Antecedents of major depressive, bipolar, and psychotic disorders: A systematic review and meta-analysis of prospective studies.

Major depressive, bipolar, or psychotic disorders are preceded by earlier manifestations in behaviours and experiences. We present a synthesis of evidence on associations between person-level antecedents (behaviour, performance, psychopathology) in childhood, adolescence, or early adulthood and later onsets of major depressive disorder, bipolar disorder, or psychotic disorder based on prospective studies published up to September 16, 2022. We screened 11,342 records, identified 460 eligible publications, and extracted 570 risk ratios quantifying the relationships between 52 antecedents and onsets in 198 unique samples with prospective follow-up of 122,766 individuals from a mean age of 12.4 to a mean age of 24.8 for 1522,426 person years of follow-up. We completed meta-analyses of 12 antecedents with adequate data. Psychotic symptoms, depressive symptoms, anxiety, disruptive behaviors, affective lability, and sleep problems were transdiagnostic antecedents associated with onsets of depressive, bipolar, and psychotic disorders. Attention-deficit/hyperactivity and hypomanic symptoms specifically predicted bipolar disorder. While transdiagnostic and diagnosis-specific antecedents inform targeted prevention and help understand pathogenic mechanisms, extensive gaps in evidence indicate potential for improving early risk identification.

Depressive symptoms in youth before and during the COVID-19 pandemic: longitudinal investigation of patterns dependent on age, sex, and family history of mental illness.

BACKGROUND: Cross-sectional studies report high levels of depressive symptoms during the COVID-19 pandemic, especially in youth and females. However, longitudinal research comparing depressive symptoms before and during the pandemic is lacking. Little is known about how the pandemic affected individuals with familial history of mental illness. The present study examines the impact of the pandemic on youth depressive symptoms, including offspring of parents with major mood and psychotic disorders. METHODS: Between March 2018 and February 2020, we measured depressive symptoms in 412 youth aged 5-25 years. We measured depressive symptoms again in 371 (90%) of these youth between April 2020 and May 2022. Two thirds (249) participants had a biological parent with a major mood or psychotic disorder. We tested the effect of the pandemic by comparing depression symptoms before and after March 2020. We examined age, sex, and family history as potential moderators. RESULTS: We found an overall small increase in youth depressive symptoms (b = 0.07, 95% CI -0.01 to 0.15, p = 0.062). This was driven by an increase in female youth without familial history of mental illness (b = 0.35, 95% CI 0.14 to 0.56, p = 0.001). There was no change in depressive symptoms among offspring of parents with mental illness or males. CONCLUSIONS: Our results provide reassurance about the wellbeing of children of parents with mental illness during a period of restricted access to resources outside the family. Rather than increasing symptoms in established risk groups, the pandemic led to a redistribution of depression burden towards segments of the youth population that were previously considered to be low-risk.

Youth Experience Tracker Instrument: A self-report measure of developmental antecedents to severe mental illness.

AIM: We sought to examine the structure, internal consistency, convergent and criterion validity of the Youth Experience Tracker Instrument (YETI), a new brief self-report measure designed to facilitate early identification of risk for severe forms of mental illness, including major depressive disorder, bipolar disorder, and schizophrenia. METHODS: We collected 716 YETIs from 315 individuals aged 8 to 27 with and without familial risk of severe mental illness. The YETI measures six developmental antecedents that precede and predict serious forms of mental illness: affective lability, anxiety, basic symptoms, depressive symptoms, psychotic-like experiences, and sleep. A battery of concurrent questionnaires and interviews measured the same constructs. RESULTS: The best-fitting bifactor model supported the validity of both total score and antecedent-specific subscales. Internal consistency was high for the total score (ω = 0.94) and subscales (ω = 0.80-0.92; ρ = 0.72). The total score captured the majority of information from the 26 YETI items (hierarchical omega ωh = 0.74). Correlations of YETI subscales with established measures of the same constructs (r = 0.45-0.80) suggested adequate convergent validity. We propose cut-offs with high negative predictive values to facilitate efficient risk screening. CONCLUSION: The YETI, a brief self-report measure of antecedents, provides an alternative to using multiple longer instruments. Future research may examine the predictive validity of the YETI for the onset of major mood and psychotic disorders.

Cognition in offspring of parents with psychotic and non-psychotic severe mental illness.

BACKGROUND: Cognitive impairment is a feature of severe mental illness (SMI; schizophrenia, bipolar disorder, major depressive disorder). Psychotic forms of SMI may be associated with greater cognitive impairment, but it is unclear if this differential impairment pre-dates illness onset or whether it reflects a consequence of the disorder. To establish if there is a developmental impairment related to familial risk of psychotic SMI, we investigated cognition in offspring of parents with psychotic and non-psychotic SMI. METHOD: Participants included 360 children and youth (mean age 11.10, SD 4.03, range 6-24), including 68 offspring of parents with psychotic SMI, 193 offspring of parents with non-psychotic SMI, and 99 offspring of control parents. The cognitive battery assessed a range of functions using standardized tests and executive function tasks from the Cambridge Automated Neuropsychological Test Battery. RESULTS: Compared to controls, offspring of parents with psychotic SMI performed worse on overall cognition (ß = -0.32; p < 0.001) and 6 of 15 cognitive domains, including verbal intelligence, verbal working memory, processing speed, verbal learning and memory, verbal fluency, and sustained attention. Offspring of parents with non-psychotic SMI performed worse than controls on 3 of the 15 domain specific cognitive tests, including verbal intelligence, visual memory and decision-making. CONCLUSIONS: Widespread mild-to-moderate cognitive impairments are present in young offspring at familial risk for transdiagnostic psychotic SMI. Offspring at familial risk for non-psychotic SMI showed fewer and more specific impairments in the domains of verbal intelligence, visual memory and decision-making.

Cognitive-behavioural interventions for prevention and treatment of anxiety in young children: A systematic review and meta-analysis.

BACKGROUND: Anxiety disorders are common and impairing throughout the life course. Propensity to anxiety disorders manifests as distress and avoidance of novel stimuli (called behavioural inhibition) as early as in infancy. Already in preschool children, anxiety disorders impact emotional development and school readiness. Anxiety disorders and behavioural inhibition are prospectively associated with increased risk of mood disorders, substance use, and suicide. Therefore, early targeted prevention and treatment need to be considered. Cognitive-behavioural interventions are effective for anxiety in older age group but their efficacy for preschool children remains to be established. METHODS: We searched PsycINFO, PubMed, and Embase until September 19th, 2019 using terms describing anxiety, behavioural inhibition, intervention, and young children. We included studies with young children participating in a cognitive-behavioural intervention for anxiety disorders, anxiety symptoms, or behavioural inhibition. We completed random-effects robust meta-analyses to (1) compare anxiety measures before and after intervention and to (2) compare intervention and control groups. RESULTS: We identified 43 samples including 2656 participants with a mean age of 5.45 (SD = 1.00) years. Anxiety decreased after cognitive-behavioural intervention (standardized mean difference [SMD] = -1.34, 95%CI -1.59 to -1.09, p < 0.0001). Anxiety decreased more in children who received intervention than in children in control conditions (SMD = -0.81, 95%CI -1.00 to -0.63, p < 0.0001). The difference remained significant after correcting for potential publication bias and outliers (SMD = -0.89, 95% CI -1.13 to -0.66, p < 0.0001). The improvement was maintained over follow-up. CONCLUSIONS: Cognitive-behavioural interventions are effective for prevention and treatment of anxiety in young children.

Visual memory and psychotic symptoms in youth.

BACKGROUND: Psychotic symptoms are common during childhood and adolescence and may indicate transdiagnostic risk of future psychiatric disorders. Lower visual memory ability has been suggested as a potential indicator of future risk of mental illness. The relationship between visual memory and clinician-confirmed definite psychotic symptoms in youth has not yet been explored. METHODS: We examined visual memory and psychotic symptoms among 205 participants aged 7-27 years in a cohort enriched for parental mood and psychotic disorders. We assessed visual memory using the Rey Complex Figure Test (RCFT) and psychotic symptoms using validated semi-structured interview measures. We tested the relationship between visual memory and psychotic symptoms using mixed-effects logistic regression. RESULTS: After accounting for age, sex, and family clustering, we found that psychotic symptoms were significantly associated with lower visual memory (OR = 1.80, 95% CI 1.06-3.06, p = 0.030). This result was unchanged after accounting for general cognitive ability. CONCLUSION: Lower visual memory performance is associated with psychotic symptoms among youth, regardless of general cognitive ability. This finding may inform future targeted early interventions.

Visual memory in offspring of parents with mental illness.

Severe mental illness (SMI) refers to impairing and frequently chronic disorders that are difficult to treat. Lower cognitive performance early in life may be a manifestation of risk for SMI. Visual memory has been highlighted as a potential cognitive predictor of future risk of developing bipolar disorder and schizophrenia. We examined visual memory in 214 participants (mean age = 12.62, SD = 4.49) using the Rey Complex Figure Test (RCFT). Our sample included 37 offspring with no parental history of mental illness, 103 offspring with parental history of non-severe mental illness (NSMI), and 74 offspring with parental history of SMI. We tested the effects of family history of mental illness on visual memory using mixed-effects linear regression. After accounting for age, sex, and family clustering, we found that as severity of parental mental illness increases, offspring visual memory performance decreases significantly (b = -3.58, 95% CI -6.79 to -0.37, p = 0.029). We found that severity of parental mental illness predicts visual memory ability. This finding may help identify youth most at risk of developing mental illness and thus inform future interventions.

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 6-17 years, 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 (ß = 0.46, 95% CI 0.17-0.76, p = 0.002) or bipolar disorder (ß = 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.

Active behaviors and screen time in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia.

Activities may be modifiable factors that moderate the risk and resilience in the development of mental health and illness. Youth who spend more time using screens are more likely to have poor mental health. Conversely, time spent engaged in active behaviors (i.e., physical activity, socializing and reading) is associated with better mental health. The choice of activities may be important in offspring of parents with mental illness, who are at increased risk for developing mental disorders. Among 357 youth of the FORBOW (Families Overcoming Risks and Building Opportunities for Well-being) cohort aged 6-21, we examined whether parental diagnosis of mental illness (i.e., major depressive disorder, schizophrenia and bipolar disorder) and current levels of depression influenced the amount of time their offspring spent using screens and engaging in active behaviors. Parental history of mental illness and higher levels of current depression in mothers were associated with less time spent engaged in active behaviors and more time spent using screens. Creating opportunities and incentives for active behaviors may redress the balance between youth with and without a familial history of mental illness.

Neurodevelopmental and genetic determinants of exposure to adversity among youth at risk for mental illness.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and lower cognitive ability have been linked with increased likelihood of exposure to adversity. We hypothesized that these associations may be partly due to genetic factors. METHODS: We calculated polygenic scores for ADHD and intelligence and assessed psychopathology and general cognitive ability in a sample of 297 youth aged 5-27 years enriched for offspring of parents with mood and psychotic disorders. We calculated an adversity score as a mean of 10 indicators, including socio-economic disadvantage, childhood maltreatment and bullying. We tested the effects of polygenic scores, externalizing symptoms and IQ on adversity scores using mixed-effects linear regression. RESULTS: Externalizing symptoms and general cognitive ability showed expected positive and negative relationships with adversity, respectively. Polygenic scores for intelligence were unrelated to adversity, but polygenic scores for ADHD were associated with adversity (ß = 0.23, 95% CI 0.13 to 0.34, p < .0001). ADHD polygenic scores uniquely explained 4.0% of variance in adversity score. The relationship between polygenic scores for ADHD and adversity was independently significant among individuals with (ß = 0.49, 95% CI 0.25 to 0.75, p < .0001) and without (ß = 0.14, 95% CI 0.02 to 0.26, p = .022) ADHD. CONCLUSIONS: A genetic score indexing liability to ADHD was associated with exposure to adversity in early life. Previously observed associations between externalizing symptoms, lower cognitive ability and adversity may be partially attributed to genetic liability to ADHD.

Basic symptoms in offspring of parents with mood and psychotic disorders.

BACKGROUND: Basic symptoms, defined as subjectively perceived disturbances in thought, perception and other essential mental processes, have been established as a predictor of psychotic disorders. However, the relationship between basic symptoms and family history of a transdiagnostic range of severe mental illness, including major depressive disorder, bipolar disorder and schizophrenia, has not been examined. AIMS: We sought to test whether non-severe mood disorders and severe mood and psychotic disorders in parents is associated with increased basic symptoms in their biological offspring. METHOD: We measured basic symptoms using the Schizophrenia Proneness Instrument - Child and Youth Version in 332 youth aged 8-26 years, including 93 offspring of control parents, 92 offspring of a parent with non-severe mood disorders, and 147 offspring of a parent with severe mood and psychotic disorders. We tested the relationships between parent mental illness and offspring basic symptoms in mixed-effects linear regression models. RESULTS: Offspring of a parent with severe mood and psychotic disorders (B = 0.69, 95% CI 0.22-1.16, P = 0.004) or illness with psychotic features (B = 0.68, 95% CI 0.09-1.27, P = 0.023) had significantly higher basic symptom scores than control offspring. Offspring of a parent with non-severe mood disorders reported intermediate levels of basic symptoms, that did not significantly differ from control offspring. CONCLUSIONS: Basic symptoms during childhood are a marker of familial risk of psychopathology that is related to severity and is not specific to psychotic illness. DECLARATION OF INTEREST: None.