Abuse (PA), Physical Neglect (PN), and Sexual Abuse (SA)—with five items for each subscale, scored on a 5-point Likert scale rating frequency of each experience [1 –5 (link)]. Emotional and PN items are reverse-scored. The minimization and denial scale makes up the remaining three items, a scale devised to help detect the under-reporting of CT [5 (link)]. The analyses reported here focused mainly on the summed score of the 25 subscale items of this questionnaire, scored on a scale of 25–125, which provides an index of the cumulative traumatic experience of an individual, consistent with previous literature (e.g. [47 (link), 48 (link)]). The questionnaire can also be used to break scores down into severity categories of none–low, low–moderate, moderate–severe, and severe–extreme, for both total CTQ score and each subscale [49 , 50 (link)].
All analyses were performed using scaled scores for the five CT subscales captured by the CTQ (and, in UKB, CTM) measures—EN, EA, PN, PA, and SA—as well as scaled composite “abuse” and “neglect” scores created by summing scores on the abuse and neglect items, respectively. Trauma subscales are often highly correlated with each other, and with summed total scores. Correlation matrices for the GS CTQ-28 and the UKB CTM subscales and total scores are presented in Supplementary Figure S1.
MDD diagnoses were derived from the SCID [43 (link), 51 (link)] taken at GS baseline recruitment; a binary variable describing presence/absence of a lifetime diagnosis encompasses single-episode, chronic, postpartum onset, and depression with manic/hypomanic features. Two individuals with manic/hypomanic episodes alone were excluded from further analyses. The Quick Inventory of Depressive Symptomatology [52 (link)] was used as a measure of continuous (and current) depressive symptom severity at the time of the imaging clinic visit.
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