Familial Risk For Mood Disorders Research Articles

Common and distinct neural correlates of emotional processing in individuals at familial risk for major depressive disorder and bipolar disorder: A comparative meta-analysis

Individuals at familial risk for mood disorders exhibit deficits in emotional processing and associated brain dysfunction prior to illness onset. However, such brain-behavior abnormalities related to familial predisposition remain poorly understood. To investigate robust abnormal functional activation patterns during emotional processing in unaffected at-risk relatives of patients with major depressive disorder (UAR-MDD) and bipolar disorder (UAR-BD), we performed a meta-analysis of task-based functional magnetic resonance imaging studies using Seed-based d Mapping (SDM) toolbox. Common and distinct patterns of abnormal functional activation between UAR-MDD and UAR-BD were detected via conjunction and differential analyses. A total of 17 studies comparing 481 UAR and 670 healthy controls (HC) were included. Compared with HC, UAR-MDD exhibited hyperactivation in the parahippocampal gyrus, amygdala and cerebellum, while UAR-BD exhibited parahippocampal hyperactivation and hypoactivation in the striatum and middle occipital gyrus (MOG). Conjunction analysis revealed shared hyperactivated PHG in both groups. Differential analysis indicated that the activation patterns of amygdala and MOG significantly differed between UAR-MDD and UAR-BD. These findings provide novel insights into common and distinct neural phenotypes for familial risk and associated risk mechanisms in MDD and BD, which may have implications in guiding precise prevention strategies tailored to the family context.

Developmental Trajectory of Body Weight in Youths at Risk for Major Mood Disorders

Mood disorders are associated with increased body weight, especially in females, but it remains unknown when the weight increase starts. To examine sex-specific weight trajectories associated with familial mood disorder risk and determine the age at which youth at familial risk for mood disorders begin to diverge in weight from controls. This community-based, single-center, acceleration cohort study of youth at familial risk for mood disorders and controls with yearly follow-ups (mean [SD], 5 [2.1] years) from January 1, 2014, to December 31, 2022, assessed 394 unaffected female and male offspring (aged 3 to 20 years) of parents with or without a mood disorder. Parents with mood (depressive or bipolar) disorders were recruited through adult mental health services. Parents of control participants were matched on age and socioeconomic factors and recruited through acquaintance referrals or schools. The youth in the familial mood risk group had at least 1 parent with a major mood disorder, whereas control youth did not have a parent with a mood disorder. Body mass indexes (BMIs) were calculated as weight in kilograms divided by height in meters squared from measured weight and height at annual assessments and then converted to age- and sex-adjusted z scores (zBMIs). Repeated-measure regressions examined the association between zBMI and age in youth at familial risk of mood disorders and controls while accounting for sex. Sensitivity analyses accounted for socioeconomic status, prematurity, and birth weight. Of 394 participants (mean [SD] age, 11.5 [3.6] years; 203 [51.5%] female), youths at familial risk for mood disorders showed overall no difference in body weight (β = 0.12; 95% CI, 0.01-0.24) from controls. A sex-specific difference was detected, with females at familial risk showing a rapid peripubertal increase in body weight, leading to significantly increased zBMIs at 12 years and older compared with controls (β = 0.57; 95% CI, 0.31-0.82) independent of socioeconomic status, prematurity, or birth weight. Males did not differ from controls at any age. In this cohort study, females with a family history of mood disorders were prone to weight gain starting around puberty and predating mood disorder onset. Early interventions aiming to prevent adverse mental and physical outcomes in this vulnerable group need to start in childhood.

Staging the bipolar disorders: Are early stages too early a stage for intervention?

Staging the bipolar disorders: Are early stages too early a stage for intervention?

Sex-Specific Transmission of Anxiety Disorders From Parents to Offspring

Although anxiety disorders are known to run in families, the relative contribution of genes and environment is unclear. Patterns of sex-specific transmission of anxiety may point to different pathways in how parents pass anxiety disorders down to their children; however, the association of parent and offspring sex with the transmission of anxiety disorders has not been previously studied. To examine whether the transmission of anxiety from parents to children is sex specific. This cross-sectional family study recruited participants from the general population (enriched for familial risk of mood disorders) in Nova Scotia, Canada, from February 1, 2013, to January 31, 2020. Anxiety disorder in the same-sex or opposite-sex parent. Semistructured interviews were used to establish lifetime diagnoses of anxiety disorder in parents and offspring. The association between anxiety disorder in the same-sex or opposite-sex parent and anxiety disorders in the offspring was tested with logistic regression. A total of 398 offspring (203 female offspring with a mean [SD] age of 11.1 [3.7] years and 195 male offspring with a mean [SD] age of 10.6 [3.1] years) of 221 mothers and 237 fathers participated in the study. Anxiety disorders in the same-sex parent (odds ratio [OR], 2.85; 95% CI, 1.52-5.34; P = .001) were associated with increased rates of anxiety disorders in the offspring, whereas anxiety disorders in the opposite-sex parent (OR, 1.51; 95% CI, 0.81-2.81; P = .20) were not. Sharing a household with a same-sex parent without anxiety was associated with lower rates of offspring anxiety (OR, 0.38; 95% CI, 0.22-0.67; P = .001), but the presence of an opposite-sex parent without anxiety was not (OR, 0.96; 95% CI, 0.56-1.63; P = .88). In this cross-sectional study of families, an association between the same-sex parent's anxiety disorder and anxiety disorders in offspring suggests an environmental mechanism, such as modeling. Future studies should establish whether treating parents' anxiety may protect their children from developing an anxiety disorder.

P283. Developmental Trajectory of Body Weight in Offspring of Parents With Major Mood Disorders

People living with major mood disorders have high rates of metabolic and cardiovascular, leading to shorter life expectancy compared to people without mental disorders. Increased body weight predicts cardiometabolic issues and is highly prevalent in individuals with mood disorders, particularly women. It is unknown when in development this relationship begins. We aim to establish at what age weight increases in individuals with familial risk for mood disorders begins.

Intrinsic Connectivity and Family Dynamics: Striatolimbic Markers of Risk and Resilience in Youth at Familial Risk for Mood Disorders

BackgroundFew studies to date have characterized functional connectivity (FC) within emotion and reward networks in relation to family dynamics in youth at high familial risk for bipolar disorder (HR-BD) and major depressive disorder (HR-MDD) relative to low-risk youth (LR). Such characterization may advance our understanding of the neural underpinnings of mood disorders and lead to more effective interventions. MethodsA total of 139 youth (43 HR-BD, 46 HR-MDD, and 50 LR) aged 12.9 ± 2.7 years were longitudinally followed for 4.5 ± 2.4 years. We characterized differences in striatolimbic FC that distinguished between HR-BD, HR-MDD, and LR and between resilience and conversion to psychopathology. We then examined whether risk status moderated FC–family dynamic associations. Finally, we examined whether baseline between-group FC differences predicted resilence versus conversion to psychopathology. ResultsHR-BD had greater amygdala–middle frontal gyrus and dorsal striatum–middle frontal gyrus FC relative to HR-MDD and LR, and HR-MDD had lower amygdala–fusiform gyrus and dorsal striatum–precentral gyrus FC relative to HR-BD and LR (voxel-level p < .001, cluster-level false discovery rate–corrected p < .05). Resilient youth had greater amygdala–orbitofrontal cortex and ventral striatum–dorsal anterior cingulate cortex FC relative to youth with conversion to psychopathology (voxel-level p < .001, cluster-level false discovery rate–corrected p < .05). Greater family rigidity was inversely associated with amygdala–fusiform gyrus FC across all groups (false discovery rate–corrected p = .017), with a moderating effect of bipolar risk status (HR-BD vs. HR-MDD p < .001; HR-BD vs. LR p = .005). Baseline FC differences did not predict resilence versus conversion to psychopathology. ConclusionsFindings represent neural signatures of risk and resilience in emotion and reward processing networks in youth at familial risk for mood disorders that may be targets for novel interventions tailored to the family context.

Emotional cognition subgroups in unaffected first-degree relatives of patients with mood disorders.

Patients with major depressive disorder (MDD) or bipolar disorder (BD) exhibit difficulties with emotional cognition even during remission. There is evidence for aberrant emotional cognition in unaffected relatives of patients with these mood disorders, but studies are conflicting. We aimed to investigate whether emotional cognition in unaffected first-degree relatives of patients with mood disorders is characterised by heterogeneity using a data-driven approach. Data from 94 unaffected relatives (33 of MDD patients; 61 of BD patients) and 203 healthy controls were pooled from two cohort studies. Emotional cognition was assessed with the Social Scenarios Test, Facial Expression Recognition Test and Faces Dot-Probe Test. Hierarchical cluster analysis was conducted using emotional cognition data from the 94 unaffected relatives. The resulting emotional cognition clusters and controls were compared for emotional and non-emotional cognition, demographic characteristics and functioning. Two distinct clusters of unaffected relatives were identified: a relatively 'emotionally preserved' cluster (55%; 40% relatives of MDD probands) and an 'emotionally blunted' cluster (45%; 29% relatives of MDD probands). 'Emotionally blunted' relatives presented with poorer neurocognitive performance (global cognition p = 0.010), heightened subsyndromal mania symptoms (p = 0.004), lower years of education (p = 0.004) and difficulties with interpersonal functioning (p = 0.005) than controls, whereas 'emotionally preserved' relatives were comparable to controls on these measures. Our findings show discrete emotional cognition profiles that occur across healthy first-degree relatives of patients with MDD and BD. These emotional cognition clusters may provide insight into emotional cognitive markers of genetically distinct subgroups of individuals at familial risk of mood disorders.

Longitudinal trajectories of brain age in young individuals at familial risk of mood disorder from the Scottish Bipolar Family Study.

Background: Within young individuals, mood disorder onset may be related to changes in trajectory of brain structure development. To date, however, longitudinal prospective studies remain scarce and show partly contradictory findings, with a lack of emphasis on changes at the level of global brain patterns. Cross-sectional adult studies have applied such methods and show that mood disorders are associated with accelerated brain aging. Currently, it remains unclear whether young individuals show differential brain structure aging trajectories associated with onset of mood disorder and/or presence of familial risk. Methods: Participants included young individuals (15-30 years, 53%F) from the prospective longitudinal Scottish Bipolar Family Study with and without close family history of mood disorder. All were well at time of recruitment. Implementing a structural MRI-based brain age prediction model, we globally assessed individual trajectories of age-related structural change using the difference between predicted brain age and chronological age (brain-predicted age difference (brain-PAD)) at baseline and at 2-year follow-up. Based on follow-up clinical assessment, individuals were categorised into three groups: (i) controls who remained well (C-well, n = 93), (ii) high familial risk who remained well (HR-well, n = 74) and (iii) high familial risk who developed a mood disorder (HR-MD, n = 35). Results: At baseline, brain-PAD was comparable between groups. Results showed statistically significant negative trajectories of brain-PAD between baseline and follow-up for HR-MD versus C-well ( β = -0.60, p corrected < 0.001) and HR-well ( β = -0.36, p corrected = 0.02), with a potential intermediate trajectory for HR-well ( β = -0.24 years, p corrected = 0.06). Conclusions: These preliminary findings suggest that within young individuals, onset of mood disorder and familial risk may be associated with a deceleration in brain structure aging trajectories. Extended longitudinal research will need to corroborate findings of emerging maturational lags in relation to mood disorder risk and onset.

Longitudinal trajectories of brain age in young individuals at familial risk of mood disorder from the Scottish Bipolar Family Study.

Background: Within young individuals, mood disorder onset may be related to changes in trajectory of brain structure development. To date, however, longitudinal prospective studies remain scarce and show partly contradictory findings, with a lack of emphasis on changes at the level of global brain patterns. Cross-sectional adult studies have applied such methods and show that mood disorders are associated with accelerated brain ageing. Currently, it remains unclear whether young individuals show differential brain structure aging trajectories associated with onset of mood disorder and/or presence of familial risk. Methods: Participants included young individuals (15-30 years, 53%F) from the prospective longitudinal Scottish Bipolar Family Study with and without close family history of mood disorder. All were well at time of recruitment. Implementing a structural MRI-based brain age prediction model, we globally assessed individual trajectories of age-related structural change using the difference between predicted brain age and chronological age (brain-predicted age difference (brain-PAD)) at baseline and at 2-year follow-up. Based on follow-up clinical assessment, individuals were categorised into three groups: (i) controls who remained well (C-well, n = 93), (ii) high familial risk who remained well (HR-well, n = 74) and (iii) high familial risk who developed a mood disorder (HR-MD, n = 35). Results: At baseline, brain-PAD was comparable between groups. Results showed statistically significant negative trajectories of brain-PAD between baseline and follow-up for HR-MD versus C-well ( β = -0.60, p corrected < 0.001) and HR-well ( β = -0.36, p corrected = 0.02), with a potential intermediate trajectory for HR-well ( β = -0.24 years, p corrected = 0.06). Conclusions: These preliminary findings suggest that within young individuals, onset of mood disorder and familial risk may be associated with a deceleration in brain structure aging trajectories. Extended longitudinal research will need to corroborate findings of emerging maturational lags in relation to mood disorder risk and onset.

Longitudinal trajectories of brain age in young individuals at familial risk of mood disorder from the Scottish Bipolar Family Study

Background: Within young individuals, mood disorder onset may be related to changes in trajectory of brain structure development. To date, however, longitudinal prospective studies remain scarce and show partly contradictory findings, with a lack of emphasis on changes at the level of global brain patterns. Cross-sectional adult studies have applied such methods and show that mood disorders are associated with accelerated brain aging. Currently, it remains unclear whether young individuals show differential brain structure aging trajectories associated with onset of mood disorder and/or presence of familial risk. Methods: Participants included young individuals (15-30 years, 53%F) from the prospective longitudinal Scottish Bipolar Family Study with and without close family history of mood disorder. All were well at time of recruitment. Implementing a structural MRI-based brain age prediction model, we globally assessed individual trajectories of age-related structural change using the difference between predicted brain age and chronological age (brain-predicted age difference (brain-PAD)) at baseline and at 2-year follow-up. Based on follow-up clinical assessment, individuals were categorised into three groups: (i) controls who remained well (C-well, n = 93), (ii) high familial risk who remained well (HR-well, n = 74) and (iii) high familial risk who developed a mood disorder (HR-MD, n = 35). Results: At baseline, brain-PAD was comparable between groups. Results showed statistically significant negative trajectories of brain-PAD between baseline and follow-up for HR-MD versus C-well ( β = -0.60, p corrected < 0.001) and HR-well ( β = -0.36, p corrected = 0.02), with a potential intermediate trajectory for HR-well ( β = -0.24 years, p corrected = 0.06). Conclusions: These preliminary findings suggest that within young individuals, onset of mood disorder and familial risk may be associated with a deceleration in brain structure aging trajectories. Extended longitudinal research will need to corroborate findings of emerging maturational lags in relation to mood disorder risk and onset.

Variable Neurobehavioral Outcomes in Youth at Familial Risk for Mood Disorders

Youth at familial risk for mood disorders have aberrant emotion regulation networks. However, the formation of these networks that lead to variability in resilient or emergent mood symptom outcomes is poorly understood.

Family Dynamics and Emotion Processing: Functional Connectivity Biomarkers of Risk and Resilience in Youth at Familial Risk for Mood Disorders

We have limited understanding of the neural mechanisms that underlie resilience (RES) versus conversion to psychopathology (CVT) in youth at familial risk for mood disorders (FR). Family function may be a key environmental influence on emotion regulation and clinical symptoms in youth, particularly in those at FR.

Elucidating Multimodal Neural Marker Predictors of Future Vulnerability to Mood Disorders Across Infancy, Childhood and Adolescence

In ongoing studies, using multimodal neuroimaging, we are examining prefrontal cortical-striatal-amygdala emotional regulation circuitry in infants, and youth at familial risk for mood disorders, to identify neural predictors of future risk for these disorders from infancy to adolescence.

Longitudinal trajectories of brain age in young individuals at familial risk of mood disorder.

Background: Within young individuals, mood disorder onset may be related to changes in trajectory of brain structure development. To date, however, longitudinal prospective studies remain scarce and show partly contradictory findings, with a lack of emphasis on changes at the level of global brain patterns. Cross-sectional adult studies have applied such methods and show that mood disorders are associated with accelerated brain ageing. Currently, it remains unclear whether young individuals show differential brain structure ageing trajectories associated with onset of mood disorder and/or presence of familial risk. Methods: Participants included young individuals (15-30 years, 53%F) from the prospective longitudinal Scottish Bipolar Family Study with and without close family history of mood disorder. All were well at time of recruitment. Implementing a structural MRI-based brain age prediction model, we globally assessed individual trajectories of age-related structural change using the difference between predicted brain age and chronological age (brain-predicted age difference (brain-PAD)) at baseline and at 2-year follow-up. Based on follow-up clinical assessment, individuals were categorised into three groups: (i) controls who remained well (C-well, n = 93), (ii) high familial risk who remained well (HR-well, n = 74) and (iii) high familial risk who developed a mood disorder (HR-MD, n = 35). Results: At baseline, brain-PAD was comparable between groups. Results showed statistically significant negative trajectories of brain-PAD between baseline and follow-up for HR-MD versus C-well ( β = -0.60, p corrected < 0.001) and HR-well ( β = -0.36, p corrected = 0.02), with a potential intermediate trajectory for HR-well ( β = -0.24 years, p corrected = 0.06). Conclusions: These preliminary findings suggest that within young individuals, onset of mood disorder and familial risk may be associated with a deceleration in brain structure ageing trajectories. Extended longitudinal research will need to corroborate findings of emerging maturational lags in relation to mood disorder risk and onset.

Affective lability in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia.

Affective lability, defined as the propensity to experience excessive and unpredictable changes in mood, has been proposed as a potential transdiagnostic predictor of major mood and psychotic disorders. A parental diagnosis of bipolar disorder has been associated with increased affective lability in offspring. However, the association between affective lability and family history of other mood and psychotic disorders has not been examined. We measured affective lability using the self- and parent-reported Children's Affective Lability Scale in a cohort of 320 youth aged 6-17years, including 137 offspring of a parent with major depressive disorder, 68 offspring of a parent with bipolar disorder, 24 offspring of a parent with schizophrenia, and 91 offspring of control parents. We tested differences in affective lability between groups using mixed-effects linear regression. Offspring of a parent with major depressive disorder (β = 0.46, 95% CI 0.17-0.76, p = 0.002) or bipolar disorder (β = 0.47, 95% CI 0.12-0.81, p = 0.008) had significantly higher affective lability scores than control offspring. Affective lability did not differ significantly between offspring of a parent with schizophrenia and offspring of control parents. Our results suggest that elevated affective lability during childhood is a marker of familial risk for mood disorders.

Neural correlates of emotion processing predict resilience in youth at familial risk for mood disorders.

Aberrant face emotion processing has been demonstrated in youth with and at a familial risk for bipolar and major depressive disorders. However, the neurobiological factors related to emotion processing that underlie resilience from youth-onset mood disorders are not well understood. Functional magnetic resonance imaging data during an implicit emotion processing task were collected at baseline from a sample of 50 youth, ages 8-17, who were healthy but also familially at high risk for either bipolar disorder or major depressive disorder, and 24 healthy controls with no family history of psychopathology (HCL). Participants were reevaluated 3 years later and classified into three groups for analysis: high-risk youth who converted to a psychiatric diagnosis (CVT; N = 23), high-risk youth who were resilient from developing any psychopathology (RES; N = 27), and HCL youth (N = 24) who remained healthy at follow-up. For happy &gt; calm faces, the CVT and RES groups had significantly lower activation in the left inferior parietal lobe (IPL), while the RES group had lower activation in the right supramarginal gyrus. For fear &gt; calm faces, the RES group had lower activation in the right precuneus and inferior frontal gyrus (IFG) compared to the CVT group. Connectivity analyses revealed the RES group exhibited higher left IPL connectivity with visual cortical regions for happy &gt; calm faces, and higher IFG connectivity with frontal, temporal, and limbic regions for fear &gt; calm faces. These connectivities were correlated with improvements in prosocial behaviors and global functioning. Our findings suggest that differential activation and connectivity in the IPL, IFG, and precuneus in response to emotional stimuli may represent distinct resilience and risk markers for youth-onset mood disorders.

F127. Neural Correlates of Emotion Processing in Youth at Familial Risk for Mood Disorders

Youth at familial risk for major depressive (MDD) and bipolar (BD) disorders have aberrant face emotion processing. However, dysregulation in emotion processing that distinguishes between youth at high risk for MDD and BD are not well understood.

Diffusion tensor imaging correlates of early markers of depression in youth at high-familial risk for bipolar disorder.

Mood disorders are familial psychiatric diseases, in which patients show reduced white matter (WM) integrity. We sought to determine whether WM integrity was affected in young offspring at high-familial risk of mood disorder before they go on to develop major depressive disorder (MDD). The Bipolar Family study is a prospective longitudinal study examining young individuals (age 16-25years) at familial risk of mood disorder on three occasions 2years apart. This study used baseline imaging data, categorizing groups according to clinical outcome at follow-up. Diffusion tensor MRI data were acquired for 61 controls and 106 high-risk individuals, the latter divided into 78 high-risk subjects who remained well throughout the study ('high-risk well') and 28 individuals who subsequently developed MDD ('high-risk MDD'). Voxel-wise between-group comparison of fractional anisotropy (FA) based on diagnostic status was performed using tract-based spatial statistics (TBSS). Compared to controls, both high-risk groups showed widespread decreases in FA (pcorr <.05) at baseline. Although FA in the high-risk MDD group negatively correlated with subthreshold depressive symptoms at the time of scanning (pcorr <.05), there were no statistically significant differences at p-corrected levels between the two high-risk groups. These results suggest that decreased FA is related to the presence of familial risk for mood disorder along with subdiagnostic symptoms at the time of scanning rather than predictive of subsequent diagnosis. Due to the difficulties performing such longitudinal prospective studies, we note, however, that this latter analysis may be underpowered due to sample size within the high-risk MDD group. Further clinical follow-up may clarify these findings.

Vulnerabilities in sequencing and task switching in healthy youth offspring of parents with mood disorders

ABSTRACTIntroduction: Visuospatial processing and task switching are impaired in individuals with mood disorders. It is unknown whether early deficits are present before mood symptom on set or are related to risk for a specific type of mood disorder. To investigate, we compared visual attention and task switching during sequencing among never-disordered youth with parental family histories of bipolar (BD) and major depressive disorders (MDD) and healthy controls (HC) with no personal or family history of psychopathology.Method: 8–17-year-old youth of parents with BD (n = 31, “BD-risk”), youth of parents with MDD (n = 49, “MDD-risk”), and demographically similar HC (n = 31, “HC”) were examined using the Delis–Kaplan Executive Functioning System Trail Making Test. Seed-based resting-state functional connectivity (RSFC) was collected from a subset of 88 participants (25 BD-risk, 37 MDD-risk, 26 HC) to investigate group differences in RSFC related to visuospatial processing.Results: BD-risk and MDD-risk offspring had impaired sequencing and task switching, demonstrated by reduced scores on visual scanning, F(2, 108) = 4.12, p = .02, number sequencing, F(2, 88) = 4.75, p = .01, letter sequencing, F(2, 108) = 4.24, p = .02, and number–letter sequencing, F(2, 108) = 4.66, p = .01, compared to scores in HC. RSFC between the posterior cingulate (PCC) and clusters in the subcallosal cortex, amygdala, and hippocampus significantly differed among HC, BD-risk, and MDD-risk groups. PCC-subcallosal/limbic RSFC was positively coupled in the MDD-risk and BD-risk groups and negatively coupled in HCs.Conclusions: Youth at familial risk for mood disorders demonstrate visuospatial deficits early in the processing stream. Improved methods for identifying at-risk children with the earliest possible neurocognitive impairments may inform remediation strategies that could prevent mood disorders.

Longitudinal differences in white matter integrity in youth at high familial risk for bipolar disorder

Previous neuroimaging studies have reported abnormalities in white matter (WM) pathways in subjects at high familial risk of mood disorders. In the current study, we examined the trajectory of these abnormalities during the early stages of illness development using longitudinal diffusion tensor imaging (DTI) data. Subjects (16-28years old) were recruited in the Scottish Bipolar Family Study, a prospective longitudinal study that has examined individuals at familial risk of mood disorder on three occasions, 2years apart. The current study concerns imaging data from the first and second assessments. We analysed DTI data for 43 controls and 69 high-risk individuals who were further subdivided into a group of 53 high-risk subjects who remained well (high-risk well) and 16 who met diagnostic criteria for major depressive disorder (high-risk MDD) at follow-up. Longitudinal differences in fractional anisotropy (FA) between groups based on diagnostic status were investigated using the tract-based spatial statistics technique (TBSS). We found a significant reduction in FA (Pcorr <.05) across widespread brain regions over 2 years in all three groups. The trajectory of FA reduction did not differ significantly between groups. These results suggest that there are similar trajectories of FA reductions for controls and high-risk young adults, despite high-risk individuals being at a disadvantaged starting point considering their reduced WM integrity detected at baseline in previous studies. Difference in WM integrity between high-risk individuals and controls could therefore occur in earlier childhood and be a necessary but not sufficient condition to develop future mood disorders.