Using brain structural neuroimaging measures to predict psychosis onset for individuals at clinical high-risk.

Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-including those from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS+ from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS+ in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings.

Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study.

INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool. METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables. RESULTS: Compared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges' g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses. CONCLUSION: EOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis.

Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age = 16.6 years, interquartile range (IQR) = 2.14, 46.4% females) and 265 adolescent healthy controls (median age = 16.2 years, IQR = 2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d = 0.37), posterior corona radiata (d = 0.32), and superior fronto-occipital fasciculus (d = 0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.

Cognitive predictors of transition and remission of psychosis risk syndrome in a child and adolescent sample: longitudinal findings from the CAPRIS study.

Cognitive impairments are proposed as predictors in the differentiation between subjects with psychosis risk syndrome (PRS) who will develop a psychotic disorder (PRS-P) and those who will not (PRS-NP). More in-depth study of the PRS-NP group could contribute to defining the role of cognitive alterations in psychosis. This study aims to analyze cognition of children and adolescents with PRS in terms of their clinical outcome at 18-month follow-up (psychosis, remission, and non-remission) and of determinate predictors of transition to psychosis and remission of PRS. The method is two-site, naturalistic, longitudinal study design, with 98 help-seeking adolescents with PRS and 64 healthy controls (HC). PRS-P (n = 24) and PRS-NP (n = 74) participants were clinically and cognitively assessed at baseline, and when full-blown psychotic disorder had developed or at 18-month follow-up. PRS-P subjects showed lower scores at baseline in processing speed, visuospatial memory, attention, and executive function (cognitive flexibility/processing speed) compared to HC. PRS-NP subjects showed lower baseline scores in verbal working memory and verbal fluency compared to HC. This deficit is also observed in the PRS group of participants still presenting attenuated psychotic symptoms at 18-month follow-up, while PRS subjects in remission showed a similar cognitive profile to HC subjects. Baseline score on processing speed, measured with a coding task, appeared to be a predictive variable for the development of a psychotic disorder. Performance in verbal working memory was predictive of remission in the PRS-NP. Post hoc comparisons indicate the need for careful interpretation of cognitive markers as predictors of psychosis. Cognitive impairments are present in both PRS-P and PRS-NP. Those individuals who recover from PRS show baseline cognitive performance comparable to the HC group. Together with sociodemographic variables, this observation could help in the differentiation of a variety of PRS trajectories in children and adolescents.

Clinical and neurodevelopmental predictors of psychotic disorders in children and adolescents at clinical high risk for psychosis: the CAPRIS study.

BACKGROUND: The neurodevelopmental hypothesis of schizophrenia represents the disorder as an expression of an alteration during the brain development process early in life. Neurodevelopmental variables could become a trait marker, and the study of these variables in children and adolescents at clinical high risk for psychosis (CHR) could identify a specific cluster of patients who later developed psychosis. The aim of this study is to describe clinical and neurodevelopment predictors of transition to psychosis in child and adolescent participants at CHR. Naturalistic longitudinal two-center study of 101 CHR and 110 healthy controls (HC) aged 10-17. CHR participants were children and adolescents aged 10-17, meeting one or more of the CHR criteria assessed at baseline and at 18 months' follow-up. Neurodevelopmental variables assessed were obstetric complications, delay in principal development milestones, and presence of a neurodevelopment diagnosis. Pairwise comparisons, linear regressions, and binary logistic regression were performed.A transition rate of 23.3% at 1.5 years was observed. Participants who developed psychosis (CHR-P) showed higher rates of grandiosity and higher proportions of antipsychotic medication intake at baseline compared to participants who did not develop a psychotic disorder (CHR-NP). In terms of neurodevelopment alterations, CHR-P group showed a higher proportion of participants reporting delay in language development than the CHR-NP and HC groups. The odds of psychosis increased by 6.238 CI 95% [1.276-30.492] for a one-unit increase in having a positive score in grandiosity; they increased by 4.257 95% CI [1.293-14.023] for a one-unit increase in taking antipsychotic medication, and by 4.522 95% [1.185-64.180] for showing language development delay. However, the p-values did not reach significance after adjusting for multiple comparisons.A combination of clinical and neurodevelopmental alterations could help predict the transition to psychotic disorder in a CHR child and adolescent sample. Our results suggest the potential utility of collecting information about neurodevelopment and using these variable multifactorial models to predict psychosis disorders.

Running in the FAMILY: understanding and predicting the intergenerational transmission of mental illness.

Over 50% of children with a parent with severe mental illness will develop mental illness by early adulthood. However, intergenerational transmission of risk for mental illness in one's children is insufficiently considered in clinical practice, nor is it sufficiently utilised into diagnostics and care for children of ill parents. This leads to delays in diagnosing young offspring and missed opportunities for protective actions and resilience strengthening. Prior twin, family, and adoption studies suggest that the aetiology of mental illness is governed by a complex interplay of genetic and environmental factors, potentially mediated by changes in epigenetic programming and brain development. However, how these factors ultimately materialise into mental disorders remains unclear. Here, we present the FAMILY consortium, an interdisciplinary, multimodal (e.g., (epi)genetics, neuroimaging, environment, behaviour), multilevel (e.g., individual-level, family-level), and multisite study funded by a European Union Horizon-Staying-Healthy-2021 grant. FAMILY focuses on understanding and prediction of intergenerational transmission of mental illness, using genetically informed causal inference, multimodal normative prediction, and animal modelling. Moreover, FAMILY applies methods from social sciences to map social and ethical consequences of risk prediction to prepare clinical practice for future implementation. FAMILY aims to deliver: (i) new discoveries clarifying the aetiology of mental illness and the process of resilience, thereby providing new targets for prevention and intervention studies; (ii) a risk prediction model within a normative modelling framework to predict who is at risk for developing mental illness; and (iii) insight into social and ethical issues related to risk prediction to inform clinical guidelines.

Cognitive reserve and its correlates in child and adolescent offspring of patients diagnosed with schizophrenia or bipolar disorder.

AIM: To analyze cognitive reserve (CR) in child and adolescent offspring of patients diagnosed with schizophrenia (SZ-off) or bipolar disorder (BD-off) and compare them with a group of community controls (CC-off). We also aimed to investigate whether there was an association between CR and clinical and neuropsychological variables according to group. METHODS: The study included 46 SZ-off, 105 BD-off and 102 CC-off. All participants completed assessments regarding CR and clinical, neuropsychological and psychosocial functioning. CR was measured with a proxy based on premorbid intelligence, parental occupational level, educational attainment, developmental milestones and sociability. The clinical assessment included the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime, the Semi-structured Interview for Prodromal Syndromes, and the Global Assessment Functioning scale. The neuropsychological assessment included measures of executive functioning, attention, verbal memory, working memory and processing speed. RESULTS: SZ-off showed a lower level of CR compared to BD-off and CC-off, while BD-off showed an intermediate level of CR between SZ-off and CC-off. Moreover, an association between higher CR and less lifetime psychopathology, fewer prodromal psychotic symptoms, higher psychosocial functioning, and a higher working memory score was observed in all groups, but it was stronger in SZ-off. CONCLUSIONS: CR seemed to be associated with psychopathology, clinical symptoms, psychosocial functioning, and some cognitive functions. SZ-off appeared to benefit more from a higher CR, therefore it could be considered a protective factor against the development of clinical symptomatology and cognitive impairment.

Age-related change in cortical thickness in adolescents at clinical high risk for psychosis: a longitudinal study.

Progression to psychosis has been associated with increased cortical thinning in the frontal, temporal and parietal lobes in individuals at clinical high risk for the disorder (CHR-P). The timing and spatial extent of these changes are thought to be influenced by age. However, most evidence so far stems from adult samples. Longitudinal studies are essential to understanding the neuroanatomical changes associated to transition to psychosis during adolescence, and their relationship with age. We conducted a longitudinal, multisite study including adolescents at CHR-P and healthy controls (HC), aged 10-17 years. Structural images were acquired at baseline and at 18-month follow-up. Images were processed with the longitudinal pipeline in FreeSurfer. We used a longitudinal two-stage model to compute the regional cortical thickness (CT) change, and analyze between-group differences controlling for age, sex and scan, and corrected for multiple comparisons. Linear regression was used to study the effect of age at baseline. A total of 103 individuals (49 CHR-P and 54 HC) were included in the analysis. During follow-up, the 13 CHR-P participants who transitioned to psychosis exhibited greater CT decrease over time in the right parietal cortex compared to those who did not transition to psychosis and to HC. Age at baseline correlated with longitudinal changes in CT, with younger individuals showing greater cortical thinning in this region. The emergence of psychosis during early adolescence may have an impact on typical neuromaturational processes. This study provides new insights on the cortical changes taking place prior to illness onset.

Debate: Child and adolescent mental health services: time to take the lead in prevention of psychosis in youth.

Children and adolescents are at risk of developing mental disorders that have lifelong consequences. This debate piece argues that youth meeting the criteria for clinical high risk for psychosis cannot be assessed and treated with the same tools as adults, given that they often present with different patterns and timecourse of symptoms, age-specific comorbidities and follow different pathways to care. It looks at the key role that Child and Adolescent Mental Health Services and other professionals can play by using an age-specific approach to detecting and preventing psychosis.

Psychopathology and mental health service use among youth in foster care admitted to a psychiatric inpatient unit: a 4-year retrospective controlled study.

Youth in foster care (FC) are at increased risk of poor psychosocial outcomes. The aim of this study was to assess psychopathology and mental health service use among youth living in FC who require psychiatric hospitalisation. All individuals admitted to our Children and Adolescent Inpatient Psychiatry Unit between 2014 and 2017 who were in FC were systematically reviewed. The control group was defined as all youth living with their immediate family and hospitalised in our unit throughout 2016. We identified 89 patients placed in FC and 247 controls. Socio-demographic and clinical data were retrospectively collected from computerised charts. A survival analysis of emergency department visits and readmission to the hospital was conducted. Compared to controls, the FC group presented significantly higher rates of conduct disorder (78.7% vs 14.6%; p < 0.001) and substance use disorder (49.4% vs 27.5%; p < 0.001), mainly cannabis use (34.8% vs 16.6%; p < 0.001); higher rates of comorbidity (96.6% vs 55.9%; p < 0.001) and mean number of comorbid diagnoses (3.3 ± 1.1 vs 2.3 ± 0.5; p < 0.001). The FC group had a higher number of emergency room visits before and after admission than controls. FC youth were also 2.77 times more likely to visit the emergency department after discharge, and in a shorter time period, than controls (p = 0.004). Disruptive behaviours, substance use disorder, and comorbid psychopathology were all more prevalent among FC youth than controls. Specific strategies are needed to optimize community mental health resources and address the increased use of emergency services by these youth before and after hospitalisation.

Major depressive disorder and attenuated negative symptoms in a child and adolescent sample with psychosis risk syndrome: the CAPRIS study.

Some 70-80% of subjects with psychotic risk syndrome (PRS) have lifetime comorbidity, with depressive disorders being the most common. A high proportion of patients with PRS present nonspecific symptoms which can be confounding factors for diagnosis. Depressive and negative symptoms may be difficult to distinguish and it is important to differentiate them. The aim of this study is to assess the presence of depressive disorder in a child and adolescent sample of PRS and to examine the presence of negative symptoms and detect possible confounding characteristics between them and depressive symptoms. This is a naturalistic multi-site study with subjects who met PRS criteria. A sample of 89 PRS adolescent patients was included. Major depressive disorder (MDD) is the most prevalent comorbid disorder (34.83%). The sample was divided into patients who met criteria for MDD (PRS-MDD, n = 31) and those who did not have this disorder (PRS-ND, n = 44). We obtained significant differences in the attenuated negative symptoms (ANS) between PRS-MDD and PRS-ND (68.18 vs. 90.32%, respectively, p = 0.021). Subjects with MDD presented a higher score in ANS and Hamilton Depression Rating Scale (HDRS). Moreover, we obtained a correlation between negative symptomatology and HDRS score with a higher score on HDRS in subjects with higher negative symptom scores (r = 0.533, p < 0.001). More research is needed to fine tune differentiation between depressive and negative symptoms and learn more about the possible impact of MDD on PRS children and adolescents.

Brain structural trajectories in youth at familial risk for schizophrenia or bipolar disorder according to development of psychosis spectrum symptoms.

BACKGROUND: The evaluation of child and adolescent offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) may help understand changes taking place in the brain in individuals at heightened risk for disease during a key developmental period. METHODS: One hundred twenty-eight individuals (33 SzO and 46 BpO, considered jointly as 'Familial High Risk' (FHR), and 49 controls) aged 6-17 years underwent clinical, cognitive and neuroimaging assessment at baseline, 2- and 4-year follow-up. Twenty FHR participants (11 SzO and 9 BpO) developed psychotic spectrum symptoms during follow-up, while 59 FHR participants did not. Magnetic resonance imaging was performed on a 3Tesla scanner; cortical surface reconstruction was applied to measure cortical thickness, surface area and grey matter volume. RESULTS: FHR participants who developed psychotic spectrum symptoms over time showed greater time-related mean cortical thinning than those who did not and than controls. By subgroups, this effect was present in both BpO and SzO in the occipital cortex. At baseline, FHR participants who developed psychotic spectrum symptoms over time had smaller total surface area and grey matter volume than those who did not and than controls. Over time, all FHR participants showed less longitudinal decrease in surface area than controls. In those who developed psychotic spectrum symptoms over time, this effect was driven by BpO, while in those who did not, this was due to SzO, who also showed less grey matter volume reduction. CONCLUSION: The emergence of psychotic spectrum symptoms in FHR was indexed by smaller cross-sectional surface area and progressive cortical thinning. Relative preservation of surface area over time may signal different processes according to familial risk. These findings lay the foundation for future studies aimed at stratification of FHR youth.

Cognitive reserve in patients with first-episode psychosis as outcome predictor at 5-year follow-up.

Cognitive reserve (CR) is the premorbid brain capacity to cope with neural damage. People with good CR can tolerate higher levels of pathological brain injuries before displaying clinical symptoms than others. This study aimed to analyze CR in a sample of patients diagnosed with first-episode psychosis (FEP) during childhood or adolescence, comparing them to a community control group (CC) and assessing the predictive value of CR regarding psychosocial functioning, clinical symptoms and neuropsychological variables at the 5-year follow-up. 57 patients diagnosed with FEP during childhood or adolescence and 37 controls completed clinical, neuropsychological, and psychosocial functioning assessments at baseline and 5-year follow-up. CR was assessed in both groups at baseline. The FEP group showed lower CR scores than the CC group. Higher CR in the FEP group was associated with fewer psychotic negative symptoms, total psychotic symptoms and depressive symptoms, higher psychosocial functioning, and less impaired memory and attention at the 5-year follow-up. CR is associated with long-term clinical, neuropsychological and psychosocial functioning outcomes in patients diagnosed with FEP during childhood or adolescence.

Neuropsychological, clinical and environmental predictors of severe mental disorders in offspring of patients with schizophrenia.

Offspring of individuals with schizophrenia (SZCOff) are at an increased risk for this disorder. Neuropsychological decline is a core feature of the disorder and researchers have reported increasing impairments in cognition during the prodromal phase in high-risk adolescents. Additionally, factors like the presence of prodromal symptoms or specific behavioral patterns could predict, together with neurocognitive functioning, the risk of conversion to severe mental disorders in SCZOff. This study aims to compare the neuropsychological functioning of a sample of 41 SCZOff children and adolescents and 105 community control offspring (CCOff) and to develop a prediction model to examine whether neuropsychological functioning, clinical and behavioral factors predict subsequent risk of severe mental disorders. We collected demographic, clinical and neuropsychological data. We found significant differences between groups in working memory, speed of processing, verbal memory and learning, visual memory and intelligence quotient (IQ). The socioeconomic status, verbal memory, working memory and positive prodromal symptoms predicted a significant proportion of the dependent variable variance. In conclusion, SCZOff showed neurocognitive impairments in several neuropsychological domains compared to CCOff. Neuropsychological functioning, environmental factors and positive prodromal symptoms could predict the risk of onset of severe mental disorders in SCZOff.

Neuropsychological profile of children and adolescents with psychosis risk syndrome: the CAPRIS study.

Neuropsychological underperformance is well described in young adults at clinical high risk for psychosis, but the literature is scarce on the cognitive profile of at-risk children and adolescents. The aim of this study is to describe the neuropsychological profile of a child and adolescent sample of patients with psychosis risk syndrome (PRS) compared to healthy controls and to analyze associations between attenuated psychotic symptoms and cognitive impairment. Cross-sectional baseline data analysis from a longitudinal, naturalistic, case-control, two-site study is presented. Eighty-one help-seeking subjects with PRS and 39 healthy controls (HC) aged between 10 and 17 years of age were recruited. PRS was defined by: positive or negative attenuated symptoms, Brief Limited Intermittent Psychotic Symptoms (BLIPS), genetic risk (first- or second-degree relative), or schizotypal personality disorder plus impairment in functioning. A neuropsychological battery was administered to assess general intelligence, verbal and visual memory, visuospatial abilities, speed processing, attention, and executive functions. The PRS group showed lower general neuropsychological performance scores at a multivariate level and lower scores than controls in general intelligence and executive functions. Lower scores on executive function and poorer attention were associated with high scores of positive attenuated psychotic symptoms. No association with attenuated negative symptoms was found. This study provides evidence of cognitive impairment in PRS children and adolescents and shows a relationship between greater cognitive impairment in executive functions and attention tasks and severe attenuated positive symptoms. However, longitudinal studies are needed to clarify the nature of cognitive impairment as a possible vulnerability marker.

Clinical high risk for psychosis in children and adolescents: a systematic review.

The concept of being at risk for psychosis has been introduced both for adults and children and adolescents, but fewer studies have been conducted in the latter population. The aim of this study is to systematically review the articles associated with clinical description, interventions, outcome and other areas in children and adolescents at risk for psychosis. We searched in MEDLINE/PubMed and PsycINFO databases for articles published up to 30/06/16. Reviewed articles were prospective studies; written in English; original articles with Clinical High Risk (CHR) for psychosis samples; and mean age of samples younger than 18 years. From 103 studies initially selected, 48 met inclusion criteria and were systematically reviewed. Studies show that CHR children and adolescents present several clinical characteristics at baseline, with most attenuated positive-symptom inclusion criteria observed, reporting mostly perceptual abnormalities and suspiciousness, and presenting comorbid conditions such as depressive and anxiety disorders. CHR children and adolescents show lower general intelligence and no structural brain changes compared with controls. Original articles reviewed show rates of conversion to psychosis between 17 and 20% at 1 year follow-up and between 7 and 21% at 2 years. While 36% of patients recovered from their CHR status at 6-year follow-up, 40% still met CHR criteria. Studies in children and adolescents with CHR were conducted with different methodologies, assessments tools and small samples. It is important to conduct studies on psychopharmacological and psychological treatment, as well as replication of the few studies found.

Temperament in child and adolescent offspring of patients with schizophrenia and bipolar disorder.

Shared vulnerability in offspring of individuals with schizophrenia (SzO) and bipolar disorder (BpO) might manifest early during development through common temperament traits. Temperament dimensions in child and adolescent BpO (N = 80), SzO (N = 34) and the offspring of community controls (CcO) (N = 101) were assessed using the Revised Dimensions of Temperament Survey. The association between temperament dimensions and lifetime psychopathology (including threshold and subthreshold DSM-IV-TR diagnoses) and current socio-academic adjustment was assessed using logistic regression. Fully adjusted models showed that both BpO and SzO scored significantly lower in the positive mood dimension and in the adaptability factor than CcO, with small-medium effect sizes (Cohen's d ~ 0.3-0.5). BpO also scored lower in the activity factor and the activity dimensions than CcO (Cohen's d ~ 0.3). Lower scores in the positive mood dimension were associated with increased risk of impaired adjustment both in BpO [OR 2.30, 95% CI (1.18-4.46)] and in SzO [OR 2.87, 95% CI (1.07-7.66)]. In BpO, lower scores in positive mood were also associated with increased likelihood of internalizing [OR 1.84, 95% CI (1.28-2.64)] and externalizing disorders [OR 1.48, 95% CI (1.01-2.18)]; in SzO, higher scores in activity and flexibility were associated with increased likelihood of internalizing [OR 2.31, 95% CI (1.22-4.38)] and externalizing disorders [OR 3.28, 95% CI (1.2-9)], respectively. Early difficulties in emotion regulation might represent a shared vulnerability phenotype in BpO and SzO. The identification of extreme temperament traits could help to characterize subgroups at greater risk of psychopathology and impaired adjustment, in which targeted interventions are warranted.

Intrinsic functional connectivity of fronto-temporal networks in adolescents with early psychosis.

Adults with psychotic disorders have abnormal connectivity of fronto-temporal networks. However, whether these abnormalities are present in adolescents with early psychosis has not been fully assessed. One-hundred and thirty-nine adolescents aged 12-18 underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging. Following motion correction, data were available for 44 participants with a psychosis risk syndrome, 34 patients with a first episode psychosis (FEP) and 35 healthy controls. Independent component analysis was performed to assess functional networks showing a fronto-temporal scope; this identified a language and a salience network. Mean fractional anisotropy was measured in clusters showing between-group differences in intrinsic functional connectivity (iFC). For the language network, there was a group effect within the right middle/inferior frontal gyrus, explained by reduced iFC in patients with an FEP relative to healthy controls, while in participants with a psychosis risk syndrome values of iFC were intermediate. In this region, values of iFC were positively correlated with mean fractional anisotropy in patients with an FEP. No group differences were observed in the salience network. Reduced iFC of the language network, in association with disrupted white matter microstructure, may characterize FEP during adolescence.

A developmental approach to dimensional expression of psychopathology in child and adolescent offspring of parents with bipolar disorder.

The aim of this is to describe psychopathology, functioning and symptom dimensions accounting for subthreshold manifestations and developmental status in child and adolescent offspring of parents with bipolar disorder ("high-risk offspring"). The study population comprised 90 high-risk offspring (HR-offspring) and 107 offspring of community control parents (CC-offspring). Direct clinical observations and parental and offspring reports based on selected standardized clinical scales were used to assess offspring threshold and subthreshold diagnoses, symptoms and functioning. All outcomes were compared between the whole HR-offspring and CC-offspring samples and then by developmental status. After controlling for potential confounders, HR-offspring showed significantly poorer adjustment for childhood (r = 0.18, p = 0.014) and adolescence (r = 0.21, p = 0.048) than CC-offspring, as well as more emotional problems (r = 0.24, p = 0.001) and higher depression scores (r = 0.16, p = 0.021). As for differences in lifetime categorical diagnoses (threshold and subthreshold) between HR-offspring and CC-offspring, the prevalence of disruptive disorders was higher in pre-pubertal HR-offspring (OR 12.78 [1.45-112.42]), while prevalence of mood disorders was higher in post-pubertal HR-offspring (OR 3.39 [1.14-10.06]). Post-pubertal HR-offspring presented more prodromal (r = 0.40, p = 0.001), negative (r = 0.38, p = 0.002), manic (r = 0.22, p = 0.035) and depressive (r = 0.23, p = 0.015) symptoms than pre-pubertal HR-offspring, as well as more peer relationship problems (r = 0.31, p = 0.004), poorer childhood adjustment (r = 0.22, p = 0.044) and worse current psychosocial functioning (r = 0.27, p = 0.04). Externalizing psychopathology is more prevalent in pre-pubertal HR-offspring, while depressive and prodromal symptoms leading to functional impairment are more prominent in post-pubertal HR-offspring. Developmental approaches and dimensional measures may be useful for identifying children at high risk of developing bipolar disorder and help guide specific preventive strategies.

Mediterranean Diet and Mental Health in Children and Adolescents: A Systematic Review.

CONTEXT: Childhood and adolescence are periods of critical importance in the development of mental health disorders. The Mediterranean diet (MD) has been linked to multiple positive health outcomes, including reduced incidence of mental health disorders and fewer psychiatric symptoms. OBJECTIVE: This study aimed to investigate the association between adherence to an MD and mental health outcomes in children and adolescents. METHODS: A systematic literature review was conducted of original research that explored the relationship between psychiatric symptoms or disorders and adherence to an MD. The literature search was conducted on PubMed, Scopus, Web of Science, MEDES, Dialnet, and Latindex from inception to November 2022, and the Newcastle-Ottawa Scale was used to evaluate the quality of studies. RESULTS: A total of 13 studies (6 cross-sectional, 4 case-control, 2 randomized clinical trials, and 1 longitudinal cohort) out of 450 met the inclusion criteria. A total of 3058 children or adolescents with a mean age range from 8.6 to 16.2 years were included. Among the reviewed studies, 5 (71.42%) of those looking at attention-deficit/hyperactivity disorder, 4 (80%) examining depression, and 2 (50%) assessing anxiety found a significant protective association. Seven articles (53.84%) were found to be of high quality and 6 (46.15%) of moderate quality. CONCLUSION: Adherence to an MD could be a protective factor for mental health in child and adolescent populations. This suggests that promoting an MD could help prevent the onset of clinical psychiatric symptoms, reduce symptom severity, and improve prognosis in young patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021276316.