Long-term course of cognitive functioning in bipolar disorder: A ten-year follow-up study.

INTRODUCTION: Cognitive impairments are common in bipolar disorder (BD), but the long-term course remains understudied. Longitudinal data on cognitive functioning from the start of the first treatment could help clarify pathophysiological processes that shape the illness outcome. We here aim to investigate the 10-year cognitive course in BD compared to healthy controls (HC) and the effects of clinical symptoms on cognitive trajectories. METHODS: Fifty-six BD participants recruited within their first year of treatment and 108 HC completed clinical and cognitive assessments at baseline and 10-year follow-up. We derived eight cognitive domain scores and a cognitive composite score, which were further investigated using linear mixed model analyses. Correlation analyses were used to assess associations between the composite score and depressive, manic and psychotic symptoms. RESULTS: BD participants performed poorer than HCs in all domains except mental speed and verbal fluency. Verbal learning and memory, verbal fluency and the composite score improved over time in both BD participants and HC, while short-term memory, mental speed, psychomotor speed and working memory were stable. We found no significant correlations between cognition and symptom level at either time point in BD participants. CONCLUSIONS: We found evidence of long-term cognitive stability or improvement in BD participants from first treatment to 10-year follow-up. Though the BD group was impaired in all domains except mental speed and verbal fluency, the change in cognitive functioning was parallel to that of HCs. These findings are not consistent with the notion of neuroprogression in BD.

Adolescence internalizing problems as a mediator between autism diagnosis in childhood and quality of life in emerging adults with and without autism: a 10-year longitudinal study.

BACKGROUND: Individuals with autism tend to have a reduced quality of life across their lifespan. This reduced quality of life may be a result of autism traits, mental distress, and poor person/environment fit. In this longitudinal study, we looked at the role of adolescence internalizing and externalizing problems in mediating the relationship between having an autism diagnosis from childhood and perceived quality of life as emerging adults. METHODS: A total of 66 participants in a group of emerging adults with autism (mean age 22.2 years), and without autism (mean age 20.9 years) were assessed in three assessment waves (T1 at 12 years, T2 at 14 years, and T3 at 22 years of age). Parents filled out the Child Behavior Checklist at T2 and participants filled out the Perceived Quality of Life Questionnaire at T3. Total and indirect effects were tested in serial mediation analysis. RESULTS: The results showed that internalizing problems fully mediated the association between childhood autism diagnosis and the quality of life in emerging adulthood, while externalizing problems did not. CONCLUSION: Our findings suggest that attention to adolescent internalizing problems is important to improve the later quality of life for emerging adults with autism.

Anomalous self-experiences and neurocognitive functioning in adolescents at risk for psychosis: Still no significant associations found between these two vulnerability markers.

BACKGROUND: Anomalous self-experiences (ASEs) and neurocognitive impairments are considered essential domains of vulnerability for developing psychotic disorders. However, little research exists of possible associations between ASEs and neurocognitive functions in individuals at-risk for psychosis. The interconnections between ASEs and neurocognitive impairments should therefore be clarified as much as possible, especially in young individuals at risk. No previous studies have investigated these two fundamental domains in non-help-seeking adolescents at risk for developing psychosis. METHODS: This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). Adolescents (N = 48, 94% females, mean age = 15.3) were invited to participate after completing a 14-year-old survey distributed by MoBA. At-risk adolescents were selected based on the 0.4% highest scores on 19 items assessing both psychotic-like experiences and ASEs. Five specifically selected and formulated items measuring ASEs were computed to an ASEs total score. Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery. RESULTS: Regression analyses revealed no significant relationships between ASEs and any neurocognitive domain. CONCLUSIONS: We did not find any significant associations between ASEs and neurocognitive functions in non-help-seeking adolescents at risk for psychotic disorders, which is in line with reports from other types of cohorts. Thus, ASEs and neurocognitive functions may be understood as two relatively separate domains that co-exist in at-risk states. These results underline the need for a wider scope when making predictions about future trajectories, e.g. the development of psychotic disorders. Including both ASEs and neurocognitive functioning in at-risk populations may increase the specificity of vulnerability criteria in this population and enhance our understanding of early psychosis psychopathology.

A randomized controlled trial of Goal Management Training for executive functioning in schizophrenia spectrum disorders or psychosis risk syndromes.

BACKGROUND: Executive functioning is essential to daily life and severely impaired in schizophrenia and psychosis risk syndromes. Goal Management Training (GMT) is a theoretically founded, empirically supported, metacognitive strategy training program designed to improve executive functioning. METHODS: A randomized controlled parallel group trial compared GMT with treatment as usual among 81 participants (GMT, n = 39 versus Wait List Controls, n = 42) recruited from an early intervention for psychosis setting. Computer generated random allocation was performed by someone independent from the study team and raters post-intervention were unaware of allocation. The primary objective was to assess the impact of GMT administered in small groups for 5 weeks on executive functioning. The secondary objective was to explore the potential of the intervention in influencing daily life functioning and clinical symptoms. RESULTS: GMT improved self-reported executive functioning, measured with the Behavior Rating Inventory of Executive Function - Adult version (BRIEF-A), significantly more than treatment as usual. A linear mixed model for repeated measures, including all partial data according to the principle of intention to treat, showed a significant group x time interaction effect assessed immediately after intervention (post-test) and 6 months after intervention (follow-up), F = 8.40, p .005, r .37. Improvement occurred in both groups in objective executive functioning as measured by neuropsychological tests, functional capacity, daily life functioning and symptoms of psychosis rated by clinicians. Self-reported clinical symptoms measured with the Symptoms Check List (SCL-10) improved significantly more after GMT than after treatment as usual, F = 5.78, p .019, r .29. Two participants withdrew due to strenuous testing and one due to adverse effects. CONCLUSIONS: GMT had clinically reliable and lasting effects on subjective executive function. The intervention is a valuable addition to available treatment with considerable gains at low cost. TRIAL REGISTRATION: Registered at clinicaltrials.gov NCT03048695 09/02/2017.

Attention-deficit/hyperactivity disorder persistence from childhood into young adult age: a 10-year longitudinal study.

INTRODUCTION: The aim of this study was to estimate ADHD persistence in a European clinical sample of children diagnosed with ADHD and followed prospectively for 10 years into young adulthood. METHODS: We assessed 85 children with ADHD at baseline (Mage = 11.6, SD = 2.1, 54% male) and re-assessed 59 at 10-year follow-up (Mage = 21.4, SD = 2.3, 54% male). ADHD symptoms at baseline were assessed with a semi-structured clinical interview (Kiddie-Schedule for Affective Disorders and Schizophrenia/Present and lifetime version) and parent rating scales (ADHD Rating Scale IV, Child Behavior Checklist). ADHD symptoms at 10-year follow-up were assessed with a semi-structured clinical interview (MINI-Plus) and self-report scales (ADHD Self-Report Scale version 1.1 screener, Adult Self Report). Functional impairment at 10-year follow-up was assessed with the Global Assessment of Functioning scale. RESULTS: At 10-year follow-up, 39% met ADHD symptom thresholds based on clinical evaluation using MINI-Plus or the ADHD Self-Report Scale version 1.1 screener or the Adult Self Report together with clinicians' rating of functional impairment. CONCLUSION: ADHD persistence rates in this European clinical sample match previous estimates and indicate that a significant proportion of those diagnosed with ADHD as children still exhibit clinical levels of ADHD symptoms in adulthood.

Similar impairments shown on a neuropsychological test battery in adolescents with high-functioning autism and early onset schizophrenia: a two-year follow-up study.

Introduction: Cognitive impairments are common in both Autism Spectrum Disorders (ASD) and schizophrenia, but it is unclear whether the pattern of difficulties is similar or different in the two disorders. This cross-sectional and longitudinal study compared the neuropsychological functioning in adolescents with ASD with adolescents with Early Onset Schizophrenia (EOS).Methods: At baseline and at two-year follow-up, participants were assessed with a brief neuropsychological test battery measuring executive functions, visual and verbal learning, delayed recall and recognition and psychomotor speed.Results: We found similar levels of neuropsychological impairment across groups and over time in the adolescents with ASD or EOS. Adolescents in both groups did not improve significantly on verbal learning, verbal delayed recall, visual learning, visual delayed recall or visual delayed recognition, and both groups performed poorer on verbal recognition. Both groups improved on measures of psychomotor processing and executive functions.Conclusion: The findings suggest that it may be difficult to differentiate adolescents with EOS and ASD based on neuropsychological task performance. An implication of the results is that adolescents with either disorder may benefit from a similar approach to the treatment of cognitive impairment in the disorders.

Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study.

INTRODUCTION: Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue and Chronic Fatigue Syndrome (CFS). This study investigated baseline predictors of chronic fatigue six months after an acute EBV infection. MATERIALS AND METHODS: A total of 200 adolescents (12-20 years old) with acute EBV infection were assessed for 149 possible baseline predictors and followed prospectively. We performed linear regression to assess possible associations between baseline predictors and fatigue (Chalder Fatigue Questionnaire total score) six months after the acute EBV infection. A total of 70 healthy controls were included for cross-sectional reference. This study is part of the CEBA-project (Chronic fatigue following acute Epstein-Barr virus infection in adolescents). RESULTS: In the final multiple linear regression model, fatigue six months after acute EBV infection was significantly and independently predicted by the following baseline variables (regression coefficient B[95% CI]): Sensory sensitivity (0.8[0.09-1.6]), pain severity (0.2[0.02-0.3]), functional impairment (1000 steps/day) (-0.3[-0.5 to -0.08]), negative emotions (anxiety) (0.4[0.2-0.6]), verbal memory (correct word recognition) (1.7[0.1-3.3]), plasma C-reactive protein (2.8[1.1-4.4] for CRP values >0.86) and plasma Vitamin B12 (-0.005[-0.01 to -0.001]). CONCLUSIONS: Development of fatigue after acute EBV infection is to a larger extent predicted by baseline variables related to symptoms and functions than to baseline variables reflecting infectious and immune processes. TRIAL REGISTRATION: ClinicalTrials, ID: NCT02335437, https://clinicaltrials.gov/ct2/show/NCT02335437.

Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later.

AIM: Acute Epstein-Barr virus (EBV) infection is a trigger of prolonged fatigue. This study investigated baseline predictors of physical activity six months after an acute EBV infection. METHODS: A total of 200 adolescents (12-20 years old) with acute EBV infection were assessed for 149 possible baseline predictors and followed prospectively. In this exploratory study, we performed linear regression analysis to assess possible associations between baseline predictors and steps per day at six months. RESULTS: In the final multiple linear regression model, physical activity six months after acute EBV infection was significantly and independently predicted by baseline physical activity (steps per day), substance use (alcohol and illicit drugs) and human growth hormone (adjusted R2  = 0.20). CONCLUSION: Baseline physical activity, substance use and plasma growth hormone are independent predictors of physical activity six months after an acute EBV infection in adolescents, whereas markers of the infection and associated immune response do not seem to be associated with physical activity six months later.

Parental reflective functioning and executive functioning in mothers with substance use disorder.

Having a substance use disorder (SUD) may adversely affect caregiving capacities. Reflective functioning (RF) and executive functioning (EF) are both important capacities for sensitive parenting, and are often impaired in a SUD. Only a few studies have explored the possible association between the two phenomena. In this study, we used a neuropsychological test battery to assess EF, and the Parent Development Interview to assess RF in a sample of mothers with a SUD (N = 43). Although parental RF (PRF) was associated with EF, when controlled for intelligence (IQ) and mental health, there was no significant association between EF and PRF. Mental health, however, showed a significant negative association with PRF. Splitting the group in two based on PRF level, mothers with a negative to low PRF exhibited more severe difficulties in SUD-related aspects, as well as in several EF components, compared to mothers with an adequate to high PRF, highlighting the association between EF and PRF. The results from this study contribute to enhance our understanding of the dynamics underlying vulnerability in PRF that mothers with small children may experience. We suggest EF to be a prerequisite for adequate PRF, and for interventions to be customized accordingly regarding parents with a SUD.

Executive control training for adolescents with ADHD: Study protocol for a randomised controlled trial.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental conditions diagnosed during childhood and adolescence. In addition to the commonly observed symptoms of inattention, hyperactivity, and impulsivity, individuals with ADHD often experience impairments in executive functions (EFs). Goal management training (GMT) is a cognitive remediation intervention targeting EFs, with empirical support from studies with adult populations, including ADHD. The objective of the upcoming trial is to assess the effectiveness of GMT for adolescents with ADHD. METHODS: This pre-registered protocol outlines a multi-centre randomised controlled trial (RCT) comparing GMT to treatment as usual (TAU) to improve EFs. We aim to recruit 120 participants, aged 12 to 18 years, recently diagnosed with ADHD. Participants will be randomly allocated to the group-based GMT intervention in addition to TAU, or the TAU condition, through block randomisation with site stratification. GMT will be delivered in groups of four to six participants, with weekly two-hour sessions for seven weeks, complemented by separate parent and teacher sessions. TAU is standard community mental health treatment. The primary outcome measure will be parent-reported EF assessed with the Behaviour Rating Inventory of Executive Function 2 (BRIEF-2). Secondary outcomes will include ADHD symptom measures, social functioning, quality of life, and neuropsychological tests (attention span, inhibition, working memory, and visuo-motor speed). The outcome assessments will be conducted at baseline, 12 weeks, 12 months, and 24 months post-treatment. CONCLUSION: The study findings will contribute to determine the effectiveness of a non-pharmacological ADHD treatment, including outcome trajectories up to 24 months post-treatment.

Effects of Goal Management Training on self-efficacy, self-esteem, and quality of life for persons with schizophrenia spectrum disorders.

Persons with schizophrenia often show executive dysfunction assessed with both subjective (self-report) and objective (neuropsychological tests) measures. In a recent randomized controlled trial (RCT), subjective executive functioning in everyday life was improved following Goal Management Training (GMT). The aim of the current study is to investigate the potential of GMT to improve secondary well-being outcomes from that RCT, including self-esteem, self-efficacy, and quality of life in persons with schizophrenia spectrum disorders. Since well-being is frequently lower in persons with schizophrenia compared to healthy individuals, further knowledge about well-being as an outcome after cognitive remediation may have implications for clinical treatment. Sixty-five participants were randomly assigned to GMT (n = 31) or a waiting list control condition (n = 34). Assessments were conducted at baseline (T1), immediately after the intervention (T2-5 weeks), and at six-month follow-up (T3). Measures included the Rosenberg Self-Esteem Scale, the Perceived Quality of Life Scale, and the General Self-Efficacy Scale. Results were analyzed using a linear mixed model analysis for repeated measures. There were no significant effects of GMT on self-esteem or quality of life. Only the GMT group showed a significant increase in self-efficacy that was most evident at six months follow-up, F(1, 34) = 10.71, p = 0.002, d = 0.71. Improved self-efficacy was found to correlate significantly with a reduction in perceived executive dysfunction in an exploratory post hoc analysis. Our findings demonstrate the potential of GMT in improving self-efficacy in schizophrenia Clinical trial registration:https://clinicaltrials.gov, NCT03048695.

"I have to charge my social battery": Perspectives from autistic young adults on Quality of Life.

LAY ABSTRACT: In this study we have asked a group of autistic young adults to describe what is important for their quality of life. The 14 participants (aged 21-29 years) were recruited from a 10-year follow-up study of autistic people. During interviews, our participants described the importance of having relationships with family, friends and pets. Having meaningful activities and being able to immerse themselves in particular interests was also reported to be important for a good quality of life. Interests had also guided their choice of what to study and what to do for work. They also spoke of how communication problems with professionals, bullying and sensory and emotional overload could have a negative impact on quality of life. Future interventions should focus on how professionals can help autistic people to connect to people/animals and meaningful activities, as the participants described this as important for having a good quality of life. These findings may be helpful in enhancing how passions and interests can be seen as opportunities for both academic and work careers for autistic people. Future research and interventions should also look at the communication barriers between autistic people and professionals, and how two-way understanding can be improved.

Neuropsychological and Symptom Predictors of Diagnostic Persistence in ADHD: A 25-Year Follow-up Study.

BACKGROUND: This study extends long-term predictive research on ADHD by including both neuropsychological and symptom measures at baseline in adolescence as predictors of diagnostic persistence 25 years later. METHODS: Nineteen males with ADHD and 26 healthy controls (HC; M/F = 13/13), were assessed in adolescence and 25 years later. Measurements at baseline included a comprehensive test battery measuring eight neuropsychological domains, an IQ estimate, the Child Behavior Checklist (CBCL), and the Global Assessment Scale of Symptoms. Differences between ADHD Retainers, Remitters, and HC were calculated with ANOVAs, and potential predictions of differences in the ADHD group by linear regression analyses. RESULTS: Eleven (58%) participants retained their ADHD diagnoses at follow-up. Motor Coordination and Visual perception at baseline predicted diagnosis at follow-up. CBCL Attention problems at baseline in the ADHD group predicted variance in diagnostic status. CONCLUSION: Lower-order neuropsychological functions related to motor function and perception are important long-time predictors of persistence of ADHD.

Predictors of Quality of Life and Functional Impairments in Emerging Adults With and Without ADHD: A 10-Year Longitudinal Study.

OBJECTIVE: We tested the hypotheses that (1) a diagnosis of ADHD in childhood or adolescence is associated with reduced quality of life (QoL) and everyday functioning in emerging adulthood, and (2) executive function (EF) deficits, internalizing difficulties, and ADHD symptoms predict reduced QoL and more functional impairments. METHOD: We assessed 85 children and adolescents with ADHD and 50 typically developing (TD) peers at baseline (Mage = 11.6 years, 58% males), 2-year follow-up, and 10-year follow-up with neuropsychological tests of EF and self-reports. RESULTS: Individuals with ADHD reported lower QoL and functional impairments in emerging adulthood compared to TD peers. More internalizing difficulties and ADHD symptoms at baseline and 2-year follow-up significantly predicted lower QoL and more functional impairments at the 10-year follow-up. CONCLUSION: ADHD and internalizing difficulties in childhood or adolescence have a negative impact on QoL and everyday functioning in emerging adulthood.

Moderators of metacognitive strategy training for executive functioning in early schizophrenia and psychosis risk.

Goal Management Training (GMT) improved self-reported executive functioning in a recent randomized, controlled trial in early intervention for psychosis participants. Little is known about the mechanism for this benefit, so this study investigates objectively measured executive function, the difference between subjective and objective executive function, independent living and employment status as potential moderators of efficacy of GMT. Baseline scores from 81 participants (GMT n = 39 vs Treatment-as-usual; TAU n = 42) were analyzed in a linear mixed model analysis for repeated measures as predictors of improvement on the self-reported Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) immediately and 30 weeks after GMT. Potential moderators were scores from objective measures of executive functioning, discrepancy between subjective and objective measures, independent living and employment status. Discrepancy was assessed by comparing four clusters of participants with differing patterns of scores. The effect of GMT remained significant regardless of initial objective executive functioning at baseline. Those with higher subjective complaints at baseline in two clusters with (i) both objective and subjective executive dysfunction, and (ii) mostly subjective executive dysfunction experienced greater change after treatment. Living arrangements or participation in education or work did not significantly moderate the effects of GMT. Poor performance on neuropsychological tasks is not an obstacle to making use of GMT, but further knowledge is needed about the benefits of strategy training for individuals with a combination of poor performance with few subjective complaints.

Childhood executive functions and ADHD symptoms predict psychopathology symptoms in emerging adults with and without ADHD: a 10-year longitudinal study.

Deficits in executive functions (EFs) are theorized to play an important role in causing functional impairment and associated psychopathology in individuals with ADHD. The objective of this study was to examine the role of EFs and ADHD symptoms as longitudinal predictors of psychopathology symptoms in individuals with ADHD and typically developing individuals. We assessed individuals with and without ADHD (N = 135) with neuropsychological tests of EFs and scales of ADHD symptoms and psychopathology symptoms at baseline (T1; Mage = 11.59, 57.8% boys), 2-year follow-up (T2; Mage = 13.63, 97% retention), and 10-year follow-up (Mage = 21.18, 75% retention). Baseline EFs predicted psychopathology symptoms at the 2- and the 10-year follow-up, explaining 17% and 12% of the variance, respectively. Baseline EFs predicted both internalizing and externalizing symptoms, and the predictive value of EFs on psychopathology symptoms at 10-year follow-up was accounted for by cognitive flexibility. Baseline ADHD symptoms were a significant predictor of all symptom domains at all time points. Thus, childhood EFs, in particular cognitive flexibility, can predict psychopathology symptoms in emerging adulthood beyond the effect of ADHD symptoms. This supports dominating theories of ADHD stating that executive dysfunction contributes to the observed phenotype, including associated psychopathology symptoms, and suggests that EFs are important targets of interventional efforts.

Childhood Executive Function Predicts Internalizing and Externalizing Symptoms in Emerging Adults With and Without Autism: A 10-Year Longitudinal Study.

Individuals with autism spectrum disorder (ASD) and typically developing individuals were assessed on three neuropsychological tests of executive function (EF) and on scales of autism symptoms and co-occurring internalizing and externalizing symptoms at baseline (T1; N = 88, Mage = 11.8 years, 73% males), 2-year (T2; 99% retention, Mage = 13.9 years), and 10-year follow-ups (T3; 75% retention, Mage = 21.4 years). An EF composite score from T1 significantly predicted internalizing symptoms at T2 (ß = .228) and internalizing and externalizing symptoms at T3 (ß = .431 and .478, respectively), when controlling for age and autism symptoms. OThe findings suggest that EF difficulties are a long-term risk factor for more co-occurring symptoms. .

Executive functions and ADHD symptoms predict educational functioning in children with ADHD: A two-year longitudinal study.

The aim of this two-year longitudinal study was to investigate whether deficits in executive functions (EF) predict impaired everyday functioning after two years in children and adolescents with ADHD. A sample of 135 participants with and without ADHD were assessed with neuropsychological tests of EF and parent ratings of everyday functioning with the Child Behavior Checklist at baseline (Mage = 11.6, SD = 2.0), and after two years (Mage = 13.6, SD = 2.1). Results showed that ADHD symptoms and impaired EF at baseline predicted lower educational functioning when controlling for general cognitive ability (i.e. "IQ") at two-year follow-up. Furthermore, the results indicated that increased ADHD symptoms predicted problems both with social functioning and functioning in leisure activities (i.e. sport/hobbies/chores/jobs), whereas higher IQ predicted better functioning in leisure activities. The current study primarily highlights the importance of detecting and treating ADHD symptoms in order to prevent reduced functional outcomes, and that EF tests may contribute to identify children in need of educational interventions targeting EF deficits.

Decision-making and Risky Behavior in Individuals with Attention-Deficit/Hyperactivity Disorder: A 10-year Longitudinal Study.

We assessed 85 children with Attention-Deficit/Hyperactivity Disorder (ADHD) and 50 typically developing children (TD) (Mage = 11.59, 57.8% boys) with the Hungry Donkey Task (HDT) at baseline and 2-year follow-up, and the Iowa Gambling Task at 10-year follow-up (75% retention). Improvement in the proportion of advantageous choices was observed from two- to 10-year follow-up, but the ADHD group improved less and was outperformed by the TD group at the 10-year follow-up. More advantageous choices on the HDT at baseline predicted less risky behavior at 10-year follow-up. Male sex and more inattentive or externalizing symptoms at baseline predicted more risky behavior.

A systematic review of premorbid cognitive functioning and its timing of onset in schizophrenia spectrum disorders.

Cognitive impairments are core features of established schizophrenia spectrum disorders (SSD). However, it remains unclear whether specific cognitive functions are differentially impaired pre-onset and at what age these impairments can be detected. The purpose of this review was to elucidate these issues through a systematic summary of results from longitudinal studies investigating impairment in specific cognitive domains as antecedents of SSD. Relevant studies were identified by electronic and manual literature searches and included any original study of cognitive domains any time pre-onset of SSDs that included a control group. Effect sizes were calculated by domain for studies comparing high-risk participants who developed SSD with those who did not. The strongest evidence for impairment pre-onset was for mental processing speed, verbal learning and memory, executive function, and social cognition. Some verbal impairments, like language abilities at age 3 and verbal learning and memory at age 7, may develop as static deficits. Conversely, some non-verbal impairments, like mental processing speed, visuospatial abilities, and visual working memory manifest as developmental lag and become significant later in life. Most effect sizes were small to moderate, except for verbal fluency (d' = 0,85), implying this impairment as central in high-risk participants who develop SSD. The present review documents extensive cognitive impairments pre-onset of SSD, and that these impairments start early in life, in line with the neurodevelopmental hypothesis of schizophrenia. Increased knowledge about cognitive impairments preonset can provide a better basis for understanding the complex pathogenesis of SSD as well as informing cognitive remediation programs.