The lived experience of mental disorders in adolescents: a bottom-up review co-designed, co-conducted and co-written by experts by experience and academics.

We provide here the first bottom-up review of the lived experience of mental disorders in adolescents co-designed, co-conducted and co-written by experts by experience and academics. We screened first-person accounts within and outside the medical field, and discussed them in collaborative workshops involving numerous experts by experience - representing different genders, ethnic and cultural backgrounds, and continents - and their family members and carers. Subsequently, the material was enriched by phenomenologically informed perspectives and shared with all collaborators. The inner subjective experience of adolescents is described for mood disorders, psychotic disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, anxiety disorders, eating disorders, externalizing disorders, and self-harm behaviors. The recollection of individuals' past histories also indexes the prodromal (often transdiagnostic) features predating the psychiatric diagnosis. The experience of adolescents with mental disorders in the wider society is described with respect to their family, their school and peers, and the social and cultural context. Furthermore, their lived experience of mental health care is described with respect to receiving a diagnosis of mental disorder, accessing mental health support, receiving psychopharmacological treatment, receiving psychotherapy, experiencing peer support and mental health activism, and achieving recovery. These findings can impact clinical practice, research, and the whole society. We hope that this co-designed, co-conducted and co-written journey can help us maintain our commitment to protecting adolescents' fragile mental health, and can help them develop into a healthy, fulfilling and contributing adult life.

A transdiagnostic prodrome for severe mental disorders: an electronic health record study.

Effective prevention of severe mental disorders (SMD), including non-psychotic unipolar mood disorders (UMD), non-psychotic bipolar mood disorders (BMD), and psychotic disorders (PSY), rely on accurate knowledge of the duration, first presentation, time course and transdiagnosticity of their prodromal stages. Here we present a retrospective, real-world, cohort study using electronic health records, adhering to RECORD guidelines. Natural language processing algorithms were used to extract monthly occurrences of 65 prodromal features (symptoms and substance use), grouped into eight prodromal clusters. The duration, first presentation, and transdiagnosticity of the prodrome were compared between SMD groups with one-way ANOVA, Cohen's f and d. The time course (mean occurrences) of prodromal clusters was compared between SMD groups with linear mixed-effects models. 26,975 individuals diagnosed with ICD-10 SMD were followed up for up to 12 years (UMD = 13,422; BMD = 2506; PSY = 11,047; median[IQR] age 39.8[23.7] years; 55% female; 52% white). The duration of the UMD prodrome (18[36] months) was shorter than BMD (26[35], d = 0.21) and PSY (24[38], d = 0.18). Most individuals presented with multiple first prodromal clusters, with the most common being non-specific ('other'; 88% UMD, 85% BMD, 78% PSY). The only first prodromal cluster that showed a medium-sized difference between the three SMD groups was positive symptoms (f = 0.30). Time course analysis showed an increase in prodromal cluster occurrences approaching SMD onset. Feature occurrence across the prodromal period showed small/negligible differences between SMD groups, suggesting that most features are transdiagnostic, except for positive symptoms (e.g. paranoia, f = 0.40). Taken together, our findings show minimal differences in the duration and first presentation of the SMD prodromes as recorded in secondary mental health care. All the prodromal clusters intensified as individuals approached SMD onset, and all the prodromal features other than positive symptoms are transdiagnostic. These results support proposals to develop transdiagnostic preventive services for affective and psychotic disorders detected in secondary mental healthcare.

On the interplay between state-dependent reconfigurations of global signal correlation and BOLD fluctuations: An fMRI study.

BACKGROUND: The dynamics of global, state-dependent reconfigurations in brain connectivity are yet unclear. We aimed at assessing reconfigurations of the global signal correlation coefficient (GSCORR), a measure of the connectivity between each voxel timeseries and the global signal, from resting-state to a stop-signal task. The secondary aim was to assess the relationship between GSCORR and blood-oxygen-level-dependent (BOLD) activations or deactivation across three different trial-conditions (GO, STOP-correct, and STOP-incorrect). METHODS: As primary analysis we computed whole-brain, voxel-wise GSCORR during resting-state (GSCORR-rest) and stop-signal task (GSCORR-task) in 107 healthy subjects aged 21-50, deriving GSCORR-shift as GSCORR-task minus GSCORR-rest. GSCORR-tr and trGSCORR-shift were also computed on the task residual time series to quantify the impact of the task-related activity during the trials. To test the secondary aim, brain regions were firstly divided in one cluster showing significant task-related activation and one showing significant deactivation across the three trial conditions. Then, correlations between GSCORR-rest/task/shift and activation/deactivation in the two clusters were computed. As sensitivity analysis, GSCORR-shift was computed on the same sample after performing a global signal regression and GSCORR-rest/task/shift were correlated with the task performance. RESULTS: Sensory and temporo-parietal regions exhibited a negative GSCORR-shift. Conversely, associative regions (ie. left lingual gyrus, bilateral dorsal posterior cingulate gyrus, cerebellum areas, thalamus, posterolateral parietal cortex) displayed a positive GSCORR-shift (FDR-corrected p < 0.05). GSCORR-shift showed similar patterns to trGSCORR-shift (magnitude increased) and after global signal regression (magnitude decreased). Concerning BOLD changes, Brodmann area 6 and inferior parietal lobule showed activation, while posterior parietal lobule, cuneus, precuneus, middle frontal gyrus showed deactivation (FDR-corrected p < 0.05). No correlations were found between GSCORR-rest/task/shift and beta-coefficients in the activation cluster, although negative correlations were observed between GSCORR-task and GO/STOP-correct deactivation (Pearson rho=-0.299/-0.273; Bonferroni-p < 0.05). Weak associations between GSCORR and task performance were observed (uncorrected p < 0.05). CONCLUSION: GSCORR state-dependent reconfiguration indicates a reallocation of functional resources to associative areas during stop-signal task. GSCORR, activation and deactivation may represent distinct proxies of brain states with specific neurofunctional relevance.

Physical Health and Transition to Psychosis in People at Clinical High Risk.

BACKGROUND: The clinical high risk for psychosis (CHR-P) construct represents an opportunity for prevention and early intervention in young adults, but the relationship between risk for psychosis and physical health in these patients remains unclear. METHODS: We conducted a RECORD-compliant clinical register-based cohort study, selecting the long-term cumulative risk of developing a persistent psychotic disorder as the primary outcome. We investigated associations between primary outcome and physical health data with Electronic Health Records at the South London and Maudsley (SLaM) NHS Trust, UK (January 2013-October 2020). We performed survival analyses using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models. RESULTS: The database included 137 CHR-P subjects; 21 CHR-P developed psychosis during follow-up, and the cumulative incidence of psychosis risk was 4.9% at 1 year and 56.3% at 7 years. Log-rank tests suggested that psychosis risk might change between different levels of nicotine and alcohol dependence. Kaplan-Meier curve analyses indicated that non-hazardous drinkers may have a lower psychosis risk than non-drinkers. In the Cox proportional hazard model, nicotine dependence presented a hazard ratio of 1.34 (95% CI: 1.1-1.64) (p = 0.01), indicating a 34% increase in psychosis risk for every additional point on the Fagerström Test for Nicotine Dependence. CONCLUSIONS: Our findings suggest that a comprehensive assessment of tobacco and alcohol use, diet, and physical activity in CHR-P subjects is key to understanding how physical health contributes to psychosis risk.

The noise in our brain: A systematic review and meta-analysis of neuroimaging and signal-detection studies on source monitoring in psychosis.

OBJECTIVES: Noisy thoughts or perceptions are characteristics of psychosis (PSY) and, they are deeply related to source monitoring (SM) - the ability to discriminate the origin of internal/external experiences. METHODS: This MOOSE, PRISMA-compliant meta-analysis compared SM performances in PSY compared to healthy controls (HC) focusing on signal-to-noise discrimination in order to: i) test whether neuroimaging procedures (fMRI/EEG) might be a group-specific source of noise for SM; ii) compare error- and accuracy-based indexes; iii) to meta-analyze signal-detection measures (i.e., discrimination index and response bias); iv) to determine the best index capturing SM deficits in psychosis. We conducted a 3-level meta-analysis for each aim to estimate pooled effect-sizes (Cohen's d). SM type, source discrimination and stimulus modality were used as meta-regressors. Heterogeneity (I2), publication bias (Egger's test) and multiple comparisons (Bonferroni correction) were considered. RESULTS: Sixteen neuroimaging, 44 error/accuracy-based behavioral and 7 signal-detection trials were included (2297 PSY, age range = 18.78-52.6; 1745 HC, age range = 21.1-53.3). The noise generated by neuroimaging procedures slightly influenced error, but not accuracy. Accuracy-based (d = -0.83), but not error-based, indexes showed significant and large SM impairments in PSY compared to HC. Overall SM performance differences between PSY and HC were larger in discrimination index (d = -0.65) and accuracy (d = -0.61), followed by response bias (d = -0.59, ns) and error-based (d = 0.35) indexes. CONCLUSION: Although both accuracy and discrimination indexes differentiate patients with PSY from HC, discrimination index is more reliable and may better capture the bi-directional nature of the internal/external source confusion.

Self-reported interoception and exteroception are atypical and excessively coupled in psychosis compared to healthy controls.

Although psychotic disorders are characterized by an impaired ability to discriminate internal and external worlds, the role of interoceptive and exteroceptive perceptions in determining this alteration is still unclear. This observational study aimed at investigating (a) increases/decreases in interoceptive and exteroceptive perceptions in patients with psychosis (PSY) compared to healthy controls (HC); (b) the association between interoception and exteroception in HC and PSY. Two hundred and ten HC and 72 PSY completed the Multidimensional Assessment of Interoceptive awareness (MAIA, 8 domains) and the Adolescent-Adult Sensory Profile (AASP, 4 domains). MAIA/AASP differences were evaluated with MANOVA, Kruskal-Wallis and Mann-Whitney tests. MAIA and AASP scores were correlated to quantify the interoceptive-exteroceptive coupling as Spearman's rho coefficients. Subgroup analyses were performed dividing PSY in schizophrenia/schizoaffective versus other psychosis. Compared to HC, PSY showed increased mean scores in four MAIA and two AASP domains (Bonferroni-p < 0.01). The interoceptive-exteroceptive coupling followed two correlation patterns in HC. A first pattern displayed negative correlations between MAIA not-worrying and AASP sensory sensitivity/sensation avoidance, while the second pattern highlighted positive correlations between MAIA scores and AASP sensation seeking. The two correlation patterns between HC and other-PSY subgroup were similar. However, schizophrenia/schizoaffective PSY did not show positive correlations in the second pattern, rather displaying negative correlations between MAIA scores and AASP domains related to passive behavioral responses. Correlation values were more extreme in PSY subgroups, indicating stronger interoceptive-exteroceptive coupling compared to HC. This study demonstrates that interoception and exteroception are atypical and excessively coupled in psychosis compared to the general population.Clinical Trials Registration: Protocol Number 20210003663 (Pavia, Ethical Committee IRCCS Policlinico San Matteo).

Should perception of emotions be classified according to threat detection rather than emotional valence? An updated meta-analysis for a whole-brain atlas of emotional faces processing.

BACKGROUND: Human navigation of social interactions relies on the processing of emotion on faces. This meta-analysis aimed to produce an updated brain atlas of emotional face processing from whole-brain studies based on a single emotional face-viewing paradigm (PROSPERO CRD42022251548). METHODS: We conducted a systematic literature search of Embase, MEDLINE and PsycINFO from May 2008 to October 2021. We used seed-based d mapping with permutation of subject images to conduct a quantitative meta-analysis of functional neuroimaging contrasts between emotional (e.g., angry, happy) and neutral faces. We conducted agglomerative hierarchical clustering of meta-analytic map contrasts of emotional faces relative to neutral faces. We investigated lateralization of emotional face processing. RESULTS: From 5549 studies identified, 55 data sets (1489 healthy participants) met our inclusion criteria. Relative to neutral faces, we found extensive activation clusters by fearful faces in the right inferior temporal gyrus, right fusiform area, left putamen and amygdala, right parahippocampalgyrus and cerebellum; we found smaller activation clusters by angry faces in the right cerebellum and right middle temporal gyrus (MTG) and by disgusted faces in the left MTG. Happy and sad faces did not reach statistical significance. Clustering analyses showed similar activation patterns of fearful and angry faces; activation patterns of happy and sad faces showed the least correlation with other emotional faces. Emotional face processing was predominantly left-lateralized in the amygdala and anterior insula, and right-lateralized in the ventromedial prefrontal cortex. LIMITATIONS: Reliance on discretized effect sizes based on peak coordinate location instead of statistical brain maps, and the varying level of statistical threshold reporting from original studies, could lead to underdetection of smaller clusters of activation. CONCLUSION: Processing of emotional faces appeared to be oriented toward identifying threats on faces, from highest (i.e., angry or fearful faces) to lowest level (i.e., happy or sad faces), with a more complex lateralization pattern than previously theorized. Emotional faces may be processed in latent grouping but organized by threat content rather than emotional valence.

Time will tell: Associations between unbalanced time perspectives and symptom severity in individuals with schizophrenia spectrum disorders.

Patients with schizophrenia spectrum disorder (SSD) experience disrupted temporality on the immediate timescale. However, insufficient information is available for longer time frames, and the interaction of temporal perspectives with the clinical manifestations of SSD is unknown. We explored the association between unbalanced time perspectives and symptom severity. Thirty-seven Italian mental health services participating in the DiAPAson project recruited 620 patients with DSM-5 SSD (68 % males, mean age = 41.3 ± 9.5 years). Time perspective biases were measured using the Deviation from the Balanced Time Perspective-revisited (DBTP-r) indicator, based on Zimbardo Time Perspective Inventory (ZTPI) scores. Psychiatric symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS) and Brief Negative Symptoms Scale (BNSS). Preliminary analyses examined the associations between ZTPI/DBTP-r and BPRS/BNSS total scores. In secondary analyses, we first tested the associations between the ZTPI/DBTP-r and BPRS/BNSS subscales and then compared ZTPI differences between patients with and without hallucinations, delusions, and conceptual disorganisation. Statistical significance was set at Holm-Bonferroni corrected p < 0.05. Low-to-moderate positive correlations were found between the DBTP-r and BPRS/BNSS total scores (r = 0.29/0.22). The strongest associations were between DBTP-r/ZTPI_Past-Negative and anxiety/depression (r = 0.34/0.36), followed by DBTP-r/ZTPI_Present-Fatalistic with thought disturbances (r = 0.22/0.20). DBTP-r was associated with BNSS anhedonia and avolition (r = 0.21/0.24). DBTP-r was higher in patients with hallucinations (ES = 0.391) and conceptual disorganisation (ES = 0.397) than in those without these symptoms. Unbalanced time perspective was positively associated with the severity of primary and secondary SSD features. These findings provide a rationale for empirical tests focused on balancing time perspectives in patients with SSD.

The lived experience of depression: a bottom-up review co-written by experts by experience and academics.

We provide here the first bottom-up review of the lived experience of depression, co-written by experts by experience and academics. First-person accounts within and outside the medical field were screened and discussed in collaborative workshops involving numerous individuals with lived experience of depression, family members and carers, representing a global network of organizations. The material was enriched by phenomenologically informed perspectives and shared with all collaborators in a cloud-based system. The subjective world of depression was characterized by an altered experience of emotions and body (feeling overwhelmed by negative emotions, unable to experience positive emotions, stuck in a heavy aching body drained of energy, detached from the mind, the body and the world); an altered experience of the self (losing sense of purpose and existential hope, mismatch between the past and the depressed self, feeling painfully incarcerated, losing control over one's thoughts, losing the capacity to act on the world; feeling numb, empty, non-existent, dead, and dreaming of death as a possible escape route); and an altered experience of time (experiencing an alteration of vital biorhythms, an overwhelming past, a stagnation of the present, and the impossibility of the future). The experience of depression in the social and cultural context was characterized by altered interpersonal experiences (struggling with communication, feeling loneliness and estrangement, perceiving stigma and stereotypes), and varied across different cultures, ethnic or racial minorities, and genders. The subjective perception of recovery varied (feeling contrasting attitudes towards recovery, recognizing recovery as a journey, recognizing one's vulnerability and the need for professional help), as did the experience of receiving pharmacotherapy, psychotherapy, and social as well as physical health interventions. These findings can inform clinical practice, research and education. This journey in the lived experience of depression can also help us to understand the nature of our own emotions and feelings, what is to believe in something, what is to hope, and what is to be a living human being.

Progressive Voxel-Wise Homotopic Connectivity from childhood to adulthood: Age-related functional asymmetry in resting-state functional magnetic resonance imaging.

Homotopic connectivity during resting state has been proposed as a risk marker for neurologic and psychiatric conditions, but a precise characterization of its trajectory through development is currently lacking. Voxel-Mirrored Homotopic Connectivity (VMHC) was evaluated in a sample of 85 neurotypical individuals aged 7-18 years. VMHC associations with age, handedness, sex, and motion were explored at the voxel-wise level. VMHC correlates were also explored within 14 functional networks. Primary and secondary outcomes were repeated in a sample of 107 adults aged 21-50 years. In adults, VMHC was negatively correlated with age only in the posterior insula (false discovery rate p < .05, >30-voxel clusters), while a distributed effect among the medial axis was observed in minors. Four out of 14 considered networks showed significant negative correlations between VMHC and age in minors (basal ganglia r = -.280, p = .010; anterior salience r = -.245, p = .024; language r = -.222, p = .041; primary visual r = -.257, p = .017), but not adults. In minors, a positive effect of motion on VMHC was observed only in the putamen. Sex did not significantly influence age effects on VMHC. The current study showed a specific decrease in VMHC for minors as a function of age, but not adults, supporting the notion that interhemispheric interactions can shape late neurodevelopment.

Time perspective affects daily time use and daily functioning in individuals with Schizophrenia Spectrum Disorders: Results from the multicentric DiAPAson study.

Time perspective (TP) influences various aspects of human life. We aimed to explore the associations between TP, daily time use, and levels of functioning among 620 patients (313 residential patients and 307 outpatients) with a diagnosis of Schizophrenia Spectrum Disorders (SSD) recruited from 37 different centres in Italy. The Brief Psychiatric Rating Scale and the Specific Levels of Functioning (SLOF) were used to assess psychiatric symptoms severity and levels of functioning. Daily time use was assessed using an ad hoc paper and pencil Time Use Survey. The Zimbardo Time Perspective Inventory (ZTPI) was used to assess TP. Deviation from Balanced Time Perspective (DBTP-r) was used as an indicator of temporal imbalance. Results showed that the amount of time spent on non-productive activities (NPA) was positively predicted by DBTP-r (Exp(ß): 1.36; p .003), and negatively predicted by the Past-Positive (Exp(ß): 0.80; p .022), Present-Hedonistic (Exp(ß): 0.77; p .008), and Future (Exp(ß): 0.78; p .012) subscales. DBTP-r significantly negatively predicted SLOF outcomes (p .002), and daily time use, in particular the amount of time spent in NPA and Productive Activities (PA), mediated their association. Results suggested that rehabilitative programs for individuals with SSD should consider fostering a balanced time perspective to reduce inactivity, increase physical activity, and promote healthy daily functioning and autonomy.

Physical Health in Clinical High Risk for Psychosis Individuals: A Cross-Sectional Study.

BACKGROUND: The clinical high risk for psychosis (CHR-P) phase represents an opportunity for prevention and early intervention in young adults, which also could focus on improving physical health trajectories. METHODS: We conducted a RECORD-compliant clinical register-based cohort study. The primary outcome was to describe the physical health of assessed CHR-P individuals, obtained via Electronic Health Records at the South London and Maudsley (SLaM) NHS Foundation Trust, UK (January 2013-October 2020). RESULTS: The final database included 194 CHR-P subjects (46% female). Mean age was 23.70 ± 5.12 years. Percentage of tobacco smokers was 41% (significantly higher than in the age-matched general population [24%]). We found that 49% of subjects who consumed alcohol had an AUDIT-C (Alcohol Use Disorder Identification Test) score above 5 (hazardous drinking), with an average score of 4.94 (significantly higher than in the general population [2.75]). Investigating diet revealed low fiber intake in most subjects and high saturated fat intake in 10% of the individuals. We found that 47% of CHR-P subjects met the UK recommended physical activity guidelines (significantly lower than in the general population [66%]). Physical parameters (e.g., weight, heart rate, blood pressure) were not significantly different from the general population. CONCLUSIONS: This evidence corroborates the need for monitoring physical health parameters in CHR-P subjects, to implement tailored interventions that target daily habits.

Quetiapine Treatment for Post-traumatic Stress Disorder: A Systematic Review of the Literature.

Paroxetine and Sertraline are the only medications approved in posttraumatic stress disorder (PTSD). However, about 60% of traumatized patients fail to show an adequate clinical response. Second generation antipsychotics are recommended as second-line monotherapy or third-line augmentation strategies and quetiapine appears as one of the most used and promising agents. Up to date, no reviews assessed the efficacy of quetiapine in the treatment of PTSD. We aimed to assess the effectiveness and general safety of quetiapine on PTSD. A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting studies that evaluated the efficacy of quetiapine on global or specific PTSD symptomatology. Ten studies (n = 894) were considered eligible for qualitative synthesis: one case report, one case series, one prospective cohort study, 3 open-label trials, 3 retrospective studies, one randomized controlled trial. Quetiapine was effective on global PTSD symptomatology assessed in 6 studies as well as on re-experiencing (4/4 studies), avoidance (4/3 studies) and hyperarousal (4/4 studies), flashbacks (2/2 studies), depressive (4/4 studies), anxiety (1/1 studies), psychotic (3/3 studies), insomnia (4/5 studies), nightmares (3/3 studies) specific symptoms and PTSD domains. Sedation was among the most frequently observed adverse effects and the main cause of drug discontinuation. Preliminary findings support the efficacy of quetiapine in ameliorating symptoms relative to PTSD and its overall safety. However, quetiapine use in PTSD cannot be recommended yet as studies mainly rely on open-label, retrospective studies or case series.

Not a matter of quantity: quality of relationships and personal interests predict university students' resilience to anxiety during CoViD-19.

During the CoViD-19 pandemic, University students may have suffered from increased anxiety due to interferences in their relationships and in academic requirements, as didactic activities have moved to distance learning systems. However, being surrounded by supportive relationships and being motivated to cultivate personal interests might have decreased anxiety. In this pilot study, we collected the responses of 174 students from Italian University merit colleges to an online questionnaire, investigating their perceived anxiety, the quality of surrounding relationships, whether they were cultivating any personal interests and whether they had spent the period of lockdown in college or at home. Regression analyses indicated that both quality of relationships and personal interests predicted low levels of anxiety (p < 0.001). However, simple slope analyses showed that personal interests were negatively related to anxiety only at medium and high quality of relationships (p < 0.001), while no association was found at low quality of relationships. No differences were found between students who stayed in college or at home. These results suggest that Universities should promote accessibility to relationships and cultivation of personal interests to protect students' mental health during mass emergencies such as the current pandemic, in the perspective of improving community resilience.

Efficacy of Olanzapine in Anxiety Dimension of Schizophrenia: A Systematic Review of Randomized Controlled Trials.

Anxiety symptoms and anxiety disorders are frequent in patients with schizophrenia and are associated with greater severity of both positive and negative symptoms, cognitive impairment, poorer functioning and quality of life. Accumulating evidence suggests that atypical antipsychotics may have a role in treating comorbid anxiety symptoms. A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting randomized control trials (RCTs) that evaluated efficacy of olanzapine on anxiety symptoms in patients diagnosed with schizophrenia and included anxiety evaluation scales. We searched PubMed and Web of Science databases for articles in English language available until September 2021. We selected 7 studies (3 with primary data analysis, 4 with secondary data analysis) regarding the use of olanzapine in patients with schizophrenia. In fours studies olanzapine was superior to haloperidol in improving anxiety symptoms. Four studies compared olanzapine versus risperidone: in two of them risperidone was superior to olanzapine, although one study was limited by a relatively small sample size. In the other two there were no significant differences between olanzapine and risperidone-treated patients. One study found that olanzapine and clozapine were comparable in terms of efficacy. Although olanzapine was superior to haloperidol in treating anxiety, this symptom was a secondary outcome measure in most of the considered studies. Future RCTs comparing different antipsychotics and larger sample sizes may allow to develop more solid treatment strategies.

State-dependent reductions of local brain connectivity in schizophrenia and their relation to performance and symptoms: A functional magnetic resonance imaging study.

State-dependent reallocation of cognitive resources is impaired in schizophrenia and may be underlined by alterations in brain local-connectivity. Increasing evidence suggests local connectivity reductions from rest to task in healthy individuals, while insufficient information is available for schizophrenia spectrum. Resting-state and stop-signal task fMRI scans of 107 healthy controls and 32 patients with DSM-IV-TR schizophrenia or schizoaffective disorder were analyzed. As primary aim we measured within-group shifts in local-connectivity from rest to task as voxel-wise Regional Homogeneity (ReHo-shift). Secondary aims were to test: i) Between-groups differences in ReHo-rest, ReHo-task and ReHo-shift; ii) ReHo covariations with task performance (=shorter reaction times) and severity of symptoms (SAPS/SANS scores). Age, sex, and education were accounted for as covariates. Motion, global-signal-regression, antipsychotic dosage and smoothing associations with ReHo were evaluated. Rest-to-task ReHo reductions occurred in both groups on a whole-brain level (False-Discovery-Rate p=0.05). Trends of greater ReHo reductions in patients versus controls were observed. Controls performed better than patients (p<0.001). ReHo negatively correlated with performance in both groups. ReHo-shift predicted worse performance in controls, but better performance in patients (uncorrected p=0.05). ReHo reductions correlated with severity of symptoms. State-dependent reconfigurations in local-connectivity provide new links between neurobiology and behavioral/clinical features of the schizophrenia spectrum.

Corrigendum: Perceived Family Functioning Profile in Adolescents at Clinical High Risk for Psychosis: Rigidity as a Possible Preventive Target.

[This corrects the article DOI: 10.3389/fpsyt.2022.861201.].

Lithium and Valproate in Bipolar Disorder: From International Evidence-based Guidelines to Clinical Predictors.

Since decades, lithium and valproate remain the pharmacological cornerstone to treat bipolar disorder. Different response patterns occur according to the phases of illness. At same time, individual pretreatment variables may concur to determine a specific drug-response. Our narrative review focuses on these two key clinical aspects to summarize the state of art. Information from i) clinical trials and ii) the most relevant international guidelines is collected to assess the clinical and preclinical factors that may guide the use of lithium rather than valproate. Lithium may be effective in treating acute mania, and lithium efficacy is maximized when used to prevent both manic and depressive episodes. Lithium may be a better treatment choice in patients with: positive family history for bipolar disorder, mania-depression-interval pattern, few previous affective episodes/hospitalizations, high risk for suicide, no comorbidities. Valproate may be more effective as antimanic rather than prophylactic agent. Valproate might be a better choice in patients with many previous affective episodes/hospitalizations and psychiatric comorbidities. Finally, neither lithium nor valproate are suggested for the treatment of acute mixed states or bipolar depression. To consider clinical and preclinical factors may thus be useful to select the best treatment strategy.

Centrality and interhemispheric coordination are related to different clinical/behavioral factors in attention deficit/hyperactivity disorder: a resting-state fMRI study.

Eigenvector-Centrality (EC) has shown promising results in the field of Psychiatry, with early results also pertaining to ADHD. Parallel efforts have focused on the description of aberrant interhemispheric coordination in ADHD, as measured by Voxel-Mirrored-Homotopic-Connectivity (VMHC), with early evidence of altered Resting-State fMRI. A sample was collected from the ADHD200-NYU initiative: 86 neurotypicals and 89 participants with ADHD between 7 and 18 years old were included after quality control for motion. After preprocessing, voxel-wise EC and VMHC values between diagnostic groups were compared, and network-level values from 15 functional networks extracted. Age, ADHD severity (Connor's Parent Rating-Scale), IQ (Wechsler-Abbreviated-Scale), and right-hand dominance were correlated with EC/VMHC values in the whole sample and within groups, both at the voxel-wise and network-level. Motion was controlled by censoring time-points with Framewise-Displacement > 0.5 mm, as well as controlling for group differences in mean Framewise-Displacement values. EC was significantly higher in ADHD compared to neurotypicals in the left inferior Frontal lobe, Lingual gyri, Peri-Calcarine cortex, superior and middle Occipital lobes, right inferior Occipital lobe, right middle Temporal gyrus, Fusiform gyri, bilateral Cuneus, right Precuneus, and Cerebellum (FDR-corrected-p = 0.05). No differences were observed between groups in voxel-wise VMHC. EC was positively correlated with ADHD severity scores at the network level (at p-value < 0.01, Inattentive: Cerebellum rho = 0.273; Hyper/Impulsive: High-Visual Network rho = 0.242, Cerebellum rho = 0.273; Global Index Severity: High-Visual Network rho = 0.241, Cerebellum rho = 0.293). No differences were observed between groups for motion (p = 0.443). While EC was more related to ADHD psychopathology, VMHC was consistently and negatively correlated with age across all networks.

Perceived Family Functioning Profile in Adolescents at Clinical High Risk for Psychosis: Rigidity as a Possible Preventive Target.

The presence of a positive family relationship has been suggested as a protective factor from parental stress and from the development of full-blown psychosis. However, to date, there is limited research on family functioning in adolescents with psychosis and at clinical high risk for psychosis (CHR-P). This study is aimed at comparing family functioning and perceived stress in parents of adolescents with either CHR-P, early onset psychosis (EOP), or other psychiatric disorders (no CHR-P). As a secondary aim, it will correlate family functioning with parental perceived stress in order to find critical targets of intervention. We conducted a Reporting of Studies Conducted Using Observational Routinely-Collected Health Data (RECORD)-compliant, real-world, cross-sectional study. One-hundred and eleven adolescents aged 12-17 who access the institute of hospitalization and care with scientific character (IRCCS) Mondino Foundation Neuropsychiatric services (Pavia, Italy) between 2017 and 2020 and their parents (n = 222) were included. Sociodemographic characteristics of adolescents and their parents were collected. Family functioning was evaluated through the Family Adaptability and Cohesion Evaluation Scale-IV (FACES-IV) and the level of stress through the Perceived Stress Scale (PSS). Twenty adolescents had EOP, 38 had CHR-P, and 59 had no CHR-P. In total, 2.6% of CHR-P adolescents were adopted, 76.3% had separated-divorced parents, and 34.2% of parents had a depressive disorder. Among the FACES-IV sub-scale, maternal rigidity was progressively increased from no-CHR-P to CHR-P to EOP group, with statistical differences between EOP and the other two groups (p = 0.01). CHR-P mothers and fathers showed a high level of PSS values, without group difference. Lastly, PSS values correlated positively with the Rigidity, Disengagement, and Chaos scale of FACES-IV and negatively with the Communication scale (p < 0.05). Our results suggest that family functioning has a central role and could represent a worthwhile target of intervention for adolescents at CHR-P, leading the way to new preventive approaches.