Barbara J Sahakian

University of Cambridge | Cam · Department of Psychiatry

Proteomic alterations preceding the onset of depression offer valuable insights into its development and potential interventions. Leveraging data from 46,165 UK Biobank participants and 2920 plasma proteins profiled at baseline, we conducted a longitudinal analysis with a median follow-up of 14.5 years to explore the relationship between plasma pro...

Resilience to emotional disorders is critical for adolescent mental health, especially following childhood abuse. Yet, brain signatures of resilience remain undetermined due to the differential susceptibility of the brain’s emotion processing system to environmental stresses. Analyzing brain’s responses to angry faces in a longitudinally large-scal...

Background: Neuropsychiatric symptoms are prevalent and commonly appear early in Huntington’s disease (HD). The HD Young Adult Study aims to characterise the HD phenotype ~24 years from predicted disease onset, in a unique cohort of gene expansion carriers (GECs) longitudinally evaluated at two visits (V1 and V2) ~4.5 years apart. Aims: To assess...

Background: With numerous disease-modification trials underway in Huntington’s disease (HD), there is considerable interest in secondary prevention treatments, yet sensitive biomarkers for early stages are lacking. HD-YAS are a unique cohort of HD Integrated Staging System (HD-ISS) Stage 0 and 1 gene expansion carriers (GECs) with deep phenotyping...

Background: Cognitive impairments in Huntington’s Disease (HD) reflect neurodegeneration, initially affecting frontal-striatal networks and later becoming more widespread. Aims: The HD Young Adult Study (HD-YAS) investigates cognition in gene expansion carriers (GECs) approximately 24 years from predicted onset, with longitudinal evaluations at tw...

Compulsive behaviour may often be triggered by Pavlovian cues. Assessing how Pavlovian cues drive instrumental behaviour in obsessive-compulsive disorder (OCD) is therefore crucial to understand how compulsions develop and are maintained. An aversive Pavlovian-to-Instrumental transfer (PIT) paradigm, particularly one involving avoidance/cancellatio...

Understanding the brain mechanisms underlying objective sleep patterns in adolescents and their implications for psychophysiological development is a complex challenge. Here, we applied sparse canonical correlation (sCCA) analysis on 3300 adolescents from Adolescent Brain Cognitive Development (ABCD) study, integrating extensive device-based sleep...

Prosocial and moral behaviors have overlapping neural systems and can both be affected in a number of psychiatric disorders, although whether they involve similar neurochemical systems is unclear. In the current registered randomized placebo-controlled trial on 180 adult male and female subjects, we investigated the effects of intranasal administra...

Emotion dysregulation is common in attention deficit hyperactivity disorder (ADHD), which is known to be clinically heterogeneous. However, it remains unclear whether emotion dysregulation represents a neuropsychological pathway to ADHD. Here, using a large population-based cohort (n = 6,053), we show that emotion dysregulation was associated with...

Food preferences significantly influence dietary choices, yet understanding natural dietary patterns in populations remains limited. Here we identifiy four dietary subtypes by applying data-driven approaches to food-liking data from 181,990 UK Biobank participants: ‘starch-free or reduced-starch’ (subtype 1), ‘vegetarian’ (subtype 2), ‘high protein...

Background Individual lifestyle choices undeniably influence the risk of developing both somatic and brain diseases. Exploring the impact of multidimensional lifestyle factors on various diseases has the potential to provide evidence-based recommendations for treatments and prevention conditions by targeting modifiable health behaviours. This study...

(1) Background: Traumatic brain injury (TBI) often results in cognitive impairments, including in visuospatial planning and executive function. Methylphenidate (MPh) demonstrates potential improvements in several cognitive domains in patients with TBI. The Tower of London (TOL) is a visuospatial planning task used to assess executive function. (2)...

Purpose of Review Cannabis use has been anecdotally linked with reduced motivation, sometimes referred to as the ‘amotivational syndrome’. In this review, we evaluate research on the association between acute and non-acute cannabis use and motivation assessed with questionnaire or behavioural task-based measures, focusing on studies published in th...

Background COVID-19 lockdowns increased the risk of mental health problems, especially for children with autism spectrum disorder (ASD). However, despite its importance, little is known about the protective factors for ASD children during the lockdowns. Methods Based on the Shanghai Autism Early Developmental Cohort, 188 ASD children with two visi...

Serotonin is critical for adapting behavior flexibly to meet changing environmental demands. Cognitive flexibility is important for successful attainment of goals, as well as for social interactions, and is frequently impaired in neuropsychiatric disorders, including obsessive–compulsive disorder. However, a unifying mechanistic framework accountin...

Selective serotonin reuptake inhibitors (SSRIs) are widely used for treating neuropsychiatric disorders. However, the exact mechanism of action and why effects can take several weeks to manifest is not clear. The hypothesis of neuroplasticity is supported by preclinical studies, but the evidence in humans is limited. Here, we investigate the effect...

Prosocial and moral behaviors have overlapping neural systems but whether they involve similar neurochemical systems is unclear. In the current pre-registered randomized placebo controlled trial on 180 adult male and female subjects we investigated effects of intranasal administration of two prosocial neuropeptides, oxytocin or vasopressin, on mora...

Adolescence is a critical developmental with increased vulnerability to mental disorders. While the positive impact of physical exercise on adult mental health is well-established, dose-response relationships and the underlying neural and genetic mechanisms in adolescents remain elusive. Leveraging data from >11,000 pre-adolescents (9-10 years, ABC...

Background Internalising disorders are highly prevalent emotional dysregulations during preadolescence but clinical decision-making is hampered by high heterogeneity. During this period impulsivity represents a major risk factor for psychopathological trajectories and may act on this heterogeneity given the controversial anxiety–impulsivity relatio...

Lifestyle factors have been acknowledged to be modifiable targets that can be used to counter the increasing prevalence of depression. This study aims to investigate combining an extensive range of lifestyle factors, including alcohol consumption, diet, physical activity, sleep, smoking, sedentary behavior and social connection, that contribute to...

Background: A growing body of neuroimaging studies has reported common neural abnormalities among mental disorders in adults. However, it is unclear whether the distinct disorder-specific mechanisms operate during adolescence despite the overlap among disorders. Methods: We studied a large cohort of more than 11 000 preadolescent (age 9-10 yr) c...

Smoking of cigarettes among young adolescents is a pressing public health issue. However, the neural mechanisms underlying smoking initiation and sustenance during adolescence, especially the potential causal interactions between altered brain development and smoking behaviour, remain elusive. Here, using large longitudinal adolescence imaging gene...

Background Comorbidity is the rule rather than the exception for childhood and adolescent onset mental disorders, but we cannot predict its occurrence and do not know the neural mechanisms underlying comorbidity. We investigate if the effects of comorbid internalizing and externalizing disorders on anatomical differences represent a simple aggregat...

Background: Cocaine use disorder is associated with cognitive deficits that reflect dysfunctional processing across neural systems. As there are currently no approved medications, treatment centres around behavioural interventions which have only short-term efficacy. This suggests that behavioural interventions are not sufficient by themselves to...

Background Compulsive behaviour is often triggered by Pavlovian cues. Assessing how Pavlovian cues drive instrumental behaviour in obsessive-compulsive disorder (OCD) is therefore crucial to understand how compulsions develop and are maintained. An aversive Pavlovian-to-Instrumental transfer (PIT) paradigm, particularly one involving avoidance/canc...

Aims: A bidirectional relationship between sleep and psychosis is established but the perceptions of clinicians about sleep and its treatment in Early Intervention in Psychosis Services (EIS) has only begun to be examined; the perceptions of service users have not been explored. We conducted surveys of clinicians and EIS users in two NHS trusts. Me...

Close friendships are important for mental health and cognition in late childhood. However, whether the more close friends the better, and the underlying neurobiological mechanisms are unknown. Using the Adolescent Brain Cognitive Developmental study, we identified nonlinear associations between the number of close friends, mental health, cognition...

Close friendships are important for mental health and cognition in late childhood. However, whether the more close friends the better, and the underlying neurobiological mechanisms are unknown. Using the Adolescent Brain Cognitive Developmental study, we identified nonlinear associations between the number of close friends, mental health, cognition...

Close friendships are important for mental health and cognition in late childhood. However, whether the more close friends the better, and the underlying neurobiological mechanisms are unknown. Using the Adolescent Brain Cognitive Developmental study, we identified nonlinear associations between the number of close friends, mental health, cognition...

Close friendships are important for mental health and cognition in late childhood. However, whether the more close friends the better, and the underlying neurobiological mechanisms are unknown. Using the Adolescent Brain Cognitive Developmental study, we identified nonlinear associations between the number of close friends, mental health, cognition...

Background The nature of cognitive flexibility deficits in obsessive-compulsive disorder (OCD), which historically have been tested with probabilistic reversal learning tasks, remains elusive. Here, a novel deterministic reversal task and inclusion of unmedicated patients in the study sample illuminated the role of fixed versus uncertain rules/cont...

Background: Childhood is a crucial neurodevelopmental period. We investigated whether childhood reading for pleasure (RfP) was related to young adolescent assessments of cognition, mental health, and brain structure. Methods: We conducted a cross-sectional and longitudinal study in a large-scale US national cohort (10 000 + young adolescents), u...

Functional impairments in cognition are frequently thought to be a feature of individuals with depression or anxiety. However, documented impairments are both broad and inconsistent, with little known about when they emerge, whether they are causes or effects of affective symptoms, or whether specific cognitive systems are implicated. Here, we show...

Background This review provides an overview of obsessive‐compulsive disorder (OCD) symptoms, including the four partially distinct subtypes of the disorder, current diagnostic criteria, and common comorbidities. Critically, it focuses on the etiology of OCD, including its underlying neuropathology, and examines cognitive dysfunction in OCD. Method...

Recent studies proposed a general psychopathology factor underlying common comorbidities among psychiatric disorders. However, its neurobiological mechanisms and generalizability remain elusive. In this study, we used a large longitudinal neuroimaging cohort from adolescence to young adulthood (IMAGEN) to define a neuropsychopathological (NP) facto...

Not everyone who uses drugs loses control over their intake, which is a hallmark of addiction. Although familial risk studies suggest significant addiction heritability, the genetic basis of vulnerability to drug addiction remains largely unknown. In the present study, we investigate the relationship between self-control, cocaine use, and the rs360...

A central question in neuroscience is how consciousness arises from the dynamic interplay of brain structure and function. Here we decompose functional MRI signals from pathological and pharmacologically-induced perturbations of consciousness into distributed patterns of structure-function dependence across scales: the harmonic modes of the human s...

Preadolescence is a critical period characterized by dramatic morphological changes and accelerated cortico-subcortical development. Moreover, the coordinated development of cortical and subcortical regions underlies the emerging cognitive functions during this period. Deviations in this maturational coordination may underlie various psychiatric di...

Close friendships are important for mental health and cognition in late childhood. However, whether the more close friends the better, and the underlying neurobiological mechanisms are unknown. Using the Adolescent Brain Cognitive Developmental study, we identified nonlinear associations between the number of close friends, mental health, cognition...

A long-running debate concerns whether dopamine or noradrenaline deficiency drives response disinhibition in Parkinson’s disease (PD). This study aimed to investigate whether damage to the locus coeruleus (LC) or substantia nigra (SN) might impact inhibitory functions of the fronto-subthalamic hyperdirect or fronto-striatal indirect pathway. Patien...

Background Adolescents may respond differently to cannabis than adults, yet no functional magnetic resonance imaging (fMRI) study has examined acute cannabis effects in this age-group. We investigated the neural correlates of reward anticipation after acute exposure to cannabis in adolescents and adults. Methods This was a double-blind, placebo-co...

Background The HD Young Adult Study provided deep phenotyping of the earliest cohort of adult HD mutation carriers to date. We previously reported elevated levels of neurofilament light protein, suggestive of early neurodegenerative change. Putaminal volumes were also significantly reduced in HD mutation carriers. However, there was no evidence of...

Background Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are both highly prevalent and comorbid psychiatric disorders. Neurocognitive dysfunction has been commonly found in MDD, but the findings in GAD are inconsistent. Few studies have directly compared cognitive performance between GAD and MDD. Therefore, the present stud...

Background: Cannabis use may be linked with anhedonia and apathy. However, previous studies have shown mixed results and few have examined the association between cannabis use and specific reward sub-processes. Adolescents may be more vulnerable to harmful effects of cannabis than adults. This study investigated (1) the association between non-acu...

The role of the adenosine neurochemical system in human cognition is under-studied, despite such receptors being distributed throughout the brain. The aim of this study was to shed light on the role of the adenosine A2A receptors in human cognition using single-dose istradefylline. Twenty healthy male participants, aged 19-49, received 20 mg istrad...

Bumetanide, a drug being studied in autism spectrum disorder (ASD) may act to restore gamma-aminobutyric acid (GABA) function, which may be modulated by the immune system. However, the interaction between bumetanide and the immune system remains unclear. Seventy-nine children with ASD were analysed from a longitudinal sample for a 3-month treatment...

Threat reversal learning and avoidance habits in generalised anxiety disorder

Background Computational research had determined that adults with obsessive–compulsive disorder (OCD) display heightened action updating in response to noise in the environment and neglect metacognitive information (such as confidence) when making decisions. These features are proposed to underlie patients’ compulsions despite the knowledge they ar...

Sleep duration, psychiatric disorders and dementias are closely interconnected in older adults. However, the underlying genetic mechanisms and brain structural changes are unknown. Using data from the UK Biobank for participants primarily of European ancestry aged 38–73 years, including 94% white people, we identified a nonlinear association betwee...

Chronic use of drugs may alter the brain’s reward system, though the extant literature concerning long-term cannabis use and neural correlates of reward processing has shown mixed results. Adolescents may be more vulnerable to the adverse effects of cannabis than adults; however, this has not been investigated for reward processing. As part of the...

Theory of Mind (ToM)—the ability of the human mind to attribute mental states to others—is a key component of human cognition. In order to understand other people's mental states or viewpoint and to have successful interactions with others within social and occupational environments, this form of social cognition is essential. The same capability o...

Hemispheric lateralization constitutes a core architectural principle of human brain organization underlying cognition, often argued to represent a stable, trait-like feature. However, emerging evidence underlines the inherently dynamic nature of brain networks, in which time-resolved alterations in functional lateralization remain uncharted. Integ...

BACKGROUND Early childhood has increasingly been recognized as an important neurodevelopmental period. However, the links between specific forms of early educational activities and cognition and mental health remain unclear. METHODS A large-scale analysis on the attainments of childhood Reading for Pleasure (early RfP) and its relationship with yo...

It is unclear how different diets may affect human brain development and if genetic and environmental factors play a part. We investigated diet effects in the UK Biobank data from 18,879 healthy adults and discovered anticorrelated brain-wide gray matter volume (GMV)-association patterns between coffee and cereal intake, coincidence with their anti...

Background . Childhood maltreatment is significantly associated with greater occurrence of mental disorders in adulthood such as depression and anxiety. As a key node of the limbic system, the amygdala is engaged in emotional processing and regulation and is dysfunctional in many psychiatric disorders. The present study aimed at exploring the assoc...

Background Findings of reward disturbances in unaffected relatives of patients with schizophrenia suggest reward disturbances as an endophenotype for schizophrenia. Twin studies, where one twin has been diagnosed with a schizophrenia spectrum disorder, can further explore this. Methods We used Danish registries to identify twin pairs with at least...

(Appeared originally in Biological Psychiatry 2019; 85:726-734) Reprinted under Creative Commons CC-BY license.

Background To determine whether depressive symptoms in traumatic brain injury (TBI) patients were associated with altered resting-state functional connectivity (rs-fc) or voxel-based morphology in brain regions involved in emotional regulation and associated with depression. Methods In the present study, we examined 79 patients (57 males; age rang...

Abstract Background Transcranial direct current stimulation (tDCS) has shown mixed results for depression treatment. The efficacies of tDCS combination therapies have not been investigated deliberately. This review aims to evaluate the clinical efficacy of tDCS as a monotherapy and in combination with medication, psychotherapy, and ECT for treating...

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