Symptoms of depression in a large healthy population cohort are related to subjective memory complaints and memory performance in negative contexts.

BACKGROUND: Decades of research have investigated the impact of clinical depression on memory, which has revealed biases and in some cases impairments. However, little is understood about the effects of subclinical symptoms of depression on memory performance in the general population. METHODS: Here we report the effects of symptoms of depression on memory problems in a large population-derived cohort (N = 2544), 87% of whom reported at least one symptom of depression. Specifically, we investigate the impact of depressive symptoms on subjective memory complaints, objective memory performance on a standard neuropsychological task and, in a subsample (n = 288), objective memory in affective contexts. RESULTS: There was a dissociation between subjective and objective memory performance, with depressive symptoms showing a robust relationship with self-reports of memory complaints, even after adjusting for age, sex, general cognitive ability and symptoms of anxiety, but not with performance on the standardised measure of verbal memory. Contrary to our expectations, hippocampal volume (assessed in a subsample, n = 592) did not account for significant variance in subjective memory, objective memory or depressive symptoms. Nonetheless, depressive symptoms were related to poorer memory for pictures presented in negative contexts, even after adjusting for memory for pictures in neutral contexts. CONCLUSIONS: Thus the symptoms of depression, associated with subjective memory complaints, appear better assessed by memory performance in affective contexts, rather than standardised memory measures. We discuss the implications of these findings for understanding the impact of depressive symptoms on memory functioning in the general population.The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) research was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/H008217/1). SS is supported by UK Medical Research Council Programme MC-A060-5PQ60; RNH and TE are supported by MC-A060-5PR10; RAK is supported by MC-A060-5PR60 and a Sir Henry Wellcome Trust Fellowship (grant number 107392/Z/15/Z)

Challenges and Solutions to the Measurement of Neurocognitive Mechanisms in Developmental Settings

Identifying early neurocognitive mechanisms that confer risk for mental health problems is one important avenue as we seek to develop successful early interventions. Currently, however, we have limited understanding of the neurocognitive mechanisms involved in shaping mental health trajectories from childhood through young adulthood, and this constrains our ability to develop effective clinical interventions. In particular, there is an urgent need to develop more sensitive, reliable, and scalable measures of individual differences for use in developmental settings. In this review, we outline methodological shortcomings that explain why widely used task-based measures of neurocognition currently tell us little about mental health risk. We discuss specific challenges that arise when studying neurocognitive mechanisms in developmental settings, and we share suggestions for overcoming them. We also propose a novel experimental approach—which we refer to as “cognitive microscopy”—that involves adaptive design optimization, temporally sensitive task administration, and multilevel modeling. This approach addresses some of the methodological shortcomings outlined above and provides measures of stability, variability, and developmental change in neurocognitive mechanisms within a multivariate framework

Corrigendum: Mutualistic Coupling Between Vocabulary and Reasoning Supports Cognitive Development During Late Adolescence and Early Adulthood

Correction to: Kievit, R. A., Lindenberger, U., Goodyer, I. M., Jones, P. B., Fonagy, P., Bullmore, E. T., the Neuroscience in Psychiatry Network, & Dolan, R. J. (2017). Mutualistic coupling between vocabulary and reasoning supports cognitive development during late adolescence and early adulthood. Psychological Science, 28, 1419–1431. doi:10.1177/095679761771078

Noradrenergic-dependent functions are associated with age-related locus coeruleus signal intensity differences.

The locus coeruleus (LC), the origin of noradrenergic modulation of cognitive and behavioral function, may play an important role healthy ageing and in neurodegenerative conditions. We investigated the functional significance of age-related differences in mean normalized LC signal intensity values (LC-CR) in magnetization-transfer (MT) images from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) cohort - an open-access, population-based dataset. Using structural equation modelling, we tested the pre-registered hypothesis that putatively noradrenergic (NA)-dependent functions would be more strongly associated with LC-CR in older versus younger adults. A unidimensional model (within which LC-CR related to a single factor representing all cognitive and behavioral measures) was a better fit with the data than the a priori two-factor model (within which LC-CR related to separate NA-dependent and NA-independent factors). Our findings support the concept that age-related reduction of LC structural integrity is associated with impaired cognitive and behavioral function

The Interplay Between Adolescent Friendship Quality and Resilient Functioning Following Childhood and Adolescent Adversity

AbstractChild and adolescent adversity (‘CA’) is a major predictor of mental health problems in adolescence and early adulthood. However, not all young people who have experienced CA develop psychopathology; their mental health functioning can be described as resilient. We previously found that resilient functioning in adolescence following CA is facilitated by adolescent friendships. However, during adolescence, friendships undergo significant change. It is unknown whether resilient functioning after CA fluctuates with these normative changes in friendship quality. We used Latent Change Score Modelling in a large sample of adolescents (i.e. the ROOTS cohort; N = 1238) to examine whether and how emergent friendship quality and resilient functioning at ages 14 and 17 inter-relate and change together. We found that friendships quality and resilient functioning had strong associations at age 14, although friendships at 14 did not predict higher resilient functioning at 17. Higher resilient functioning in 14-year-olds with a history of CA was associated with a positive change in friendships from age 14 to 17. Finally, improvements in friendship quality and resilient functioning went hand-in-hand, even when taking into account baseline levels of both, the change within friendship quality or resilient functioning over time, and the association between resilient functioning and change in friendship quality over time. We show that friendship quality and resilient functioning after CA inter-relate and change together between ages 14 and 17. Our results suggest that improving friendship quality or resilient functioning within this timeframe may benefit this vulnerable adolescent group, and this should be tested in future research.</jats:p

A watershed model of individual differences in fluid intelligence

Fluid intelligence is a crucial cognitive ability that predicts key life outcomes across the lifespan. Strong empirical links exist between fluid intelligence and processing speed on the one hand, and white matter integrity and processing speed on the other. We propose a watershed model that integrates these three explanatory levels in a principled manner in a single statistical model, with processing speed and white matter figuring as intermediate endophenotypes. We fit this model in a large (N=555) adult lifespan cohort from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) using multiple measures of processing speed, white matter health and fluid intelligence. The model fit the data well, outperforming competing models and providing evidence for a many-to-one mapping between white matter integrity, processing speed and fluid intelligence. The model can be naturally extended to integrate other cognitive domains, endophenotypes and genotypes

Credit assignment to state-independent task representations and its relationship with model-based decision making

Model-free learning enables an agent to make better decisions based on prior experience while representing only minimal knowledge about an environment’s structure. It is generally assumed that model-free state representations are based on outcome-relevant features of the environment. Here, we challenge this assumption by providing evidence that a putative model-free system assigns credit to task representations that are irrelevant to an outcome. We examined data from 769 individuals performing a well-described 2-step reward decision task where stimulus identity but not spatial-motor aspects of the task predicted reward. We show that participants assigned value to spatial-motor representations despite it being outcome irrelevant. Strikingly, spatial-motor value associations affected behavior across all outcome-relevant features and stages of the task, consistent with credit assignment to low-level state-independent task representations. Individual difference analyses suggested that the impact of spatial-motor value formation was attenuated for individuals who showed greater deployment of goal-directed (model-based) strategies. Our findings highlight a need for a reconsideration of how model-free representations are formed and regulated according to the structure of the environment

Multiple determinants of lifespan memory differences

Memory problems are among the most common complaints as people grow older. Using structural equation modeling of commensurate scores of anterograde memory from a large (N = 315), population-derived sample (www.cam-can.org), we provide evidence for three memory factors that are supported by distinct brain regions and show differential sensitivity to age. Associative memory and item memory are dramatically affected by age, even after adjusting for education level and fluid intelligence, whereas visual priming is not. Associative memory and item memory are differentially affected by emotional valence, and the age-related decline in associative memory is faster for negative than for positive or neutral stimuli. Gray-matter volume in the hippocampus, parahippocampus and fusiform cortex, and a white-matter index for the fornix, uncinate fasciculus and inferior longitudinal fasciculus, show differential contributions to the three memory factors. Together, these data demonstrate the extent to which differential ageing of the brain leads to differential patterns of memory loss.The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) research was supported by the Biotechnology and Biological Sciences Research Council (BB/H008217/1); R.N.H., S.E. and T.E. are additionally supported by the UK Medical Research Council (MC_A060_5PR10). RAK is supported by the Wellcome Trust (grant number 107392/Z/15/Z and the UK Medical Research Council (MC-A060-5PR61). We are grateful to the Cam-CAN respondents and their primary care teams in Cambridge for their participation in this study. We also thank colleagues at the MRC Cognition and Brain Sciences Unit MEG and MRI facilities for their assistance

Adolescent friendships predict later resilient functioning across psychosocial domains in a healthy community cohort

$\textbf{BACKGROUND}$: Adolescence is a key time period for the emergence of psychosocial and mental health difficulties. To promote adolescent adaptive ('resilient') psychosocial functioning (PSF), appropriate conceptualisation and quantification of such functioning and its predictors is a crucial first step. Here, we quantify resilient functioning as the degree to which an individual functions better or worse than expected given their self-reported childhood family experiences, and relate this to adolescent family and friendship support. $\textbf{METHOD}$: We used Principal Component and regression analyses to investigate the relationship between childhood family experiences and PSF (psychiatric symptomatology, personality traits and mental wellbeing) in healthy adolescents (the Neuroscience in Psychiatry Network; $\textit{N}$ = 2389; ages 14-24). Residuals from the relation between childhood family experiences and PSF reflect resilient functioning; the degree to which an individual is functioning better, or worse, than expected given their childhood family experiences. Next, we relate family and friendship support with resilient functioning both cross-sectionally and 1 year later. $\textbf{RESULTS}$: Friendship and family support were positive predictors of immediate resilient PSF, with friendship support being the strongest predictor. However, whereas friendship support was a significant positive predictor of $\textit{later}$ resilient functioning, $\textit{family}$ support had a $\textit{negative}$ relationship with later resilient PSF. $\textbf{CONCLUSIONS}$: We show that friendship support, but not family support, is an important positive predictor of both immediate and later resilient PSF in adolescence and early adulthood. Interventions that promote the skills needed to acquire and sustain adolescent friendships may be crucial in increasing adolescent resilient PSF.This work was supported by a strategic award from the Wellcome Trust to the University of Cambridge and University College London (095844/Z/11/Z), a Netherlands Organization for Scientific Research Rubicon grant (AlvH, NO 446-13-006), and a Royal Society Dorothy Hodgkin Fellowship (AlvH; No DH150176). Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Cambridge. P.F is in receipt of a National Institute for Health Research (NIHR) Senior Investigator Award (NF-SI-0514-10157)and is in part supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North Thames at Barts Health NHS Trust. E.T.B. is employed half-time by the University of Cambridge and half-time by GlaxoSmithKline; he holds stock in GlaxoSmithKline

In vivo visualization of age-related differences in the locus coeruleus

The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, may play an important role in neuropsychiatric disorders including Parkinson's disease and Alzheimer's disease. The pattern of age-related change of the LC across the life span is unclear. We obtained normalized, mean LC signal intensity values, that is, contrast ratios (CRs), from magnetization transfer-weighted images to investigate the relationship between LC CR and age in cognitively normal healthy adults (N = 605, age range 18-88 years). Study participants were part of the Cambridge Centre for Ageing and Neuroscience-an open-access, population-based data set. We found a quadratic relationship between LC CR and age, the peak occurring around 60 years, with no differences between males and females. Subregional analyses revealed that age-related decline in LC CR was confined to the rostral portion of the LC. Older adults showed greater variance in overall LC CR than younger adults, and the functional and clinical implications of these observed age-related differences require further investigation. Visualization of the LC in this study may inform how future scanning parameters can be optimized, and provides insight into how LC integrity changes across the life span