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.

Exploration of cannabis use and polygenic risk scores on the psychotic symptom progression of a FEP cohort.

Cannabis use is highly prevalent in first-episode psychosis (FEP) and plays a critical role in its onset and prognosis, but the genetic underpinnings promoting both conditions are poorly understood. Current treatment strategies for cannabis cessation in FEP are clearly inefficacious. Here, we aimed to characterize the association between cannabis-related polygenic risk scores (PRS) on cannabis use and clinical course after a FEP. A cohort of 249 FEP individuals were evaluated during 12 months. Symptom severity was measured with the Positive and Negative Severity Scale and cannabis use with the EuropASI scale. Individual PRS for lifetime cannabis initiation (PRSCI) and cannabis use disorder (PRSCUD) were constructed. Current cannabis use was associated with increased positive symptoms. Cannabis initiation at younger ages conditioned the 12-month symptom progression. FEP patients with higher cannabis PRSCUD reported increased baseline cannabis use. PRSCI was associated with the course of negative and general symptomatology over follow-up. Cannabis use and symptom progression after a FEP were modulated by cannabis PRS, suggesting that lifetime initiation and use disorders may have partially independent genetic factors. These exploratory results may be the first step to identify those FEP patients more vulnerable to cannabis use and worse outcomes to ultimately develop tailored treatments.

The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications.

We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010-08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes.

Neutrophil to Lymphocyte Ratio in Patients With a First Episode of Psychosis: A Two-Year Longitudinal Follow-up Study.

BACKGROUND AND HYPOTHESIS: A pro-inflammatory phenotype has been related to psychotic disorders. The neutrophil-lymphocyte ratio (NLR) is an accessible biomarker that could be helpful to characterize this systemic inflammation state. STUDY DESIGN: This study evaluated the NLR in a cohort of 310 subjects with a first episode of psychosis (FEP) and a matched group of 215 healthy controls, recruited in 16 Spanish centers participating in the PEPs Project. We investigated the NLR measures over 2 years in a prospective, naturalistic study. STUDY RESULTS: At baseline, the FEP group showed a significant higher mean NLR compared to the control group (1.96 ± 1.11 vs 1.72 ± 0.74, P = 0.03). These ratio differences between groups grew at the 24 months follow-up visit (2.04 ± 0.86 vs 1.65 ± 0.65, P < 0.001). Within the FEP group, there were no significant differences in NLR across the follow-up visits, between genders or diagnosis groups (affective vs nonaffective). NLR values did not correlate with the Positive and Negative Symptoms Scale scores. The group of patients who did not reach remission criteria at the end of the study showed a significant higher NLR than those who remitted (2.1896 ± 0.85 vs 1.95 ± 0.87, P = 0.042). A significant correlation between antipsychotic doses and NLR was found at the two-years follow-up visit (r=0.461, P < 0.001). CONCLUSIONS: Our results highlight the existence of an underlying predisposition of FEP patients to present an increased mean NLR. The use of NLR in clinical practice could be helpful to identify this inflammatory imbalance.

Impact of previous tobacco use with or without cannabis on first psychotic experiences in patients with first-episode psychosis.

OBJECTIVE: There is high prevalence of cigarette smoking in individuals with first-episode psychosis (FEP) prior to psychosis onset. The purpose of the study was to determine the impact of previous tobacco use with or without cannabis on first psychotic experiences in FEP and the impact of this use on age of onset of symptoms, including prodromes. METHODS: Retrospective analyses from the naturalistic, longitudinal, multicentre, "Phenotype-Genotype and Environmental Interaction. Application of a Predictive Model in First Psychotic Episodes (PEPs)" Study. The authors analysed sociodemographic/clinical data of 284 FEP patients and 231 matched healthy controls, and evaluated first psychotic experiences of patients using the Symptom Onset in Schizophrenia Inventory. RESULTS: FEP patients had significantly higher prevalence of tobacco, cannabis, and cocaine use than controls. The FEP group with tobacco use only prior to onset (N = 56) had more sleep disturbances (42.9% vs 18.8%, P = 0.003) and lower prevalence of negative symptoms, specifically social withdrawal (33.9% vs 58%, P = 0.007) than FEP with no substance use (N = 70), as well as lower prevalence of ideas of reference (80.4% vs 92.4%, P = 0.015), perceptual abnormalities (46.4% vs 67.4%, P = 0.006), hallucinations (55.4% vs 71.5%, P = 0.029), and disorganised thinking (41.1% vs 61.1%, P = 0.010) than FEP group with previous tobacco and cannabis use (N = 144). FEP patients with cannabis and tobacco use had lower age at first prodromal or psychotic symptom (mean = 23.73 years [SD = 5.09]) versus those with tobacco use only (mean = 26.21 [SD = 4.80]) (P = 0.011). CONCLUSIONS: The use of tobacco alone was not related to earlier age of onset of a first psychotic experience, but the clinical profile of FEP patients is different depending on previous tobacco use with or without cannabis.

The effect of family environment and psychiatric family history on psychosocial functioning in first-episode psychosis at baseline and after 2 years.

The aim of the present study was to evaluate the contribution of family environment styles and psychiatric family history on functioning of patients presenting first-episode psychosis (FEP). Patients with FEP and healthy controls (HC) were assessed at baseline and after 2 years. The Functional Assessment Short Test (FAST) was used to assess functional outcome and the Family Environment Scale (FES) to evaluate family environment. Linear regressions evaluated the effect that family environment exerts on functioning at baseline and at 2-year follow-up, when FEP patients were diagnosed according to non-affective (NA-PSYCH) or affective psychoses (A-PSYCH). The influence of a positive parents' psychiatric history on functioning was evaluated through one-way between-groups analysis of covariance (ANCOVA) models, after controlling for family environmental styles. At baseline, FEP patients presented moderate functioning impairment, significantly worse than HC (28.65±16.17 versus 3.25±7.92; p<0.001, g = 1.91). At 2-year follow-up, the functioning of NA-PSYCH patients was significantly worse than in A-PSYCH (19.92±14.83 versus 12.46±14.86; p = 0.020, g = 0.50). No specific family environment style was associated with functioning in FEP patients and HC. On the contrary, a positive psychiatric father's history influenced functioning of FEP patients. After 2 years, worse functioning in NA-PSYCH patients was associated with lower rates of active-recreational and achievement orientated family environment and with higher rates of moral-religious emphasis and control. In A-PSYCH, worse functioning was associated with higher rates of conflict in the family. Both family environment and psychiatric history influence psychosocial functioning, with important implications for early interventions, that should involve both patients and caregivers.

Exploring Risk and Resilient Profiles for Functional Impairment and Baseline Predictors in a 2-Year Follow-Up First-Episode Psychosis Cohort Using Latent Class Growth Analysis.

Being able to predict functional outcomes after First-Episode Psychosis (FEP) is a major goal in psychiatry. Thus, we aimed to identify trajectories of psychosocial functioning in a FEP cohort followed-up for 2 years in order to find premorbid/baseline predictors for each trajectory. Additionally, we explored diagnosis distribution within the different trajectories. A total of 261 adults with FEP were included. Latent class growth analysis identified four distinct trajectories: Mild impairment-Improving trajectory (Mi-I) (38.31% of the sample), Moderate impairment-Stable trajectory (Mo-S) (18.39%), Severe impairment-Improving trajectory (Se-I) (12.26%), and Severe impairment-Stable trajectory (Se-S) (31.03%). Participants in the Mi-I trajectory were more likely to have higher parental socioeconomic status, less severe baseline depressive and negative symptoms, and better premorbid adjustment than individuals in the Se-S trajectory. Participants in the Se-I trajectory were more likely to have better baseline verbal learning and memory and better premorbid adjustment than those in the Se-S trajectory. Lower baseline positive symptoms predicted a Mo-S trajectory vs. Se-S trajectory. Diagnoses of Bipolar disorder and Other psychoses were more prevalent among individuals falling into Mi-I trajectory. Our findings suggest four distinct trajectories of psychosocial functioning after FEP. We also identified social, clinical, and cognitive factors associated with more resilient trajectories, thus providing insights for early interventions targeting psychosocial functioning.

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.

Gene-environment interaction between an endocannabinoid system genetic polymorphism and cannabis use in first episode of psychosis.

Alterations of the endocannabinoid system (ECS) may play an important role in the development of schizophrenia and other psychotic disorders. Cannabis use is one of the environmental factors more repeatedly related to an increase the risk of developing a psychotic episode, while its use modifies the ECS normal function. In the present study we purposed to examine the gene by environment (GxE) interaction between 15 selected single nucleotide polymorphisms (SNPs) related to the ECS and cannabis use in a cohort of 321 patients with a first episode of psychosis (FEP) and 241 matched healthy controls. We found the fatty-acid amide hydrolase (FAAH) rs2295633 SNP genetic polymorphism was associated with a greater risk of presenting a FEP in subjects with relevant cannabis use, but not in subjects without a history of cannabis use. The probability of presenting a FEP was tenfold higher (OR: 10.69) in cannabis users who were homozygote carriers of the T allele of the FAAH rs2295633 SNP, compared to users of cannabis without this genotype. We also found that a higher a proportion of TT carriers of the FAAH rs2295633 SNP with a positive history of cannabis use was treated with high potency antipsychotic. This study has identified a GxE-environment interaction between a genetic polymorphism from the ECS and cannabis use involved in the risk of presenting a FEP. Although this preliminary data should be replicated with independent samples, our results highlight the importance of the pro-psychotic effects of exogenous cannabis use over the ECS in certain subjects.

Gray matter changes and cognitive predictors of 2-year follow-up abnormalities in early-onset first-episode psychosis.

This study aims to examine regional gray matter (GM) changes over a period of 2 years in patients diagnosed with early-onset first-episode psychosis (EO-FEP), and to identify baseline predictors of abnormalities at the follow-up. Fifty-nine patients with EO-FEP aged 11-17 years were assessed. Magnetic resonance imaging was carried out at admission and 2 years later. Changes over time were assessed with voxel-based morphometry. Fifty-nine patients (34 schizophrenia-SCZ, 15 bipolar disorder-BP, and 10 other psychotic disorders) and 70 healthy controls were assessed. At baseline no differences were found between the EO-FEP groups and control subjects. Over time, SCZ patients presented a larger GM decrease in the orbitofrontal cortex, anterior midline frontal cortex, cingulate, left caudate, and thalamus. BP patients also had a larger GM decrease in the right putamen, right orbitofrontal cortex, and anterior and midline region of the right superior frontal gyrus and left caudate, but with fewer areas showing significant differences than in the comparison between SCZ and controls. In the cross-sectional analysis, only SCZ patients showed differences with respect to controls in some GM areas. Significant baseline predictors of a 2-year reduction in GM were IQ and working memory. EO-FEP patients did not show differences in GM compared to controls at baseline. Both SCZ and BP patients showed a greater decrease in specific areas during the first 2 years. At follow-up, only SCZ patients differed significantly from controls in specific brain areas. The GM reduction was predicted by baseline cognitive variables.

Persistent Negative Symptoms in First-Episode Psychosis: Early Cognitive and Social Functioning Correlates and Differences Between Early and Adult Onset.

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.

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.

Neuropsychological characteristics of child and adolescent offspring of patients with schizophrenia or bipolar disorder.

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.

Neuropsychological characteristics of child and adolescent offspring of patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a severe mental disorder with a strong genetic component. The assessment of child and adolescent offspring of patients diagnosed with BD (BDoff) provides an opportunity to investigate vulnerability factors and the first abnormalities associated with the disorder. Previous literature in child and adolescent BDoff is scarce and controversial. However, some studies concur in identifying significant impairment in executive functions, memory and attention. The present study aims to compare global neuropsychological characteristics of child and adolescent offspring of patients with bipolar disorder with a group of offspring of parentswith no history of psychotic disorder, and to assess the influence of psychopathology on neuropsychological performance. METHODS: This research was part of The Bipolar and Schizophrenia Young Offspring Study (BASYS). A group of BDoff (N= 90) and a group of offspring of parents with no history of psychotic disorder (CC) (N = 107) were assessed with a complete neuropsychological battery. Intellectual quotient, working memory, processing speed, verbal memory and learning, visual memory, attention and executive functions were included in the cognitive assessment. RESULTS: BDoff showed significantly worse performance in processing speed and immediate recall of visual memory relative to CC. When the presence of any lifetime psychopathology was analysed, the results showed that belonging to the BDoff group was the main explicative factor for the scores obtained in both processing speed and visual memory immediate recall, regardless of the presence of psychopathology. CONCLUSIONS: These findings suggest that processing speed and visualmemory should be taken into consideration in future research on vulnerability markers of BD.

The human cerebral cortex flattens during adolescence.

The human cerebral cortex appears to shrink during adolescence. To delineate the dynamic morphological changes involved in this process, 52 healthy male and female adolescents (11-17 years old) were neuroimaged twice using magnetic resonance imaging, approximately 2 years apart. Using a novel morphometric analysis procedure combining the FreeSurfer and BrainVisa image software suites, we quantified global and lobar change in cortical thickness, outer surface area, the gyrification index, the average Euclidean distance between opposing sides of the white matter surface (gyral white matter thickness), the convex ("exposed") part of the outer cortical surface (hull surface area), sulcal length, depth, and width. We found that the cortical surface flattens during adolescence. Flattening was strongest in the frontal and occipital cortices, in which significant sulcal widening and decreased sulcal depth co-occurred. Globally, sulcal widening was associated with cortical thinning and, for the frontal cortex, with loss of surface area. For the other cortical lobes, thinning was related to gyral white matter expansion. The overall flattening of the macrostructural three-dimensional architecture of the human cortex during adolescence thus involves changes in gray matter and effects of the maturation of white matter.

Twenty-four months of antipsychotic treatment in children and adolescents with first psychotic episode: discontinuation and tolerability.

OBJECTIVE: The Child and Adolescent First-Episode Psychosis Study is a longitudinal study of early-onset first psychotic episodes. This report describes the naturalistic psychopharmacological treatment administered during a 24-month follow-up period, as well as discontinuation rates, reasons for discontinuation, and adverse effects. METHODS: The sample comprised 110 patients, aged 9 to 17 years, with a first psychotic episode. Pharmacological treatment, changes, reasons for discontinuation, and the UKU (Udvalg for Kliniske Undersogelser) Side Effect Rating Scale were registered at 6, 12, and 24 months of follow-up. RESULTS: Second-generation antipsychotics, especially risperidone, quetiapine, and olanzapine, were the most commonly used. The discontinuation rate was 44.5% at 6 months, 59.1% at 12 months, and 70.9% at 24 months. Discontinuation rates or reasons for discontinuation (adverse reaction, insufficient response, and other) did not differ significantly between antipsychotics. At 6 months, significant differences were found in body mass index increase and body mass index z score increase, which were higher with olanzapine, and in neurological effects, which were higher with risperidone; at 12 and 24 months, these differences were no longer significant. High maintenance rates were found in the clozapine group, although they had higher scores on the autonomic subscale of the UKU. CONCLUSIONS: A long follow-up period reveals high discontinuation rates similar to those observed in adults, particularly during the first year. No differences were found between antipsychotics. Differences in adverse effects were found at 6 months but not subsequently after changes in treatment. Clozapine had a high maintenance rate, and its tolerability was comparable to that of other antipsychotics.

Frequency, characteristics and management of adolescent inpatient aggression.

BACKGROUND: Inpatient aggression is a serious challenge in pediatric psychiatry. METHODS: A chart review study in adolescent psychiatric inpatients consecutively admitted over 24 months was conducted, to describe aggressive events requiring an intervention (AERI) and to characterize their management. AERIs were identified based on specific institutional event forms and/or documentation of as-needed (STAT/PRN) medication administration for aggression, both recorded by nursing staff. RESULTS: Among 408 adolescent inpatients (age: 15.2±1.6 years, 43.9% male), 1349 AERIs were recorded, with ≥1 AERI occurring in 28.4% (n=116; AERI+). However, the frequency of AERIs was highly skewed (median 4, range: 1-258). In a logistical regression model, the primary diagnosis at discharge of disruptive behavior disorders and bipolar disorders, history of previous inpatient treatment, length of hospitalization, and absence of a specific precipitant prior to admission were significantly associated with AERIs (R(2)=0.32; p<0.0001). The first line treatment of patients with AERIs (AERI+) was pharmacological in nature (95.6%). Seclusion or restraint (SRU) was used at least once in 59.4% of the AERI+ subgroup (i.e., in 16.9% of all patients; median within-group SRU frequency: 3). Treatment and discharge characteristics indicated a poorer prognosis in the AERI+ (discharge to residential care AERI+: 22.8%, AERI-: 5.6%, p<0.001) and a greater need for psychotropic polypharmacy (median number of psychotropic medications AERI+: 2; AERI-: 1, p<0.001). CONCLUSIONS: Despite high rates of pharmacological interventions, SRU continue to be used in adolescent inpatient care. As both of these approaches lack a clear evidence base, and as adolescents with clinically significant inpatient aggression have increased illness acuity/severity and service needs, structured research into the most appropriate inpatient aggression management is sorely needed.

Antioxidant defense system and family environment in adolescents with family history of psychosis.

BACKGROUND: Our objective was to determine antioxidant defence activity in healthy controls (HC) and healthy unaffected second-degree relatives of patients with early onset psychosis (HC-FHP), and to assess its relationship with familiar environment measured using the Family Environment Scale (FES). METHODS: We included 82 HC and 14 HC-FHP aged between 9 and 17 years. Total antioxidant status, lipid peroxidation, antioxidant enzyme activities and glutathione levels were determined in blood samples. RESULTS: There was a significant decrease in the total antioxidant level in the HC-FHP group compared with the HC group (OR = 2.94; p = 0.009), but no between-group differences in the Global Assessment of Functioning (GAF) scale scores. For the FES, the HC-FHP group had significantly higher scores in the cohesion (p = 0.007) and intellectual-cultural dimensions (p=0.025). After adjusting for these two FES dimensions, total antioxidant status remained significantly different between groups (OR = 10.86, p = 0.009). CONCLUSIONS: Although causal relationships cannot be assumed, we can state that family environment is not playing a role in inducing oxidative stress in these healthy subjects. It could be hypothesized that families with affected relatives protect themselves from psychosis with positive environmental factors such as cohesion and intellectual-cultural activities.

Decreased glutathione levels predict loss of brain volume in children and adolescents with first-episode psychosis in a two-year longitudinal study.

Progressive loss of cortical gray matter (GM), as measured by magnetic resonance imaging, has been described early in the course of first-episode psychosis. This study aims to assess the relationship between oxidative balance and progression of cortical GM changes in a multicenter sample of first-episode early-onset psychosis (EOP) patients from baseline to two-year follow-up. A total of 48 patients (13 females, mean age 15.9±1.5 years) and 56 age- and gender-matched healthy controls (19 females, 15.3±1.5 years) were assessed. Magnetic resonance imaging (MRI) scans performed both at the time of the first psychotic episode and 2 years later were used for volumetric measurements of left and right gray matter regions (frontal, parietal, and temporal lobes) and total sulcal cerebrospinal fluid (CSF). Total glutathione (GSH) blood levels were determined at baseline. In patients, after controlling for possible confounding variables, lower baseline GSH levels were significantly associated with greater volume decrease in left frontal (B=0.034, 95% confidence interval (CI): 0.011 to 0.056, r=0.620, p=0.006), parietal (B=0.039, 95% CI: 0.020 to 0.059, r=0.739, p=0.001), temporal (B=0.026, 95% CI: 0.016 to 0.036, r=0.779, p<0.001), and total (B=0.022, 95% CI: 0.014 to 0.031, r=0.803, p<0.001) gray matter, and with greater increase in total CSF (B=-0.560, 95% CI: -0.270 to -0.850, r=-0.722, p=0.001). Controls did not show significant associations between brain volume changes and GSH levels. GSH deficit during the first psychotic episode was related to greater loss of cortical GM two years later in patients with first-episode EOP, suggesting that oxidative damage may contribute to the progressive loss of cortical GM found in patients with first-episode psychosis.

QTc prolongation: is clozapine safe? Study of 82 cases before and after clozapine treatment.

OBJECTIVE: The most feared cardiological consequence of clozapine is sudden cardiac death. A potential marker of it is QTc interval (QTc) prolongation. This study aimed to determine the prevalence of QTc prolongation in patients before and after 18 weeks of clozapine treatment and to detect predictors of QTc prolongation. METHODS: Patients undergoing treatment with clozapine who had been given an electrocardiogram prior to the treatment and had their electrocardiogram, serum clozapine and norclozapine levels taken on the 18th week were selected. Exclusion criteria were thioridazine, pimozide, diuretics or beta-blocker treatment, electrolytic alteration, heart diseases and substance misuse diagnosis. Prolonged QTc was defined as >450 ms in men and >470 ms in women. RESULTS: No significant differences were detected in prevalence of prolonged QTc or mean QTc before and after 18 weeks of clozapine treatment (p = 0.15, p = 0.32, respectively). Age, heart rate at 18th week and QTc prior to clozapine treatment had significant effects on QTc at follow-up. Prolonged QTc during previous treatment and heart rate >95 beats/min at 18 weeks were found to be predictors of QTc prolongation. CONCLUSION: No significant differences were detected in prevalence of QTc prolongation or mean QTc among patients before and after 18 weeks on clozapine.