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BackgroundDisruption in white matter integrity has been consistently observed in individuals with psychosis. However, whether such abnormalities are already present at illness onset or are related to downstream processes remains elusive. The study of adolescents with a recent onset of psychosis provides the opportunity to evaluate white matter integrity proximally to disease onset.MethodsTwenty-six adolescents (aged 15.9 ± 1.3 years) with a first episode of psychosis (FEP) (less than 6 months duration) were compared with 26 age and sex-matched healthy controls (HC) (16.8 ± 2 years). In participants with a FEP, clinical diagnoses were confirmed after a minimum of 1 year follow-up (main categories: schizophrenia, bipolar disorder, or schizoaffective disorder). Anatomical images and diffusion tensor sequences were acquired using a 1.5T scanner. Whole brain, voxel-wise group differences in fractional anisotropy (FA) were investigated between participants with a FEP and controls.ResultsRelative to HC, FEP participants displayed decreased FA in the right posterior cingulate gyrus, encompassing the right superior and posterior corona radiata, and the right parahippocampal gyrus, including the cingulum and fornix. FEP patients showed no areas of increased FA relative to HC. The results remained significant after controlling for medication, cannabis use and intelligence.ConclusionOur findings indicate that adolescents with recent onset of psychotic disorders show decreased white matter integrity in circuits implicated in cognitive functions and emotion regulation.

BACKGROUND: Non-suicidal self-injury (NSSI) is a serious public health concern among adolescents, especially in clinical settings. Social support plays a critical role in the onset and maintenance of NSSI in adolescence. NSSI is closely associated with borderline personality disorder (BPD), yet no previous work has analyzed the mediating role of borderline traits in the relationship between perceived social support (PSS) and NSSI. This study aimed to address this gap. METHODS: Participants were 228 adolescent patients (12 to 18 years old), who completed a clinical interview and self-report measures of BPD-traits, current psychological distress, emotion dysregulation and PSS. They were grouped based on the presence (vs. absence) of NSSI. Univariate and multivariate logistic regression analyses were used to identify risk factors of NSSI, and a mediation analysis was conducted to examine the intermediary role of borderline traits in the relationship between PSS and NSSI. RESULTS: NSSI was highly prevalent in our sample (58%) and was associated with higher clinical severity. Low PSS predicted NSSI in univariate, but not multivariate regression. Mediation analyses showed that borderline traits fully accounted for the relationship between low PSS and NSSI, even when controlling for current psychological distress and gender. LIMITATIONS: Cross-sectional design through self-report assessment. CONCLUSIONS: Findings suggest that adolescents with low PSS are especially vulnerable for developing NSSI due to elevated BPD traits. In clinical settings, interventions aimed to reduce borderline symptoms may be a promising treatment option for adolescents with NSSI and low PSS.

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.

The current study aims to: 1) investigate cognitive differences among adolescents at risk for suicide versus healthy controls (HC) and 2) identify cognitive changes associated with response to psychotherapy among adolescents at high risk for suicide. Thirty-five adolescents at high risk for suicide (HR), and 14 HC adolescents were recruited. Clinical and cognitive assessments were conducted in both groups at baseline and 16 weeks later (after the patients completed psychotherapy). HR and HC adolescents were compared at baseline and at completion of the study. We also conducted further analysis by separating into two groups the HR adolescents who responded to psychotherapy (n=17) and those who did not (n=11). At baseline, the HR group had significantly lower performance on verbal memory and processing speed than the HC group. At week 16, HR adolescents performed as well as HC adolescents in all cognitive domains. Among patients, better performance on visual memory was observed in those who responded to psychotherapy compared to those who did not. We concluded that lower performance on verbal memory and processing speed may be associated with a high risk for suicide among adolescents. Improvement in visual memory might be related to a lower risk for suicide in adolescents.

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.

Objective To compare the offspring of patients with SZ (SZoff) with those of a community control group (CC-off) to determine the variables associated with attenuated psychotic symptoms (APS), general symptomatology and functioning that may help to differentiate those at genetic risk for SZ. Methods 41 SZ-off and 107 CC-off aged 6–17 years were included. The Structured Interview for Prodromal Symptoms (SIPS), scored on the Scale of Prodromal Symptoms (SOPS), was administered by a child psychiatrist blinded to parental diagnoses, together with other clinical and functional scales. Results The SZ-off group presented higher scores in positive (p = 0.000), negative (p = 0.012), and disorganized (p = 0.009) subscale scores, as well as in the total score (p = 0.001) on the SOPS when compared with the CC-off group. Other scales indicated significant emotional (p = 0.028), behavioral (p = 0.000) and peer-related problems (p = 0.025), lower performance at school (p = 0.025) and increased dysfunction score (p = 0.005) in the SZ-off group. Logistic regression analysis revealed lower socioeconomic statuses (OR: 0.92, 95%CI: 0.87–0.97) and higher SOPS positive subscale scores (OR: 2.41, 95%CI: 1.31–4.42) in the SZ-off group. Conclusions SZ-off presented significantly more APS and higher mean scores in psychopathological scales than CC-off, together with increased dysfunction scores. These early warning signs and follow-up for those at genetic high risk for schizophrenia will provide useful information about symptom progression, facilitating early intervention to improve short and long-term outcomes in youths with a positive family history.

Outcome measurement in outpatient and day-care mental health facilities for children and adolescents in Spain remains limited, in part due to a lack of validated scales. To address this issue, we translated HoNOSCA (glossary, score sheet, self-rated questionnaire, and parent/legal guardian questionnaire) into Spanish and Catalan using a reverse translation approach. We ascertained the validity and psychometric quality of the HoNOSCA in Spanish by assessing correlation with the Children's Global Assessment Scale (C-GAS). We recruited 64 participants 7-17 years of age in five day-care Psychiatry hospitals in Catalonia (Spain). Two evaluators administered both instruments twice, two weeks apart. Patients and parents/legal guardians completed the corresponding HoNOSCA versions. We calculated Cronbach's alpha for assessing internal consistency, intra-class correlation coefficients (ICC) for inter-rater and test-retest reliability, and Pearson's correlation coefficients for validity. We found that all HoNOSCA versions in Spanish presented satisfactory internal consistency, inter-rater and test-retest reliability. Concurrent validity for HoNOSCA-Glossary was also acceptable, with Pearson's coefficients of -0.543 and -0.519 for evaluators in the first administration, and of -0.675 and -0.685 in the second administration. HoNOSCA was also successfully translated into Catalan; acceptability was determined using cognitive interviews.

ObjectiveTo examine the prevalence and correlates of suicidal behavior among adolescents with bipolar disorder (BD).Methods47 adolescents, ages 12 to 19 years (15.8 ± 2), meeting DSM-5 criteria for BD-I (n=40) and BD-II (n=7) were assessed using the KSADS-PL and tested with a battery of tests measuring mood, psychotic symptoms, life events and functioning. History of suicidal attempts (SA) was ascertained using the K-SADS-PL.Results: One third (n=15, 32%) of the BD sample had a lifetime history of SA. There were no differences in socio-demographics factors between SA versus non- SA. BD adolescents with lifetime SA, were more likely to have lower weight at birth, a lifetime history of comorbid eating disorder, non-suicidal self-injurious behavior, 2nd degree family history of suicide attempt, and more stressful life events as compared with non-attempters. Adolescents with lifetime history of SA also showed statistically significant higher scores in depression, suicidal ideation and anxiety as compared with BD adolescents without lifetime SA. Logistic regression analysis found that the most robust correlates of SA in adolescents with BD were having 2nd degree family history of SA, the interaction of self-injury behavior and comorbid eating disorder and increased number of life events. Limitations: Retrospective data. Small sample size. Since this is a cross-sectional study, no inferences regarding causality can be made. Conclusion: One third of the adolescents with BD have attempted suicide. These results are in agreement with previous studies. History of SA in adolescents with BD is strongly associated with family history of suicidal behavior, lifetime self-injury behavior with comorbid eating disorder and increased number of stressful life events.DisclosureNo significant relationships.

Background Cognitive Reserve (CR) is defined as the ability of the brain to cope and deal with physiological or pathological brain injuries. In the field of psychiatry, higher levels of CR have been associated with lower levels of psychotic symptoms, higher psycho-social functioning and higher cognitive performance, suggesting that CR should be considered as a protective factor (Barnett et al., 2006; Amoretti et al., 2016). This study aims to compare CR levels in a sample of adolescents and young adult offspring of patients with schizophrenia or bipolar disorder who are at high risk of developing these disorders (HR) and compared them with a group of healthy controls (HC). We also assess the utility of CR in predicting clinical and cognitive variables. Methods Participants were 85 HR and 45 HC. A CR proxy was calculated based on premorbid IQ, socio-occupational attainment and social activities. Clinical assessment included: the Structured Interview for Prodromal Symptoms (SOPS), the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS). Neuropsychological assessment included: Working Memory, Processing Speed, Verbal Memory, attention and executive functioning. A factorial analysis was conducted in order to obtain a single CR measure. Differences between groups in CR were assessed via MANCOVA and linear regressions were conducted to check the effectiveness of CR in predicting clinical and neuropsychological variables. Results No significant differences were observed in age or gender between HR and HC groups. Socioeconomic status was lower in HR subjects (F=8.100, p=0.005).CR was significantly lower in the HR group than in the HC group (F=17.522; p Discussion HR subjects have lower CR than controls. CR is associated with clinical and neuropsychological variables. To our knowledge no previous studies have assessed CR in high risk samples. Nevertheless, studies conducted in adult first episode psychotic samples have shown an association between CR and the severity of symptoms.

Background Having one parent diagnosed with a severe mental disorder is considered one of the main risk factors for developing that disorder in adulthood and it also increases the risk of a wide range of mental disorders in the offspring from early childhood and adolescence. The aim of this study is to analyze the prevalence of several psychopathological diagnoses, the presence of prodromal symptoms and global functioning in schizophrenia offspring (SZoff) or bipolar offspring (BDoff) compared to community control offspring (CCoff) at baseline and 2-year follow-up. Methods 41 SZoff, 97 BDoff and 107 CCoff between 7 and 17 years were included. Clinical assessment consisted of a clinical evaluation using the following instruments: structured interview KSADS-PL or SCID-I, semi-structured Interview for Prodromal Syndromes (SIPS) and the Children’s Global Assessment Scale (CGAS). To test between-group differences in DSM-IV diagnoses multilevel mixed-effect logistic regression models (categorical variables) or linear (continuous variables) regression models were conducted with group (SZoff, BDoff and CCoff), time (baseline or 2-year follow-up), interaction time x group, age, gender and socio-economic status as fixed variables. Results Significant differences between groups were found in any lifetime axis I disorder (F=8.720; p Discussion Screening patients’ children is clinically relevant since, as a group, they have an elevated risk of developing a psychiatric disorder and of experiencing their first symptoms during childhood and adolescence.

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.

Objectives: Key neurobiological factors contribute to vulnerability to nonsuicidal self-injury (NSSI) among adolescents and how they respond to treatment targeted to reduce such behaviors....

Having one parent diagnosed with a severe mental disorder is considered one of the main risk factors for developing that disorder in adulthood, and it also increases the risk of a wide range of mental disorders in the offspring. The aim of this study is to compare the prevalence of several psychopathological diagnoses, the presence of prodromal symptoms, and global functioning in offspring of parents with schizophrenia or bipolar disorder and in offspring of controls at baseline and 2-year follow-up. This study included 41 offspring of parents with schizophrenia, 90 offspring of parents with bipolar disorder, and 107 offspring of controls (mean age 11.7 ± 3.2 at baseline and 13.9 ± 3.2 at follow-up). The prevalence of psychopathology and comorbidity was higher in offspring of parents with schizophrenia and offspring of parents with bipolar disorder than in offspring of controls at baseline and at 2-year follow-up. Interestingly, mood disorders were more prevalent in offspring of parents with bipolar disorder and disruptive disorders were more prevalent in offspring of parents with schizophrenia. Prodromal symptoms were more frequent in offspring of parents with schizophrenia than in offspring of controls, while the offspring of parents with bipolar disorder showed an intermediate pattern. Finally, global functioning was lower in the offspring of parents with schizophrenia than the offspring of parents with bipolar disorder and the offspring of controls. Screening patients’ children is clinically relevant, since, as a group, they have an elevated risk of developing a psychiatric disorder and of experiencing their first symptoms during childhood and adolescence.

Bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD) share numerous clinical features, which can make the differential diagnosis challenging. Studies conducted in adults suggest that patients with BD and ADHD have different sleep patterns. However, in pediatric populations, data on these potential differences are scant. The present preliminary study was conducted to identify potential differences in sleep alterations among youths diagnosed with BD or ADHD compared to healthy controls (HC). A total of 26 patients diagnosed with BD (n?=?13) or ADHD (n?=?13) were compared to 26 sex- and age-matched HC ([HC(BD)], n?=?13, and [HC(ADHD)], n?=?13). All participants underwent polysomnography. The mean duration of stage N2 sleep was shorter in the BD group than in controls (HC(BD)). The BD group also had higher (non-significant) REM density (REMd) scores than controls while mean REMd scores were lower in the ADHD group versus controls. Compared to the ADHD group, the BD group presented a shorter N2 stage, a longer first REM sleep duration (R1), and greater REMd. According to our findings, these three variables-N2 stage, REMd, and R1-appear to differentiate patients with BD from those with ADHD and from HC.

Objective This study is a pragmatic randomized controlled trial, which compares the effectiveness of an adapted form of Dialectical Behavior Therapy for Adolescents (DBT-A) and treatment as usual plus group sessions (TAU + GS) to reduce suicidal risk for adolescents in a community health mental clinic. Method Thirty-five adolescents from a community outpatient clinic, with repetitive NSSI alone or with SA over the last 12 months and with current high suicide risk as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS), were enrolled. Participants were randomly assigned to undergo either DBT-A (n = 18) or TAU + GT (n = 17) treatments over a 16-week period. Primary outcomes were the difference between NSSI and SA recorded during the first 4 weeks and the final 4 weeks of treatment. Secondary outcomes included changes in Children's Global Assessment Scale (C-GAS), Suicidal Ideation Questionnaire (SIQ-JR), and Beck Depression Inventory-II (BDI-II). Results Dialectical Behavior Therapy for Adolescents was more effective than TAU + GS at reducing NSSI, use of antipsychotics, and improving C-GAS. No SAs were reported in the two groups at the end of the treatment. Both treatments were equally effective in decreasing SIQ-JR and BDI-II scores. Conclusions These findings support the feasibility and effectiveness of DBT-A for adolescents at high risk of suicide in community settings.

Schizophrenia (SZ) and bipolar disorder (BD) are severe mental diseases associated with cognitive impairment, mood disturbance, and psychosis. Both disorders are highly heritable and share a common genetic background. The present study assesses, for the first time, differences in genotype frequencies of polymorphisms located in genes involved in neurodevelopment and synaptic plasticity between genetic high-risk individuals (offspring of patients with SZ or BD; N=100: 31 and 69, respectively) and control subjects (offspring of community controls; N=96). Individuals from both groups had similar ages, around 12 years. A higher percentage of men were included in the genetic high-risk group (58%) compared with the control group (40.6%). A total of 244 validated SNPs located in 35 candidate gene regions were analyzed in 196 participants. Multivariate methods based on logistic regression analysis were performed to assess differences in genotype frequencies. Bonferroni correction was applied for the multiple comparisons performed. Two polymorphisms, CACNA1C rs10848683 and SYNE1 rs214950, showed significant differences. The frequency of heterozygotes for CACNA1C rs10848683 in genetic high-risk individuals was double that in controls (OR=3.15; P=0.00016). For SYNE1 rs214950, higher frequencies of heterozygotes (OR=1.97) and homozygotes for the minor allele (OR=17.89; P=0.00020) were found in the genetic high-risk group than in the control group. In conclusion, polymorphisms in CACNA1C and SYNE1 could confer a greater risk of developing SZ and BD in individuals who are already at high risk because of their family history. This could help identify subjects with a very high genetic risk, in whom early detection and early intervention could lead to better prognosis.

Background Bipolar Disorder (BD) is a major psychiatric illness defined by episodic mood changes, which in approximately 50% of cases is associated with psychotic features. Over the past decades, a large amount of research has identified brain structural and functional alterations in patients with this mental disorder. Some findings have been found to be specific to patients with psychotic symptoms, raising suggestions that this could represent a biological subtype of the disorder. Recent interest has been addressed to Early-Onset Bipolar Disorder (EOBD, onset prior to age 18). Latest reviews in EOBD samples have pointed to abnormalities in the frontal lobe and limbic structures, with some inconsistencies in the reported results possibly caused by differences in the methodology. In addition, no study so far has examined the neural structural correlates of psychotic symptoms in adolescent-onset bipolar disorder (AOBD). The aim of the present study is to examine the impact of psychosis on the neurobiological architecture in a sample of patients with AOBD. To our knowledge, this is the first study comparing gray matter structure between AOBD patients with or without psychotic features. Methods We conducted a cross-sectional study collecting T1-weighted structural magnetic resonance neuroimaging (3T-MRI) data in patients diagnosed with Bipolar Disorder type I or II between 12 and 19 years old (N=46, mean age (SD)=15.89 (1.94), gender=52.2% females). All patients were recruited from child and adolescent mental health services of the Hospital Clinic of Barcelona, Spain. Diagnoses were confirmed with a semi-structured clinical interview (Kiddie-Sads present and lifetime version) by child and adolescent psychiatrists. Images were pre-processed employing FreeSurfer 5.3.0, and data corresponding to Cortical Thickness (CTH) and Subcortical Volumes (SCV) was obtained. Groups were compared according to whether patients had experienced psychotic symptoms at any point during their illness: Non-Psychotic Bipolar Disorder (NPSBD, N=25) and Psychotic Bipolar Disorder (PSBD, N=21). No differences in age (t=0.498, p=0.621) or sex (χ2=0.001, p=0.979). Group effects in relation to both CT and SCV were examined with a general linear model. The main effect of group on CTH and SCV, was performed for the whole brain, performing a correction for multiple comparisons (Montecarlo correction, threshold = 0.05). Results Between-group analyses showed smaller CTH in a cluster in the left medial orbitofrontal cortex (cluster size= 1142.58 mm2) in PSBD relative to NPSBD (x, y, z: 25.63, 89.61, -42.74; p=0.002). In addition, we observed a smaller right hippocampus volume (p=0.025) in PSBD relative to NPSBD. No other statistically significant differences were obtained. Discussion PSBD showed smaller cortical thickness in the left medial orbitofrontal cortex, as well as a volumetric reduction in the right hippocampal volume. Similar results have been reported in a study comparing adolescent patients with psychotic BD and healthy controls. These results add evidence about the role of these two structures in the genesis of psychotic symptoms in a population diagnosed with AOBD. Interestingly, one study has reported a surface area decreased of the orbitofrontal cortex in adolescent patients with a non-bipolar psychotic disorder, which suggests that they may be a common substrate to psychotic symptoms during adolescence regardless of co-occurring affective symptoms. In summary, this study points to the existence of a distinct biological nature between bipolar patients according to psychotic symptoms, underpinned by a different neurobiological architecture. Future research should focus on replication and on examining the clinical value of this finding.

Activation is a behavioral adverse event related to the use of psychotropic medication. Its high incidence in pediatrics and in childhood-onset neuropsychiatric disorders suggests it may be linked to neurodevelopment. However, previous studies have scarcely examined the role that factors relevant to developmental pharmacokinetics, such as body weight, may play in the onset of activation in children and adolescents.We conducted a retrospective analysis of hospitalized patients to identify the risk factors for activation in children and adolescents treated with selective serotonin reuptake inhibitors. Our focus was on factors related to development, including body weight, to explore the relationship between activation and neurodevelopmental processes.Among the 139 participants (mean age, 14 ± 2.3 years), activation appeared in 29 (20.9%). Age 12 years or younger and comorbid diagnosis of autism spectrum disorder were associated with statistically significant increases in the risk of activation, but no association was found regarding body weight.Our findings support the hypothesis that activation is closely linked to brain development processes. Longitudinal studies are needed to explore this line of research further.

Background Early clinical manifestations predating schizophrenia (SZ) and bipolar disorder (BP) have not been fully characterized. Child offspring studies are a valuable opportunity to study the natural history of the illness from its earliest stages. However, there is limited evidence assessing young offspring of SZ and BP simultaneously. We set out to assess rates of psychiatric disorders in child and adolescent offspring of SZ and BP, relative to offspring of community controls, so as to characterize the early phenotype of the disorders comparatively. Methods SZ and BP parents with offspring aged 7–17 years were recruited through adult mental health services of two tertiary hospitals. Community control (CC) parents were recruited from the same geographical area. Ninety BP-offspring, 41 SZ-offspring and 107 CC-offspring were assessed using the K-SADS-PL by child psychiatrists blinded to parental status. Differences in prevalence of psychiatric disorders between groups were adjusted for confounders and for sibling correlation using generalised estimating equations. Results We found a gradient of clinical severity and social disadvantage between SZ, BP and CC-offspring. After adjusting for socio-demographic confounders, SZ and BP-offspring presented higher rates of attention deficit hyperactivity disorder (ADHD) than CC-offspring. ADHD was more prevalent in SZ-offspring than BP-offspring, and BP-offspring presented a higher prevalence of depression than CC-offspring. Conclusions The higher rates of ADHD in SZ-offspring suggest that abnormal neurodevelopmental processes may exert a stronger influence in SZ than BP. Follow-up of these children will help elucidate the role of ADHD and depression phenotypes in predicting future transition to SZ or BP.

Lithium (Li) and valproate (VPA) are used in the treatment of bipolar disorder (BD), with narrow therapeutic window requiring periodic control of serum levels. This prevents intoxication, lack of efficacy due to low serum concentrations, and allows monitoring adherence. We aimed at evaluating the bioequivalence of salivary and blood levels of LI or VPA in a sample of adult BD patients. Secondarily, lithium bioequivalence was evaluated across different patients' lifespans. BD patients treated with either Li or VPA underwent contemporary standard serum and salivary measurements. Blood levels of both drugs were taken according to standard procedures. Li salivary levels were performed by an adapted potentiometric method on the AVL9180 electrolyte analyzer. VPA salivary levels were taken with an immune-assay method with turbidimetric inhibition. A total of 50 patients (38 on Li, 12 on VPA) were enrolled. Blood-saliva bioequivalence for VPA was not found due to a high variability in salivary measures. Li measures resulted in a high correlation (r=0.767, p

Background Studies in child and adolescent offspring of patients with schizophrenia or bipolar disorders may help understand the influence of neurodevelopmental factors on the premorbid phenotype of these disorders. Aims To assess whether a combination of neurodevelopmental factors discriminates between young offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) and community controls (CcO). To assess the association between these factors and rates of psychiatric diagnoses in high risk (HR) youth. Methods One hundred thirty-three HR offspring (47 SzO and 86 BpO) and 84 CcO, aged 6-17, underwent cross-sectional clinical, neurocognitive, and structural neuroimaging assessment. Information on perinatal events and early childhood development was also obtained. General linear mixed models were performed to assess group discrimination and association with lifetime axis I psychiatric disorders. Results Multivariate analyses revealed that greater neurological soft signs (NSS), less total grey matter volume (GMV) and a higher frequency of obstetric complications discriminated HR offspring from CcO. When comparing each group individually, greater NSS and a higher frequency of obstetric complications discriminated SzO from CcO, and BpO from CcO, while lower intelligence also discriminated SzO from CcO and from BpO. Within HR offspring, lower intelligence and less total GMV were associated with lifetime incidence of psychiatric disorders. Conclusions Both SzO and BpO showed evidence of neurodevelopmental insult, although this may have a greater impact in SzO. Lower intelligence and less total GMV hold potential as biomarkers of risk for psychiatric disorders in HR youth.

OBJECTIVE To characterize the early cognitive and social functioning characteristics of a sample of first-episode psychosis patients with and without persistent negative symptoms (PNS) and to examine the prevalence and cognitive and functional correlates of PNS in patients with early-onset versus adult-onset first-episode psychosis. METHODS Participants were 235 patients with first-episode psychosis (51 early-onset, 184 adult-onset) and 240 healthy controls from a multicenter longitudinal study (recruited between 2009 and 2011). Standard instruments were used to evaluate symptoms, cognition, and social functioning. Diagnoses were determined according to DSM-IV criteria. PNS proxy was derived from clinical assessments (Positive and Negative Syndrome Scale and Montgomery-Asberg Depression Scale) at 2-, 6-, and 12-month follow-up. Association tests were used to compare the prevalence of PNS in the early-onset versus adult-onset groups. Multivariate analysis of variance was used to examine differences in early cognitive and social functioning (at the 2-month assessment) between patients with and without PNS and between early-onset and adult-onset patients with PNS. RESULTS Thirty-eight patients (16.2%) met criteria for PNS during the first year. This PNS group showed a selective deficit in executive functions and in global, community, and occupational functioning (P < .05). Having PNS was associated with a diagnosis of a schizophrenia spectrum disorder at the 12-month follow-up. The prevalence of PNS was almost double for those patients with an early-onset (0.25 vs 0.14; OR = 2.18; 95% CI, 1.02-4.64), and this was associated with greater cognitive (P < .05) but not social deficits. CONCLUSIONS There was an early, detectable, social and executive dysfunction associated with PNS in first-episode psychosis and a high risk of having PNS in early-onset first-episode psychosis, which in turn was associated with more widespread cognitive impairment. Specific therapeutic interventions for PNS in early-onset first-episode psychosis might be needed.

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.

Background Schizophrenia (SZ) and bipolar disorder (BD) are considered neurobiological disorders which share some clinical, cognitive and neuroimaging characteristics. Studying child and adolescent offspring of patients diagnosed with bipolar disorder (BDoff) or schizophrenia (SZoff) is regarded as a reliable method for investigating early alterations and vulnerability factors for these disorders. This study compares the neuropsychological characteristics of SZoff, BDoff and a community control offspring group (CC) with the aim of examining shared and differential cognitive characteristics among groups. Methods 41 SZoff, 90 BDoff and 107 CC were recruited. They were all assessed with a complete neuropsychological battery which included intelligence quotient, working memory (WM), processing speed, verbal memory and learning, visual memory, executive functions and sustained attention. Results SZoff and BDoff showed worse performance in some cognitive areas compared with CC. Some of these difficulties (visual memory) were common to both offspring groups, whereas others, such as verbal learning and WM in SZoff or PSI in BDoff, were group-specific. Conclusions The cognitive difficulties in visual memory shown by both the SZoff and BDoff groups might point to a common endophenotype in the two disorders. Difficulties in other cognitive functions would be specific depending on the family diagnosis.

Objective Cortical surface area and thickness abnormalities have been observed in patients with schizophrenia and bipolar disorders; however, no study thus far has examined cortical morphologic measurements in children and adolescents at genetic risk for the disorders comparatively. Method One hundred thirty-seven participants, including 36 offspring of patients with schizophrenia (SzO), 54 offspring of patients with bipolar disorder (BpO), and 47 offspring of community controls (CcO), 6 to 17 years old, were assessed with clinical and neuroimaging methods. Sixty-nine percent of the sample was reassessed at a 27.6-month (mean) follow-up. Cortical surface reconstruction was applied to measure cortical area and thickness using FreeSurfer; mixed-effects models were used to investigate cross-sectional and longitudinal differences in global and lobar morphologic measurements. Results The SzO group exhibited a cross-sectional decrease in global, parietal, and occipital lobe surface area compared with the CcO group, and in the occipital lobe compared with the BpO group. In the SzO group, global and parietal surface area values were inversely associated with attenuated positive and negative prodromal symptom scores. No cross-sectional differences in cortical thickness were observed. Division of the sample by pubertal status showed group-by-time interactions in the pubertal and postpubertal SzO subgroup, with less longitudinal decrease in cortical surface area and thickness than in the CcO and BpO subgroups, respectively. Conclusion The SzO, but not the BpO, group was characterized by cross-sectional decreases in surface area, and this was associated with prodromal symptoms. Longitudinal changes in cortical morphology associated with risk for schizophrenia may be expressed differently according to developmental stage.

Introduction High rates of psychopathology and worse performance in cognitive areas have been described in high risk (HR) first degree relatives of subjects with schizophrenia. The present study aimed to examine clinical and neuropsychological characteristics in two different groups of first degree relatives of patients with schizophrenia – one of siblings (HRs), and one of offspring (HRo) – and compare them with healthy controls (HC). Methods Participants were 30 HRo, 26 HRs and 33 HC, all aged between 7 and 16 years. Clinical and neuropsychological assessments were completed by all participants. Results No significant differences were observed between HR groups in DSM-IV diagnoses. The most prevalent diagnosis in both HR samples was attention deficit/hyperactivity disorder (ADHD) followed by oppositional defiant disorder and generalized anxiety disorder. Both HR groups obtained worse scores than HC on prodromal symptoms, premorbid adjustment and behavioral problem scales. In cognitive areas, HRo performed worse than HC on most WISC-IV index scores, logical memory, visual memory and perceptual organization, whereas HRs only performed worse in WISC-IV indexes, logical memory and perceptual organization. Most of these differences remained stable after controlling for ADHD. The comparison between HRo and HRs showed significant differences in prodromal symptoms and working memory after controlling for ADHD. Conclusion Similar abnormalities in HRo and HRs were found in relation to clinical and neuropsychological variables. Subtle differences were found between HR groups with HRo showing difficulties in more clinical and neuropsychological areas than HRs and HC. This suggests that, the specific kind of family relationship should to be taken into account in future HR research.

Suicidal behaviour is a major complication ofbipolar disorder. Between 30% and 50% of bipolarpatients may attempt suicide in their lifetime (1, 2).Previous studies have reported a higher odds ratiofor lifetime history of suicide in bipolar patients incomparison with patients with any other psychiat-ric disorder (2–5). Although recent investigationshave described sustained reductions of death bysuicide (6), suicide-related morbidity in terms ofmedical consequences, impairment of quality of lifeSa´nchez-Gistau V, Colom F, Mane´A, Romero S, Sugranyes G, Vieta E.Atypical depression is associated with suicide attempt in bipolardisorder.Objective: There is a dearth of research focusing on factors associatedwith suicide attempts. High rates of atypical depression have beenreported in studies including unipolar and bipolar II patients. In thisstudy, the association between suicide attempt and atypical depression,in addition to other major risk factors, was evaluated in 390 bipolar Iand II out-patients.Method: Variables were defined according to DSM-IV criteria, andassessed with a Structured Interview for DSM-IV (axis I and II).History of suicide attempt was obtained through interviews withpatients and relatives. Attempters and non-attempters were comparedusing univariate and multivariate analysis.Results: Attempters showed significantly higher rates of atypicaldepression, family history of completed suicide, depression at indexepisode and cluster B personality disorder.Conclusion: Our results highlight the relevance of atypical depressionin bipolar disorder. A more accurate identification of potentialattempters may contribute to the development of effective preventivetreatment strategies.

OBJECTIVE This study examined the association between family history of completed suicide and suicidal behavior and other clinical variables in subjects with bipolar disorder. METHOD 374 outpatients aged from 19 to 88 years (mean +/- SD age = 41.9 +/- 4.1 years) (54.3% female) meeting DSM-IV criteria for bipolar disorder type I or II or schizoaffective disorder, bipolar subtype, were included in the study. Forty-eight subjects with a family history of completed suicide were compared to 326 subjects without a family history of completed suicide regarding several clinical and demographic variables. The study was conducted from 2001 to 2004. RESULTS There were no statistically significant demographic differences between bipolar disorder subjects with and without a family history of suicide. Bipolar disorder subjects with a family history of suicide showed higher rates of cluster C personality disorders than subjects without a family history of suicide (14.9% vs. 2.5%, OR = 6.72, 95% CI = 2.31 to 19.51, p < .001). Subjects with a family history of suicide also demonstrated a significantly greater lifetime prevalence of suicide attempts (52.2% vs. 25.5%, OR = 3.19, 95% CI = 1.7 to 6.0, p < .001). Results remained significant after controlling for all possible interactions. CONCLUSION Family history of completed suicide is a significant risk factor associated with suicidal attempts in patients with bipolar disorder. These findings underscore the importance of identifying patients with a family history of suicide in order to provide prompt treatment and careful follow-up.

Objectives: To compare family environmental characteristics of families with at least one bipolar parent and families with parents without any Axis I disorder. Methods: Family environment of 24 families with at least one parent with bipolar disorder (BPD) and 27 families with healthy parents (healthy families, HF) were assessed using the Family Environment Scale (FES). We compared FES subscale scores between BPD and HF. We also compared FES normative scores with scores of BPD families. Results: Seventeen (71%) of the 24 BPD families had at least one child with a mood disorder and one (3.7%) of the 27 HF had a child with a mood disorder. Families with BPD reported lower cohesion (p = 0.009) and expressiveness (p = 0.03) scores compared with HF, after controlling for group socioeconomic status differences. Bilineal BPD families had higher cohesion scores than unilineal BPD families (p = 0.05). We found no significant differences in any subscales between BPD families with (n = 9) versus without (n = 15) children with BPD. Compared with normative FES data BPD families reported lower cohesion (C) (p = 0.02) and independence (IND) (p = 0.004) scores and higher conflict (CON) (p = 0.02), intellectual-cultural orientation (ICO) (p = 0.05), moral-religious emphasis (MRE) (p

PurposeTo investigate rates of psychopathology in the offspring of subjects with bipolar disorder (BP-offspring) compared to the offspring of healthy subjects (HC-offspring) in a Spanish sample and to study possible predictors of psychopathology in BP-offspring.SubjectsFifty BP-offspring from 36 families and 25 HC-offspring from 25 families.MethodsPsychopathology was compared in BP-offspring and HC-offspring. Factors associated with DSM-IV axis I disorders in BP-offspring were analyzed using logistic regression.ResultsHalf of BP-offspring fulfilled the diagnostic criteria for at least one axis I disorder with attention-deficit/hyperactivity disorder (30%), anxiety disorders (14%) and affective disorders (10%) as the most frequent. After controlling for having more than one sibling in the study, the odds ratio for BP-offspring presenting an axis I disorder was 15.02 when a biological parent had bipolar disorder with a lifetime history of psychotic symptoms and 3.34 when one parent had bipolar II disorder. Moreover, a higher Global Assessment of Functioning score in the biological co-parent was associated with a significantly lower frequency of axis I disorders in BP-offspring.Discussion and conclusionsPsychopathology in BP-offspring should be routinely assessed, with special emphasis on children from parents with specific disease characteristics (psychosis, BP II disorder) in order to establish an early diagnosis and appropriate interventions.

Introduction Studies have shown higher rates of psychopathology and cognitive difficulties among relatives of schizophrenia patients than among the general population. This study aimed to analyze the relationship between clinical and neuropsychological characteristics in children and adolescents at high genetic risk for schizophrenia. Methods Participants were 26 children and adolescent first-degree relatives of subjects diagnosed with schizophrenia (high-risk [HR] group) and 20 controls whose parents and siblings did not meet DSM-IV criteria for any psychotic disorder. These two groups were matched by age, sex and socio-economic status and clinical and neuropsychological assessments were completed by all participants. Results Among HR children 42.3% were diagnosed with one or more DSM-IV axis I psychiatric disorders. The most common diagnoses were attention deficit/hyperactivity disorder (ADHD) (34.6%) and generalized anxiety disorder (3.8%) There were significant differences between HR children and controls with respect to prodromal symptoms, behavioral problems and premorbid adjustment, as well as on the majority of intelligence subscales, working memory and logical memory. When differences between HR with ADD (HR-ADD), HR without ADD (HR-NADD) and controls were analyzed, significantly higher scores on clinical scales of prodromal symptoms, behavioral problems and premorbid adjustment were found in HR-ADD than in HR-NADD or controls. There were no significant differences in cognitive domains between HR-ADD and HR-NADD, but there were between HR-ADD and controls and between HR-NADD and controls on the Verbal Comprehension Index, Perceptual Reasoning Index, Working Memory Index and GAI. Conclusions Compared to controls, HR children showed more clinical symptoms and cognitive abnormalities. HR children with ADD had worse clinical symptoms than did HR without ADD, although there were no differences in terms of cognitive abnormalities. Both HR groups seem to have similar deficits in neuropsychological performance.

Objective To study the relationship between negative life events and demographic and clinical variables in youth with bipolar I disorder, bipolar II disorder, and bipolar disorder not otherwise specified (NOS), as well as to compare the rates of life events in youth with bipolar disorder, depressive and/or anxiety disorders (DEP-ANX), and healthy controls. Method Subjects included 446 youth, aged 7 to 17 years, meeting DSM-IV criteria for bipolar I, bipolar II, or an operationalized definition of bipolar disorder NOS, and were enrolled in the Course and Outcome of Bipolar Illness in Youth study. Subjects completed the Life Events Checklist. Sixty-five DEP-ANX and 65 healthy youth were obtained from previous studies using similar methodology. The study was conducted from October 2000 to July 2006. Results Older age, lower socioeconomic status, living with nonintact family, non-Caucasian race, anxiety, and disruptive disorders were associated with greater number of total negative life events. Specifically, increased independent, dependent, and uncertain negative life events were associated with lower socioeconomic status, nonintact family, and comorbid disruptive disorders. Increased independent negative life events were additionally associated with non-Caucasian race and comorbid anxiety disorders. Increased dependent and uncertain negative life events were also associated with older age. DEP-ANX youth reported a similar rate of negative life events as bipolar youth, and both groups had more negative life events than the healthy controls. Bipolar youth reported fewer total and dependent positive life events compared to DEP-ANX and healthy youths. Conclusions Similar to DEP-ANX youth, bipolar youth are exposed to excessive negative independent and dependent life events, which may have implications in the long-term outcome and negative consequences associated with this disorder.